bluuebunny/crossref_metadata_2025 huggingface dataset:
Colorectal Cancer Detected by Machine Learning Models Using Conventional Laboratory Test Data
Authors: Li Hui , Lin Jianmei , Xiao Yanhong , Zheng Wenwen , Zhao Lu , Yang Xiangling , Zhong Minsheng , Liu Huanliang
Published: November 2021

Background: Current diagnostic methods for colorectal cancer (CRC) are colonoscopy and sigmoidoscopy, which are invasive and complex procedures with possible complications. This study aimed to determine models for CRC identification that involve minimally invasive, affordable, portable, and accurate screening variables. Methods: This was a retrospective study that used data from electronic medical records of patients with CRC and healthy individuals between July 2017 and June 2018. Laboratory data, including liver enzymes, lipid profiles, complete blood counts, and tumor biomarkers, were extracted from the electronic medical records. Five machine learning models (logistic regression, random forest, k-nearest neighbors, support vector machine [SVM], and naïve Bayes) were used to identify CRC. The performances were evaluated using the areas under the curve (AUCs), sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV). Results: A total of 1164 electronic medical records (CRC patients: 582; healthy controls: 582) were included. The logistic regression model achieved the highest performance in identifying CRC (AUC: 0.865, sensitivity: 89.5%, specificity: 83.5%, PPV: 84.4%, NPV: 88.9%). The first four weighted features in the model were carcinoembryonic antigen (CEA), hemoglobin (HGB), lipoprotein (a) (Lp(a)), and high-density lipoprotein (HDL). A diagnostic model for CRC was established based on the four indicators, with an AUC of 0.849 (0.840-0.860) for identifying all CRC patients, and it performed best in discriminating patients with late colon cancer from healthy individuals with an AUC of 0.905 (0.889-0.929). Conclusions: The logistic regression model based on CEA, HGB, Lp(a), and HDL might be a powerful, noninvasive, and cost-effective method to identify CRC.
Electroacupuncture Plus Auricular Acupressure on Chemotherapy-Related Insomnia in Patients With Breast Cancer (EACRI): Study Protocol for a Randomized, Sham-Controlled Trial
Authors: Zhang Jialing , Yang Mingxiao , So Tsz Him , Chang Tien Yee , Qin Zongshi , Chen Haiyong , Lam Wing Lok , Yeung Wing Fai , Chung Ka Fai , Jiang Fei , Lao Lixing , Zhang Zhang-Jin
Published: November 2021

Objective

Insomnia is a highly prevalent and disturbing symptom in breast cancer patients under or post chemotherapy. If not appropriately treated, it can persist for years after the completion of cancer treatments. Acupuncture has been widely used for alleviating insomnia. The aim of this study is to examine the feasibility, efficacy and safety of acupuncture for chemotherapy-related insomnia among patients with breast cancer.

Materials and Methods

This is a trial protocol for a randomized, sham-controlled, subject- and assessor-blinded clinical trial. A total of 138 eligible participants will be assigned randomly to acupuncture or sham control group at a ratio of 1:1. Participants in acupuncture group will receive electroacupuncture (EA) plus auricular acupressure (AA) treatment, while subjects in sham acupuncture group will receive sham EA plus sham AA. Both acupuncture and sham treatments will be given twice weekly for 6 weeks, followed by maintenance treatments once every 4 weeks for 12 weeks (15 sessions totally). The primary outcome is the change of Insomnia Severity Index score between baseline and the end of 6-week treatment. Secondary outcome measurements include Actiwatch, sleep diary, Pittsburgh Sleep Quality Index, Functional Assessment of Cancer Therapy-Breast Cancer, Hospital Anxiety and Depression Scale, Brief Pain Inventory-Short Form, Brief Fatigue Inventory, Acupuncture Expectancy Scale, credibility, and adverse events. Participants will be followed up to 42 weeks.

Conclusions

This trial will expand our understanding of the feasibility, efficacy, and safety of acupuncture as a treatment for alleviating chemotherapy-related insomnia in patients with breast cancer. EA plus AA, if proven to be effective, can be implemented into routine settings to play a role in insomnia management for patients with breast cancer.
Factors associated with maternal near-miss at public hospitals of South-East Ethiopia: An institutional-based cross-sectional study
Authors: Mekonnen Ashenafi , Fikadu Genet , Seyoum Kenbon , Ganfure Gemechu , Degno Sisay , Lencha Bikila
Published: November 2021

Introduction:

Maternal near-miss precedes maternal mortality, and women are still alive indicating that the numbers of near-misses occur more often than maternal mortality. This study aims to assess the prevalence of maternal near-miss and associated factors at public hospitals of Bale zone, Southeast Ethiopia.

Methods:

Facility-based cross-sectional study design was carried out from 1 October 2018 to 28 February 2019, among 300 women admitted to maternity wards. A structured questionnaire and checklist were used to collect data. Epi-info for data entry and statistical package for social science for analysis were used. The descriptive findings were summarized using tables and text. Adjusted odds ratio with 95% confidence interval and p-value < 0.05 were used to examine the association between the independent and dependent variables.

