bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of avatrombopag in the treatment of chemotherapy-induced thrombocytopenia in children with acute lymphoblastic leukemia: a single-center retrospective study
Authors: Yang Huiyan , Gao Jingyu , Ruan Yongsheng , Chen Zhaokun , Fang Ruihan , Zhang Lei , Wang Zhibiao , Yi Tiantian , Zhang Qian , Luo Yang , Chen Libai , Wu Xuedong
Published: December 2024

Background:

Chemotherapy-induced thrombocytopenia (CIT) commonly exacerbates the difficulty of cancer treatment, increasing bleeding risks and potentially reducing chemotherapy dosage, ultimately impacting its efficacy. However, there are limited studies about avatrombopag application in acute lymphoblastic leukemia (ALL) CIT.

Objectives:

We aimed to evaluate the efficacy and safety of avatrombopag in treating CIT patients diagnosed with ALL.

Design:

This retrospective study, using propensity score matching, included 42 pairs of cases treated with and without avatrombopag (CAT: 54 cases, CAT+: 30 cases).

Methods:

Data of CIT-ALL children were retrospectively collected. The primary endpoint was platelet count (PC) response rate on day 10 ± 2 (defined as an increase of PC to ⩾75 × 109/L with the exclusion of platelet transfusion). Secondary efficacy endpoints, safety endpoints, and factors that predict PC response were also analyzed.

Results:

In the avatrombopag group, the PC response rate was prominently higher on day 10 ± 2 (89.1%) versus the control group (56.4%, p = 0.005). On day 10 ± 2, the difference in median PC change from baseline was predominantly distinct in the avatrombopag group compared to the control group ( p = 0.001). In the avatrombopag group, platelet recovery to ⩾25 and ⩾50 × 109/L was faster ( p = 0.001, p = 0.002), and quicker platelet reaching ⩾75 × 109/L and ⩾100 × 109/L was achieved ( p = 0.023, p = 0.011). The avatrombopag group not only increased the nadir PC ( p = 0.009) but also reduced the total platelet transfusion compared to the control group ( p = 0.047). Only one case (2.4%) experienced bleeding events after medication. Nine cases of secondary thrombocythemia were noted without other adverse events. There was no difference in event-free survival between the two groups ( p = 0.648). Drug administration was prediction factor for PC response.

Conclusion:

Avatrombopag is a potentially safe and effective treatment option for CIT in pediatric ALL.
Illusory shrinkage of objects under backward masking
Authors: Kaneko Sae , Anstis Stuart , Cavanagh Patrick
Published: December 2024

Backward masking is a powerful phenomenon that can reduce, often to zero, the visibility of targets. Here, we show that when the masking is less than completely effective so that the target remains visible, the masking has other effects, specifically reducing the perceived size of the target.
Urgent percutaneous coronary intervention in type 2 Wellens’ syndrome: A case report of an atypical presentation in an elderly patient
Authors: Diallo Thierno Hamidou , Djafarou Boubacar Raynatou , Azday Illy Sawssen , Fellat Rokya , Fellat Nadia
Published: December 2024

Traditionally reflecting critical stenosis of the proximal left anterior descending (LAD) artery, Wellens’ syndrome (WS) is an electrocardiogram (ECG) pattern of biphasic or deeply inverted T waves in leads V2 and V3. This critical stenosis can progress to an extensive anterior myocardial infarction (MI) if early and appropriate management is not received promptly. The diagnosis of severe stenosis of the LAD coronary artery can be made by using electrocardiographic changes in Wellens’ syndrome. Due to the significant area that the LAD vascularizes, patients who exhibit symptoms and test results suggestive of this syndrome should be referred right away for an angiographic exploration in order to confirm the diagnosis and guide treatment. We report a case of a 71-year-old male admitted to our department for acute chest pain. His ECG showed Wellens’ syndrome type 2 during both chest pain and pain free with slightly elevated troponin. His TIMI score was 3 and the GRACE score was 136. Critical stenosis of the LAD coronary artery was found in the coronary angiography, which required a drug-eluting stent. The patient was discharged asymptomatic from medical therapy. The diagnosis was established on the basis of the patient’s interview, ECG analysis, and coronary angiography.
Management of a large basal cell carcinoma masquerading as psoriasis using Mohs and serial excisions
Authors: Nanda Rahul , Thuraisingam Thusanth
Published: December 2024

Basal cell carcinoma (BCC) is the most common type of skin cancer. The superficial subtype of BCC may present as a scaly erythematous plaque. This case report discusses a large BCC on the left scalp of an elderly patient who was treated for many years as plaque psoriasis. This report also discusses scouting biopsies as a valuable tool for the dermatologic surgeon to aid in cancer mapping. Finally, we describe the use of serial excisions using Mohs micrographic surgery on the advancing edge as a therapeutic option for large BCCs in high-tension areas.
A transcutaneous electrical nerve stimulation device for the relief of neuropathic pain in NMOSD: A randomized, double-blind, sham-controlled trial
Authors: Vishnevetsky Anastasia , Romanow Gabriela , Levy Michael
Published: December 2024

Background

Individuals with neuromyelitis optica spectrum disorder (NMOSD) often suffer from severe, disabling, and treatment-refractory neuropathic pain. Transcutaneous electrical nerve stimulation (TENS) therapy is a non-invasive, pain-modifying device.

Objective

To determine whether TENS therapy is safe, tolerable, and effective for neuropathic pain in patients with NMOSD.

