bluuebunny/crossref_metadata_2025 huggingface dataset:
SURG-09. REACTIVATION OF HERPES SIMPLEX VIRUS AFTER NEUROLOGIC SURGERY
Authors: Almeida Carlos , Mançano Bruna Minniti , Prado Seila Israel , Almeida Gisele Caravina , Souza Fernanda Magalhães , Lourenço Lucas Dias
Published: December 2020

BACKGROUND

Herpes simplex virus encephalitis (HSVE) is a rare complication after neurosurgery, and its clinical picture mimics features of other most frequent infectious complications of bacterial origin. Probable triggering factors are manipulation and surgical stress, since most cases occur due to reactivation rather than primary infection. The main symptoms include fever and altered consciousness. DNA identification of HSV by PCR has accuracy. Even with adequate treatment, HSVE is associated with a mortality of 30%, and potential neurologic sequelae such as cognitive and motor. CASE REPORT: An 18-year-old male patient presented with loss of vision due to cystic craniopharyngioma. We inserted an Omaya catheter and drained the cyst. On the third day, he presented with fever, seizures, and decreased consciousness. Magnetic resonance imaging (MRI) showed high signal intensity on T2-weighted and FLAIR images in the left frontal and temporal lobe, cingulate gyrus, and corpus callosum, with mass effect. He was submitted to decompressive craniectomy and empirical antibiotic therapy. CSF and blood cultures were negative. Due to inexpressive clinical improvement after 48 hours, CSF was collected for polymerase chain reaction (PCR), and we performed a brain biopsy and started intravenous acyclovir. Histology and PCR confirmed HSVE type 1 and 2. He received antiviral for two weeks and was discharged after CSF PCR negative.

CONCLUSION

Clinical suspicion, CSF PCR, and imaging are of paramount importance for early diagnosis of HSVE, which should be considered in the differential diagnosis of recent postoperative neurologic surgery in cases of unexplained postoperative fever with altered consciousness.
SURG-10. SPECTROSCOPIC MEASUREMENT OF 5-ALA-INDUCED INTRACELLULAR PROTOPORPHYRIN IX IN PEDIATRIC BRAIN TUMORS
Authors: Schwake Michael , Kaneko Sadahiro , Morina Eric Suero , Stummer Walter
Published: December 2020

OBJECTIVE

5-ALA guided resection of glioma in adults enables better delineation between tumor and normal brain, allowing improved resection and improved patients’ outcome. Recently, several reports were published regarding 5-ALA for resection of pediatric brain tumors. The aim of the study was to determine the intracellular fluorescence of PPIX in pediatric brain tumors by hyperspectral imaging and to compare it with visually observed intraoperative fluorescence.

METHODS

5-ALA was administered orally four hours prior to surgery. During tumor resection the surgeon assessed the fluorescence signal to be strong, weak or absent. Subsequently, fluorescence intensity of samples was measured via spectroscopy. In addition, clinical data, imaging and laboratory data were analyzed.

RESULTS

Eleven children (1–16 years) were operated. Tumor entities included: three medulloblastomas, two pilocytic astrocytomas (PA), two anaplastic ependymomas and one diffuse astrocytoma, anaplastic astrocytoma, pilomyxoid astrocytoma and anaplastic pleomorphic xanthoastrocytoma. Strong fluorescence was visible in all anaplastic tumors and one PA; one PA demonstrated weak fluorescence. Visible fluorescence was strongly associated with intracellular fluorescence intensity and PPIX concentration (P<0.05). Within all tumors with visible fluorescence the intracellular PPIX concentration was greater than 4 µg/ml. Except for moderate and transient elevation of liver enzymes, no 5-ALA related adverse events were reported.

CONCLUSION

We demonstrate a strong association between intraoperative observations and spectrometric measurements of PPIX fluorescence in tumor tissue. As in former studies, fluorescence signal was more commonly observed in malignant glial tumors. Further prospective controlled trials should be conducted to investigate the feasibility of 5-ALA guided resection of pediatric brain tumors.
SURG-16. SURGICAL TECHNIQUES TO AVOID COMPLICATIONS DURING REPEAT RESECTIONS FOR PEDIATRIC BRAIN TUMORS
Authors: Shibahara Ichiyo
Published: December 2020

Complications due to repeat resection for recurrent pediatric brain tumors remain unclear. The present study focused on surgical techniques to avoid surgical morbidities during repeat resections for pediatric brain tumors. This study included 57 consecutive repeat resections for 28 pediatric patients under the age of 15 with recurrent brain tumors. Resections were performed 2–14 times for each patient by the senior author (TK). Reviewed factors were wound-related complications, bleeding/ischemic complications, and Eastern Cooperative Oncology Group performance status (PS) before and after surgery. No patients presented any complications to decrease PS, postoperatively. No wound-related complications were worthy of special mention. Surgical techniques to prevent wound-related complications are as follows: 1) shaving the hair around the previous skin incision just before the surgery; 2) washing and disinfecting around the skin incision using chlorhexidine soap and an alcohol swab, followed by Povidone-Iodine solution; 3) after craniotomy, removing all granulation tissues, residual titanium plates, and screws; 4) brushing all surgical fields and a bone flap before opening the dura mater using Povidone-Iodine solution followed by normal saline; 5) maintaining a bone flap in normal saline with antibiotics; 6) changing all the surgical instrument and gloves; 8) closing the dura mater completely to prevent CSF leakage, and 8) using postoperative antibiotics for six days. Meticulous dissecting postsurgical adhesion of brain and dura mater, arteries and nerves; usage of neuronavigation system and neuromonitoring to understand the anatomy radiologically and functionally; applying papaverine hydrochloride for spastic arteries, are important to avoid complications during the intracranial procedure.
SWK-04. A MOBILE AUGMENTED REALITY APP FOR SURGICAL PREPARATION FOR CHILDREN WITH BRAIN TUMORS
Authors: Granville Sharon , Spat-Lemus Jessica , Rice Blakely , Pzena Allison , Stieg Phil , Greenfield Jeffrey , Souweidane Mark
Published: December 2020