Result:

The prevalence of maternal near-miss in our study area was 28.7%. Age < 20 years, age at first marriage < 20 years, husbands with primary education, and being from rural areas are factors significantly associated with the prevalence of maternal near-miss. The zonal health department in collaboration with the education department and justice office has to mitigate early marriage by educating the community about the impacts of early marriage on health.
TLRs in COVID-19: How they drive immunopathology and the rationale for modulation
Authors: Mabrey F. Linzee , Morrell Eric D , Wurfel Mark M
Published: November 2021

COVID-19 is both a viral illness and a disease of immunopathology. Proximal events within the innate immune system drive the balance between deleterious inflammation and viral clearance. We hypothesize that a divergence between the generation of excessive inflammation through over activation of the TLR associated myeloid differentiation primary response (MyD88) pathway relative to the TIR-domain-containing adaptor-inducing IFN-β (TRIF) pathway plays a key role in COVID-19 severity. Both viral elements and damage associated host molecules act as TLR ligands in this process. In this review, we detail the mechanism for this imbalance in COVID-19 based on available evidence, and we discuss how modulation of critical elements may be important in reducing severity of disease.
Falls From Height, Facial Injuries and Fatalities: An Institutional Review
Authors: Mollica Pasquale G. , McEwen Ellie C. , Hoffman Gary R.
Published: November 2021

Study Design

Retrospective cohort review.

Objective

To investigate the relationship between falls from height and facial injuries.

Methods

This is a retrospective cohort study, conducted over a 7-year period, of the medical records of all patients who presented to hospital for a maxillofacial injury following a fall from height. Fall heights were classified as low falls (1–3 m), high falls (3–10 m) and very high falls (≥10 m).

Results

A total of 111 patients with 218 facial bone fractures were identified (78 men, 33 women and mean age 50.3 years). High falls were the most common (n = 58, 52.3%). Multiple fractures were identified in 51 (46.0%) patients. Orbital and middle third fractures were the most prevalent. Nasal, mandible, bilateral and fractures involving more than one facial third, increased as fall height increased, as did the requirement for operative fixation. The majority of patients had an associated injury (n = 100, 90.1%) and overall mortality was 6.3%.

Conclusions

Falls from height are prevalent and there is a trend towards increased severity of facial injury, surgical intervention and associated morbidity as fall height increases. Falls from height are a significant public health concern and an important facet of maxillofacial trauma to recognise, as is the requirement for an interdisciplinary approach as they present to hospital.
Progenitor Cells in Healthy and Osteoarthritic Human Cartilage Have Extensive Culture Expansion Capacity while Retaining Chondrogenic Properties
Authors: Rikkers M. , Korpershoek J.V. , Levato R. , Malda J. , Vonk L.A.
Published: November 2021

Objective

Articular cartilage-derived progenitor cells (ACPCs) are a potential new cell source for cartilage repair. This study aims to characterize endogenous ACPCs from healthy and osteoarthritic (OA) cartilage, evaluate their potential for cartilage regeneration, and compare this to cartilage formation by chondrocytes.

Design

ACPCs were isolated from full-thickness healthy and OA human cartilage and separated from the total cell population by clonal growth after differential adhesion to fibronectin. ACPCs were characterized by growth kinetics, multilineage differentiation, and surface marker expression. Chondrogenic redifferentiation of ACPCs was compared with chondrocytes in pellet cultures. Pellets were assessed for cartilage-like matrix production by (immuno)histochemistry, quantitative analyses for glycosaminoglycans and DNA content, and expression of chondrogenic and hypertrophic genes.

Results

Healthy and OA ACPCs were successfully differentiated toward the adipogenic and chondrogenic lineage, but failed to produce calcified matrix when exposed to osteogenic induction media. Both ACPC populations met the criteria for cell surface marker expression of mesenchymal stromal cells (MSCs). Healthy ACPCs cultured in pellets deposited extracellular matrix containing proteoglycans and type II collagen, devoid of type I collagen. Gene expression of hypertrophic marker type X collagen was lower in healthy ACPC pellets compared with OA pellets.

Conclusions

This study provides further insight into the ACPC population in healthy and OA human articular cartilage. ACPCs show similarities to MSCs, yet do not produce calcified matrix under well-established osteogenic culture conditions. Due to extensive proliferative potential and chondrogenic capacity, ACPCs show potential for cartilage regeneration and possibly for clinical application, as a promising alternative to MSCs or chondrocytes.
A reflective review on gay and bisexual men in China
Authors: Tsang Eileen Y.H.
Published: November 2021

Pre-Exposure Prophylaxis (PrEP), Treatment as Prevention (TasP), and undetectability affect the experience of gay and bisexual men living with HIV. They also link ‘risk’ and ‘safety’ to raw sex and the use of recreational drugs as they relate to sexual practices among gay and bisexual men. From these insights, we can think about the complex connections between biomedical innovations in the field of HIV, sexual practices, subjectivity, pleasure, spaces, and technologies. This commentary offers a sociocultural perspective based on a study with 28 male sex workers (hereafter MSWs) on gay and bisexual men – mainly male sex workers – and their wives (Tongqi) in China.
“I shy away from them because they are very identifiable”: A qualitative study exploring user and non-user's perceptions of wearable activity trackers
Authors: Burford Katie , Golaszewski Natalie M , Bartholomew John
Published: November 2021

Objective

Wearable activity trackers hold potential as a research tool to increase physical activity. However, long-term wearable adherence is low among users, which may be due to the limited understanding of the factors related to use and relation to health behavior theory. The purpose of this study was to qualitatively explore the perceptions of wearables among active adult users and non-users. Findings will inform potential barriers and facilitators for the adherence and adoption of wearables through the application of the Self-Determination Theory.

Methods

Six focus groups were conducted and equally stratified to wearable users ( n = 10) and non-users ( n = 10). Data were audio recorded, transcribed, and analyzed using an iterative approach creating first-level codes. This was followed by developing second-level codes that allowed for generating themes.