Methods

We conducted a four-week, randomized, double-blind, sham-controlled, remote trial of TENS in patients with NMOSD who have neuropathic pain, followed by a 12-week open-label extension period. The difference in the Numeric Rating Scale current pain scores between 0 weeks and 4 weeks was the primary outcome measure.

Results

Forty-six patients (23 per arm) were enrolled in this trial, of which 40 were included in the primary analysis (four in the intervention arm and two in the sham arm withdrew prior to assessment of the primary outcome). Both the sham and intervention arms demonstrated significant decreases in average pain, worst pain, and current pain rating between baseline and 4 weeks, but there was no significant difference between the two arms.

Conclusions

In conclusion, there was no demonstrated benefit of TENS over sham TENS treatment, however, both arms demonstrated significant decreases in reported pain between baseline and 4 weeks. This trial is registered with ClinicalTrials.gov, NCT04614454.
Longitudinal Associations Between TikTok Use, Self-Concept Clarity, and Anxiety Among Chinese Emerging Adults: Exploring Differential Impacts of Active and Passive TikTok Use
Authors: Liu Qingqi , Wen Jiani , Wang Ningxi , Wang Manjun
Published: December 2024

Short-form video applications, such as TikTok, have gained significant popularity among emerging adults. We conducted a longitudinal study to gather data at three time points from two universities in South China. A total of 590 university students ( M age = 19.83; SD age = 1.24) completed the questionnaires measuring active and passive TikTok use behaviors at time 1 (T1, April 2022), self-concept clarity at time 2 (T2, October 2022), and anxiety both at Time 1 (T1, April 2022) and at Time 3 (T3, April 2023). The results showed that T1 active TikTok use had a negative correlation with T3 anxiety ( r = −0.23, p < .001), while T1 passive TikTok use had a positive correlation with T3 anxiety ( r = 0.30, p < .001). Both T1 active TikTok use (95% CI [0.03, 0.09]) and T1 passive TikTok use (95% CI [0.07, 0.16]) can predict T3 anxiety indirectly by reducing T2 self-concept clarity. Moreover, even after considering T2 self-concept clarity, the direct impact of T1 active TikTok use on T3 anxiety remained significant (95% CI [−0.24, −0.09]), but the direct effect of T1 passive TikTok use on T3 anxiety was not significant (95% CI [−0.04, 0.12]).
Curable Sexually Transmitted Infections Among a Population of South African Nonhealth Seeking Men Who Have Sex With Men Who Were Invited for Screening—A Brief Report
Authors: Malefo Matshidiso Adelaide , Ayo-Yusuf Olalekan Abdulwahab , Mokgatle Mathildah Mpata
Published: December 2024

Background: This study assessed sexually transmitted infection (STI) results among nonhealth-seeking men who have sex with men (MSM) who had not previously screened for curable STIs. Methods: Secondary data analysis of a sample of 164 MSM who were STI infection naïve was performed. Data were collected in the Clinical Research Unit (MeCRU) among the MSM in the Tshwane North area, South Africa. Results: Over half of the sample (58.5%; n = 96) were in casual relationships, 81.7% ( n = 134) had reported testing for HIV in the previous 3 months, and 68.9% tested positive for STIs. Logistic regression revealed that the odds of a positive STI test result were significantly higher among those who had reportedly tested for HIV in the previous 3 months compared to those who had not (OR = 2.43; 95% CI = 1.06-5.69). Conclusion: The study revealed a high prevalence of STI among nonhealth seeking MSM and STI diagnosis was associated with having tested for HIV in the previous 3 months. It is, therefore, important to offer regular STIs screening services to the MSM community.
Promoting Equitable Human and Planetary Health Co-Benefits: An Opportunity for U.S. Leadership
Authors: White Kristi E. , Nogueira Leticia M. , Oyeyemi Adewale L.
Published: December 2024

Climate change is a public health emergency, and many communities have called on policymakers to address its far-reaching consequences on human and planetary health. As research shows, the hierarchical ordering of people and other living beings as more or less worthy of protection has contributed to environmental degradation and the current state of the climate crisis, which impact everyone regardless of hierarchical position. Several climate solutions have health co-benefits that can promote collective well-being when designed and implemented equitably. The United States has an opportunity to become a global leader by advancing transformative policies that harness the potential of these human-and-planet co-benefit solutions. Active (human-powered) transportation and use of green spaces represent two co-benefit solutions that show promise for equitably addressing public and planetary health. Policymakers are encouraged to work alongside communities to identify, develop, and implement co-benefit solutions that meet the collective needs of local populations while benefiting public and planetary health more broadly.
Magnitude and Determinants of job Stress among pre-Hospital Care Providers Working in Ambulance Centers, Addis Ababa
Authors: Alehegn Selamawit , Abraha Mebratu , Fikadu Ayele , Kasahun Gashaw , Mekonen Migbar Sibhat , Tiruneh Kasie Gebeyehu , Ashine Taye Mezgebu , Mesfin Edmealem Getahun
Published: December 2024

Introduction

Pre-hospital care personnel, including paramedics and emergency medical technicians (EMTs), are crucial frontline responders in emergency medical situations. They are critical in delivering timely medical assistance to individuals in emergencies. However, the demanding nature of their work can subject them to significant job stress, which may adversely affect their well-being and job performance.

Objectives

This study aimed to assess the levels of job stress and explore associated factors among pre-hospital care providers in Addis Ababa.

