bluuebunny/crossref_metadata_2025 huggingface dataset:
Collective redress and workers’ rights in the Netherlands
Authors: de Vaate Vivian Bij
Published: November 2021

This contribution discusses the Dutch possibilities of collective redress in the domain of labour law. More specifically, it examines the legal options of bringing collective actions and obtaining collective redress in Dutch courts in labour cases, and elaborates on the relevant legal framework as well as the extent to which these opportunities have been used in practice. Findings imply that the Netherlands was among one of the first European countries to introduce a general collective action system. This general collective action regime allows unions and other interest groups to raise cases to protect workers’ rights, even outside the scope of collective labour agreements. Such a collective action regime, however, is not commonly used in practice. Nevertheless, as of January 2020 the admissibility criteria for this general collective redress mechanism have been expanded and it has become an ‘opt-out’ regime, without the need for individual workers to initiate individual follow-up proceedings in the event of a successful case. The latter could improve the effective enforcement of workers’ rights in practice and could provide an incentive for trade unions and other organisations that are active in the protection of workers’ rights to incite a collective action.
Sepsis in children: state-of-the-art treatment
Authors: Peshimam Niha , Nadel Simon
Published: November 2021

Sepsis is a common, complex condition that requires early recognition and aggressive management to improve outcomes. There has been significant improvement in the management of sepsis and septic shock in the last decade; however, it continues to be a leading cause of mortality, morbidity and burden on healthcare services globally. Several guidelines with evidence-based recommendations for the management of children with septic shock and associated organ dysfunction have been produced with the objective of helping clinicians in various settings to provide standardised high-quality care. This article aims to increase awareness among all clinicians, including those working in emergency departments, general paediatric wards and primary care physicians, about the management of sepsis in children.
Association between proteinuria and placental pathology in preeclampsia: A retrospective study
Authors: Genest Dominique Suzanne , Dal Soglio Dorothée , Girard Sylvie , Rey Evelyne
Published: November 2021

Introduction:

Preeclampsia develops due to placental insufficiency and systemic proinflammatory and antiangiogenic mediator release, with ensuing systemic endothelial dysfunction. Nephrotic-range proteinuria appears to be associated with worse pregnancy outcomes. The relationship between differing degrees of proteinuria and the severity of placental alterations has not been studied.

Methods:

This is a single-centre retrospective comparison of 150 singleton pregnancies complicated by preeclampsia and varying degrees of proteinuria. Maternal demographic, obstetrical and fetal outcome data were obtained from chart review. The placental histologic evaluations were performed by a placental pathologist blinded to all other clinical information.

Results:

Preeclamptic women with massive proteinuria had evidence of more severe maternal vascular malperfusion lesions. The severity of the lesions was progressive through mild, moderate and massive proteinuria. Women with massive proteinuria had a higher incidence of renal dysfunction and severe hypertension, and had earlier preterm deliveries compared to preeclamptic women with mild and moderate proteinuria (p < 0.05).

Conclusion:

Preeclampsia with more severe proteinuria is associated with a higher prevalence of placental maternal vascular malperfusion.
Atypical presentation of isolated traumatic ascending aortic dissection with cardiac tamponade
Authors: Ono Shunya , Tateishi Retsu , Shioya Masato , Itoda Yoshihumi , Tsukioka Yusuke , Nakahara Yoshinori , Kanemura Takeyuki
Published: November 2021

Blunt traumatic aortic injury is a rare but life-threatening condition, usually following high-energy trauma. We present the case of a 79-year-old man who was transferred to a hospital complaining of nausea after being struck on the chest. Computed tomography led to diagnosis of ascending aortic dissection with cardiac tamponade. Emergent ascending aortic replacement was performed successfully and he was discharged home on postoperative day 24 without any complications. The key to early diagnosis of blunt traumatic aortic injury is careful and detailed history-taking. If trauma patients complain of unexplained symptoms, the threshold for conducting computed tomography should be lowered to avoid misdiagnosis or therapeutic delay.
A case report of a reverse sural flap for posterior ankle soft-tissue defect following an injury in a patient from Tanzania
Authors: Msemwa Joseph R , Mweya Clement N
Published: November 2021

In the treatment and management of severe wounds, microsurgical repair remains the gold standard. However, it is difficult to transfer free tissue from a Tanzanian perspective due to donor site morbidity, longer operational times, bulky forms, recipient vessel stress, sophisticated surgical expertise, and high costs of the equipment. Meanwhile, the reverse sural flap has been considered as the ultimate tissue restoration technique. This study reviews a case of a 35-year-old man who was admitted at Mbeya Zonal Referral Hospital in the Department of Orthopaedics, Trauma, and Neurosurgery in Mbeya, Tanzania. The patient had a 9-day injury to the rear of his right ankle due to a cut he suffered after tripping over a toilet seat in the washroom. After the diagnosis, the plan involved surgical debridement, tendon repair, and reverse sural flap rotation. Despite the difficult working environment requiring advanced learning experience, our patient fully recovered after 3 weeks. Proving that reverse sural flap is one of the few available possibilities in the protection of vital structures such as bone or tendons, in the distal areas of the leg, ankle, and foot especially when the medical treatment facility lacks a strong microsurgery team and equipment.
Primary Hyperoxaluria Type 1 (PH1) Presenting With End-Stage Kidney Disease and Cutaneous Manifestations in Adulthood: A Case Report
Authors: Poyah Penelope , Bergman Joel , Geldenhuys Laurette , Wright Glenda , Walsh Noreen M. , Hull Peter , Roche Kristina , West Michael L.
Published: November 2021

Rationale:

Primary hyperoxaluria (PH) is a rare autosomal recessive disorder more commonly diagnosed in children or adolescents. Owing to its rarity and heterogeneous phenotype, it is often underrecognized, resulting in delayed diagnosis, including diagnosis after end-stage kidney disease (ESKD) has occurred or recurrence after kidney-only transplantation.