Results

For users, the wearables’ feedback provided them with validation, a sense of achievement, and other-determined motivation. Users appreciated the functionality of wearables, particularly with simpler and newer models. They also reported improvements in health behaviors . While both users and non-users had a general positive feeling towards wearables, they held similar concerns about cost, guilt, dependency, and accuracy. Non-users were unique in their concerns for materialism and functionality (i.e. ease of use and charge) associated with wearables. They also seemed to be more intrinsically motivated to be physically active by relying less on external sources of motivation as potentially provided by wearables.

Conclusions

Findings show that while both adult users and non-users held positive perceptions of wearables and concerns for feelings of guilt and dependency, widespread adoption and adherence may be prevented by differences in motivation for physical activity and concerns for cost, materialism, and functionality.
The Teacher Education Program’s Impact on Preservice Teachers’ Reflective Thinking in Pakistan
Authors: Aslam Sarfraz , Hali Ali Usman , Zhang BaoHui , Saleem Atif
Published: November 2021

The importance of reflective thinking among teachers has long been recognized, and it remains a crucial indicator of learning and ensures teachers’ professional development. This study’s aim is to understand a teacher education program’s impact on the reflective thinking of preservice teachers in Pakistan. Utilizing a mixed-method approach, 400 teacher education candidates participated in the quantitative analysis, which involved a follow-up that included 10 semi-structured interviews by teacher education candidates. The results showed that teacher education in Pakistan is characterized by the production of more graduates but lacks the focus to develop and generate reflective practitioners in the field. This research contributes to our understanding about the importance of reflective thinking in terms of how it can improve preservice teachers’ thinking patterns and nurture teacher education. Furthermore, this study suggests that teacher-training institutions should focus on improving the quality of the trainings for students.
A Qualitative Exploration of Acculturation Practices of Pakistani Scholars in Dutch Society
Authors: Bashir Asma , Brinkman Dine , Biemans Harm J. A. , Khalid Ruhi
Published: November 2021

The psychosocial adaptation of international scholars is a growing area of inquiry in social sciences. Currently, almost 47,164 Pakistani international scholars are enrolled in various universities worldwide but there is a dearth of literature concerning their psychosocial adjustment. This qualitative inquiry focuses on Pakistani graduate and postgraduate international scholars’ insights concerning their adaptation practices in Dutch culture and society. The study is grounded in a sociocultural adaptation model. The primary data was collected through in-depth interviews with ten Pakistani international students who are currently registered in three Dutch universities. The seven central themes that emerged out of in-depth interviews were the perception of cultural disparity, linguistic challenges, limited interaction with host nationals, discrimination, difficulties practicing religious obligations, acculturation attitudes, and participants’ coping strategies applied during the adjustment process. The findings of the current study highlight both barriers and protective factors within the scope of theoretical assumptions and literature. The current study contributes to the gap in the available literature concerning Pakistani international scholars’ experiences. A limited number of studies have discussed acculturation practices of Muslim students and from a specific region. The present findings would be useful for Pakistani international scholars who intend to study abroad and the administration of the host universities receiving Pakistani international scholars to facilitate their adjustment to the new context.
Job Satisfaction Level and Associated Factors Among Rural Health Extension Workers of Sidama Region, Southern Ethiopia
Authors: Kare Assefa Philipos , Gujo Amelo Bolka , Yote Nigussie Yohanes
Published: November 2021

Background

Rural health extension workers (HEWs) are essential for the implementation of the promotion and prevention-based health care policy of Ethiopia. Job satisfaction is believed to be one of the key factors that influence their performance. Information regarding job satisfaction and associated factors are limited in the study area. Therefore, this study was aimed at assessing job satisfaction level and associated factors among rural Health Extension Workers of Sidama Region, Southern Ethiopia.

Method

A facility-based cross-sectional study was conducted among 341 rural HEWs from 1 March to 30 April 2021. Data was collected using trained data collectors using pre-tested and self-administered questionnaires. SPSS version-25 was used for data analysis. Bi-variable and multi-variable logistic regressions were used to observe the association between the outcome variable and associated factors. The outputs are presented using an adjusted odds ratio (AOR) with a 95% confidence interval (CI).

Result

This study revealed that 36.6% (95% CI: 31.6%-41.6%) of the rural HEWs were satisfied with their job. Increased odds of satisfaction were observed among rural HEWs who got training opportunities (AOR: 3.74, 95% CI: 2.01, 6.98), education opportunities (AOR: 3.06, 95% CI: 1.56, 7.46), management support (AOR: 4.59, 95% CI: 2.44, 8.67), supervisor support (AOR: 7.40, 95% CI: 3.84, 14.26), and a better salary/payment (AOR: 4.18, 95% CI: 2.19, 7.88) compared to their counterparts.