BACKGROUND

Children with brain tumors experience significant anxiety secondary to diagnosis and interventions such as surgical management. Preoperative anxiety is known to adversely affect operative outcomes and overall quality of life. Programs that utilize “child-friendly” approaches have been shown to ease anxiety, decrease analgesic requirements, shorten hospital stay, and contribute toward better outcomes. Implementation of these programs is limited due to time, cost, and staffing constraints as well as sociodemographic factors (i.e., language barriers). Therefore, an effective and cost-efficient method could be advantageous. We sought to develop a universally available APP that can assist with these goals and address the current barriers.

METHODS

In conjunction with a philanthropic resource (Brain Tumor Foundation, New York, NY, USA) a developer was tasked with creating an App for children with brain tumors. The developer integrated published clinical research, multi-specialty input, and patient and family testimonials for possible integration into the tool.

RESULTS

A mobile App was developed that is modifiable for patient-specific features (age, language, and ethnicity). Initial evaluations of the prototype by healthcare providers, appropriately aged children, and their parents have demonstrated positive engagement, appeal, and ease of use.

CONCLUSIONS

The mobile App provides a rapid, affordable, and modifiable platform for assisting children with brain tumors cope with their diagnosis and intervention options. Validation with measurable outcomes is planned. The App is currently being evaluated for purposes of psycho-social clinical research tool.
SWK-05. EDUCATIONAL APPROACH TO GRIEF MANAGEMENT
Authors: DeRosa Veronica , Madrid Nina
Published: December 2020

Pediatric neuro-oncology has a high mortality rate compared to other childhood cancers. This project sought to bring Awareness to the Grief and Trauma that families undergo during treatment through end of life. It also sought to create a pool of parent partners to support families receiving palliative care and to mend the healthcare relationship that is severed when a child passes away. The educational series included Grief Workshops for Bereaved Parents using the ATTEND model, a mindfulness-based bereavement model and seminars with traumatic grief experts for providers. This provided a better understanding on how healthcare workers are influential in the “death story” of a child and how this can dictate the family’s lifelong grief journey. Grief workshops consisted of 2 English and 1 Spanish speaking cohort each with 10–12 bereaved parents. The curriculum provided psychoeducation with the goal of creating a safe space to validate, clarify, and understand the events that happened in their child’s life; support for the parent as they explore emotional awareness; relief of emotional tension; support as the parent expresses their perspective of their new world to others that are in their life; and support as the parent finds meaning in their child’s life and untimely death. At the end of each group surveys showed that parents found that the group provided a safe community, a place to say their child’s name, a place to share their story, and a need to advocate for future oncology parents who undergo this journey.
SWK-06. ANSWERING 900 VOICES: A NATIONAL NONPROFIT ORGANIZATION RESPONDS TO A NATIONWIDE COMMUNITY HEALTH NEEDS ASSESSMENT THAT ELUCIDATED KEY CHALLENGES FACED BY PEDIATRIC BRAIN TUMOR FAMILIES
Authors: Riley Kathy
Published: December 2020

The five-year relative survival rate for childhood primary brain and other central nervous system tumors is nearly 75 percent (Central Brain Tumor Registry of the United States, 2017). Nevertheless, childhood brain tumor survivors often suffer from lifelong side effects caused by their illness or treatments such as surgery, radiation and chemotherapy. To define the nature and extent of problems survivors and their families face, the Pediatric Brain Tumor Foundation (PBTF), the world’s largest nonprofit solely dedicated to children and teens with brain tumors, conducted a 2017 national community health needs assessment in collaboration with the Sol Price Center for Social Innovation at the University of Southern California. The assessment found that pediatric brain tumor patients and their families face key challenges in four general areas: 1) interpersonal and emotional support, 2) logistical and financial support, 3) information and medical education gathering, and 4) educational and vocational anxieties. In 2020, the PBTF’s response to the 900 assessment participants who represent the thousands living with the effects of this disease includes the launch of a national Peer to Peer Mentoring program to meet the ongoing challenges families face; the disbursement of emergency financial assistance to hundreds of families in the throes of treatment; and the distribution of a resource notebook for newly diagnosed families and a comprehensive guidebook for survivors and their families. The results of the needs assessment suggest additional clear, actionable areas for impact not only by the PBTF but by medical professionals, other nonprofit organizations and governmental agencies.
SWK-08. DELAYED DIAGNOSIS OF CENTRAL NERVOUS SYSTEM (CNS) TUMORS IN CHILDREN: PERSPECTIVE FROM THE FRONTLINE
Authors: Jogendran Manisha , Ronsley Rebecca , Goldman Ran D , Cheng Sylvia
Published: December 2020