Case Presentation:

A 40-year-old Caucasian Canadian woman with a history of recurrent nephrolithiasis since age 19 presented with ESKD and cutaneous symptoms. She had no known prior kidney disease and no family history of kidney disease or nephrolithiasis.

Diagnosis:

A diagnosis of primary hyperoxaluria type 1 (PH1) due to homozygous splice donor mutation (AGXT c.680+1G>A) was made with kidney and cutaneous pathology demonstrating calcium oxalate deposition and ultrasound suggestive of nephrocalcinosis.

Interventions:

She was initiated on frequent, high-efficiency, high-flux conventional hemodialysis and oral pyridoxine. Lumasiran was added 11 months later, after she developed bilateral swan-neck deformities.

Outcomes:

After 14 months of high-intensity dialysis and 3 months of lumasiran, there have been no signs of renal recovery, and extra-renal involvement has increased with progressive swan-neck deformities, reduced cardiac systolic function, and pulmonary hypertension. The patient has been waitlisted for kidney-liver transplantation.

Teaching Points:

This case report describes an adult presentation of PH1. The case highlights the importance of timely workup of metabolic causes of recurrent nephrolithiasis or nephrocalcinosis in adults which can be a presenting sign of PH and genetic testing for PH to facilitate early diagnosis and treatment especially in the era of novel therapeutics that may alter disease course and outcomes. The case also demonstrates the value of testing for PH in adults presenting with unexplained ESKD and a history of recurrent nephrolithiasis or nephrocalcinosis due to implications for organ transplantation strategy and presymptomatic family screening.
Cardiorespiratory fitness and moderate-to-vigorous physical activity in older adults with multiple sclerosis
Authors: Motl Robert W , Baird Jessica F
Published: November 2021

Background

Cardiorespiratory fitness (VO2peak) may be a modifiable indicator of health status and well-being in older adults with multiple sclerosis.

Purpose

We examined differences in VO2peak and moderate-to-vigorous physical activity between older adults with multiple sclerosis and healthy controls, and whether moderate-to-vigorous physical activity accounted for group differences in VO2peak.

Methods

Older adults with multiple sclerosis ( n = 31) and healthy controls ( n = 29) completed a cardiopulmonary exercise test and wore an accelerometer for measuring moderate-to-vigorous physical activity. The data were analyzed using the Baron and Kenny approach for examining moderate-to-vigorous physical activity as a mediator of group differences in VO2peak.

Results

The multiple sclerosis group had significantly lower VO2peak and moderate-to-vigorous physical activity than healthy controls. VO2peak had a large correlation with moderate-to-vigorous physical activity ( r = .59). Group initially explained 8% of the variance in VO2peak ( β  =  −0.29). The inclusion of moderate-to-vigorous physical activity accounted for an additional 27% of the variance in VO2peak, but only moderate-to-vigorous physical activity ( β  =  0.57) was a statistically significant correlate of VO2peak. The effect of Group was attenuated and non-significant with the addition of moderate-to-vigorous physical activity in Step 2 (Group β Step 1  =  −0.29, Group β Step 2  =  −0.05).

Conclusions

Our results provide initial support for targeting moderate-to-vigorous physical activity as an approach for improving VO2peak in older adults with multiple sclerosis.
Economic Stress and Body Weight During the COVID-19 Pandemic
Authors: Mathieu-Bolh Nathalie
Published: November 2021

The COVID-19 pandemic has caused income loss for many households, disrupting food consumption patterns and contributing to weight loss for some, and weight gain for others. In this article, I build a dynamic theoretical model that explains those empirical facts. The novelty of this paper is to incorporate stress caused by a lower than ideal income (economic stress) in a model of optimal intertemporal food consumption decisions made by a rational eater. In this framework, economic stress causes disutility and individuals can cope by increasing high-calorie food consumption (stress eating). The limitation to this coping mechanism is that being overweight from excessive calorie intake also decreases utility. Thus, a decrease in income causes updates of the constraints faced by rational consumers of food, which are a budget constraint, a stress constraint and a weight gain constraint. As a consequence, the effect of a decrease in income on body weight reflects a competing income effect as well as two effects specific to economic stress, which are an intertemporal substitution effect and a stress eating effect. Those effects explain opposite weight patterns observed during the pandemic.

