bluuebunny/crossref_metadata_2025 huggingface dataset:
Using social media for vaccination promotion: Practices and challenges
Authors: Steffens Maryke S , Dunn Adam G , Leask Julie , Wiley Kerrie E
Published: November 2020

Objective

Vaccination misinformation is widespread on social media. Vaccine-promoting organisations are working to curb its influence, but face obstacles. We aimed to analyse their social media strategies and the challenges they encounter.

Methods

In this qualitative study, we purposively sampled 21 participants responsible for social media from vaccine-promoting organisations. We used Framework Analysis to explore the data.

Results

Vaccine-promoting organisations faced obstacles using social media, including fast-paced change, limited resources, and insufficient organisational buy-in. They experienced difficulties reaching audiences, exploiting social media listening, and measuring impact. Consequently, they may miss opportunities to counter misinformation, connect with groups low in vaccine confidence, and determine diverse audience responses. They lack strong evidence linking social media strategies with behaviour change, and have difficulty understanding silent audiences.

Conclusions

Vaccine-promoting organisations have an opportunity to embrace the participatory nature of social media. They could share listening insights with like-minded groups, and conduct research exploring associations between social media strategies and community attitude/behaviour change. Social media platforms could assist by renewing vaccine-promoting organisations' organic reach, supporting the development of tailored listening and credibility tools, and strengthening collaborations to promote credible content.
Phytotherapeutic modalities for the management ofHelicobacter pyloriassociated peptic ulcer
Authors: Zahid Rabia , Akram Muhammad , Riaz Muhammad , Munir Naveed , Shehzad Muhammad
Published: November 2020

Due to an imbalance between aggressive factors known as hydrochloric acid (HCl), pepsin, leukotrienes, refluxed bile, defensive factors and reactive oxygen species, the peptic ulcer is formed in the stomach and duodenum which mostly include the function of prostaglandins, mucus bicarbonate barrier, enzymatic antioxidants, and some growth factors. H. pylori infection remained one of the considerable causes of peptic ulcer as it caused hypochlorhydria and struck off the defense mechanism of the stomach. The nonsteroidal anti-inflammatory drugs (NSAIDs) and stress are the most prevailing causes of peptic ulcer disease. Lack of physical exercise, little rest and due to poor leisure cause the peptic ulcer disease. Candies, chocolate, coffee, cigarettes, stress, and alcohol are the cause of peptic ulceration and suppression of acid in the stomach due to the utilization of antacid medication. Most of the ancient medical practices in the traditional alternative medicinal system include Unani, Ayurveda, Siddha, Homeopathy, Naturopathy, Chinese customary medicine, African conventional medicine, and Native American medicine. Without a hostile effect, the rate of curing the disease is the significance of natural products research. Peptic ulcer disease is the widespread nature of peptic ulcer in all class of population, which mostly may be due to rapidly changing the food habits and stress, causing the imbalance between gastric offensive and defensive factors. Curcuma longa is the most effective plant for the cure of peptic ulcer. Curcuma longa has anti-inflammatory and antioxidant activity. Curcuma longa remarkably reduces the level of inflammatory mediator (IL1) and (TNF) which was increased during the formation of an ulcer. In the rhizome of Curcuma longa, yellow pigment is present and widely used for the treatment of ulcer and decrease the inflammatory response. Symptoms include abdominal pain after taking a meal, nausea, vomiting, Anorexia and lose weight.
Role of Additional Inferomedial Supporting Screws in Osteoporotic 3-Part Proximal Humerus Fracture: Finite Element Analysis
Authors: Kim Hyojune , Lee Wonhee , Choi SeungHyun , Kholinne Erica , Lee Euisop , Alzahrani Wael Mohammed , Koh Kyoung Hwan , Jeon In-Ho , Kim Shinseok
Published: November 2020

Introduction:

Importance of inferomedial supporting screws in preventing varus collapse has been investigated for the proximal humerus fracture. However, few studies reported the results of osteoporotic complex fracture. This study aimed to demonstrate the stress distribution pattern, particularly in osteoporotic 3-part proximal humerus fractures involving greater tuberosity (GT) with different screw configurations.

Materials and methods:

Using the computed tomography (CT) images of 2 patients, who had osteoporosis and the other had normal bone density, 3-part fractures involving the GT, without medial support were reconstructed. To reflect the osteoporosis or real bone density, Hounsfield unit of CT scans were utilized. A force of 200 N was applied in 30° varus direction. The proximal screws were set in 2 ways: 6 screws without inferomedial supporting screws and 9 screws with inferomedial supporting screws. Qualitative and quantitative analysis of internal stress distribution were performed.

Results:

The most proximal part area near humeral head vertex and near the 1st screw’s passage and tip had more stress concentrated in osteoporotic 3-part fractures. The stress distribution around the proximal screws was found near the GT fracture line and its lateral side, where the local max values located. Inferomedial supporting screws decreased these effects by changing the points to medial side from the GT. The ratio in osteoporotic bone model decreased to that in normal bone model when inferomedial supporting screws were applied (normal bone, 2.97%–1.30%; osteoporosis bone, 4.76%–1.71%).