Conclusion and Recommendation

The job satisfaction level among rural HEWs in the study area was low. Strategies to stimulate and strengthen recognition of management, supportive supervision, performance-based regular salary increment, and career developments are recommended.
COVID-19 Pandemic, Personality and Geriatric Population: Proposed Pragmatism
Authors: Dubey Souvik , Sengupta Samya , Ghosh Ritwik , Dubey Mahua Jana , Chatterjee Subham , Das Gautam , Roy Dipayan , Ray Biman Kanti , Benito-León Julián
Published: November 2021

The elderly population is a sensitive and delicate cohort of society who is being compelled to bear the significant smoulders of disruptive social behavior of humankind amidst the COVID-19 pandemic. Our aim for this review was (1) to find out the root of disruption of societal integrity and self-centeredness by analyzing the spokes of HEXACO; (2) to delineate their possible relationships with the formation of Neuroticism and eventually Psychopathy, which have endangered human civilization the most in this pandemic; and (3) to search for the potential ways to get rid of these dark times. The constellation of different negative human behaviors probably originate from the negative deflection of components of the HEXACO model of personality towards the genesis of the dark triad. COVID-19 pandemic and upsurge of the dark triad in the form of Neuroticism, Narcissism and Machiavellianism potentially portend major mental health threats. Cultivation and practice of positive emotions and triumph of honesty, humility and humanity are imperative to save the mankind from the savagery of this pandemic.
Effect of processing temperatures on the thermal and mechanical properties of leather waste-ABS composites
Authors: Owen Macaulay M. , Achukwu Emmanuel O. , Arukalam Innocent O. , Muhammad Mustakim , Romli Ahmad Z.
Published: November 2021

The effect of varying processing temperatures (200, 220 and 240°C) on the thermal and mechanical properties of uncoated and epoxy-coated chrome-tanned leather wastes-ABS composites has been studied. The results obtained showed that the mechanical properties of the composites decreased as the processing temperature increased. Epoxy-coated leather wastes fibre-ABS (CLWABS) composite yielded better mechanical properties compared to the uncoated leather wastes-ABS composite (LWABS). These results were obtained at an optimized processing temperature of 200°C. Furthermore, the results were confirmed by the field emission scanning electron microscopy (FESEM) studies. The differential scanning calorimetry (DSC) studies revealed that the epoxy-coated leather wastes fibres (CLW) showed higher onset and melting temperatures of 131.8 and 179.35°C than the uncoated leather wastes fibres (LW) with glass transition (Tg) and melting (Tm) temperatures of 128.2 and 169.4°C, respectively. When the LW and CLW fibres were mixed with Acrylonitrile butadiene styrene (ABS), the Tg and Tm of CLWABS composite were found to be 94.9 and 269.8°C, respectively, higher than the LWABS composite with Tg and Tm of 89.1 and 261.6°C, respectively. Thus, this study has demonstrated that utilization of epoxy-coated chrome-tanned leather wastes fibres as fillers in the design of ABS-based composites will help a great deal in addressing the problem of solid waste pollutants in our environment.
Novel Mechanisms of Thrombopoietin Generation: The Essential Role of Kupffer Cells
Authors: Karakas Danielle , Li June , Ni Heyu
Published: November 2021

Thrombopoietin (TPO) is the physiological regulator of hemopoietic stem cell niche and megakaryocyte differentiation, and therefore platelet production. Prevailing theory posits that TPO is constitutively expressed by hepatocytes, and levels are fine-tuned through platelet and megakaryocyte internalization/clearance via the c-Mpl receptor. Our lab has previously shown that platelet glycoprotein (GP) Ibα is indispensable for platelet-mediated TPO generation (Blood 2018), and recent reports have demonstrated that Kupffer cells, the tissue resident macrophages of the liver, contribute to the clearance of desialylated platelets. However, whether Kupffer cells may contribute to TPO generation has never been explored.

To determine the possible role of Kupffer cells in TPO production, clodronate liposome was intravenously administered to deplete Kupffer cells in wild-type mice. Wild-type, Kupffer cell depleted mice showed a TPO decrease of 43.6% (±16%) 2 days post depletion, with only a gradual insignificant increase in TPO levels to day 6. Interestingly, TPO levels could not be significantly increased in wild-type Kupffer cell depleted mice even when transfused 2x10 8 wild-type or desialylated platelets, or 50mU neuraminidase. Kupffer cell depletion in IL4Rα/GPIbα-transgenic mice, which lack platelet-mediated TPO generation, showed a TPO decrease of 22.5% (±5%) from baseline 2 days post depletion, with only a gradual increase in levels to day 6, suggesting that Kupffer cells are required for constitutive in addition to platelet-mediated TPO production. As our lab has previously shown that platelet GPIbα drives platelet-mediated TPO generation, and that Kupffer cells now required, WT and GPIbα -/- platelets were co-cultured with Kupffer cells to assess interaction. Desialylated WT platelets interacted significantly more with Kupffer cells as analyzed by flow cytometry than GPIbα -/- platelets. Interestingly, desialylation of GPIbα -/- platelets did not increase binding to Kupffer cells, consolidating that desialylated GPIbα is required for Kupffer cell interaction, and subsequent TPO generation.

This data demonstrates the novel and unexpected finding that Kupffer cells are required for both platelet-mediated and baseline hepatocellular TPO generation. Elucidation of the role of Kupffer cells in this crucial mechanism will provide a better understanding of why thrombocytopenias may occur in pathological states, as well as contribute to the development of TPO mimetic therapies.

Disclosures

No relevant conflicts of interest to declare.
CD38 x ICAM1 Bispecific Antibody Is a Novel Approach for Treating Multiple Myeloma and Lymphoma
Authors: Chen Xiaocheng , Wong Oi Kwan , Post Leonard
Published: November 2021