JEL Classification: D11, D91, I12, I14
School Based Motor Skill Interventions for Developmentally Delayed and Non-Delayed Children
Authors: Bryce Colby J. C.
Published: November 2021

Introduction: A mere 33% of all children meet the recommended minimum physical activity guidelines for adequate health maintenance. Available literature however suggests children are more likely to be active when they are competent with their own motor ability. This review aimed to evaluate how several regimented motor skills training courses and interventions improve motor skill competence among children compared with age matched control peers. Method: Electronic databases were searched and included Medline Complete and Psych INFO (both hosted by EBSCO Host). The search syntax examined titles and abstracts. The study aimed to create novelty by examining participants with and without developmental delays simultaneously from studies around the globe. Included interventions were aimed at the most crucial developmental years for children (between 3 and 11 years). Results: Results were found in favor of the motor skill intervention groups (from pre-to post-test). Included interventions involved weekly motor skills exposure of 60 to 120 minutes for periods of between 2 and 6 months. Over 50% of included interventions involved alterations to current school curriculums. The included studies were of moderate to high quality. Conclusion: The findings suggest that for those with and without developmental delays, several interventions can be effectively applied in once weekly 60-minute sessions (over eight or more weeks) to improve children’s motor skill abilities. Applying appropriate difficulty to interventions seems equally influential. Implications are discussed.
Generating Ecotrust: A Relational Response to the Infodemic
Authors: Hirschmann Krista , Isgro Kirsten
Published: November 2021

Trust has been studied by a variety of disciplines and perspectives, with many pointing towards the need for a more complex and dynamic approach to understanding trust as a relational process. This paper introduces the concept of ecotrust within healthcare as means to capture a co-produced, relational response to the abundance of (mis)information produced by the current infodemic. As an approach that recognizes the contributions of and impact on all members of the system, ecotrust encourages research that explores the process by which trust emerges as a shared reality from both the provider's or healthcare team's perspectives, as well as the patient experience, potentially leading to new conversations and strategies for partnering together. Finally, ecotrust encourages the skills of relationship-centered communication as a specific strategy for entering conversations with curiosity and empathy, thus encouraging relationship-building as a humanistic first step for responding to (mis)information.
Assessing quality and agreement of structured data in automatic versus manual abstraction of the electronic health record for a clinical epidemiology study
Authors: Brazeal Joseph Grant , Alekseyenko Alexander V , Li Hong , Fugal Mario , Kirchoff Katie , Marsh Courtney , Lewin David N , Wu Jennifer , Obeid Jihad , Wallace Kristin
Published: November 2021

Objective

We evaluate data agreement between an electronic health record (EHR) sample abstracted by automated characterization with a standard abstracted by manual review.

Study Design and Setting

We obtain data for an epidemiology cohort study using standard manual abstraction of the EHR and automated identification of the same patients using a structured algorithm to query the EHR. Summary measures of agreement (e.g., Cohen’s kappa) are reported for 12 variables commonly used in epidemiological studies.

Results

Best agreement between abstraction methods is observed among demographic characteristics such as age, sex, and race, and for positive history of disease. Poor agreement is found in missing data and negative history, suggesting potential impact for researchers using automated EHR characterization. EHR data quality depends upon providers, who may be influenced by both institutional and federal government documentation guidelines.

Conclusion

Automated EHR abstraction discrepancies may decrease power and increase bias; therefore, caution is warranted when selecting variables from EHRs for epidemiological study using an automated characterization approach. Validation of automated methods must also continue to advance in sophistication with other technologies, such as machine learning and natural language processing, to extract non-structured data from the EHR, for application to EHR characterization for clinical epidemiology.
Comparison of D-Dimer Level on Mild, Moderate and Severe COVID-19 at Immanuel Hospital Bandung City October 1 st - December 31 st, 2020
Authors: Gustian Hary , Pratiwi Regina Anjani Budi , Riantie Rini
Published: November 2021

Background: Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In COVID-19 there is a process of thrombosis and coagulopathy, which are systemic inflammation and endothelial disorders resulting in hypercoagulability. D-dimer is a laboratory test that can determine coagulation activation (hypercoagulability) and fibrinolysis. D-dimer can be used as a guide of anticoagulant and thrombolytic therapy and prognostic parameter in COVID-19 patients, where its value runs parallel to the severity of the disease and is associated with increased mortality.

Materials and methods: The whole sampling was taken from 59 medical records of inpatients confirmed with COVID-19 through the RT-PCR examination at Immanuel Hospital, Bandung City for the period of October 1 st - December 31 st, 2020. The value of d-dimer was taken from whole blood, tested with sandwich ELISA method with cut-off value (normal value) < 0.5μg/ml. COVID-19 patient classification was based on the COVID-19 guideline from Indonesian Ministry of Health. The research method was observational analytical with cross-sectional design. Statistical test used was Kruskal-Wallis test with Mann-Whitney advanced test (α = 0.05).

Results: The mean d-dimer value in patients with mild, moderate, and severe COVID-19 was 0.3034 µg/mL; 0.5138 µg/mL; and 1.1751 µg/mL. The results of Kruskal-Wallis test showed a very significant difference in mean d-dimer values in mild, moderate, and severe COVID-19 patients. Mann-Whitney test showed that there was a very significant difference in the mean d-dimer value between mild and severe COVID-19 patients, also between moderate and severe COVID-19 patients with a value of p = 0.000 (p <0.01). But there was no difference in the mean d-dimer value between mild and moderate COVID-19 patients, p = 0.454 (p> 0.05).

Conclusion: There is a very significant difference in d-dimer values between mild, moderate and severe COVID-19 patients. The d-dimer value increases with the severity of COVID-19.