Conclusions:

In osteoporotic 3-part proximal humerus fracture, the stress distribution was concentrated on the area near the humeral vertex, 1st row screw tips, and lateral side region from the GT fracture line. Moreover, inferomedial supporting screws ensured that the stress distribution is similar to that in normal bone setting, particularly in osteoporotic condition.
School Counseling District Supervisors’ Experiences and Perceptions Regarding School Counselor Preparation for Practice
Authors: Goodman-Scott Emily , Upton Amy , Colburn Anita Neuer
Published: November 2020

District-level school counseling supervisors assist with school counselors’ induction into the school counseling field; however, related research is lacking. As a result, we conducted an exploratory thematic analysis to investigate district supervisors’ experiences and perceptions regarding novice school counselors’ transition from preservice to practice. Results included three themes, largely encompassing school counselor preparation: (a) preparation program variation, (b) preferring face-to-face preparation modalities, and (c) suggestions for strengthening school counseling preparation and practice.
Bioarcheological Indicators Related to Human–Environmental Interactions in a Roman–Byzantine Settlement in Southeast Romania: Ibida Fortress
Authors: Stanc Simina , Danu Mihaela , Paraschiv Dorel , Bejenaru Luminița
Published: November 2020

The Roman–Byzantine fortress of (L)Ibida (Slava Rusă, Tulcea County, Romania) has preserved archeozoological and archeobotanical remains (i.e., phytoliths) that allowed an evaluation of the human–environmental interactions in that period. Bringing together bioarcheological data, this study contributes to understand the subsistence economy during a period of sociopolitical changes in the region. The stratigraphical sequences and the preliminary observations made on the archeological materials (ceramics, metal artifacts, coins) indicate a relative chronology beginning with the second to third centuries AD and lasting until the sixth century AD. Phytolith analysis highlights the clear domination of the grasses (Poaceae) and indicates the presence of cereals within the fortress. In the surroundings of the fortress, it appears to have existed an open environment. Although modest, the percentage of the Spheroid phytoliths suggests the presence of woody dicots, indicating the fact that the wooded surfaces existed near the fortress. The archeozoological data confirm the fact that the fortress was placed in an open environment, where people bred especially cattle ( Bos taurus) and sheep/goat flocks ( Ovis aries/Capra hircus), and they hunted species such as hare ( Lepus europaeus); also, the forest existed nearby, as indicate the remains of hunted species, among which we found the red deer ( Cervus elaphus) and the wild boar ( Sus scrofa).
High bonding strength between zirconia and composite resin based on combined surface treatment for dental restorations
Authors: li Rui , Wang Chen , Ma Shi Qing , Liu Zi Hao , Zang Cheng Cheng , Zhang Wen Yi , Sun Ying Chun
Published: November 2020

Zirconia is the preferred material for dental restorations; however, dental restorations are usually affected by zirconia fractures due to chipping and delamination of the veneer ceramic. One effective solution for repairing chemically inert zirconia frameworks is to strongly chemically bond them with the composite resin via surface modification. Thus, the bonding strength between the zirconia and composite resin determines the performance of dental restoration. Herein, we investigate the shear bond strength between zirconia ceramic and two ceramic repair systems before and after thermal cycling based on different surface pretreatments, including air-abrasion and a novel silane coupling agent. When treated with combined sandblasting, novel silane and 10-methacryloyloxydecyl hydrogen phosphate act as a bonding agent for the zirconia surface, and the maximum shear bond strength achieves 27.5 MPa, as measured by a universal testing machine through the average of 16 separate measurements. The results show that the combined treatment resists the interface damage caused by expansion and contraction during thermal cycling. The long-term bond durability is due to the micro-mechanical bond force formed by resin and ceramic, and the chemical bonds of Zr-O-Si at the interface. Results indicate that selective pretreating the surface results in high bond strength between the zirconia and the composite resin, which is meaningful to optimize dental restoration.
Development of a phase change microcapsule to reduce the setting temperature of PMMA bone cement
Authors: Xia Xue , Shi Rui , Huang Jinhui , Li Yubao , Zuo Yi , Li Jidong
Published: November 2020

The aim of the current study is to alleviate the adverse effect of the strongly exothermic polymerization of polymethyl methacrylate (PMMA) bone cement in clinical applications. In this study, paraffin/poly(methyl methacrylate–methylene bisacrylamide) (paraffin/P(MMA-MBA)) phase change microcapsules (MPn; n = 1, 2) were developed via the emulsion polymerization method. The reduction of the maximum temperature of polymerization (Tmax) and physicochemical properties were evaluated after doping commercial PMMA cement with MPn in specific proportions (10%, 20%, and 30%). The results reveal that the MPn-doped PMMA exhibited an effective reduction in Tmax, which can help alleviate the adverse effect of the strong exothermic reactions during PMMA setting. After doping with the MPn, the mechanical properties of the PMMA cement decrease and the values are close to that of body cancellous bone. The Tmax of the cement doped with 20 wt% MP1 is 37.6°C, which is close to body temperature. Significantly, the setting and compressive properties of the optimized group can still adhere to clinical requirements. The MPn doping PMMA technique holds much promise in clinical practice.
Sensor-guided technology helps to reproduce medial pivot kinematics in total knee arthroplasty
Authors: Cochetti Andrea , Ghirardelli Stefano , Iannotti Ferdinando , Giardini Piero , Risitano Salvatore , Indelli Pier Francesco
Published: November 2020

Achieving a well-balanced total knee arthroplasty (TKA) is a difficult task, but the use of real-time sensing technology could provide intraoperative dynamic feedback regarding stability and load. This study compared intraoperative data and clinical outcomes between two cohorts, where one cohort had a sensor-guided medial pivot TKA performed.