Methodology

A cross-sectional study was conducted at a healthcare facility, involving 134 ambulance healthcare providers. Participants were selected through a simple random sampling technique. Data collection employed pretested, self-administered questionnaires utilizing a nursing stress scale. Descriptive statistics were utilized to summarize the findings. Logistic regression analysis was employed to ascertain associations between variables while controlling for potential confounders. The strength of the association between dependent and independent variables was evaluated using odds ratios with a 95% confidence interval.

Result

Of the 134 study participants, 47% (95% CI: 38.2, 55.8) of them had job stress. Notably, several factors were significantly associated with job stress among pre-hospital healthcare providers working in ambulances. Conflict with leaders (AOR = 5.07; 95% CI: 2.98, 12.53), fear of mistakes (AOR = 8.22; 95% CI: 1.86, 36.34), lack of resources (AOR = 11.06; 95% CI: 5.19, 22.41), overloaded with ambulance care (AOR = 18.94; 95% CI: 4.33, 38.73) and inadequate information from dispatchers (AOR = 7.35; 95% CI: 3.32, 16.62) were identified as significant associated factors of job stress among these providers. These findings highlight the critical need to address leadership conflicts, fear of errors, and communication deficiencies to mitigate job stress among pre-hospital healthcare providers working in ambulances.

Conclusion

This study highlights the prevalence of job stress among pre-hospital healthcare providers working in ambulances, and found it as a significant problem. Notably, conflict with leaders, fear of mistakes, lack of resources, work overload and inadequate information from dispatchers emerged as significant associated factors contributing to job stress among pre-hospital health care providers. Efforts to foster better communication channels between providers and dispatchers, promote supportive leadership practices, and implement error-reduction strategies are essential. By addressing these challenges, healthcare organizations can create a more conducive work environment that supports the mental and emotional health of pre-hospital healthcare providers.
Pharmacology Knowledge Among Nurses Working in Nursing Homes in Norway: A Cross-Sectional Study
Authors: Taasen Siv Eriksen , Kvam Fred-Ivan , Blytt Kjersti Marie , Messaoudi El Houcine
Published: December 2024

Introduction

The administration of drugs is an important part of nurses’ professional practice. A basic knowledge of pharmacological principles is required to make accurate decisions about drug management and conduct patient medication education. However, several studies have suggested that nurses have inadequate knowledge of pharmacology and medication management.

Objective

To explore the level of knowledge in pharmacology and medication management among nurses working in nursing homes (NHs).

Methods

We conducted a cross-sectional study at 24 NHs in Norway. The nurses took a multiple-choice test in pharmacology with 35 questions at their workplace. Each question had four alternative answers with one answer being correct. One point was awarded for a correct answer and zero for a wrong answer. The test included categories in general pharmacology, clinical pharmacology, and medication management.

Results

In total, 145 nurses completed the questionnaire. In the range of 0–35 correct responses, the mean score for the sum of all questions was 22.5, which equates to 66% of responses being correct. Linear multiple regression showed no association regarding gender, age distribution among the nurses, years since completing basic education in nursing, years of work experience in NHs, postgraduate education, and knowledge of pharmacology and medication management. Knowledge was better in the category medication management ( p < 0.001) than in the category's general pharmacology and clinical pharmacology. When evaluating specific test questions, 38.9% of the nurses answered a question on opioids correct, 64.1% a question on anticoagulants correct, 33.5% knew the prerequisites for generic substitution, and 45.5% did not know the difference between agonists and antagonists.

Conclusion

Our results are in line with previous findings. The participating nurses working in the NHs have insufficient knowledge in pharmacology and medication management. This may cause harm and undermine patient safety.
Practice and Evaluation of Competence in Assessment of Arterial Circulation of the Lower Limbs among Medical Students and Physicians in Training – A Systematic Review
Authors: Macek Martin , Eek Frida , Wrede Axel , Butt Talha , Acosta Stefan
Published: December 2024

Introduction

A recent study on patients with acute lower limb ischemia showed that the proportion of inadequate examination of lower extremity circulation was associated with higher rate of amputation and death. The aim of this systematic review was to explore evidence for how practical competence in performing a peripheral vascular status of the lower limb among medical students and junior doctors should be taught and examined.

Methods

The systematic review followed PRISMA guidelines and was published in PROSPERO. Articles were searched for in PubMed, Cochrane Library and Embase. The result was processed by two researchers. After title- and abstract screenings, articles were scrutinized in full text for inclusion, result extraction, risk of bias assessment through Medical Education Research Study Quality Instrument (MERSQI), and evidence grading with the GRADE approach.

Results

Thirteen studies were included. Two studies were randomized controlled trials (RCTs). Study samples varied between medical students (n = 9), junior doctors (n = 3) and residents (n = 3). Interventions varied between theoretical, practical, repetitive training, feedback-based learning, and clinical experience. Assessed measurements (outcomes) were ankle-brachial index (ABI) (n = 9), theoretical knowledge (n = 4), pulse palpation (n = 1) and complete vascular status (n = 1). Experienced residents had better theoretical knowledge than inexperienced residents, but performance of the entire ABI procedure without any mistake according to guidelines was inadequate in both groups. One RCT showed that experimental training significantly increased ability to perform ABI measurements, but this ability decreased after six months without repetition.