Keywords: COVID-19, mild COVID-19, moderate COVID-19, severe COVID-19, d-dimer

Disclosures

No relevant conflicts of interest to declare.
Hematopoietic Stem Cell Regeneration through Paracrine Regulation of the Wnt5a-Prox1 Signaling Axis
Authors: Lin Qiqi , Chatla Srinivas , Wu Limei , Chowdhury Fabliha , Du Wei
Published: November 2021

The crosstalk between bone marrow (BM) microenvironment (niche) and hematopoietic stem cells (HSCs) is critical for HSC regeneration after injury. Here we show that deletion of the genes encoding the DNA repair-deficient syndrome Fanconi anemia (FA), Fanca and Fancc, in mice dampens HSC regeneration through both direct effects on HSCs and indirect effects on BM niche cells. Specifically, Fanca- or Fancc-deficiency compromises hematologic recovery and dampens HSC regeneration following irradiation. FA HSCs show persistent upregulation of the Wnt target Prox1, a homeobox transcription factor, in response to total body irradiation (TBI). Accordingly, lineage-specific deletion of Prox1 improves long-term repopulation of the irradiated FA HSCs. Forced expression of Prox1 in wild-type (WT) HSC mimics the defective repopulation phenotype of FA HSCs. By analyzing paracrine factors in Wnt signaling, we found that WT mice, but not FA mice, show significant induction by TBI of BM stromal Wnt5a protein, which is produced in LepR +CXCL12 + BM stromal cells. Wnt5a treatment of irradiated FA mice enhances hematopoietic recovery and HSC regeneration. Conversely, Wnt5a neutralization in co-cultured LepR + BM stromal cells inhibits HSC regeneration and hematopoietic recovery following TBI. Mechanistically, Wnt5a secreted by LepR +CXCL12 + BM stromal cells inhibits b-catenin accumulation, thereby repressing Prox1 transcription in irradiated HSPCs. The detrimental effect of deregulated Wnt5a-Prox1 signaling on HSC regeneration and hematopoietic recovery is also observed in aged mice. Irradiation induces upregulation of Prox1 in the HSCs of aged mice, and deletion of Prox1 in aged HSCs improves HSC regeneration and hematopoietic recovery after irradiation. Finally, treatment of aged mice with Wnt5a enhances hematopoietic repopulation. Collectively, these findings identify the novel paracrine Wnt5a-Prox1 signaling axis in regulating HSC regeneration under conditions of injury and aging.

Disclosures

No relevant conflicts of interest to declare.
Effective Central Nervous System (CNS) Prophylaxis Chemotherapy Approach in High Risk Diffuse Large B-Cell Lymphoma (DLBCL): A Network Meta-Analysis
Authors: Haddad Philip A , Hammoud Dalia , Gallagher Kevin M.
Published: November 2021

Introduction: CNS relapses with DLBCL tend to be uncommon. The risk increases with certain DLBCL types and certain risk features. There is no consensus regarding the optimal approach to CNS prophylaxis for high-risk DLBCL patients. While some favor prophylaxis with high-dose systemic therapy or intrathecal chemotherapy (IT), some experts advocate combining both approaches. In the absence of randomized trials, the role of CNS chemotherapy prophylaxis remains controversial in DLBCL with contradictory comparative studies. The purpose of this meta-analysis is to evaluate the impact of CNS prophylaxis approaches on the clinical outcomes of high-risk DLBCL.

Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of DLBCL diagnosis, English language, IT or high-dose systemic prophylactic chemotherapy, and comparative studies reporting CNS recurrence rates. A frequentists and Bayesian network meta-analyses were conducted using the netmeta package and random-effects model.

Results: Twenty-one comparative studies with a total of 11,507 patients were included and analyzed. The relative risk (RR) of CNS recurrence was not statistically different between IT prophylaxis, high-dose chemotherapy, and no prophylaxis. However, the combination of IT prophylaxis and high-dose chemotherapy was found to be significantly associated with a reduced RR of CNS recurrence when compared to IT prophylaxis (RR=0.28, 95%CI 0.13-0.58), high-dose chemotherapy (RR=0.34, 95%CI 0.14-0.80), and no prophylaxis (RR=0.41, 95%CI 0.19-0.87).

Conclusions: This network meta-analysis is the first to compare the different CNS prophylactic approaches. It indicates that IT prophylaxis and high-dose chemotherapy each were not better than no prophylaxis. However, the combination of IT prophylaxis with high-dose chemotherapy was significantly superior to each approach alone as well as no prophylaxis. In the absence of randomized clinical trials, this network meta-analysis represents the most compelling data supporting the use of CNS prophylaxis in patients with high-risk DLBCL.

Disclosures

No relevant conflicts of interest to declare.
Comparison of Treatment Modalities in Frontline Therapy of Stages I/IE Extranodal NK/T-Cell Lymphoma-Nasal Type (ENKTL-N): An up-to-Date Network Meta-Analysis
Authors: Haddad Philip A , Hammoud Dalia , Gallagher Kevin M.
Published: November 2021

Introduction: Despite many studies reporting on the optimal therapies for early stage ENKTL-N in the front-line setting, this area continues to be subject to a significant controversy regarding single modalities versus combination or sequential approaches. All these comparative studies were small non-randomized studies that combined stages I & II. The results were often inconclusive and occasionally conflicting. In the absence of direct head-to-head randomized controlled trials in this clinical setting, a network meta-analysis was conducted to compare these therapeutic approaches and their respective impact on 5-year survival in stage I/IE ENKTL-N.

Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of stage I/IE ENKTL-N, treatment with chemotherapy (CT), radiation (RT), sequential CT and RT (SEQ), and chemoradiotherapy (CRT), comparative studies that reported predominantly (>70%) I/IE 5-year overall survival (OS) and disease-free survival (DFS) rates. Studies that reported on mixed samples of early and advanced ENKTL were excluded. A frequentist network meta-analysis was conducted using the netmeta package and random-effects model.