Methods:

Two cohorts of 50 patients each were preoperatively matched to receive the same TKA, having a J-curve femoral design with an adapted “medially congruent” polyethylene insert; the second cohort (group B) underwent the intraoperative sensor-check. Intraoperative sensor data were recorded as tibiofemoral load at 10°, 45°, and 90°. We considered stable knees those with a pressure <50 lbs on the medial compartment, <35 lbs on the lateral, and a mediolateral inter-compartmental difference <15 lbs. Clinical outcomes were evaluated according to the Oxford Knee Score (OKS) and Knee Society Score (KSS).

Results:

All patients (group A: no sensor; group B: sensor) were available at 2-year minimum follow-up (FU; min. 24 months, max. 34 months); no preoperative statistical differences existed between groups in the average range of motion (ROM), OKS, KSS, and body mass index. There were no statistical differences at final FU between groups in the average OKS (group A: 41.1; group B: 41.5), in the average KSS (group A: 165.7; group B: 166.3), or in final ROM (group A: 123°; group B: 124°). One patient in each group required a manipulation under anesthesia. In the sensor group, an accessory soft tissue release/bone recut was necessary after sensor testing with trial components in 24% to obtain the desired loads; in the same group, the level of constraint in the final components was increased to posterior-stabilized in 12% because of an inter-compartmental difference >40 lbs. Surgical time was 8 min longer in the sensor group.

Conclusion:

The use of this sensing technology did not improve the clinical outcome but supported multiple intraoperative decisions aimed to better reproduce the medial pivot kinematic of the normal knee.
Hypericum perforatum L.: A Potent Antioxidant Source for the Treatment of Oxidized Dentin: An Experimental In Vitro Study
Authors: Yilmaz Nasibe Aycan , Yavaser Rukiye , Karagozler Arife Alev
Published: November 2020

Aim:

To evaluate the therapeutic antioxidant effect of Hypericum perforatum L. (HPL) extract on oxidized dentin as well as to address the following research question: Is experimental HPL-derived antioxidant treatment protocol as effective as sodium ascorbate in terms of reversing the compromised resin bonding to bleached dentin?

Materials and Methods:

Eighty bovine permanent mandibular incisors were included in the shear bond strength (SBS) test and randomly assigned into four groups ( n = 20) as follows: negative control (NC), positive control (PC), sodium ascorbate (SA), and Hypericum perforatum L. (HPL). Group NC did not receive bleaching treatment. All specimens except the NC group were oxidized by bleaching with 35% hydrogen peroxide. Experimental antioxidant solutions were prepared from SA powder and HPL extract at 10% concentrations. The bleached specimens in the SA and HPL groups were treated with respective antioxidant solutions. The SBS test was performed at a crosshead speed of 1 mm/min. The SBS data were analyzed with one-way analysis of variance using the post-hoc Bonferroni correction. The total phenolic content and the antioxidant activity of HPL extract were assessed by using the Folin–Ciocalteu assay and the 2,2-diphenyl-1-picrylhydrazyl free-radical scavenging activity test, respectively.

Results:

Considering the SBS test results, statistically significant the highest and the lowest mean values were observed in NC and PC, respectively ( P <.05). SA and HPL were not significantly different ( P > .05). The total phenolic content (104 ± 1.740 mg gallic acid equivalents (GAE)/gram (GAE/g) dry HPL extract) and the antioxidant activity of the HPL extract were demonstrated.

Conclusions:

The natural HPL plant extract was as effective as SA in reversing the compromised resin bonding to bleached dentin. Antioxidant treatment derived from the HPL extract may enable immediate resin restoration of oxidized dentin.
A Comprehensive Systematic Review In Search Of Evidence for Pragmatic Altercations in Simplified Denture
Authors: Kachhara Saloni , Nallaswamy Deepak , Ganapathy Dhanraj M. , Maiti Subhabrata
Published: November 2020

Aim:

To explore the evidence available to evaluate if simplified dentures could be as effective as the conventional complete dentures.

Materials and Methods:

A total of 1,482 articles were obtained using keywords in a Boolean search operator in the PubMed search engine, Google Scholar and Cochrane Library. Duplicates were removed and the remaining articles were subjected to a title analysis which yielded a total of 20. Further analysis of the article abstracts led to an exclusion of four articles. The remaining 16 articles were subjected to full text analysis which finally yielded a total of 11 articles.

Results:

The cumulative results of the meta-analysis for oral health-related quality of life, patient satisfaction and professional quality of denture show no significant difference ( P > .05) between conventional and simplified dentures.