Delayed diagnosis of CNS tumors in children is well documented, partially due to challenges in recognizing rare diagnoses. Our objective was to describe Canadian family physicians’ attitudes and confidence in diagnosing and managing pediatric CNS tumors. A standardized questionnaire was administered at a Canadian national family physicians’ conference. Items were based on observations from our institutional study of prediagnostic symptomatic interval in pediatric CNS tumors. 449 surveys were completed. 302/443 (68%) physicians practice in cities. 153/447 (34%) report encountering parents that inquire about their children having brain tumors. 261/449 (58%) have not managed a pediatric brain tumor. 153/447 (34%) report they are not confident, 255/447 (57%) somewhat confident and 39/447 (9%) confident in managing a suspected brain tumor in a stable child. 259/447 (58%) would refer directly to a hospital/specialist. The reported median time for suspicion of a brain tumor was 8–14 days for children with vomiting and/or headache and 1 day for children with seizure and/or ataxia. 410/447 (97%) report not knowing any guidelines to help with management. 235/447 (53%) suggested barriers they experience to include 52/235 (22%) wait times for imaging/specialists, 37/235 (16%) geographical location of the child, 27/235 (12%) knowledge, 25/235 (11%) access to imaging/specialist, and 15/235 (6%) patient-related factors or system barriers, and 8/235 (3%) specialist attitudes. 68/235 (29%) identified no barriers in their practice. This study provides insight into family physicians’ perceived challenges and barriers in diagnosing and managing new suspected pediatric CNS tumors. Educational effort and overcoming systemic perceived barriers may increase physicians’ confidence.
SWK-09. SELF-CARE OUTCOMES AND INTERVENTIONS FOR CHILDREN WHO HAVE HAD A BRAIN TUMOUR: EVIDENCE AND HYPOTHESES. WHAT SHOULD SELF-CARE INTERVENTIONS FOR CHILDREN WITH PAST OR PRESENT BRAIN TUMOUR BE?
Authors: Rowen Elizabeth , Kolehmainen Niina , Bailey Simon
Published: December 2020

OBJECTIVE

To determine the evidence with regards to self-care outcomes and interventions for children who have been treated for a brain tumour and identify when best to intervene.

METHODS

A scoping review of the literature with regards to self-care interventions, outcomes and mechanisms was undertaken. The information from these themes were populated onto a logic model alongside the clinical expertise of the team. The logic model was used to develop hypotheses to inform subsequent research; and identified areas for further patient and public involvement.

RESULTS

Of 27 papers found, 13 were deemed relevant. The literature suggested the diagnosis of a brain tumour can have a long-term negative impact on self-care outcomes whilst evidence with regards to interventions to promote self-care is scarce. The child’s physical and cognitive functions were identified as hypothesised factors influencing self-care, while health related quality of life and participation in other life domains were secondary consequences of self-care. The team expertise was further used to hypothesise that parent factors (emotions, identity, actions), the child’s emotional functions and personal factors as well as peer relationships and norms may influence children’s self-care. These factors were not covered in the existing literature.

CONCLUSIONS

Subsequent research will investigate the hypotheses developed to further specify factors that self-care interventions for children and young people with a brain tumour should target. This will involve specifying when, how and to whom interventions should be targeted.
SWK-11. ASSESSMENT OF THE INDIRECT COSTS ASSOCIATED WITH PROTON THERAPY TREATMENT FOR ALBERTA PATIENTS REFERRED OUT OF COUNTRY
Authors: Black Karina , Middleton Jackie , Ghosh Sunita , Eisenstat David , Patel Samor
Published: December 2020

BACKGROUND

Proton therapy for benign and malignant tumors has dosimetric and clinical advantages over photon therapy. Patients in Alberta, Canada are referred to the United States for proton treatment. The Alberta Heath Care Insurance Plan (AHCIP) pays for the proton treatment and the cost of flights to and from the United States (direct costs). This study aimed to determine the out-of-pocket expenses incurred by patients or their families (indirect costs).

METHODS

Invitation letters linked to an electronic survey were mailed to patients treated with protons between 2008 and 2018. Expenses for flights for other family members, accommodations, transportation, food, passports, insurance, and opportunity costs including lost wages and productivity were measured.

RESULTS

Fifty-nine invitation letters were mailed. Seventeen surveys were completed (28.8% response rate). One paper survey was mailed at participant request. Nine respondents were from parent/guardian, 8 from patients. All patients were accompanied to the US by a family member/friend. Considerable variability in costs and reimbursements were reported. Many of the accompanying family/friends had to miss work; only 3 patients themselves reported missed work. Time away from work varied, and varied as to whether it was paid or unpaid time off.

CONCLUSIONS

Respondents incurred indirect monetary and opportunity costs which were not covered by AHCIP when traveling out of country for proton therapy. Prospective studies could help provide current data minimizing recall bias. These data may be helpful for administrators in assessing the societal cost of out-of-country referral of patients for proton therapy.
TBIO-08. BASE-RESOLUTION METHYLOMES OF GLIOMAS BEARING HISTONE H3.3 MUTATIONS REVEAL A G34 MUTANT-SPECIFIC SIGNATURE SHARED WITH BONE TUMORS
Authors: Sangatsuda Yuhei , Miura Fumihito , Araki Hiromitsu , Mizuguchi Masahiro , Hata Nobuhiro , Kuga Daisuke , Hatae Ryusuke , Akagi Yojiro , Amemiya Takeo , Fujioka Yutaka , Arai Yasuhito , Shibata Tatsuhiro , Yoshimoto Koji , Ito Takashi , Iihara Koji
Published: December 2020

BACKGROUND

Two recurrent mutations, K27M and G34R/V, in H3F3A, encoding non-canonical histone H3.3, are reported in pediatric and young adult gliomas, whereas G34W mutation was prevalent in bone tumors. In contrast to K27 mutation, it remains elusive how G34 mutations affect the epigenome. Here we performed whole-genome bisulfite sequencing of four G34R-mutated gliomas and the G34V-mutated glioma cell line KNS-42. Similarly, we analyzed seven and three gliomas harboring K27M and no mutations in H3F3A, respectively. These data were compared with those on bone tumors.