Results: Seven studies comprising a total of 397 participants were included. Our network meta-analysis revealed that upfront RT tended to have better 5-year OS and DFS than CRT, SEQ, though it did not reach statistical significance. However, RT had a significantly superior 5-year OS when compared to CT (RR=0.43, 0.19-0.97). Based on the pair-wise and network meta-analyses, RT was ranked as the most effective first-line treatment approach followed by CRT, SEQ, and CT in decreasing order. Analysis of the 5-year DFS yielded similar findings. Inconsistency analysis did not reveal any significant differences between direct and indirect estimates.

Conclusion: This is the first network meta-analysis to compare all commonly utilized upfront treatment modalities in stages I/IE ENKTL-N. It indicates that upfront RT alone may be sufficient as there was no signal that chemotherapy added any OS or DFS advantages. Adequately powered randomized trials are warranted.

Disclosures

No relevant conflicts of interest to declare.
The Prognostic Significance of the Stage of Reaching MRD-Negative for Patients with Multiple Myeloma Received ASCT
Authors: Sun Qian , Li Juan
Published: November 2021

Objective: To explore the prognostic significance of the stage of reaching MRD-negative for patients with newly diagnosed multiple myeloma (NDMM) patients who received autologous hematopoietic stem cell transplantation (ASCT).

Methods: A retrospective analysis of 186 NDMM patients who received "induction therapy-ASCT-maintenance therapy" in our center and reached MRD-negative, according to the stage when the patient's MRD status turned negative (induction therapy, 3 months after ASCT, maintenance therapy) is divided into three stages, A, B, and C (Figure 1). We compared the clinical characteristics and prognosis of patients in the three stages.

Results: The median time to progress (TTP) of 186 patients was not reached, the median overall survival (OS) was 113.8 months, and the median follow-up time was 67.6 months; the number of cases in the three stages of A, B, and C was 73 (39.2%), 42 (22.6%), and 71 (38.2%), respectively (Figure 2). The median TTP of the patients in the three stages was not reached (P=0.013), and the median OS was not reached, not reached, and 71.2 months, respectively (P=0.026). Among the 124 standard-risk cytogenetics patients, the median TTP of the three stages of patients was not reached (P=0.121), and the median OS was not reached, not reached, and 99.6 months, respectively (P=0.091) (Figure 3). Among the 38 high-risk cytogenetics patients, the median TTP of patients in the three stages were unreached, 53.9 months, and 35.8 months (P=0.060), and the median OS was not reached, 71.2 months, and 60.2 months (P=0.625) (Figure 4). Among the 157 R-ISS Ⅰ-Ⅱ patients, the median TTP of the three stages was not reached (P=0.174), and the median OS was not reached, not reached, and 99.6 months (P=0.186) (Figure 5). Among 29 cases of R-ISS Ⅲ, the median TTP of the 3 stage patients was unreached, unreached, and 35.1 months (P<0.001), and the median OS was unreached, unreached, and 48.5 months, respectively (P=0.020) (Figure 6).

Conclusion: For the same patients with MRD negative, the prognosis of patients reaching MRD-negative at different stages is different. The stage of reaching MRD-negative can predict the prognosis of patients with R-ISS stage Ⅲ, but cannot predict the prognosis of patients with R-ISS Ⅰ-Ⅱ.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
A Prospective Clinical Study of the Efficacy and Adverse Reactions of Azacitidine Combined with IA Regimen As the Induction Treatment of Newly Diagnosed AML
Authors: Kuang Lifen , Li Juan
Published: November 2021

Objective:

This single-arm prospective research (ChiCTR2100044731) aimed to evaluate the efficacy and safety of azacitidine combined with IA regimen in the induction treatment of newly diagnosed acute myeloid leukemia (AML), with a view to further improving the efficacy of acute myeloid leukemia with poor prognosis.

Methods:

Newly diagnosed AML (non-M3) patients who received azacitidine combined with IA regimen induction chemotherapy in the Department of Hematology of the First Affiliated Hospital of Sun Yat-sen University from November 2019 to February 2021 were enrolled, and the efficacy and side effect were analyzed.

Results: A total of 33 patients were enrolled. The median age of the enrolled patients was 43.36 years (17-63), including 16 males (48.5%) and 17 females (51.5%). According to NCCN risk stratification, there were 3 patients (9.1%) in the favor group (9.1%) ,13 cases (39.4%) in the intermediate group and 17 cases (51.5%) in the poor group.The CR rate of one cycle of azacitidine combined with IA regimen was 66.7%, with a PR rate of 12.1% and a NR rate of 21.2%. After propensity score matching with the newly diagnosed AML patients who received IA regimen as induction chemotherapy in our center, a paired study was carried out. The results showed that there was no significant difference between the 2 groups in the treatment CR rate (66.7% for azacitidine combined with IA vs 54.5% for IA, P=0.592, Fig1). Subgroup analysis (table 1) showed combination of azacitidine with IA significantly improved the CR rate of patients with a ratio of blasts in the bone marrow greater than 67% (83.3% vs 30.8%, P=0.014) and patients in the intermediate NCCN risk group (100.0% vs 37.5%, P=0.001).The duration of agranulocytosis in the azacitidine combined with IA chemotherapy group was longer than that in the IA group (21 days vs 19 days, P=0.045). There was no significant difference in the number of platelet transfusions and the number of red blood cell transfusions between the two groups, and there was no significant difference in the incidence of infection between the two groups (table 2).