Conclusion:

Based on the available evidence adjusted for the potential literature/geographic bias, we conclude that the conventional procedures in complete denture fabrication such as facebow and gothic arch tracing do not improve the quality of the denture outcome from patients’ perspective and simplified dentures are equally effective as conventional complete dentures.
Absorption and Enjoyment During Listening to Acoustically Masked Stories
Authors: Herrmann Björn , Johnsrude Ingrid S.
Published: November 2020

Comprehension of speech masked by background sound requires increased cognitive processing, which makes listening effortful. Research in hearing has focused on such challenging listening experiences, in part because they are thought to contribute to social withdrawal in people with hearing impairment. Research has focused less on positive listening experiences, such as enjoyment, despite their potential importance in motivating effortful listening. Moreover, the artificial speech materials—such as disconnected, brief sentences—commonly used to investigate speech intelligibility and listening effort may be ill-suited to capture positive experiences when listening is challenging. Here, we investigate how listening to naturalistic spoken stories under acoustic challenges influences the quality of listening experiences. We assess absorption (the feeling of being immersed/engaged in a story), enjoyment, and listening effort and show that (a) story absorption and enjoyment are only minimally affected by moderate speech masking although listening effort increases, (b) thematic knowledge increases absorption and enjoyment and reduces listening effort when listening to a story presented in multitalker babble, and (c) absorption and enjoyment increase and effort decreases over time as individuals listen to several stories successively in multitalker babble. Our research indicates that naturalistic, spoken stories can reveal several concurrent listening experiences and that expertise in a topic can increase engagement and reduce effort. Our work also demonstrates that, although listening effort may increase with speech masking, listeners may still find the experience both absorbing and enjoyable.
Technology-assisted supplemental work, psychological detachment, and employee well-being: A daily diary study
Authors: Eichberger Clara , Derks Daantje , Zacher Hannes
Published: November 2020

Information and communication technologies facilitate connectivity to work-related matters after official working hours. Therefore, more and more employees engage in technology-assisted supplemental work (TASW) during recovery time. However, research on the association between TASW and well-being has shown mixed results. To shed further light on this relationship, we tested a moderated mediation model. Drawing upon the extended stressor-detachment model (Sonnentag and Fritz, 2015), we proposed that psychological detachment mediates the relationship between TASW and well-being (i.e. affect and vigor). Further, we expected appraisal to moderate the relationship between TASW and psychological detachment, as well as cognitive coping to moderate the relationship between psychological detachment and well-being. To test these hypotheses, we analyzed daily diary data from 100 employees. As hypothesized, daily psychological detachment after hours mediated the positive association between daily TASW and daily negative affect at bedtime. Contrary to expectations, daily TASW was not significantly related to daily positive affect at bedtime and daily vigor in the next morning. Additionally, we found no support for the moderating roles of appraisal and cognitive coping. These results suggest that TASW can be associated with negative well-being states via impaired recovery, but that further studies are needed to explore the ambiguous outcomes of TASW. We discuss practical implications and future research avenues regarding individual differences in the experience of TASW.
Integration of Thermoplastic Splinting for Palatal Stabilization and Hemorrhage Control in Trauma and Oncology
Authors: Racker Blair H. , Sloan Chad S. , Chandra Srinivasa R.
Published: November 2020

Traumatic injury and pathological palatal defects can present a challenge in both acute care and clinical settings. Due to the vascularity of the maxillary region, thin mucosa, and difficulty of isolated stabilization, effective management and treatment planning are paramount to long-term patient outcomes. Palatal and dentoalveolar splinting has been widely used to manage palatal defects both intraoperatively and postsurgically with acrylic or polyvinyl chloride vacuum form materials as the basis for splint fabrication. We propose a method for palatal stabilization and hemorrhage control through the use of thermoplastic splinting material.
A Description of Treatment Patterns of Psoriasis by Medical Providers and Disease Severity in US Women
Authors: Tajalli Mahroo , Li Tricia , Drucker Aaron M. , Qureshi Abrar A. , Cho Eunyoung
Published: November 2020

Background:

Studies on treatment patterns of psoriasis are valuable to evaluate how efficiently individuals with psoriasis are treated and may facilitate improved outcomes for these patients.

Objective:

To describe treatment patterns of psoriasis among US women.

Methods:

In the Nurses’ Health Study II (NHS II), a prospective study of female nurses, 2107 women reported to have a diagnosis of psoriasis made by a clinician. We sent them the Psoriasis Screening Tool-2, a validated diagnostic tool for psoriasis, which queries age at diagnosis, treatments, type of psoriasis lesions, body surface area involved, and the provider who made the diagnosis.

Results:

A total of 1382 women completed and returned the survey, with 1243 of them validated for having psoriasis. 30% of the patients were diagnosed by non-dermatologists. 79% of the patients reported mild, 17% moderate and 4% severe disease. Psoriasis phenotypes were as follows: plaque 41%, scalp 49%, inverse 27%, nail 22% and palmoplantar 15%. Treatment patterns for mild psoriasis were as follows: only topical treatment 58%, systemic therapy and/or phototherapy 16% and no treatment 26%. Treatment patterns for moderate-to-severe disease were as follows: only topical treatment 42%, systemic therapy and/or phototherapy 47% and no treatment 11%.