RESULTS

G34R-mutated gliomas exhibited lower global methylation levels, similar CpG island (CGI) methylation levels, and compromised hypermethylation of telomere-proximal CGIs compared with those bearing K27M and no mutations. Hypermethylated regions specific to G34R-mutated gliomas were enriched for CGIs, including those of OLIG1, OLIG2, and canonical histone genes in the HIST1 cluster. These CGIs were hypermethylated in osteosarcomas with, but not without, the G34W mutation. In KNS-42 cells, CGIs with G34V-mutated histone H3.3 exhibited higher methylation levels than those with wild-type histone H3.3. This effect was also observed in the G34R-mutated glioma samples.

CONCLUSIONS

Gliomas bearing G34R/V mutations display characteristic methylomic alterations, some of which are shared by osteosarcomas with the G34W mutation. Deposition of G34 variants may lead to elevated methylation of otherwise hypomethylated, histone H3.3-bearing CGIs.
TBIO-11. DEEP LEARNING-BASED SINGLE-CELL RNA SEQUENCING DIFFERENTIATION IDENTIFIES SIMPLE AND COMPLEX TRANSCRIPTIONAL NETWORKS FOR SUBPOPULATION CLASSIFICATION
Authors: Prince Eric , Hankinson Todd
Published: December 2020

BACKGROUND

Genomic assays capable of cellular resolution (i.e. scRNA-seq) are becoming ubiquitous in biomedical research. Machine learning, and the subtype known as Deep Learning, have broad application within scRNA-seq analytics. However, methods to facilitate the classification of cell populations are lacking. We present the novel computational framework HD Spot, which generates interpretable and robust Deep Learning classifiers that enable unbiased interrogation of linear and non-linear genomic signatures.

METHODS

HD Spot is written in python and relies on Google’s TensorFlow2 deep learning framework. Four datasets of immune cells were obtained from the publicly available Seurat repository, generated using the 10X chromium platform. Data preprocessing used standard Seurat methodology. HD Spot generated optimized classifiers via a custom platform. Network interpretability was achieved using Shapley values. Ontology analysis was performed using Metascape.

RESULTS

HD Spot identified meaningful ontologic signatures across all tested datasets. In the binary case of control versus IFN-B stimulated CD4+ T cells, gene ontologies reflected Th0 and Th2 T cell populations, congruent with T cell activation. In the 9-class case of PBMCs, HD Spot identified meaningful gene networks characteristic of the ground-truth populations using raw feature counts alone. When feature counts are processed into expression values, HD Spot demonstrates increased specificity of top genes and respective ontologies between subpopulations.

CONCLUSION

This work introduces a broadly applicable computational tool for the advanced bioinformatician to decipher complex cellular heterogeneity (e.g., tumors) in an unbiased way. Additionally, HD Spot lowers the barrier for novice bioinformaticists to derive actionable insights from their data.
TBIO-24. USING MOLECULAR GUIDED THERAPY IN PEDIATRIC NEURO ONCOLOGY PATIENTS: THE SUCCESS AND BARRIERS
Authors: Armstrong Beth , Schmitt Morgan , VonBergen Jayne
Published: December 2020

Remarkable advances have been made in pediatric brain tumor treatments, however many of these children suffer significant side effects from standard chemotherapy-based treatment. Recent advances in precision medicine offer great hope to pediatric patients in terms of improved therapeutic precision, safety, and efficacy. However, there are barriers to implementing precision medicine that are best approached from a multi-disciplinary perspective. The goals of the Riley Hospital for Children at Indiana University Health Precision Genomics Neuro Oncology program are to optimize the treatment of children by assessing children’s cancers for actionable molecular targets and finding available, affordable therapies that treat those actionable targets. Children are referred to the Riley Precision Genomics Neuro Oncology program at the time of diagnosis or with relapse. Tumor tissue is tested for somatic and germline findings. Riley’s Precision Genomics Neuro Oncology program has received 55 patient referrals. Of these 55 patients, 46 (84%) had molecular analysis completed, and the results of 40 (87%) patients indicated actionable targets. Of the 40 patients with results, 23 (58%) patients went on to receive genomics guided therapy. Limited availability of tissue has accounted for 6 (13%) patients’ lack of results. Many guided therapy options are oral medications, which positively impact patient’s quality of life. The learner will increase their knowledge of how molecular guided therapy is now innovatively being used to treat children with cancer, and the challenges involved.
THER-01. AWAKING THE IMMUNE SYSTEM WITH AN IMMUNO-ONCOLYTIC VIRUS AS A THERAPEUTIC STRATEGY FOR DIPGs
Authors: Laspidea Virginia , Puigdelloses Montse , Ausejo-Mauleon Iker , Hambardzumyan Dolores , Chen Zhihong , Martinez-Velez Naiara , Zalacain Marta , de Larraya Jaime Gallego Perez , Becher Oren , Fueyo Juan , Gomez-Manzano Candelaria , Alonso Marta M
Published: December 2020

Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumour, being the leading cause of paediatric death caused by cancer. Despite all the advances made regarding effective therapies, the survival is dismal. Our lab has engineered the oncolytic virus Delta-24-ACT armed with the costimulatory ligand 41BBL in order to increase the antitumoral effect of the adenovirus. 41BB is a costimulatory receptor which promotes the expansion of activated T cells and the generation and maintenance of CD8 T memory cells. Therefore, we propose the use of Delta-24-ACT as a therapeutic approach for DIPG tumours. We observed that Delta-24-ACT is able to infect and replicate in NP53 and PDGFB-driven, two DIPG murine cell lines. Furthermore, 41BBL is expressed in the membranes of the infected cells and results with immunogenic cell death as shown by the different DAMPs. Injection of Delta-24-ACT in DIPG model was safe, showed no sign of toxicity and led to a significantly increase in the median overall survival, generating anti-glioma memory in long-term survivors. Mechanistic experiments, showed an increase of T cell infiltration (mainly CD8), decrease of proliferating cells and a reduction of the number of vessels in FFPE brain samples in the treated mice. We are currently performing nanostring analyses to assess the changes in the transcriptional immune phenotype of treated versus control mice. In summary, our data suggest that Delta-24-ACT is safe and induces a potent antitumor immune response in DIPG models mainly based in the activation of CD8 lymphocytes recruited by the viral activity.
THER-06. THERAPEUTIC EFFICACY OF RRV-MEDIATED PRODRUG ACTIVATOR GENE THERAPY IN CLINICAL TRIALS OF RECURRENT HIGH-GRADE GLIOMA AND IN MURINE ORTHOTOPIC MODELS OF INTRACEREBRAL GLIOMA AND INTRACEREBELLAR MEDULLOBLASTOMA
Authors: Richardson Angela , Collins Sara , Inagaki Akihito , Armstrong Valerie , Robbins David , Ayad Nagi , Gruber Harry , Jolly Douglas , Cloughesy Timothy , Kasahara Noriyuki
Published: December 2020

Toca 511, a clinical-stage tumor-selective retroviral replicating vector (RRV), encodes optimized yeast cytosine deaminase (CD), which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil (5-FU) within infected cancer cells. In preclinical models of intracerebral glioblastoma, 5-FU generated locally by Toca 511 (RRV-CD) prodrug activator gene therapy has also been shown to kill immunosuppressive myeloid cells in the tumor microenvironment, leading to anti-cancer immune activation and long-term survival. Early-phase clinical trials of Toca 511 in recurrent high-grade glioma showed highly promising evidence of therapeutic benefit, leading to a Phase III trial completed in late 2019 (n=400 patients, randomized 1:1 vs. standard chemotherapy), which appeared to show negative results overall. However, additional analysis showed possible efficacy in prespecified subgroups, and further clinical investigation is being pursued. In preclinical studies, we have also evaluated RRV for use in medulloblastoma, the most common malignant tumor of the pediatric nervous system. Both established and primary human medulloblastoma cell lines supported efficient RRV replication in vitro, with spread to >90% of cells by day 10 post-inoculation, and RRV-CD-transduced medulloblastoma cells showed significant dose-dependent reduction of viability upon exposure to 5-FC, compared to controls. In an intracerebellar HDMB03 medulloblastoma model, RRV-CD-treated mice exhibited long-term survival while on sequential cycles of 5-FC prodrug, until prodrug treatment was stopped, after which 25% long-term survival was observed (median survival 110 days) as compared to controls (median survival 28 days, 100% lethality) (p=0.00007). These results support further evaluation of RRV-mediated prodrug activator gene therapy for pediatric brain tumors.
THER-07. INHIBITION OF THE RAS SIGNALING ENHANCES VIRAL ONCOLYSIS IN MALIGNANT GLIOMAS
Authors: Arakawa Yoshiki , Yamaguchi Makoto , Tanji Masahiro , Mineharu Yohei , Miyamoto Susumu
Published: December 2020

Pediatric malignant glioma indicates rapid proliferation, widely infiltrative properties and resistance to various therapies, and carries a very poor prognosis. There are methods of using virus within novel therapies under development against malignant neoplasms, which have been studied for many years already. We examined the treatment with sunitinib or GW5074 to our experimental model of vaccinia virus therapy for malignant glioma, and then evaluated changes in the tumoricidal activity, the viral infectivity, and the impact on the Ras signaling pathway. Glioma cells (U251MG, LN229, LN18, rat C6) infected with vaccinia virus was fatal, in its course of death, apoptosis and autophagy were induced. The activity of Ras signaling in vaccinia-infected cells heightened in the early stage and declined in the late stage Inhibition of the Ras signaling pathway at the early stage of viral infection prevented vaccinia virus replication, while viral oncolysis was not inhibited when the pathway was blocked after sufficient viral spread. Glioma cells infected with vaccinia virus are led to cell death. Vaccinia virus regulates Ras or other survival signaling pathways in the infected cells. It enhances the signaling in the early stage (viral replicative period), however suppresses in the later stage (virus-releasing stage). Inhibition of the Ras signaling pathway at the early stage of viral infection prevents vaccinia virus from replicating, while viral oncolysis appears to be accelerated when the pathway was blocked after sufficient viral reproduction.
More about illusory trusts: is “tantamount” to ownership the same as “ownership”? The Privy Council takes a step too far
Authors: Nitikman Joel
Published: December 2020

In Webb v. Webb,1 a decision of the Privy Council on appeal from the Cook Islands, the Board2 had to consider a number of issues arising from matrimonial proceedings. One of the issues was whether Mr Webb had created a valid trust or whether he had retained such extensive powers in relation to the trust that the trust was an “illusion”. The Board held that the trust was invalid. In doing so, the Board purported to follow the reasoning of the New Zealand Supreme Court in another matrimonial decision, Clayton v. Clayton,3 about which I have written before.4 But, for the reasons discussed below, in my opinion, the Board in Webb went beyond what the Supreme Court decided in Clayton. I believe that the Board has taken a step too far in its reasoning.
Which Characteristics of Fecal Incontinence Predispose Incontinence-Associated Dermatitis? A Classification and Regression Tree Analysis
Authors: Hoedl Manuela , Eglseer Doris
Published: December 2020

OBJECTIVE

To investigate which characteristics of fecal incontinence (FI) are predictors for incontinence-associated dermatitis (IAD) using the Classification and Regression Tree method.