Targeting cluster of differentiation 38 (CD38) with monoclonal antibodies has resulted in outstanding responses in patients with multiple myeloma (MM). However, a significant portion of patients failed to respond and nearly all patients eventually relapsed. Furthermore, daratumumab, an anti-CD38 antibody, only showed limited monotherapy activity in relapsed/refractory Non-Hodgkin lymphoma (NHL) patients in a phase 2 study. One of the mechanisms of resistance has been partially attributed to lower CD38 expression. Intercellular adhesion molecule 1 (ICAM1), an immunoglobulin (Ig)-like cell adhesion molecule, is highly expressed in multiple myeloma and lymphoma. Antibody against ICAM1, bersanlimab (BI505, BioInvent), was well-tolerated, but only showed limited clinical efficacy in MM patients. Here, we generated bispecific CD38 x ICAM1 antibody to target ICAM1 + tumor types with low to medium CD38 expression. RNA sequencing (RNAseq) results from the Cancer Cell Line Encyclopedia (CCLE) database showed that ICAM1 is highly expressed on myeloma and lymphoma cell lines. ICAM1 expression levels for selected myeloma and lymphoma cell lines were then validated using flow cytometry. The CD38 x ICAM1 bispecific antibody was constructed by paring a novel CD38 antibody and a novel ICAM1 antibody through an asymmetric three chain knob-into-hole format. The bispecific antibody showed potent in vitro antibody-dependent cellular cytotoxicity (ADCC) activities on ICAM1 + tumor cells with medium to low CD38 levels, where daratumumab has low or minimal effect. The bispecific antibody also showed potent in vitro antibody-dependent cellular phagocytosis (ADCP) activities on cell lines with a range of CD38 expression. The CD38 x ICAM1 bispecific antibody further demonstrated potent tumor inhibition activities in in vivo myeloma and lymphoma cell line-derived xenograft (CDX) models, including cell lines with low to medium CD38 expression. We then evaluated CD38 and ICAM1 expressions in lymphoma patient-derived xenograft (PDX) samples by RNAseq. Among the 37 PDX samples, 27 of them showed ICAM1 expression above 2 5 fragments per kilobase of transcript per million map reads (FPKM). On the contrary, there is a wide range of CD38 expression levels with only 6 samples having CD38 expression above 2 5 FPKM. The ICAM1 and CD38 expressions in the selected PDX samples were further validated with IHC staining. Most importantly, the CD38 x ICAM1 bispecific antibody showed complete tumor inhibition in a rituximab-resistant lymphoma PDX model, whereas daratumumab only showed minimal efficacy. In conclusion, the CD38 x ICAM1 bispecific antibody demonstrated improved efficacy and specificity toward CD38 + and ICAM1 + tumor cells and represents a novel approach for treating multiple myeloma and lymphoma.

Disclosures

No relevant conflicts of interest to declare.
Trial in Progress: Real-World Safety and Effectiveness of Brentuximab Vedotin in Adults with CD30+ Lymphoma in China
Authors: Xu Pengpeng , Cai Mingci , Zhang Wendy , Zhao Wei Li
Published: November 2021

Background: Clinical trials have demonstrated the effectiveness of the CD30-targeted antibody-drug conjugate brentuximab vedotin (BV) for the treatment of classical Hodgkin lymphoma (HL) and non-Hodgkin lymphoma(e.g. ALCL, PTCL-NOS, AITL, CTCL and etc.). While clinical trials are critical for establishing efficacy, collection of real-world data outside of the controlled trial setting is important to evaluate how interventions are applied and assess the effectiveness of new treatments in routine clinical practice. Inclusion criteria are often rather restrictive compared with the patient populations seen by physicians in daily practice. There are limited real-world data related to treatment with BV in China. Our study aims to obtain timely real-world knowledge in terms of safety and effectiveness of BV in CD30+ lymphoma patients in China.

Study Design and Methods: The study (NCT04837222) is a real-world, prospective, multicenter study to evaluate the safety and effectiveness of BV in patients with CD30+ lymphoma in China. Consecutive CD30+ lymphoma patients treated with BV as a part of standard clinical practice will be enrolled. Key inclusion criteria includes adult patients undergoing treatment with BV or to be received with BV, patient/legal guardian must be able to read, understand, and sign the Informed Consent Form, CD30+ lymphoma by INV (any CD30 expression). Exclusion criteria includes patient who currently participates in or with plan to participate in any interventional clinical trial, any other reason that, in the investigator's opinion, makes the patient unsuitable to participate in this study. As CD30+ lymphoma is not a common disease and the affordability of novel treatment is limited, 1000 patients with CD30+ lymphoma will be recruited from almost 30 hematology centers. The physician will determine the treatment regimen, as well as the frequency of laboratory and clinical assessment according to her/his routine practice. All patients will be followed up per routine clinical practice and data will be documented at baseline/3/6/9/12/18/24 months unless withdrawal of Informed Consent, death or loss of follow-up, whichever comes first. Loss to follow-up will be minimized through active contact with participating patients thereafter to ensure almost all clinically relevant outcomes will be captured. The primary endpoint is serious adverse events. Secondary endpoints include adverse events, adverse drug reaction, dose adjustment, characteristics of patients receiving BV, use of BV, number of BV cycles administered, disease characteristics, time to next treatment, overall response rate, duration of response, progression free survival rate, overall survival rate, quality of life and cost-effectiveness ratio. Descriptive analysis will be performed for data analysis.

Disclosures

Zhang: Takeda Pharmaceuticals: Current Employment.
Rivaroxaban or Placebo for Extended Antithrombotic Prophylaxis after Laparoscopic Surgery for Colorectal Cancer. the PRO-LAPS II Study
Authors: Becattini Cecilia , Pace Ugo , Pirozzi Felice , Avruscio Giampiero , Donini Annibale , Rondelli Fabio , Visonà Adriana , Boncompagni Michela , De Prizio Marco , Chiari Damiano , Muratore Andrea , Guerra Francesco , De Luca Raffaele , Portale Giuseppe , Milone Marco , Righini Marc , Castagnoli Giampaolo , Persiani Roberto , Martellucci Jacopo , Frasson Stefania , Dentali Francesco , Delrio Paolo , Sciuto Antonio , Gussoni Gualberto , Agnelli Giancarlo
Published: November 2021

Background The clinical benefit of extending prophylaxis for venous thromboembolism (VTE) beyond hospital discharge after laparoscopic surgery for cancer is unclear. The efficacy and safety of thromboprophylaxis with direct oral anticoagulants in cancer surgery is unexplored.