Conclusions:

The remission rate of induction chemotherapy for azacitidine combined with IA regimen and IA regimen in newly diagnosed non-M3 AML patients is comparable. Patients with a ratio of immature cells in bone marrow greater than 67% and patients in the intermediate NCCN risk group may benefit from azacitidine combined with the IA regimen. The combination of azacitidine with IA regimen aggravated granular bone marrow suppression.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
The Immediate Effect of COVID-19 Vaccination on Anticoagulation Control in Patients Using Vitamin K Antagonists
Authors: Visser Chantal , Biedermann Joseph S. , Nierman Melchior C. , Van der Meer Felix J. M. , Gulpen Anouk J. W. , Moors Yvonne C. F. , Cannegieter Suzanne C. , Lijfering Willem M , Kruip Marieke J.H.A. , Dutch COVID & Thrombosis Coalition The
Published: November 2021

Background: In January 2021, the Dutch vaccination programme against SARS-CoV-2 was started. Clinical studies have shown that systemic reactions occur in up to 50% of vaccine recipients. Therefore, COVID-19 vaccination could affect anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications.

Aims: To investigate whether the BNT162b2 vaccine affects anticoagulation control in outpatients using Vitamin K antagonists (VKAs).

Methods: A case-crossover study was performed in a cohort of outpatient VKA users from four Dutch anticoagulation clinics who received a BNT162b2 vaccine. INR results and VKA dosages before the first vaccination, the reference period, were compared with those after the first and second vaccination.

Results: A total of 3148 outpatient VKA users were included, with a mean age (standard deviation (SD)) of 86.7 (8.7) years, of whom 43.8% were male, 67.0% used acenocoumarol and 33.0% phenprocoumon. We observed a decrease of 8.9% of INRs within range in the standard intensity group (target INR 2.0-3.0). There was both an increased risk of supratherapeutic [OR=1.34 (95% CI 1.08-1.67)] and subtherapeutic levels [OR=1.40 (95% CI 1.08-1.83)] after first vaccination. In the high-intensity group (target INR 2.5-3.5), the risk of a supratherapeutic INR was 2.3 times higher after first vaccination [OR=2.29 (95% CI 1.22-4.28)] and 3.3 times higher after second vaccination [OR 3.25 (95% CI 1.06-9.97).

Conclusion: BNT162b2 was associated with an immediate negative effect on anticoagulation control in patients treated with vitamin K antagonists, so it is advisable to monitor the INR short after vaccination, even in stable patients.

Figure 1 Figure 1.

Disclosures

Kruip: Daiichi Sankyo: Research Funding; Bayer: Honoraria, Research Funding.
Efficacy of Autologous Stem Cell Transplantation in Adult Burkitt/ Burkitt-like Lymphoma: A Systematic Review
Authors: Joshi Utsav , Bhatt Vijaya R. , D'Angelo Christopher
Published: November 2021

Introduction: Burkitt and Burkitt-like lymphoma (BL/BLL) are highly proliferative germinal or post-germinal B cell tumors. Few studies have evaluated the impact of autologous stem cell transplantation (ASCT) on disease outcomes. We performed a systematic review to analyze the efficacy of ASCT in upfront consolidation and for treatment of relapsed/ refractory cases in adult BL/BLL.

Methods: A systematic search of the electronic database (PubMed, Cochrane, Google Scholar, and EMBASE) was conducted for relevant studies. Any clinical trial, prospective study, or retrospective study with clear outcome measures on the efficacy of ASCT in adult patients with BL/BLL were eligible for inclusion. The overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), and progression or relapse were used to assess the efficacy.

Results: For patients who underwent ASCT in first CR, 5-year PFS and OS ranged between 70-78% and 70-83%, respectively. For relapsed/refractory disease, 5-year PFS and OS were reduced at 27% and 31%, respectively. Patients undergoing ASCT for chemoresistant disease fared poorly with an OS of 7% at 3 years versus 37% for chemosensitive disease (p ≤ 0.00001). The overall response rate (CR or PR) to ASCT for patients transplanted in first CR ranged between 71% and 92%. This was reduced to 37% for patients who were transplanted in disease status other than first CR. Disease progression/relapse was observed in 16% to 29% of the patients transplanted in first CR, and 55% to 60% in relapsed disease.

Conclusion: Our systematic review found insufficient evidence to support ASCT over chemotherapy alone in the first remission for adult BL/BLL. Evidence supports guidelines recommending ASCT for chemosensitive disease but suggests there is no benefit to ASCT for chemoresistant disease. Prospective studies of ASCT are required to definitively understand the value of ASCT for BL/BLL.

Figure 1 Figure 1.