Conclusion

Theoretical training alone is not sufficient in ensuring proficiency in vascular examination of the lower limbs. Continuous practice and clinical exposure are crucial to maintain proficiency in performing vascular examination of the lower limbs. Data is limited and heterogenous. The level of certainty for the evidence was judged to be very low.
Knowledge and practice toward menstrual hygiene management and associated factors among visual impaired adolescent girls: a case of two selected institutions in Rwanda
Authors: Ishimwe Bazakare Marie Laetitia , Ngabo Rwabufigiri Bernard , Munyanshongore Cyprien
Published: December 2024

Background:

Menstruation is a universal and normal phenomenon during the reproductive age of females; adolescence is an essential period where females are preparing and adjusting themselves to manage their menstrual bleeding safely and cleanly. Menstrual hygiene management (MHM) is an issue that is insufficiently acknowledged and has not received adequate attention among visually impaired adolescent girls (VIAGs).

Objectives:

The purpose of this study was to determine the knowledge and practice of MHM and associated factors among VIAGs of selected institutions in Rwanda.

Design:

This study consisted of a cross-sectional study design using a quantitative approach.

Methods:

A cross-sectional study was conducted in April and May 2021 on 92 VIAGs. They were recruited from educational institutions in two Provinces in Rwanda. Voluntary participation and confidentiality were assured. Socioeconomic and demographic data, menstruation, and menstrual hygiene questionnaires were used to obtain the required information. Statistical Packages for the Social Sciences (SPSS) for Windows version 25 was used. Descriptive statistics, Chi-square test, and logistic regressions were used for data analysis.

Results:

The study reached 92 respondents. The majority of the respondents, 67.4% had a poor level of menstruation and menstrual hygiene knowledge while only 32.6% had a good level of menstruation and menstrual hygiene knowledge. Also, it is confirmed that the majority of respondents, 52.1% had a good level of practice, while 47.8% had a poor level of menstrual hygiene practice. The multivariable analysis revealed that factors associated with the menstrual hygiene practice were as follows: the mother’s education (odds ratio (OR): 5.979; 95% CI: [1.700–21.032]; p value: 0.005) and level of knowledge of menstruation and menstrual hygiene (OR: 0.132; 95% CI: [0.028–0.622]; p value: 0.010).

Conclusion:

The knowledge and practice of MHM among VIAGs were poor. Recommendations included the need for mothers to assist their daughters in improving learning and practice of menstrual hygiene, as well as the integration of MHM into school curricula. Further research is suggested to better understand MHM among Rwandan adolescent girls, both visually impaired and non-blind.
Mesenchymal Stem Cells Regulate Oxidative Stress-Induced Hematopoiesis Via Peroxisomal Metabolism
Authors: Lund Troy , Orchard Paul , Gupta Ashish O.
Published: December 2024

The role of peroxisomes in hematopoiesis and the bone marrow microenvironment remains poorly understood. Peroxisomes are small, membrane-bound organelles found in the cytoplasm of virtually all eukaryotic cells. They play a key role in various metabolic processes, primarily involving the breakdown of fatty acids, regulation of oxidative stress, the detoxification of hydrogen peroxide (H₂O₂), and the synthesis of plasmalogens. Past efforts in understanding the biology of peroxisomes has relied on knockout mice, but has been limited due to the effects on hematopoiesis and embryonically lethality. The novel PEX1-Gly844Asp knock-in hypomorphic mouse lacks peroxisome formation and is peroxisome deficient, but has survival into adulthood. We observed that peroxisome deficient animals had up to 50% greater numbers of peripheral lymphocytes, neutrophils, and platelets which contained 2-fold greater reactive oxygen species (ROS, p = 0.0002) compared to wild-type (WT) animals. Assessment of the bone marrow showed 2-fold greater numbers of total cells and colony forming units compared to WT (CFU, p = 0.0009 and < 0.0001, respectively). We found expansion (up to 3-fold) in the hematopoietic stem and progenitor cell (HSPC) compartment compared to that of WT demonstrated by in vivo enumeration of LSK (p < 0.0001) and LSK-SLAM (p < 0.0001). Importantly, through competitive bone marrow transplant experiments we show that peroxisome deficient cells outcompete WT by 50% (6 months after primary and secondary transplant). Interestingly, we further demonstrate that peroxisome deficient HSPC harbor very high levels of intrinsic ROS which are attenuated after repopulation. Isolation of mesenchymal stem cells (MSC) isolated from peroxisome deficient mice also showed 2-fold elevated levels of ROS compared to WT MSC. Finally, we found elevated levels of stem cell factor (SCF aka cKIT ligand) in the plasma of peroxisome deficient mice and peroxisome deficient MSC expressed 2-fold more SCF compared to WT. LSK expanded in the absence on SCF on peroxisome deficient MSC >10-fold greater than on WT MSC (p < 0.0001) in in vitro coculture assays. In conclusion, the increase in HSPC number we observed in peroxisome deficient animals is, in part, driven by a response to ROS in the microenvironment leading to increased SCF secretion. These data add new insight into the role of peroxisomes and oxidative stress in the bone marrow microenvironment and hematopoiesis.
Multi-Omics Reveal Immune Microenvironment Alterations in Multiple Myeloma and Its Precursor Stages
Authors: Cheng Yan , Sun Fumou , Alapat Daisy V. , Wanchai Visanu , Mery David E. , Siegel Eric , Xu Hongwei , Johnson Sarah K. , Guo Wancheng , Bailey Clyde , Ashby Cody , Bauer Michael Anton , Al Hadidi Samer , Schinke Carolina , Thanendrarajan Sharmilan , Zangari Maurizio , van Rhee Frits , Tricot Guido , Shaughnessy, Jr John D , Zhan Fenghuang
Published: December 2024

Introduction: Tumor immune microenvironmental alterations occur early in multiple myeloma (MM) development. Deep molecular characterization of the immune profiles and their crosstalk with tumor cells in MM and its precursor conditions is needed to advance treatment development and discover safe and efficient strategies to prevent disease progression. In this study, we aim to systematically characterize the tumor immune microenvironment (TME) and the tumor-immune interactions from precursor stages, i.e., monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM), to newly diagnosed MM, comparing these to healthy donors.