Methods PROLAPS II is an investigator-initiated, prospective, randomized, double-blind study aimed at assessing the efficacy and safety of extended prophylaxis with rivaroxaban compared with placebo after laparoscopic surgery for colorectal cancer (NCT03055026). All patients received antithrombotic prophylaxis with low molecular-weight heparin for 7±2 days and were then randomized to receive rivaroxaban (10 mg once daily) or placebo for the following 3 weeks (up to day 28±2 from surgery).

The primary study outcome was the composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected deep vein thrombosis (DVT) or VTE-related death within 28±2 days from laparoscopic surgery. The primary safety outcome was ISTH-defined major bleeding. By assuming an 8% incidence of primary study outcome in patients randomized to placebo and a 60% reduction with rivaroxaban, 323 patients per group were necessary to show the superiority of rivaroxaban.

Results. Patient recruitment in PROLAPS II study was preliminary closed in June 7 th, 2021 due to study drug expiry, after the inclusion of 577 patients. The main patients features are reported in the Table. Study results will be available after the last study patient will complete the 90-day follow-up (scheduled on September 7th, 2021) and will be ready to be presented at the ASH 2021 Congress.

Conclusion PROLAPS II is the first study with an oral anti-Xa agent in cancer surgery. The study has the potential to improve clinical practice by assessing the clinical benefit of extending prophylaxis after laparoscopic surgery for colorectal cancer.

Figure 1 Figure 1.

Disclosures

Becattini: Bayer HealthCare: Honoraria; Daiichi Sankyo: Honoraria; Bristol Myers Squibb: Honoraria. Dentali: Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria; Daiichi Sankyo: Honoraria; Bayer: Honoraria; Sanofi: Honoraria; Novartis: Honoraria; Boehringer: Honoraria; Alfa Sigma: Honoraria. Agnelli: Bayer HealthCare: Honoraria; Daiichi Sankyo: Honoraria; Pfizer: Honoraria; Bristol Myers Squibb: Honoraria.
Realgar Indigo Formula Plus ATRA As Postremission Treatment in an Rral and Chemo-Free Model for High-Risk Acute Promyelocytic Leukemia Patients: A Prospective, Multicenter, Phase II Study
Authors: Zhu Hong-hu , Ma Ya-fang , Chen Suning , Lu Ying , Huang Jiang , Wang Huai-Yu , Xu Xiaohua , Xie Bing-Shou , Lou Yinjun , Jin Jie
Published: November 2021

Background:

Low-risk patients with acute promyelocytic leukemia (APL) can be cured using only ATRA and arsenic trioxide (ATO), without chemotherapy(Lo-Coco F, et al. NEJM 2013) .Our group simplified the protocol by replacing iv ATO with oral arsenic, referred to as RIF, allowing for outpatient, oral and chemotherapy-free treatment for an increasing number of APL patients (Zhu HH, et al. NEJM 2014; 371:2239-41;Zhu HH, et al. Lancet Oncol 2018;19:871-879; Zhu HH, et al. Blood 2019;134:597-605). We also reported a promising single-center results using chemo-free postremission treatment for high-risk APL patients (Zhu HH, Blood 2018;131:2987-2989), which need to be confirmed in a well designed multi-center trial.

Objective:

To evaluate the efficacy of safety Realgar indigo formula plus retinoic acid as postremission treatment in an oral and chemo-free model for high-risk APL patients .

Design, setting and participants:

a prospective, multicenter, single-arm, phase II clinical trial conducted in the First Affiliated Hospital, Zhejiang University College of Medicine, China. Eligible patients (>18 years old) with newly diagnosed APL and achieved complete remission(CR) were enrolled since May 2019, with final follow-up in July 31,2021.

Interventions:

The consolidation therapy included realgar-Indigo naturalis formula (60 mg/kg daily in an oral divided dose) in a 4-week-on and4-week-off regimen for 4 cycles and ATRA (25 mg/m 2 daily in anoral divided dose) in a 2-week-on and 2-week-off regimen for 7 cycles. The primary endpoint was the 2-year DFS. Secondary endpoints included complete molecular remission (CMR) defined as the absence of detectable PML-RARA transcripts., event-free survival (EFS), OS, and safety.

Main outcomes and measures:

38 eligible patients were enrolled including 18 males and 20 females and the median age was 41 years old (18-77 years). The median of WBC count is 25.39（10.2-113.9）×109/L[ >50×10 9/L n=10; (20-50)×10 9/L n=14，(10-20)×10 9/L n=14].All the patients achieved CMR during post-remission treatment phase (7 months). Until now, no molecular, hematologic recurrence,and central nervous system leukemia has happened with median follow-up of 13 months. What's more, this chemotherapy-free, completely oral regimen was well tolerated.

C onclusions:

These exciting results proved that RIF plus retinoic acid as postremission treatment of high-risk APL was effective, safe and convenient. The study is ongoing, and the effective of this regimen need to be evaluated by more patients and longer time.