Conclusion:

The majority of women in NHS II with psoriasis have mild disease. A large proportion of psoriasis patients were diagnosed by non-dermatologists. More than half of people with moderate-to-severe disease received no treatment or only topical medications. A considerable percentage of people with psoriasis reported phenotypes other than chronic plaque psoriasis.
Overflow: The oppositional life of an environmental impact study in a Senegalese mining negotiation
Authors: Fent Ashley
Published: November 2020

Since the 1980s, environmental impact assessment has been adopted by numerous countries in the Global North and Global South to evaluate the effects of industrial and mining development. However, as scholars of mining capitalism have suggested, this has become a technology of environmental government that often serves to bolster and legitimize extractive projects rather than improving environmental outcomes or opening space for public participation. Focusing on oppositional uses of an environmental impact study in a mining controversy in Casamance, Senegal, this article examines the work that environmental assessment does, and argues that it can be used as a tool of resistance, extended delay, and debate. Activists and local residents opposed to the proposed mining project highlighted “overflows”—ways in which the document and its strategies exceeded the intention of legitimizing the mine within Senegalese legal frameworks. As both a representational and material object, the study was used by activists to highlight conflicts of interest inherent in the evaluation process, to emphasize errors and flaws in the text, and to fuel alternative predictions about the mine’s effects. This article suggests greater attention to the oppositional lives of bureaucratic processes, and the ways in which community groups draw upon governmentalized technologies to undermine extractive development.
Pulmonary Embolism in Children with Asymptomatic Proximal Deep Vein Thromboembolism: Single-Center Experience from Sweden
Authors: Allahyani Bader , Ljung Rolf
Published: November 2020

Introduction:

Pulmonary embolism (PE) is rare in childhood but a potentially fatal condition in the venous thromboembolism spectrum. However, the incidence of PE in children has been steadily increasing, which can be multifactorial. Adults data suggested that the finding of asymptomatic proximal DVT on routine ultrasonography is associated with increased mortality. Data on pulmonary embolism in children are scarce.

Objective:

To evaluate the relationship between asymptomatic proximal deep vein thrombosis detected in children presented with Pulmonary embolism.

Methods:

We conducted a retrospective chart review of all consecutive ICD 9 codes of Pulmonary Embolism (PE) in children over 10 years (January 1, 2000, to December 31, 2010) in Skåne university hospital in Sweden, using an electronic diagnosis hospital database. Eligible subjects were children aged 1-18 years presenting with PE diagnosed with imaging, and having undergone complete lower extremities radiological screening workup for DVT and lacking symptoms of acute lower extremity DVT. Data regarding subject demographics and medical history, risk stratification, low risk, massive or submissive PE, location of the proximal DVT, imaging method, presence of congenital vascular anomaly, time from symptom onset to diagnosis of the pulmonary embolism. Coagulation studies at primary investigation including at least plasma concentrations of protein C, protein S, antithrombin, resistance to activated protein C, and the genotypes FVG1691A and FIIG20210A. Also, plasma values for coagulation factors, VIII, cardiolipin antibodies, management, duration of anticoagulant, and the outcome were analyzed.

Results:

A total of 20 children enrolled. Age range 10-18 years (mean 15.8), 18 (90%) were female. Time from symptom onset to diagnosis of the PE: mean 4.8 days (range 1-28). All were low risk, and 6 (30%) associated with asymptomatic proximal DVT. The most common acquired risk factor was OCP/hormonal therapy was in 11 (55%). Minor thrombophilia in 5 (25%) of the cohort. All received anticoagulation therapy for 6 months, non-received pharmacologic thrombolysis. No bleeding, recurrence, nor thrombosis related mortality in 4 years follow uptime.

Conclusion:

PE is rare in children, and it is associated with asymptomatic proximal DVT is not uncommon. Our finding demonstrated the prevalence of PE associated with asymptomatic proximal DVT is 30%. This finding highlighted the importance of anticoagulant therapy for all patients with incidental proximal DVT.

Figure

Disclosures

No relevant conflicts of interest to declare.
Priapism in Patients with Chronic Myeloid Leukemia
systematic Review of Case Reports
Authors: Ali Elrazi Awadelkarim A , Soliman Ashraf Tawfiq , De Sanctis Vincenzo , Nussbaumer Doris , Yassin Mohamed A
Published: November 2020

Introduction:

Priapism is a persistent penile erection not associated with sexual stimulation lasting for more than 4 hours. It is seen in up to 1.9% of patients with CML in some centers. Priapism adversely affects the quality of life, sexual function, of the affected patients. Long-lasting priapism is associated with a drastic effect on male fertility. The underlying pathophysiology involves disturbed autoregulation of the penile circulation through nitrous oxide (NO) and phosphodiesterase enzyme dysregulation.