DESIGN AND SETTING

Data collected from 2014 to 2016 during the Austrian Nursing Quality Measurement 2.0, an annually conducted, cross-sectional, multicenter prevalence study, were merged and analyzed.

MAIN OUTCOME MEASURE

The duration, frequency, and amount of FI were used as predictors for IAD. Nurses were asked if the participants suffered from IAD based on their clinical judgment (yes/no).

MAIN RESULTS

In total, 1,513 participants with FI were included in this analysis. More than 75% of the participants with FI were to a great extent or completely care dependent. Of all FI participants, nearly 6% suffered from IAD, and more than 70% received special skin care for IAD prevention. Participants with FI had the highest risk of developing IAD if they experienced FI every day, had FI for less than 3 months, and had developed the FI in their current institution.

CONCLUSIONS

Nurses face many challenges while helping patients with FI maintain healthy skin. Knowledge of the results of this study and accumulated knowledge about the specific characteristics of FI that are associated with the development of IAD can help healthcare personnel prevent IAD. Based on these results, improving patient education for persons with newly diagnosed FI to prevent IAD is recommended. Research studies should use the definition of FI established by the International Continence Society.
Efficacy and safety of Shexiang Baoxin pill (MUSKARDIA) in patients with stable coronary artery disease: a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial
Authors: Ge Jun-Bo , Fan Wei-Hu , Zhou Jing-Min , Shi Hai-Ming , Ji Fu-Sui , Wu Yang , Zhao Yu-Lan , Qian Jun , Jin Yuan-Zhe , Liu Ying-Wu , Wang Sheng-Huang , He Sheng-Hu , Yang Ping , Wu Jie , Lu Feng , Hou Zi-Shan
Published: December 2020

Background:

The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD.

Methods:

A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to a MUSKARDIA or placebo group for 24 months. Both groups received OMT according to local tertiary hospital protocols. The primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary outcomes included all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or heart failure, peripheral revascularization, angina stability and angina frequency.

Results:

In all, 99.7% of the patients were treated with aspirin and 93.0% with statin. After 2 years of treatment, the occurrence of MACEs was reduced by 26.9% in the MUSKARDIA group (MUSKARDIA: 1.9% vs. placebo: 2.6%; odds ratio = 0.80; 95% confidence interval: 0.45–1.07; P 
= 0.2869). Angina frequency was significantly reduced in the MUSKARDIA group at 18 months (P = 0.0362). Other secondary endpoints were similar between the two groups. The rates of adverse events were also similar between the two groups (MUSKARDIA: 17.7% vs. placebo: 17.4%, P = 0.8785).

Conclusions:

As an add-on to OMT, MUSKARDIA is safe and significantly reduces angina frequency in patients with stable CAD. Moreover, the use of MUSKARDIA is associated with a trend toward reduced MACEs in patients with stable CAD. The results suggest that MUSKARDIA can be used to manage patients with CAD.

Trial registration

chictr.org.cn, No. ChiCTR-TRC-12003513
Association between use of amiodarone for non-valvular atrial fibrillation and patient survival: from the prospective China Atrial Fibrillation Registry
Authors: Hou Xiao-Xia , He Liu , Du Xin , Wang Guo-Hong , Dong Jian-Zeng , Ma Chang-Sheng
Published: December 2020

Background

Post hoc analysis of the landmark atrial fibrillation follow-up investigation of rhythm management trial revealed that amiodarone was associated with higher risks of mortality, intensive care unit admission, and non-cardiovascular death. We aim to evaluate the association between amiodarone use and patient survival under updated medical mode and level using data from the China Atrial Fibrillation (China-AF) Registry study.

Methods

Clinical data of 8161 non-valvular atrial fibrillation (NVAF) patients who were antiarrhythmic drug (AAD)-naive before enrollment into the China-AF Registry, recruited between August 2011 and February 2017, were collected. The primary outcome was all-cause mortality. A Cox proportional hazard regression model was used to evaluate the association between amiodarone use and the outcome. We also calculated the rate of sinus rhythm maintenance at the penultimate follow-up.

Results

Compared with 6167 patients of non-AAD group, 689 patients of the amiodarone group were younger (mean age 65.6 vs. 68.6 years), more frequently completed high school education, had fewer comorbidities such as chronic heart failure, prior bleeding, and stroke, and were more likely to be treated in tertiary hospitals while less hospitalization. The proportion of persistent AF was much lower among users of amiodarone, who were also less likely to be taking oral anticoagulants. The patients in the amiodarone group had a statistically insignificant lower incidence of all-cause mortality (2.44 vs. 3.91 per 100 person-years) over a mean follow-up duration of 300.6 ± 77.5 days. After adjusting for potential confounders, amiodarone use was not significantly associated with a lower risk of all-cause mortality (adjusted hazard ratio, 0.79; 95% confidence interval, 0.42–1.49). Sub-group analysis revealed the consistent results. The rate of sinus rhythm maintenance at the penultimate follow-up in the amiodarone group was significantly higher than in the non-AAD group.