Figure 1. The overall survival(OS) and disease-free survival (DFS) of high-risk APL patients.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
Rusfertide (PTG-300), a Hepcidin Mimetic, Maintains Liver Iron Concentration in the Absence of Phlebotomies in Patients with Hereditary Hemochromatosis
Authors: Kowdley Kris V , Modi Nishit B , Valone Frank , Priego Victor M. , Ferris Christopher , Cole Frank , Gupta Suneel K
Published: November 2021

Introduction: Patients with hereditary hemochromatosis (HH) require continued phlebotomies to limit end-organ damage. Approximately 25% of patients in maintenance felt receiving phlebotomies was "inconvenient" or "very inconvenient" (Brisott et al, 2011). Patient compliance with phlebotomies generally declines with time (Hicken et al, 2003), and therapeutic phlebotomies may not be medically suitable for some HH patients. Rusfertide, a peptide mimetic of hepcidin, is an effective regulator of iron distribution and utilization that has demonstrated control of iron in an animal model of HH.

Methods: We conducted an open-label, dose-finding efficacy study that investigated subcutaneous rusfertide in HH patients on a stable phlebotomy regimen of 0.25 to 1 phlebotomy per month for at least 6 months. Patients with clinical laboratory abnormalities and those receiving iron chelation therapy or erythrocytapheresis were excluded. Subjects received individually titrated rusfertide doses once or twice a week to maintain transferrin saturation (TSAT) below 45% and were followed for 6 months. Study measures included TSAT, serum iron, transferrin and ferritin, liver iron concentration (LIC) measured by MRI, and adverse events (AEs).

Results: Sixteen subjects (10 male/6 female) were enrolled. Mean age and weight were 62.5 years and 88.1 kg, respectively. LIC values were maintained at pre-study levels, with minimal use of phlebotomies during the duration of the study (Figure 1A). Average pre-study phlebotomy rate was 0.27 phlebotomies/month compared to 0.03 phlebotomies/month during the study (p<0.0001; Figure 1B). There was a dose- and concentration-dependent decrease in serum iron and TSAT (Figure 2A and 2B). Transferrin levels were relatively constant over the course of the study. There were no notable changes in hematological parameters such as hematocrit, erythrocytes, leucocytes, or platelets. Rusfertide was generally well tolerated. Adverse events reported in 2 or more subjects included diarrhea, fatigue, injection site reactions (erythema, induration, pain, pruritis), dizziness, and headache.

Conclusions: Rusfertide demonstrated a pharmacodynamic effect in reducing TSAT and serum iron, with corresponding significant reduction in the number of phlebotomies, and with LIC maintained at pre-study levels with minimal use of phlebotomies. These data indicate rusfertide was well tolerated in patients with HH and controls LIC, supporting development of rusfertide as a potential treatment for HH.

Figure 1 Figure 1.

Disclosures

Kowdley: PTG: Consultancy, Research Funding. Modi: Protagonist Therapeutics: Current Employment. Valone: Protagonist Therapeutics: Current Employment, Current equity holder in publicly-traded company. Gupta: Protagonist Therapeutics: Current Employment.
Elucidating the Characteristics of Two Tumor Cell Populations in Small Cell Variant of Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma
Authors: Noguchi Kazuhiro , Ikawa Yasuhiro , Takenaka Mika , Sakai Yuta , Fujiki Toshihiro , Kuroda Rie , Wada Taizo
Published: November 2021

The small cell variant of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (SC-ALCL) is a subtype defined as comprising two distinct tumor cell populations in immunohistochemistry: small cells staining negative or weakly positive for ALK and CD30 protein; and large cells staining strongly positive for those proteins. Although the constitution of these two different cell populations might contribute to the poor prognosis, detailed characterization of each population by molecular-based approaches has not been done due to the difficulty of cell separation from solid tumor sample. In this paper, we have analyzed the characterization of each tumor cell population using the patient sample from SC-ALCL leukemic phase obtained from peripheral blood by molecular-based approaches. Flow cytometric analysis revealed two distinct abnormal populations. The major population comprising 74% of total leukocytes was positive for CD3 and CD8, and negative for CD4, CD5, CD25 and CD30. The minor population comprising 5% of total leukocytes was positive for CD25, CD30, CD11b and CD13. Fluorescent in situ hybridization with ALK break-apart probes and RT-PCR analysis confirmed that most of the cells including both populations were rearranged with NPM-ALK gene. To elucidate the cause underlying the distinct levels of ALK protein expression in each population, we separated those tumor cells by CD30-PE antibody and a magnetic bead separation kit, extracted DNA and RNA from each population, and compared NPM-ALK mRNA expression levels by droplet digital polymerase chain reaction. The expression level of NPM-ALK mRNA in the CD30-negative population was ten-fold less than that in the CD30-positive population (Table). This result indicated that the two tumor cell populations expressed the distinct level of NPM-ALK mRNA, although both populations possessed NPM-ALK fusion gene. To assess the effectiveness of various chemotherapies in each tumor cell population, we monitored each population in peripheral blood by flow cytometric analysis (small cell; CD30-5-8+, large cell; CD30+) over time. Intriguingly, CD30-negative population behaved as chemo-resistant cells in clinical course, however alectinib, a second-generation ALK-inhibitor, eradicated both populations inducing first complete remission. This study revealed two definitive features regarding the small CD30-negative population of SC-ALCL, with a lower expression level of NPM-ALK mRNA transcripts and chemoresistance. The cause of distinct ALK staining levels in immunohistochemistry was revealed depending on the distinct expression level of NPM-ALK mRNA transcripts. Finally, since both populations were sensitive to ALK-inhibitor, early administration of ALK-inhibitor might be the reasonable option for SC-ALCL.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
An in Depth Analysis of Factors Contributing to Diagnostic Delay in Myeloma: A Retrospective UK Study of Patients Journey from Primary Care to Specialist Secondary Care
Authors: Hossain Md Imran , Hampson Peter , Nowell Craig , Khan Shamshad , Sen Ranjoy , Sundararaman Sharadha , Adiyodi Jagdish , Basu Supratik
Published: November 2021

Introduction

Patients with Multiple Myeloma (MM) often have a significant delay between onset of symptoms and diagnosis of disease. As a result, a significant number of patients present via emergency routes with severe co-morbidities which affect survival rates. Timely diagnosis relies on the early recognition of symptoms and blood test results which may indicate disease.