Methods: Most current studies rely on BM aspirates, which often get contaminated by peripheral blood and lose mature granulocytes during processing. To address this limitation, we evaluated the BM cell content using a whole BM gene expression-based computational technique, CIBERSORT, and investigated the correlation of immune cell proportions with patient outcome after 5-20 years of follow-up. We also analyzed BM immune cell functional marker expression using mass cytometry in a large cohort of patients and examined BM immune cell gene expression in paired stable or progressive MM precursor conditions and MM samples using single-cell RNA sequencing (sc-RNA seq).

Results: By integrating results from CIBERSORT, mass cytometry, and sc-RNA seq, we demonstrate an altered balance of innate and adaptive immunity persisting from MGUS to MM. Specifically, the proportion of neutrophils decreasing in the tumor microenvironment (TME), predicts SMM progression and MM outcomes. HLA-DR is reduced in CD16+ monocytes and plasmacytoid dendritic cells. Myeloid dendritic cells are also decreased, and their expression of stress and immune-response genes is inhibited in MM and its precursor stages. We find that NK cells and CD8 T cells show common features with a shift from GZMK+ to GZMB+ cytotoxic phenotype in the TME compared to normal BM and this is accompanied by increased expressions of inhibitory markers TIM3 and TIGIT. Finally, we show that patient-specific GZMB+ CD8 T cell subtypes demonstrate limited changes in paired precursor and MM samples despite the increased numbers and heterogeneity of MM subclones in overt MM.

Conclusion: Overall, these results provide a comprehensive immune landscape of MM and its precursor stages. Enhancing neutrophil and NK cell cytotoxicity, tumor antigen presentation, and CD8 T cell versatility in precursor stages may prevent MM progression.
Acute Erythroid Leukemia Clinicopathologic Determinants of Survival: Analysis of a Pooled Database
Authors: Haddad Philip A , Vutukuri Sireesha , Gupta Ankita
Published: December 2024

Background

Acute erythroid leukemia (AEL), a rare and aggressive subtype of acute myeloid leukemia (AML), is characterized by the predominant proliferation of immature erythroid precursors in the bone marrow and peripheral blood. Representing less than 5% of AML cases, AEL poses significant diagnostic and therapeutic challenges due to its atypical clinical presentation and the lack of standardized treatment protocols. AEL's prognosis remains poor. The determinants of survival outcomes in this disease are not very well defined. Therefore, we conducted this pooled real-world database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies that influence survival in this rare disease.

Methods

To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, prognostic factors, and survival, we compiled a pooled database of cases that satisfy the diagnostic criteria for AEL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS).

Results

A total of 169 patients with confirmed AEL were identified. The median age was 62. There was a male preponderance with M:F of 2.7. The median duration of symptoms before diagnosis was 5.5 months. Constitutional symptoms and splenomegaly were present in 67% and 10% of the cases, respectively. The median OS of the cohort was 3 months. While majority of the cases were de novo AEL (65%), some cases developed in the context of hematologic malignancies (14%), solid cancers (2%), and MDS/MPN (18%). Patients older than 65 had worse median OS (2 vs. 4 months, p=0.0001). Those who presented with >80% erythroblasts also had worse OS (2 vs 4 months, p=0.004). However, de novo AEL was associated with better OS (4 vs 2.8 months, p=0.003). Sex, levels of WBC, Hgb, and Platelets, IHC/Immunophenotype, and presence of constitutional symptoms did not impact OS. Compared to no treatment, chemotherapy and stem cell transplant had incrementally superior OS (1 vs. 3 vs. 9 months, p=0.0001). Those who received intensive AML regimens also had better OS (p=0.005). Furthermore, patients who achieved CR as their best response also had a superior median OS (9 vs. 2.6 months, p<0.0001).

Conclusion

This study presents updated clinicopathologic data from a large, pooled cohort of patients with AEL. It identifies age, % marrow erythroblasts, intensity of therapy, and quality of response to treatment as critical determinants of OS.
The Role of Intensive Chemotherapy and Radiotherapy in Plasmablastic Lymphoma: Optimizing Survival Outcomes
Authors: Haddad Philip A , Lerner Jaren , Gupta Ankita , Gupta Supriya
Published: December 2024

Background: Plasmablastic Lymphoma (PBL), a rare and aggressive subtype of non-Hodgkin's lymphoma, often arises in immunosuppressed patients, including those with HIV or undergoing immunosuppressive treatments. Due to its rarity, a standardized approach to its management has been elusive. Our study evaluated the effectiveness of intensive chemotherapy and radiotherapy on survival outcomes in patients with PBL.

Methods: We conducted a comprehensive analysis using a pooled database, encompassing demographic data, molecular characteristics, and treatment responses of a retrospective cohort with confirmed PBL cases. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the survival impacts of various treatments.