Conclusions

Our study indicated that amiodarone use was not significantly associated with a lower risk of 1-year all-cause mortality compared with a non-AAD strategy in “real-world” patients with NVAF.
A Primer on the Good Samaritan Act
Authors: McDevitt Diane , McDevitt Meaghan
Published: December 2020

This article explores the various legal and ethical facets for healthcare professionals to consider in order to avoid legal liability when rendering aid in an emergency. A general overview of Good Samaritan legislation enacted throughout the United States is discussed along with varying levels of assistance required or protected by law in selected states. Moral considerations for Christian nurses are addressed.
Faith Community Nursing
Authors: May Indea , George Nancy
Published: December 2020

The high prevalence of hypertension among African Americans makes faith-based education programs culturally appropriate. Faith-enhanced health education is a way to reach these often healthcare-disenfranchised populations. With Every Heartbeat is Life (WEHL), a community-based heart health program, was enhanced with Scripture and prayer for this project. The program took place in an African American nondenominational church. The Scripture-enhanced WEHL program emphasized biblical teachings of self-care with standard lessons on nutrition, exercise, smoking cessation, and disease management interventions that increased knowledge of hypertension and associated cardiovascular risks.
Enhancing Personhood in the Care of Older Adults with Dementia
Authors: Rajamohan Santhiny
Published: December 2020

Using a biblical worldview, this article develops a philosophical discussion about what comprises an individual's personhood. The author contends for the perspective of a person as a human being created in the image of God based on who he or she is, not on the basis of how well he or she functions. Understanding the biblical concept of personhood allows the establishment of meaningful relationships with people with dementia, resulting in compassionate, quality care.
Measurement of SBP at home by parents using hand-held Doppler device and aneroid sphygmomanometer: a single-centre experience
Authors: Newton Joanna , Singh Cheentan , Sinha Manish D.
Published: December 2020

Objective:

We taught parents to use at
h
ome a hand-held
D
oppler device and aneroid sphygmomanometer for S
BP

m
easurement (HDBPM).

Methods:

Retrospective study including all children referred to evaluate hypertension over a 6-year period. Each child underwent HDBPM measurements performed by parents while awake over 2 weeks with three measurements performed twice daily.

Results:

Of n = 155 children, 145 (93.5%) were successful and aged median (interquartile range) 2.48 (1.01, 5.12) years, including 85 boys. Overall, there were 25, 19, 30 and 26% aged less than 1, 1 to less than 2, 2 to less than 5 and at least 5 years old, respectively. Seventy-eight (54%) had been referred for confirming diagnosis and 67 (46%) for ongoing monitoring of treated hypertension. Following HDBPM, 70 of 78 (90%) patients in the ‘Diagnosis subgroup’ were observed to have normal blood pressure (BP). In the monitoring subgroup, treated hypertension that required no medication changes was recorded in 35 of 67 (52%) and medication changed in 32 of 67 (48%), [increased, decreased or changed] in 22, 6 and 5%, respectively. In 10 of 67 (15%) medication was weaned and stopped completely following HDBPM. None of the children required admission to hospital to evaluate their BP level or manage hypertension.

Conclusion:

Out-of-office BP monitoring using HDBPM is acceptable to children and families of young children when parents are taught to measure BP and supported by health professionals. We report evidence of the feasibility and clinical utility of HDBPM in a challenging population of children who are either too young or unable to tolerate 24-h ambulatory BP monitoring for both the diagnosis and ongoing management of clinically relevant hypertension.
Temperature-adjusted hypertension prevalence and control rate: a series of cross-sectional studies in Guangdong Province, China
Authors: Hu Jie , He Guanhao , Luo Jiali , Xu Yanjun , Xu Xiaojun , Song Xiuling , Chen Shaowei , Ji Guiyuan , Chen Zihui , Jiang Qi , Liu Tao , Hu Jianxiong , Xiao Jianpeng , Zeng Weilin , Guo Lingchuan , Lin Lifeng , Lin Peng , Ma Wenjun
Published: December 2020

Background:

Previous studies have shown negative relationships between ambient temperature and blood pressure (BP). However, few studies estimated temperature-adjusted hypertension prevalence and control rate in different population.

Objective:

To estimate the effects of temperature on BP, and further calculate temperature-adjusted hypertension prevalence and control rate.

Methods:

Meteorological and BP data in Guangdong Province from 2004 to 2015 were collected. There were 31 351 participants aged 18 years and over. Based on 2018 European society Arterial Hypertension Guidelines, participants were divided into normotensive patients (n = 23 046), known hypertensive patients (n = 2807), and newly detected hypertensive patients (n = 5498). We first used generalized additive model to establish the nonlinear relationship between daily mean temperature and BP, and then calculated the linear effects of temperature on BP among populations with different hypertension status. Finally, we calculated the temperature-adjusted hypertension prevalence and control rate.

Results:

Generally, there is an inverse relationship between temperature and BP. For a 1 °C increase in temperature, the decreased SBPs for normotensive patients, newly detected hypertensive patients, and known hypertensive patients were 0.37 [95% confidence interval (CI): −0.40, −0.33] mmHg, 0.21 (95% CI: −0.32, −0.10) mmHg and 0.81 (95% CI: −1.02, −0.59) mmHg, while reduced DBPs were 0.19 (95% CI: −0.21, −0.16) mmHg, 0.01 (95% CI: −0.06,0.08) mmHg, and 0.44 (95% CI: −0.56, −0.32) mmHg, respectively. At 5, 10, 15, 20, and 25 °C, the hypertension prevalence rates were 32.5, 29.7, 27.7, 26.0, and 25.0%, respectively, and the control rates were 12.0, 17.5, 23.5, 30.1, and 37.1%, respectively.