Method

Literature searched in google scholar, PubMed, and Scopus search engines with keywords priapism, chronic myeloid leukemia, chronic granulocytic leukemia, and chronic myelogenous leukemia (English literature between 1960 to 2020)

Results

One hundred cases of priapism were reported in patients with CML. Most patients were below the age of 40 with mean 27.4years. The youngest was 7 weeks old and the oldest was 60 years old. Most patients had priapism as the first presentation of CM, 3 developed priapism after starting the treatment, 2 after stopping treatment, one noncompliant with treatment,1 previously diagnosed, and 1 patient post-splenectomy. The majority of patients' priapism occurred during the chronic phase of the disease and only 5/100 had priapism during the blast and accelerated phase. They had a mean WBC = 321.29 × 109/ (n=92), and mean platelet count = 569,000 (n=69). The lowest WBC count associated with priapism was 37 x10^9/L, the highest was 782 x10^9/L. Treatment modalities included medications, aspiration and irrigation of the corpora cavernosa, radiation to the penis, leukoreduction, and surgical shunts. Medications were used in (N = 50), aspiration of the corpora cavernosa in (N = 45) patients, leukapheresis in (N = 14), radiotherapy in (N= 9), and shunt in (N = 32). Surgical shunt relieved priapism in (N = 16), another 5 had shunt with partial response and needed chemotherapy to control the priapism. 19 patients responded to aspiration and irrigation, and another 2 required chemotherapy to control priapism. Radiation was helpful in resolving the priapism in 3 patients and Leukapheresis was useful in 5 patients. Medications alone were used to terminate priapism in 10 patients, however, priapism persisted for a longer duration compared to other modalities.

It has been known that priapism lasting > 24 hours poses a high risk of permanent erectile dysfunction (94% or more). In 76 of CML patients with priapism, the mean time from onset to the presentation was 78.28 hours (three times longer than the high-risk period). The erectile function was affected in 24/100, not affected in 15/100, and not addressed in 61/100.

Conclusion:

Although priapism is an uncommon complication of CML, its fast diagnosis and management is crucial to avoid permanent erectile dysfunction.

Disclosures

No relevant conflicts of interest to declare.
TLR, RAGE, and HMGB1 in the Inflammatory Response in Ph(-) Myeloproliferative Neoplasm
Authors: Shi Guanfang , Nair Kiron , Ramachandran Preethi , Chen Chi , Wong Ching , Joseph Gardith , Gotlieb Vladimir , Liaukovich Maksim , Wang Jen-Chin
Published: November 2020

Recent evidence of increased constitutional symptoms and inflammatory cytokines in Philadelphia chromosome negative (Ph (-)) MPN suggests that an inflammatory response is important in the pathogenesis of Ph (-) MPN. Toll-like receptors (TLR), Receptor for Advanced Glycation End products (RAGE) and High mobility group protein B1 (HMGB1) are the important pathways for the inflammatory response. All these three important pathway proteins were studied in MPN diseases in the current studies.

Materials and Methods:

TLR assay. TLR 2,3, 4, 7, 9 quantification was performed by immuno-staining of 1×106 mononuclear cells (peripheral blood) which were incubated with fluorescence-conjugated anti-TLR-2,3, 4, 7, 9 antibodies and assayed by flow cytometry. HMGB1assay:HMGB1 ELISA kit from Immuno-Biological Laboratories, Inc. (IBL-America) were used. The plasma samples were diluted four times with the provided sample dilution buffer, and assayed in duplicate according to the manufacturer's suggestion. RAGE (RT-PCR) Assay: Total RNA was extracted from normal control or patient mononuclear cells. Predesigned primers for RAGE, and internal control genes were ordered from Qiagen (Germantown, MD). Real-time PCR was performed using SsoAdvanced™ Universal SYBR® Green Supermix (Bio-Rad, Hercules, CA) on Bio-Rad iQ5 Multicolor Real-Time PCR Detection System. At least three house-keeping genes (ribosomal protein L4, TATA box binding protein, and tubulin-α 1b) were used as normalization controls. The expression of RAGE were compared with each internal control. Average of three was used to calculate the ratio of final patient to normal

Results: Total of 97 patients with MPN were studied 1) TLR: TLR 3,7,9 was not significantly different from controls. But TLR 2 was significantly increased in both PV, as well as in the MPN group when PV, ET and MF were grouped together as MPN (Fig A). TLR 4 was not significantly increased in PV, ET, MF individually but was found to be significantly increased than the controls, when they are grouped together as MPN (Fig B). 2) RAGE: No significant difference was found between ET, PV, MF individually or when they were grouped together as MPN than the controls (Fig C). 3) HMGB1: No significant difference was seen between ET, PV, MF or when they were grouped as MPN (Fig D).

Conclusion: Current study suggests that TLR pathway especially TLR2, and to a lesser extent TLR4 are the important pathways for inflammatory response with increased inflammatory cytokines in MPN, while HMGB1 and RAGE pathways were not different from controls.

Figure

Disclosures

No relevant conflicts of interest to declare.
Single Centre Retrospective Analysis: Transformation of Waldenström's Macroglobulinemia to Diffuse Large B-Cell Lymphoma
Authors: Heyrman Bert , Granacher Nikki , Wu Ka Lung
Published: November 2020

Introduction: The incidence and outcome of Waldenström's macroglobulinemia (WM) patients with transformation to diffuse large B-cell lymphoma (DLBCL) are unclear. We performed a retrospective analysis to determine the incidence, clinicopathological characteristics and treatment outcome of WM patient with histologic transformation to DLBCL in our centre.