Results: The study cohort comprised 300 confirmed PBL cases with a median age of 49. It predominantly consisted of males (M:F ratio of 2.7). Approximately 51% were diagnosed at advanced stages (III/IV), and 62% had an immunocompromised status, 47% due to HIV. Analysis showed a median overall survival (OS) and disease-free survival (DFS) of 25 and 15 months, respectively. Significant factors influencing OS included bone marrow, liver, lung/pleura, and upper GI tract involvements; all were associated with poorer outcomes. Conversely, early-stage <2 disease (p<0.0001), head and neck involvement (p=0.0001), and attaining CR (p<0.0001) were linked to better survival. Compared to no treatment, chemotherapy (CT) and stem cell transplant had incrementally better OS (2 vs. 27 vs. NR months, p<0.0001). Patients who underwent frontline intensive chemotherapy (ICT) had a superior OS compared to those treated with CHOP-like or myeloma protocols in decreasing order (p<0.0001). ICI survival benefit persisted when analyzed by early vs. advanced stages (p=0.0009). Radiotherapy (RT) improved OS when added to intensive and non-intensive CT (p=0.03). However, upon further analysis, RT benefits were restricted to those with early stages (I&II) H&N PBL (NR vs. 27mo; p=0.0008).

Conclusion: Our findings support an aggressive chemotherapy approach in managing Plasmablastic Lymphoma with the addition of radiotherapy in H&N early-stage disease. This approach maximizes survival and highlights the importance of tailored treatment strategies based on disease stage and location.
Impact of Protein Energy Malnutrition on Hospitalized Patients with Multiple Myeloma: A United States Population-Based Cohort Study
Authors: Syal Arshi , Arya Yajur , Casipit Bruce Adrian , Dourado Claudia , Leighton John Charles
Published: December 2024

Background

Multiple myeloma poses a significant burden to the society and the healthcare system. With newer advances in therapeutics and prolonged survival, these patients are predisposed to multiple co-morbidities, including cancer-related cachexia, systemic inflammation, and adverse effects of therapy, often leading to varying degrees of protein-energy malnutrition (PEM). PEM can further complicate the clinical picture, leading to an inability to tolerate therapy & propagation of this vicious cycle. Thus, the impact of PEM on outcomes among patients with multiple myeloma needs further exploration.

Methods

We utilized the 2020 National Inpatient Sample (NIS) Database to conduct this retrospective cohort study. We identified patients with multiple myeloma and PEM using appropriate ICD-10 diagnostic codes. We stratified patients with multiple myeloma 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 multiple myeloma.

Results

We identified a total of 19025 hospitalized patients with multiple myeloma, of which 12.50% (2380/19025) had co-morbid PEM. The overall in-hospital mortality among patients with multiple myeloma was 4.33% (825/19025). Among those with concomitant PEM, the mortality rate was significantly higher at 9.24% (220/2380, 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 2.53; 95% (confidence interval [CI] 1.70-3.76; p<0.001), longer LOS (coefficient 3.78; CI 2.29-5.27; p<0.001), higher total hospitalization charge ($59042; CI $28467-$89617; p<0.001), and increased need for mechanical ventilation (adjusted OR 2.92; CI 1.78-4.79; p<0.001).

Conclusion

Our analysis demonstrated that PEM was widely prevalent in patients with multiple myeloma. 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 sizes are warranted to better understand these associations.
Clinical Characteristic Outcomes and Mortality Among Cancer and Non-Cancer Patients Presented with Incidental Pulmonary Embolism
Authors: Chai-Adisaksopha Chatree , Chaiwong Warawut , Niprapan Piangrawee , Tantiworawit Adisak , Bumroonkit Chaiwat
Published: December 2024

Introduction: Cancer patients are at risk of developing venous thromboembolism, which includes pulmonary embolism (PE) and deep vein thrombosis. Advances in multidetector computed tomography (CT) scanners have led to increased detection of PE. However, the natural course of incidental PE, particularly in cancer patients, remains controversial. The objectives of this study were to determine characteristics of PE and mortality among patients with and without cancer.

Methods: This retrospective cohort study was conducted at a tertiary medical center in Thailand. Patients aged 15 or older who were diagnosed with PE between 2011 and 2020, identified by the International Classification of Diseases, 10th Revision codes, were included in this study. Electronic medical records were reviewed to confirm the diagnosis of PE, which was defined as radiological evidence of PE by CT with contrast or V/Q scan. Patients were classified into two groups: the incidental PE (iPE) group and the suspected PE (sPE) group. Incidental PE was defined as cases where patients underwent CT without a specific request to investigate PE. The primary outcome was 30-day mortality.