Disclosures

Bhatt: Pfizer: Research Funding; Tolero Pharmaceuticals, Inc: Research Funding; Incyte: Consultancy, Research Funding; Jazz: Research Funding; Abbvie: Consultancy, Research Funding; Partnership for health analytic research, LLC: Consultancy; Servier Pharmaceuticals LLC: Consultancy; Rigel: Consultancy; National Marrow Donor Program: Research Funding; Abbvie: Consultancy, Research Funding; Genentech: Consultancy.
A Randomized Phase II Trial Comparing a Calcineurin Inhibitor-Free Graft-Versus-Host Disease Prophylaxis Regimen with Post-Transplantation Cyclophosphamide and Abatacept to Standard of Care
Authors: Koura Divya , Tzachanis Dimitrios , Ball Edward D. , Costello Caitlin , Goodman Aaron M , Mangan James K. , Mulroney Carolyn , Maroge Joseph , Padilla Michelle , Breslin Peggy , Garrett Jodi , McConnell Kimberly
Published: November 2021

Background: Graft versus host disease (GVHD) is one the major causes of mortality and morbidity after an allogeneic stem cell transplantation. We hypothesized that we can induce post-transplant tolerance by using the combination of post-transplant cyclophosphamide (PTCy) and abatacept (CTLA4Ig) for GVHD prophylaxis. PTCy when given on Days +3 and +4 can eliminate host-reactive donor T cells. CTLA4Ig blocks the costimulatory signals given through CD28 to naïve donor T cells thus favoring an anergic phenotype that promotes tolerance towards recipient derived antigens. CTLA4Ig gives an activating signal to NK cells and therefore has the ability to preserve the graft-versus-tumor effect.

Methods: We have initiated a 50 patient randomized clinical trial. Patients with hematologic malignancies in need of a transplant and with an 8/8 matched donor are randomized 1:1 to tacrolimus and methotrexate for GVHD prophylaxis (standard of care arm) or PTCy on days +3 and +4 followed by CTLA4Ig on days +5, +14,+28, +56, +84, +112, +140 and +168. Patients are stratified by conditioning regimen (myeloablative vs reduced intensity) and by donor type (matched sibling vs matched unrelated donor). The primary endpoint is chronic GVHD at 1 year as a marker of tolerance induction. Secondary endpoints include acute GVHD rate, relapse rate, overall survival, GVHD-relapse-free-survival, transplant related mortality and infection rate. Post-transplantation immune reconstitution studies include measuring T cell and NK cell phenotype, PD-1 expression, and alloreactivity to recipient and third party at predetermined time points.

Results: 25 patients have been treated on this study, 10 of which are on the experimental arm. Patients on the experimental arm have been followed for up to 516 days post-transplant. So far no cases of chronic GVHD or grade 3-4 acute GVHD have been observed in the experimental arm. All the patients have engrafted and there have been no treatment related deaths.

Conclusions: The combination of PTCy and CTLA4Ig for GVHD prophylaxis is feasible. This ongoing study will examine its ability to induce post-transplant tolerance.

Disclosures

Tzachanis: Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; Partner: Consultancy; Fate Therapeutics: Research Funding; Genentech: Research Funding; Bristol Myers Squibb: Research Funding; Incyte: Research Funding; EUSA: Consultancy; Takeda: Consultancy, Speakers Bureau; Magenta: Consultancy; Kyowa Kirin: Consultancy. Goodman: Seattle Genetics: Consultancy, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria. Mangan: Elevate Bio: Other: ad board.

OffLabel Disclosure:

abatacept: using as part of graft versus host disease prophylaxis
Plasma Lipidome Acts As Diagnostic Marker and Predictor for Cyclosporin Response in Patients with Aplastic Anemia
Authors: Ruan Jing , Han Bing , Wang Zhao , Yang Chen , Du Yali , Chen Miao
Published: November 2021

Background：The lipid metabolomic profile has been well defined in the pathogenesis and differential diagnosis in patients with different myeloid diseases. However, the role of plasma lipidome was rarely explored, especially in aplastic anemia (AA), a disease which has close connection with lipid metabolism.

Methods: Peripheral fasting serum levels of patients newly diagnosed with AA from March 2019 to December 2019 were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the serum lipid profiles. Meanwhile, the lipidomes for patients with hypocellular myelodysplastic syndrome (h-MDS) and age and sex matched healthy volunteers were taken as controls. The lipid profiles were tested again 6 months after standard cyclosporin A（CsA）treatment in patients with AA. For all the patients, those with a history of hyperlipidemia, diabetes, obesity (body mass index > 28 kg/m 2) or complications with other malignant diseases at diagnosis were excluded.

Results: The study enrolled 15 patients with AA, 11 patients with h-MDS and 20 healthy controls. All the enrolled AA patients were non-severe and transfusion dependent, and were treated with CsA 3-5mg/kg/d for at least 6 months. For h-MDS patients, five were MDS with single lineage dysplasia, three were MDS with multilineage dysplasia, and three were MDS-Excess Blasts 1 (MDS-RAEB1). Metabolites in arachidonic acid pathway and retinol metabolism were significantly decreased in the AA patients compared with the healthy controls (P<0.05). AA patients had decreased arachidonic acid pathway metabolites and retinol metabolism-related metabolites as compared with h-MDS（P<0.05), whereas h-MDS patients had increased metabolism of proline and threonine and abnormal sphingolipid metabolism compared with AA patients and the normal controls. After 6-month of CsA treatment, leukotriene B4, 15(S)-HETE, all-trans-retinal and protectin D1 decreased significantly. Patients who had response to CsA had higher levels of baseline protectin D1 (p=0.011), leukotriene B4 (p=0.011), 15(S)-HETE (p=0.004) and all-trans-retinal (p=0.000) than those who had no response.

Conclusion: The lipid profiles showed significant difference not only between patients with AA and healthy controls, but also between AA and h-MDS. Meanwhile, some of baseline value and the change in lipid molecules may predict the CsA response at 6 months.