Methods: Single centre chart review of WM patients in the past 10 years. Patients with histologic diagnosis of DLBCL after the diagnosis WM were included in our analysis.

Results: Three of the 79 WM patients had histological transformation to DLBCL, two male and one female. Mean age at DLBCL development was 76,6 years. The mean time to transformation since diagnosis of WM was 8,3 years (14, 8 and 3 years). All three patients received at least one prior line of treatment in relation to WM (2, 1 and 3 prior lines). Different regimens used were cyclophosphamide/dexamethasone, rituximab/bendamustin, chlorambucil monotherapy, fludarabine monotherapy, R-CVP and ibrutinib monotherapy. The patients were in clinical CR from WM at the time of transformation, two patients were still on treatment.

All three patients presented with advanced disease (stage IIIB, IVB, and IVA) non-GCB subtype DLBCL with at least 2 extra nodal sites. R-IPI scores were 4,5 and 4.

Two patients were treated with R-miniCHOP, one patient received R-CHOP. The first patient achieved a CR at the end of treatment and is now 1,5 years in follow-up. The second patient died from pneumonia one year after achieving a CR. The third patient is in follow op since 3 months after reaching a CR at the end of treatment.

Conclusion: Over the past decade transformation of WM to DLBCL was 3.7% in our centre. This is in accordance with previous data suggesting an 2.4% risk of transformation over 10 years.Time to transformation varies and no association with prior WM therapy and response to treatment can be found.All patients presented with more aggressive DLBCL in an advanced stage.All three patients achieved a CR following treatment for DLBCL, one patient died from pneumonia, two others are now in follow-up 1,5 years and 3 months respectively.

Disclosures

Heyrman: Celgene:Research Funding.
Is Anaemia Another Bleeding Risk in Cancer-Associated-Thrombosis?
Authors: Janus Nicolas
Published: November 2020

INTRODUCTION AND AIMS:

Anaemia is very common in cancer patients. However, the impact of anaemia in venous thromboembolic (VTE) patients on the risk of bleeding is not well-known. Consequently, the question of the impact of anaemia in cancer-associated-thrombosis (CAT) patients is important.

METHODS:

All the literature (PubMed) was reviewed about the potential links between cancer, CAT and anaemia. However, there were no dedicated studies on this topic. Furthermore, the WHO definition of anaemia was the one used in most of the publications

RESULTS:

Several studies investigated about all the risks of bleeding/VTE in atrial fibrillation and VTE patients, including anaemia. Most of them reported that anaemia exposed VTE patients to a higher risk of bleeding. The COMMANDER study, evaluated the influence of anaemia in VTE patients and reported that VTE patients with mild and moderate/severe anaemia had higher risk for major bleeding and that the risk for major bleeding increased according to the severity of anaemia. The RIETE (Registro Informatizado Enfermedad Tromboembólica) reported that anaemia was found in 57% of the patients with cancer and in 28% without cancer (odds ratio 3.46; 95% CI 3.33-3.60), exposing to a higher risk of major bleeding. The same registry reported also that in CAT patients, anaemia had a two-fold higher rate of major bleeding and fatal bleeding than CAT patients without anaemia. This link between anaemia and bleeding in cancer patients are multifactorial. Indeed, there are both quantitative and qualitative changes in red blood cells that could affect bleeding and thrombosis, as well as interactions of red blood cells with cellular and molecular components of the haemostatic system. Indeed, for example, low haematocrits are associated with bleeding. Finally, it is interesting to notice that there is a gap between the definition of anemia in CAT patients when compared to not CAT cancer patients. Indeed, WHO definition is quite common in VTE and CAT patients but EORTC/NCCN are used in cancer patients for several reasons. As a consequence, it could be important to align on this point.

CONCLUSIONS:

Anaemia, cancer and thrombosis are closely linked. It is important to screen and manage both anaemia in CAT patients because of the increased risk of bleeding. Consequently, it is important to consider this bleeding risk in CAT patients before initiating an anticoagulants treatment or prophylaxis in cancer patients.

Disclosures

Janus: Bayer:Honoraria, Research Funding;Pierre Fabre Oncology:Research Funding;Novartis:Honoraria;Gilead:Honoraria, Research Funding;Vifor Pharma:Honoraria, Research Funding;Fresenius Medical Care:Honoraria;Amgen:Honoraria, Research Funding;B-Braun:Honoraria;Guerbet:Research Funding;TEVA:Research Funding;IPSEN:Honoraria;Pfizer:Consultancy, Honoraria;Roche:Honoraria, Research Funding;Daichii-Sankyo:Honoraria, Research Funding;LEO Pharma A/S:Current Employment, Honoraria.
SGN-CD30C, an Investigational CD30-Directed Camptothecin Antibody-Drug Conjugate (ADC), Shows Strong Anti Tumor Activity and Superior Tolerability in Preclinical Studies
Authors: Ryan Maureen , Lyski Ryan , Bou Lauren , Heiser Ryan , Grogan Bryan , Meyer Dave , Jin Steven , Simmons Jessica , Conerly Melissa , Senter Peter , Jeffrey Scott
Published: November 2020

SGN-CD30C, an investigational CD30-directed ADC, utilizes a potent novel camptothecin derivative as the cytotoxic payload. SGN-CD30C targets the same antigen as brentuximab vedotin (BV), though the payload has a different mechanism of action, namely inhibiting topoisomerase I rather than disrupting microtubules. Unlike monomethyl auristatin E, camptothecin-based therapies do not cause peripheral neuropathy clinically, suggesting that SGN-CD30C may have the potential to avoid one of the most common adverse events associated with BV.