Results: A total of 736 patients with acute PE were included in the study, with 281 classified as iPE and 455 as sPE. The mean age was 58.8 ± 14.3 years in the iPE group and 57.5 ± 16.2 years in the sPE group. Active cancer was more common in the iPE group compared to the sPE group (70.8% versus 46.6%, P<0.001). Patients in the sPE group were more likely to exhibit PE-related symptoms, including dyspnea (P<0.001), chest pain (P<0.001), tachycardia (P<0.001), tachypnea (P<0.001), shock (P<0.001), and oxygen saturation <90% (P<0.001). The sPESI score identified 84.9% of patients in the iPE group as high-risk and 94.0% in the sPE group. There was no significant difference in the risk of 30-day mortality between the iPE and sPE groups (odds ratio [OR] 0.73, 95% CI 0.52-1.04, P=0.08). However, subgroup analysis revealed that cancer patients with iPE had lower 30-day mortality compared to those in the sPE group (OR 0.40, 95% CI 0.26-0.61, P<0.001). There were no significant differences in 30-day mortality among non-cancer patients with iPE versus sPE (OR 1.31, 95% CI 0.66-2.59, P=0.44). Multivariable analysis showed that cancer patients with PE who had dyspnea (hazard ratio [HR] 1.92, 95% CI 1.13-3.37, P=0.016), tachycardia (HR 1.66, 95% CI 1.13-2.45, P=0.01), oxygen saturation <90% (HR 1.67, 95% CI 1.06-2.65), and ECOG performance status >1 (HR 1.98, 95% CI 1.22-3.21) were associated with a significantly increased risk of death.

Conclusions: Although the overall mortality rate of patients with iPE was not significantly different from those with sPE, patients with active cancer had a higher risk of 30-day mortality, particularly if they exhibited symptoms related to PE.
Health Related Quality of Life (HrQoL) in Patients with Bleeding Disorder of Unknown Cause (BDUC)
Authors: Monard Amaury , Tegels Sanne , Merry Inge , Derikx Floor , Henskens Yvonne , Beckers Erik AM , Moenen Floor CJI
Published: December 2024

Background: Patients with an increased bleeding tendency without any abnormalities in laboratory hemostasis tests are classified as having a bleeding disorder of unknown cause (BDUC). Data on health related quality of life (HrQoL) in BDUC patients and other patients with an increased bleeding tendency are scarce. The aim of this study was to investigate HrQoL in patients with BDUC and by extension in other patients with an increased bleeding tendency.

Methods: 237 patients from the prospective Predictors of Bleeding Evaluation in Adult Hematologic Patients with Bleeding Tendencies cohort (ProBe-AHP study), in which patients with an increased bleeding tendency are included, were invited to complete the 36-item Short Form Health Survey (RAND-36). This questionnaire consists of 36 questions within eight subcategories including physical functioning, energy, emotional wellbeing, social functioning, pain, general health and role limitations due to physical health or emotional problems. These subcategories can be combined into the physical component summary (PCS) and the mental component summary (MCS). Scores range from 0-100, with 0 being the lowest HrQoL and 100 the highest. The ProBe-AHP study population consists of patients with an established bleeding disorder (BD), patients with BDUC and patients with no bleeding disorder (NBD). Data from a Dutch RAND-36 population survey were used as a reference (general population).

Results: A total of 97/237 RAND-36 questionnaires were completed and returned. From the 97 returned questionnaires, 20% (n=19) were filled in by NBD patients, 34% (n=33) by BDUC patients and 46% (n=45) by BD patients. The median PCS score and the median MCS score was not statistically significant different between these three groups (Median PCS score [IQR]: NBD (84 [66-93], BDUC (61 [35-90]) and BD (72 [34-88]), median MCS score [IQR]: NBD (79 [53-87]), BDUC (75 [51-86]) and BD (68 [41-82]). Compared to the general population, BDUC patients had a statistically significant decreased score on the role limitations in physical health, energy, social functioning, pain and general health subcategories.

Conclusion: HrQoL is impaired in BDUC and BD compared to the general population. No statistically significant difference in RAND-36 score was found between NBD, BDUC and BD patients in the ProBE-AHP cohort. These results suggest that HRQoL-related issues should be an integral part of the personalized management of BDUC and BD patients.
Identifying Gut Microbiota and Immune Host Factors Associated with Bleeding Risk in Children with Immune Thrombocytopenic Purpura
Authors: Saini Shelly , Koh Andrew Y. , Zia Ayesha
Published: December 2024

Background:

Immune thrombocytopenia (ITP) may cause clinically significant bleeding episodes that can adversely affect a patient's quality of life. The gut microbiome plays a critical role in host immune system education and response in both healthy and diseased states. Previous studies comparing microbial taxa and cytokine levels in ITP patients have focused on differences between healthy controls and ITP participants. The role of the microbiome and cytokine levels in bleeding risk among ITP patients remains unclear.

Methods:

In our prospective cohort study, we analyzed stool and blood samples from 30 pediatric ITP participants at platelet levels ≤30,000/uL at time of diagnosis. Participants were divided into two groups, mild or moderate-severe bleeding phenotype, using the Buchanan-Adix bleeding score with mild participants having a score ≤3a and moderate-severe with a score ≥3b. Microbiome data was obtained using 16S rRNA gene sequencing on stool samples and cytokine profiling was obtained using Luminex assays on blood samples. Microbial diversity, microbial abundance, and cytokine levels were then compared between participants with mild and moderate-severe bleeding phenotype.

Results:

Of the 30 participants, the median age was 5.5 years (IQR 2-9.5). 11 (36.7%) were diagnosed with mild phenotype and 19 (63%) with moderate-severe bleeding phenotype. The median platelet count in the moderate-severe group was 4,000/uL (IQR 4-6) and in the mild group 6,000/uL (IQR 4-15) with no difference found between the two groups (p>0.05). The gut microbiota taxa that were significantly enriched in moderate-severe versus mild bleeders included the bacterial families Erysipelotrichaseae (LDA score 3.75), Ruminococaceae (LDA score 3.16), and Oscillospiraceae (LDA score 2.81), as assessed by LEfSe. Mild phenotype had increased Megamonas (LDA score 4.33) and Fusobacterium (LDA score 3.65) taxa compared to moderate-severe. Systemic cytokine profiling revealed a significant increase in IL-1ar in the moderate-severe group compared to those with mild phenotype (p=0.0447) with a significant positive correlation seen between Ruminococcus gut microbiota and IL-1ar cytokine levels (p=0.0865).