Disclosures

No relevant conflicts of interest to declare.
CD44 Expression in Different Plasma Cell Diseases
Authors: Ning Xueqin , Wei Xiaolei , Chen Bingyuan , Li Zhen , Zheng Zhongxin , Yi Zhengshan , Feng Ru , Wei Yongqiang , Liu Qifa
Published: November 2021

CD44 expression in different plasma cell diseases

Introduction

Myeloma is a genetically complex disease which develops via a multistep process whereby plasma cells are driven towards malignancy through the accumulation of genetic "hits" over time. This multistep process permits myeloma to have four recognisable clinical stages including monoclonal gammopathy of undetermined significance (MGUS) , smouldering multiple myeloma (SMM) , multiple myeloma (MM) and plasma cell leukemia (PCL). CD44 as a complex adhesion molecule, is highly expressed in a variety of solid tumors and involved in metastasis and chemotherapy resistance . Previous studies had found that CD44 was also highly expressed in MM, and associated with advanced clinical stage, extramedullary myeloma (EM) and poor survival. However the relation of CD44 expression in different plasma cell disease remain unknown.

Patients and Methods

Newly diagnosed MGUS (n=12), SMM (n=11), MM (n=133) and PCL (n = 8) patients who were hospitalized in our hospital from December 2017 to December 2020 were enrolled. The diagnosis was based on the criteria of the International Myeloma Working Group. CD44 was detected by flow cytometry as follows: 2 ml of heparin anticoagulated bone marrow was collected from the patients at the time of diagnosis, 1×10 6 cells were detected, and a gate was set for identifying abnormal plasma cells characterized by CD138 and CD38. CD44 positive was defined as more than 20% of the plasma cells expressed CD44.

Results

From December 2017 to December 2020, a total of 164 patients diagnosed in our hospital were included in the study, including 12 MGUS patients, 11 SMM patients, 133 MM patients and 8 PCL patients. The expression proportion (7.9%±11.9%, 11.2%±15.5%, 40.2%±37.7%, 81.9%±25.6%, P < 0.001) and expression intensity (the mean fluorescence intensity was 1 742.8±1 023.1, 2 915.7±923.0, 6 692.6±11 275.5, 25 359.6±22 604.5, P=0.001) of CD44 on the monoclonal plasma cells of MGUS, SMM, MM and PCL patients gradually increased. In 133 MM patients, 73 cases were for CD44 positive. CD44 positive patients were more likely to show ＞3 focal bone lesion (75.3% VS 50.0%, P=0.002), and international staging system（ISS）III stage (68.5% VS 51.7%, P=0.048) compared those with CD44 negative. CD44 expression rate was significantly higher in MM patients with extramedullary disease (n=26) than those without (n=107) (56.7%VS 36.2%, P=0.031)

Conclusion: Our study showed that from MGUS, SMM, MM to PCL, the CD44 expression on abnormal plasma cells was gradually increased. CD44 overexpression was associated with osteolytic lesions, advanced ISS staging and extramedullary myeloma. The results indicated that CD44 was related to the invasion degree of plasma cell disease, and could be used as a marker for differential diagnosis between different plasma cell disease.

Disclosures

No relevant conflicts of interest to declare.
Complete Remissions to PD-1 Blockade in Combination with Reduced-Dose ICE Chemotherapy in Two Cases of Relapsed or Refractory Classical Hodgkin Lymphoma with Bulky Lung Involvement after Failed PD-1 Blockade
Authors: Xiu Bing , Li Bing , Zhu Xinyu , Xiao Gangfeng , Luo Xiu , Yang Zhi-Zhang , Liang Aibin
Published: November 2021

Objective: To report 2 cases of relapsed or refractory classical Hodgkin lymphoma with bulky lung involvement who failed PD-1 blockade, obtained long-term complete remission after treatment with PD-1 blockade in combination with ICE chemotherapy, and provide an alternative regimen for this kind of patient.

Methods: The clinical data of 2 patients suffering refractory or relapsed Hodgkin's lymphoma with bulky lung involvement who were resistant to PD-1 monoclonal antibody were collected, the treatment processes, efficacy and toxic side effects of the patients were summarized.

Results: Both HL patients relapsed after multi-line chemotherapies and radiotherapy. One patient relapsed after autologous hematopoietic stem cell transplantation. The main manifestations were cough and dyspnea caused by large lung masses. Both patients received 3 kinds of PD-1 blockade. One progressed after stopping Nivolumab and enrolled the clinical trial of decitabine and Camrelizumab for 6 courses and got stable disease（SD）, then changed to Camrelizumab combined with ICE for 4 cycles and obtain complete metabolic remission（CMR）. The other patient progressed with Nivolumab or Camrelizumab combined with A (B) VD regimen, and 2 courses of BV. She was then treated with Sintilimab combined with ICE for 4 cycles and obtain CMR. Both patients' cough and dyspnea were significantly improved, and lung lesions were significantly reduced after receiving 1 cycle of PD-1 blockade with ICE regimen and the quality of life was greatly improved. After 4 courses of treatment, the PET/CT assessment achieved CMR. The main side effect was a second-degree bone marrow suppression and can be tolerable for the patient.

Conclusion: PD-1 blockade combined with ICE regimen chemotherapy has significant curative effect and mild adverse reactions, can be used to treat cases of relapsed or refractory classic HL with bulky lung involvement resistant to PD-1 blockade.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.