Conclusion:

Low temperature increased BP for all populations, especially for known hypertensive patients, which makes hypertension prevalence increase and control rate decrease if temperature reduce. Our findings suggest that temperature should be considered in hypertension clinic management and epidemiological survey.
Primary pure large cell neuroendocrine carcinoma of the ovary
Authors: Peng Xue , Wang Hongjing
Published: December 2020

Introduction:

Ovarian large cell neuroendocrine carcinoma (LCNEC), or ovarian non-small cell neuroendocrine carcinoma, which is a newly described tumour in the classification of primary ovarian neoplasms by the World Health Organization, is a rare entity that is frequently associated with a surface epithelial and germ cell neoplasm component. Few cases have been reported in the literature, and only 18 primary pure ovarian LCNEC cases have been reported so far, including our 1 case. Ovarian LCNEC is a highly aggressive tumor with a poor prognosis even at an early stage.

Patient concerns:

We report a case of a 55-year-old postmenopausal woman who complained of abdominal pain. CT examination revealed a mass in the right adnexial region and CA125 level was elevated.

Diagnosis:

She underwent a exploratory laparotomy, and diagnosed as LCNEC histopathologically.

Interventions:

Cytoreductive surgery was administered to the patient, and had accepted 5 cycles of chemotherapy consisting of paclitaxel and cisplatin.

Outcomes:

Follow-up for 12 months showed no clinical or radiological evidence of disease recurrence.

Conclusion:

This case is 1 of the ovarian LCNEC which is a rare and extremely malignant tumor. Diagnosis requires histopathology and immunohistochemistry. The treatment includes primary cytoreductive surgery followed by chemotherapy.
Rapid screening for safety of donation from donors with central nervous system malignancies
Authors: Zhu Mingxin , Bian Yi , Jiang Jipin , Lei Ting , Shu Kai
Published: December 2020

With the increasing demand on organ transplants, it has become a common practice to include patients with primary central nervous system (CNS) malignancies as donors given the suggested low probability metastatic spread outside of the CNS. However, an extra-CNS spread of the disease cannot be excluded raising potential risks of cancer transmission from those donors. In order to balance between the risk of donor-derived disease transmission and the curative benefit for the recipient, a careful donor and organ selection is important. We performed a literature research and summarized all reported studies of organ transplants from donors suffered from primary CNS malignancies and determined the risk of tumor transmission to recipients. There were 22 cases of transplant-transmitted CNS tumors onto recipients since 1976. The association risks of cancer transmission were attributed to donor tumor histology, disruption of the blood-brain barrier, cerebrospinal fluid extra-CNS, and false diagnosis of primary intracranial tumor as well as the molecular properties of the primary tumor such as the existence of EGFR-amplification. The association risks and features of CNS tumors transmission recipients indicated that we need to reassess our thresholds for the potential fatal consequences of these donors.
Clinical assessment of synbiotics for treating chronic kidney disease
Authors: Li Xiao-Jun , Lu Yan-Yan , Wang Yuan
Published: December 2020

Background:

This research aims to evaluate the efficacy and safety of synbiotics for treating chronic kidney disease.

Methods:

Related articles written in English were sourced from EMBASE, PubMed, Cochrane Library, and China National Knowledge Infrastructure. These articles were used in the evaluation of the effect of synbiotics for treating chronic kidney disease. The extent of the relationship was assessed by calculating the pooled risk ratio, mean differences or standardized mean difference along with the equivalent 95% confidence intervals. The risk of bias introduced through each study was considered by adopting the Cochrane Risk of Bias Tool. Suitable statistical research methods were utilized for the synthesis of the data. The RevMan 5.3 software was used to conduct all statistical analysis.

Results:

The final results of the current study is due to be included in a peer-reviewed journal.

Conclusion:

The final remarks of the current study will be useful evidence for determining whether synbiotics is an effective and safe therapeutic method for treating chronic kidney disease.

OSF registration number:

DOI 10.17605/OSF.IO/UASF4 (https://osf.io/uasf4/).
Successful treatment of a critically ill patient with acute respiratory distress syndrome from COVID-19 using mechanical ventilation strategy with low levels of positive end-expiratory pressure
Authors: Guo Wei-guang , Fang Bin , Xian Yan-shan , Yu Zhi-hui , Zhou Li-xin
Published: December 2020

Introduction:

Acute respiratory distress syndrome (ARDS) secondary to COVID-19 is different from the ARDS caused by other infections. Conventional mechanical ventilation strategies using high levels of PEEP may not be beneficial and can even be harmful to patient with ARDS from COVID-19. So the ventilation strategies should be adjusted in order to improve the pulmonary ventilation function and oxygenation status, and outcomes of the patient.

Patient concerns:

Herein, we present a 76-year-old male patient with ARDS secondary to COVID-19. We describe our experience with mechanical ventilation strategy and the changes in respiratory mechanics in the patient during treatment.

Diagnosis:

The patient had tested positive for coronavirus (COVID-19) in nucleic acid test. Chest CT showed multiple ground glass shadows in both lungs.

Interventions:

The patient received mechanical ventilation with low tidal volume and low PEEP.

Outcomes:

After treatment, the patients condition, as well as oxygenation status was improved, and he tested negative for the coronavirus several times.

Conclusion:

This case demonstrated that the low tidal volume with low levels of PEEP ventilation strategy may be more suitable for ARDS from COVID-19.