Conclusion:

Pediatric patients with acute ITP and a moderate-severe bleeding phenotype are enriched in the anti-inflammatory bacteria Ruminococcus and cytokine IL-1ra, while those with a mild phenotype have higher relative amounts of pro-inflammatory bacteria Megamonas and Fusobacterium. These findings suggest that gut microbiota modulates bleeding risk in pediatric ITP. This study provides novel insight into the altered composition of gut microbiota and cytokines in ITP patients with variable bleeding phenotype at similar platelet counts.
Erythroferrone Overexpression Mitigates Anemia and Improves Kidney Function in a Mouse Model of CKD
Authors: Czaya Brian , Nemeth Elizabeta , Ganz Tomas
Published: December 2024

Chronic kidney disease (CKD) affects over 800 million people worldwide, most of whom develop anemia caused by relative erythropoietin deficiency, increased levels of the iron-regulatory hormone hepcidin, as well as absolute and functional iron deficiency.

Erythropoietin-stimulating agents (ESAs) and iron supplementation ameliorate anemia in CKD but patients often become hyporesponsive to ESAs. Increasing ESA doses may heighten risks of thrombosis and cardiovascular mortality, highlighting the need for alternative strategies.

Erythroferrone (ERFE) is an erythroid suppressor of hepcidin, facilitating iron mobilization for erythropoiesis. In CKD, diminished marrow erythroblasts contribute to decreased ERFE production, likely further increasing hepcidin.

To explore the potential therapeutic use of ERFE in CKD, we tested the impact of augmented ERFE on systemic iron homeostasis and kidney function. Transgenic mice with erythroid overexpression of ERFE (ERFE-Tg) had similar iron stores to WT mice at weaning but became iron overloaded as they aged. To prevent early iron overload, we placed ERFE-Tg on 4ppm diet at weaning. 8-week-old male ERFE-Tg and wild-type (WT) mice were then fed 0.2% adenine-rich diet containing 100 ppm Fe for 8 weeks to induce CKD.

At 16 weeks, both WT and ERFE-Tg mice developed CKD and anemia but ERFE-Tg had higher hemoglobin, MCV and serum iron, as well as lower liver hepcidin mRNA/liver iron content ratio, indicating effective suppression of hepcidin by ERFE. Furthermore, kidney function (BUN and serum creatinine) was less impaired in ERFE-Tg. Thus, ERFE overexpression in adenine-induced nephropathy improves CKD-associated anemia and renal dysfunction, suggesting that ERFE has therapeutic potential in CKD.
The Endocannabinoid N-Arachidonoyl Dopamine Induces Leukemia Cell Pyroptosis to Overcome the Venetoclax Resistance
Authors: Wu Min , Tang Lingyun , Jiao Bo , Liu Ping , Li Junmin , Ren Ruibao
Published: December 2024

Bcl-2 inhibitor has largely changed the treatment options in elderly acute myeloid leukemia patients, while drug insensitivity and resistance still hinder the overall survival. In our previous study, a natural product, N-arachidonoyl dopamine (NADA), was discovered to inhibit NRAS membrane translocation and induced “oncosis-like” cell death. In this study, we found that NADA induced pyroptosis of the leukemia cells by promoting Caspase -1 (CASP1) mediated Gasdermin D (GSDMD) cleavage. Cell dynamic monitoring and western blot analysis revealed that NADA induced typical pyroptosis cell blebbing and the cleavage of GSDMD and CASP1 in leukemia cells. Additionally, the activity of NADA on GSDMD cleavage and pyroptosis induction could be selectively rescued by the CASP1 inhibitor. Moreover, in GSDMD and CASP1 knock-down/knock-out leukemia cells and GSDMD-/- mice, the cell viability inhibition effect of NADA was impaired significantly. To explored the molecular target of NADA in pyroptosis induction, we performed a click chemistry assay with N3 tagged NADA (N3-NADA). In the analysis of cell death pathway proteins binding to N3-NADA, GSDMD was identified in three independent assays, suggesting a direct or indirect binding of NADA to GSDMD. Subsequently, molecular docking analysis showed a direct binding between NADA and GSDMD, with NADA embedding into the pocket between the N and C terminal of GSDMD with lower binding free energy. Molecular dynamics simulation further revealed the GSDMD N domain in the NADA-GSDMD-CASP1 complex is more rigid than that in the GSDMD-CASP1 complex, resulting in a shorter distance between the GSDMD P1 site residue D275 and the key residues of catalytic site in CASP1, leading to higher cleavage efficiency. Thus, NADA could directly bind to GSDMD and promote its CASP1 dependent cleavage, leading to cell pyroptosis. As the overexpression of anti-apoptotic protein other than BCL-2 is one of the main causes of venetoclax (ABT-199) resistance, therapy surpasses the apoptosis pathway could be effective. Therefore, we used NADA in combination with ABT-199 in both in vitro and in vivo studies to test its anti-tumor effects. The results showed that NADA significantly increased the sensitivity of ABT-199 resistant (VENR) cells to ABT-199. In summary, these findings provide a new strategy to overcome drug resistance and help to develop novel therapies for leukemia.