In preclinical studies, SGN-CD30C demonstrated strong monotherapy activity, inducing durable tumor regressions in multiple lymphoma models and eliciting cures in a BV-resistance tumor model (Figure 1). Moreover, SGN-CD30C exhibits many of the desirable attributes associated with BV, notably, bystander activity and CD30+ T regulatory cell (Treg) depletion. Using an admixed model of CD30+ and CD30-tumor cells, SGN-CD30C demonstrated robust anti-tumor activity in vivo, confirming SGN-CD30C can induce bystander killing of antigen-negative tumor cells in CD30-heterogeneous tumors. Additionally, SGN-CD30C depleted CD30+ Treg cells in vitro (Figure 2), suggesting it has the potential to exert activity through multiple mechanisms of action.

SGN-CD30C was well-tolerated in non-human primate toxicology studies and demonstrated ~6-fold higher maximum tolerated dose when compared to BV. The primary toxicity for SGN-CD30C in non-human primates (NHP) studies was anemia due primarily to bone marrow suppression of erythropoiesis. SGN-CD30C had no effect on neutrophil counts and caused only minimal to mild decreases in platelets. The lack of significant neutropenia seen with SGN-CD30C contrasts with BV, indicating the two ADCs may have non-overlapping dose limiting toxicities. Hematology parameters show SGN-CD30C is tolerated at a 10-fold higher dose than BV with weekly dosing, suggesting SGN-CD30C may offer the potential for increased dose density.

In summary, our data show SGN-CD30C is a compelling therapeutic candidate for CD30-positive malignancies. The distinct mechanism of action, strong anti-tumor activity, and enhanced tolerability provide a strong rationale to clinically investigate SGN-CD30C across the CD30-expressing lymphoma landscape. A Phase 1 clinical trial is planned to investigate SGN-CD30C in relapsed and refractory lymphoma.

Disclosures

Heiser: Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Grogan:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Jin:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Conerly:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company.
Novel Germline TRAF3IP3 Mutation in a Dyad with Familial Acute B Lymphoblastic Leukemia
Authors: Pommert Lauren , Burns Robert , Furumo Quinlan , Pulakanti Kirthi , Brandt Jon , Burke Michael J , Rao Sridhar
Published: November 2020

Acute lymphoblastic leukemia (ALL) is the most common single malignancy in children, representing 25% of all new cancer diagnoses. Advances in genomic sequencing has demonstrated that inherited genetic risk factors play a larger role in leukemia development than previously appreciated. We identified a father-daughter dyad with childhood B cell acute lymphoblastic leukemia (B-ALL) and obtained their diagnostic bone marrow samples from the Children's Oncology Group (COG) bank in addition to germline samples via remission marrow (daughter) or buccal swab (father). Whole Exome Sequencing (WES) was performed and compared to a panel of normal to identify large genomic changes and single nucleotide variants. In parallel, RNA-sequencing (RNA-seq) was performed on the diagnostic marrows. We discovered a novel germline chromosomal structural variant in chromosome 1q32.2 within the TRAF3IP3 gene. TRAF3IP3 regulates B cell lymphopoiesis and this mutation likely resulted in a predisposition to leukemia by causing expansion of immature B-cell precursors which are highly vulnerable to secondary somatic mutations. This mutation has not been previously described in ALL, however based on the function of TRAF3IP3 in B cell lymphopoiesis, we conclude this likely represents a mutation predisposing to the development of leukemia. WES revealed this dyad had no shared SNVs that are associated with leukemia in the literature and that they had only a few shared SNVs within the leukemia samples, none of which were identified as clinically significant; which suggests the spectrum of their somatic mutations were distinctly different. Given the lack of concordance in their somatic mutational spectrum, we wondered if the two leukemia samples would exhibit a shared transcriptome, implying convergent leukemogenic pathways were altered within the two specimens since they were both clinically reported as hyperdiploid. In comparing the leukemia gene expression profiles identified by RNA-seq to 216 cases of sporadic B-ALL from the TARGET database (The Therapeutically Applicable Research to Generate Effective Treatments program), we discovered that these two leukemia samples did not cluster together but did cluster with other cases of childhood B-ALL. We suspect that this germline TRAF3IP3 mutation increased this dyad's susceptibility to leukemia development but that the somatic mutational spectrum drove the leukemia development and dictated its phenotype. This research may have identified a novel gene involved in leukemogenesis which may also be involved in de novo cases of ALL. Additional studies are needed to further characterize this TRAF3IP3 structural variant, the co-occurring somatic mutations within these leukemia samples and their combined role in leukemogenesis.

Disclosures

No relevant conflicts of interest to declare.