Methods

We examined the medical records of 142 newly diagnosed MM patients (121 intact immunoglobulin and 21 light chains) across 2 UK Hospitals. Patients included had not previously been diagnosed with a plasma cell dyscrasia, including Monoclonal Gammopathy of Undetermined Significance (MGUS). Clinical symptoms and blood test results were examined from the time of initial presentation to the healthcare system with symptoms indicative of MM, to the point of diagnosis in order to highlight patterns of symptoms and blood tests results which may give an early indication of disease. Blood tests results recorded included globulin, calcium, creatinine, erythroid sedimentation rate and haemoglobin. Time to diagnosis from presentation with symptoms indicative of MM was also measured as well as the patient pathway from the point of presentation to the point of diagnosis.

Results

The median time to diagnosis from initial presentation was 77 days (range 0 - 12,986). Initial presentation was most commonly via primary care (58.1%). Urgent secondary care presentation was documented in 28.5% which included acute medical unit (15.6%), the emergency department (7.1%), and other secondary care specialities (5.7%) respectively. Multiple GP visits were common prior to haematology referral with a median of 3 visits (range 1 - 40). Initial presenting symptoms varied, but of those with data recorded (n=107) back/bone pain was the most common (58.2%) followed by anaemia (18.7%), fracture (7.5%), recurrent infection (7.5%) and renal impairment (3.7%) respectively. Interestingly, analysis of evaluable blood test results revealed a raised globulin was most often evident prior to diagnosis with 58% of patients recording an abnormal globulin a median of 140 days (range 3 - 4297) prior to diagnosis of disease.

Conclusions

Multiple GP visits prior to establishing a diagnosis of myeloma is very common. Inclusion of abnormal globulin to reflex electrophoresis request and serum free light chain assay may serve as a useful trigger for investigation when interpreted alongside presenting symptoms and other blood test results. Increased awareness of myeloma warning signs in primary care may reduce diagnostic delay and avoid presentation with severe co-morbidities in emergency settings.

Disclosures

No relevant conflicts of interest to declare.
The Interaction of Sickle Cell Trait and Anticardiolipin Antibodies in Venousthromboembolism
Authors: Ezekekwu Chinedu A , Kotila Taiwo R , Anyanwu-Yeiya Chinonso Chiemeka , Akingbola Titilola S. , Tayo Bamidele
Published: November 2021

Introduction

Among the risk factors for venous thromboembolism (VTE) are inheritance of the sickle cell gene and antiphospholipid syndrome. Antiphospholipid antibodies are elevated in sickle cell disease but there is little information on its levels in sickle cell trait. The prevalence of anticardiolipin antibodies and association with VTE is equally not known in the Nigerian population.

Methods

A case control study involving 50 consecutive patients with Doppler confirmed venous thromboembolism at the University College Hospital Ibadan and 50 apparently healthy individuals. Haemoglobin electrophoresis was carried out using cellulose acetate membrane. IgG and IgM anticardiolipin antibodies were assayed by ELISA.

Results

The mean age of the patients was 58.7±18.5years, range of 21-89 years, there were 21 males (42%). Majority of the patients (42 (84%)) had deep venous thrombosis while five (10%) patients presented with pulmonary embolism, one had both deep venous thrombosis and pulmonary embolism. A patient had portal vein thrombosis and another, an intracardiac clot. Sedentary lifestyles, hypertension and concomitant malignancy were the most prevalent risk factors (34% each) (figure I). Both sedentary lifestyle and cancer were significantly associated with VTE (p<0.001). Sickle cell trait (Hb AS) occurred in the same number of patients and controls (eleven each). Higher levels of both IgG and IgM anticardiolipin antibodies were found among the VTE patients with sickle cell trait than controls. (Table 1) The mean levels of IgG antibody in Hb AS patients was 31.7 ± 12.8 GPL compared to 25 ± 13.8 GPL in the controls (p= 0.254) and mean IgM anticardiolipin antibodies in Hb AS patients was 18.7 ± 6.2 GPL while that of the controls was 16.8 ± 11.6 GPL (p= 0.633). The global mean levels of IgG and IgM anticardiolipin antibodies in the patients with VTE were 29.7 ± 9.1 GPL and 24.8 ±16.7 GPL respectively versus 28.5 ±13.7 GPL and 25.2 ±16.2 GPL in the controls. A multivariable logistic regression showed age, sedentary lifestyle and anemia as independent risk factors while a positive IgM anticardiolipin antibody appeared protective for VTE. (Table 2)

Conclusion

The prevalence of sickle cell trait and anticardiolipin levels did not differ between VTE patients and healthy controls. Age, hypertension, sedentary lifestyle and malignancies were identified risk factors in our cohort of patients. Larger prospective studies may be helpful in determining the influence of sickle cell trait and antiphospholipid antibodies in venous thromboembolism.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.