bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of the concurrent administration of contraindicated medications in patients with cancer treated with tyrosine kinase inhibitors (TKIs): A pilot study from the IU Simon Comprehensive Cancer Center.
Authors: Alhaffar Dana , Han Yan , Darling Julianne , Skaar Todd C. , Fausel Christopher A. , Hanna Nasser H.
Published: June 2021

e18714

Background: Polypharmacy may result in drug-drug interactions that reduce efficacy or increase toxicities to patients. Tyrosine kinase inhibitors (TKIs), which is standard therapy for many patients with cancer, have interactions with many commonly prescribed drugs (including proton pump inhibitors [PPIs] and cytochrome inhibitors/inducers) which alter their metabolism. Methods: Retrospective study of 100 consecutively chosen patients with advanced cancer treated with TKIs were identified. Patients < 18 years of age, participating in clinical trials, or taking an investigational treatment for their cancer were excluded. TKI start date and concurrent medications were identified from chart reviews. Documentation was undertaken to record co-administration of drugs that could prolong QT interval, PPIs, and CYP3A inhibitors and inducers. QT prolonging medications were divided into those with known risk (KR), conditional risk (CR), and probable risk (PR). IUSM Clinical Pharmacology Flockhart table was utilized for cytochrome drug interactions. All three categories of cytochrome inhibitors (strong, moderate, and weak) were included in the analysis. The primary objective was to estimate the percentage of patients treated with TKIs co-administered these classes of drugs with a potential for harmful drug-drug interaction. Results: Median age of 100 pts was 57 and median duration of treatment with the TKI was 441 days. 85 of 100 pts receiving TKIs for their cancer were also prescribed at least 1 drug with the potential for drug-drug interaction, including 39 with a QT prolonging drug with known risk and 25 with a CYP3A inducer or inhibitor. 53% had documentation of EKG while on TKI treatment. Conclusions: Most patients in this chart review were co-administered TKIs with other agents with a potential for harmful drug-drug interactions. Continual monitoring of medications is necessary to optimize efficacy of TKIs and reduce the chance for harmful side effects.[Table: see text]
The real-word evidence of first-line treatment of pembrolizumab in advanced NSCLC.
Authors: Li Pin , Gadgeel Shirish M. , Poisson Laila
Published: June 2021

e18731

Background: For advanced non-small cell lung cancer (NSCLC), evidence from clinical trials indicates the superiority of pembrolizumab (P) than chemotherapy (C) in PD-L1 positive patients and superiority of P+C than C among PD-L1 unselected patients. Meta-analysis from different clinical trials stated P+C failed to improve overall survival (OS) or progression-free survival (PFS) compared with P alone. This study used real-world data of PD-L1+ patients with advanced NSCLC to compare treatment effect of P with P+C. Methods: A retrospective analysis of adult patients diagnosed between 2015-2020 with stage IV NSCLC with PD-L1+ and without EGFR/ALK mutation was examined using de-identified Syapse Learning Health Network(LHN). We compared the patients with first-line (1L) treatment of pembrolizumab + carboplatin + chemo (P+C) and patients with 1L treatment of P only (P). Patient characteristics and survival outcomes including real-world OS (rwOS) and real-world time to next treatment (rwTTNT) were collected. Results: 485 patients were included: 231 on P+C and 254 on P. The two groups are similar in race, primary tumor histology and ECOG, and P are older in age and have more female. The median rwOS for P+C is longer than P (13.2 vs 11.0 month), 1 year survival probability is higher (55% vs 49%), but 2 year survival probability is lower (34% vs 39%). Coxph model shows no significant difference between two groups (HR=0.89, 95% CI 0.69-1.14, p=0.34). Subgroup analysis of patients age≥75 shows median rwOS for P+C is shorter than P (8.7 vs 13.2 month), 1 year survival probability is lower (46% vs 51%). Coxph model shows no significant difference between two groups (HR=1.32, 95% CI 0.81-2.16, p=0.27). In each treatment group, the median rwOS for female is longer than male (13.2 vs 7.9 month in P, 15.8 vs 12.2 month in P+C), and 1 year survival probability is higher (52% vs 45% in P, 59% vs 53% in P+C). Coxph model shows no significant difference between female and male (HR=0.81, 95% CI 0.58-1.15, p=0.23 in P; HR=0.90, 95% CI 0.62-1.30, p=0.57 in P+C). Conclusions: Among patients with PD-L1+ advanced NSCLC, there is no significant difference in rwOS for patients with 1L treatment of P+C or P alone.[Table: see text]
The impact of the COVID-19 pandemic on oncology clinical trial recruitment in an Irish cancer center.
Authors: McLaughlin Ronan Andrew , Madigan Valerie , O'Grady Maureen , Mahgoub Thamir Andrew , Kalachand Roshni Andrew , Osman Nemer , Korpanty Greg , Coate Linda E.
Published: June 2021

e18756

Background: The COVID-19 pandemic has created unprecedented disruptions to cancer clinical trial research across the world due to a temporary global suspension of patients’ recruitment to cancer clinical trials. Access to clinical trials permits better treatment options and best clinical practice standards for patients with cancer. We present the impact of the COVID-19 pandemic on cancer clinical trial activity at the Cancer Clinical Trials Unit (CCTU) at the Mid-Western Cancer Centre, University Hospital Limerick (UHL). Over the last 4 years 28 clinical trials, both interventional and translational, have opened here, across a variety of primary disease sites, with 5 trials opened in 2017, 11 in 2018, 7 in 2019 but only 2 in the first 10 months of 2020 until 3 further trials were opened in December. Methods: CCTU records were reviewed to identify the number of patients screened and consented to participate in cancer clinical trials at UHL in 2020, which were compared directly with corresponding numbers for 2019. Results: In 2019, 17 clinical trials were open and recruiting at the CCTU, UHL. During 2020, 19 trials were recruiting although during the 1st surge of the COVID-19 pandemic recruitment was essentially suspended and CCTU staff were redeployed throughout the hospital. 1st Six months 2020 vs 2019 In the six months from January 2020 until the end of June 2020, 99 patients were screened and only 15 (15.2%) signed informed consent to participate in a cancer clinical trial. When these figures are directly compared with the first six months of 2019, there is a 33% reduction in patients screened for participation (147 vs 99) and a 60% reduction in patients consented (37 vs 15) to clinical trials. 12 Months 2020 vs 2019 In total during 2019, 376 patients were screened for inclusion to participate and 49 (13%) patients signed informed consent to participate in a clinical trial within CCTU at UHL. In 2020, 914 patients were screened for participation with 51 patients consented to participate (5.6%). The majority (45/51 (88%)) of patients consented to cancer clinical trials in 2020 at the CCTU, UHL were recruited to translational based studies and only 6 (12%) consented to interventional studies compared with 2019 when 30/49 (61%) consented to translational and 30/49 (39%) to interventional studies. Conclusions: During the COVID-19 pandemic, the percentage of patients consented to participation in a clinical trial reduced significantly, as compared to the previous year (5.6% vs 13%). Fewer interventional studies have recruited patients during 2020. As we enter the third surge of COVID-19 infections in Ireland, we must continue to monitor and identify effective strategies to navigate the ever-changing situation for cancer clinical trials, in an attempt to maintain access to high quality cancer clinical trial opportunities for our patients.
Description of asymptomatic cancer patients with COVID-19 infection: Experience of the ACHOCC-19 study in one Latin American country.
Authors: Ospina Serrano Aylen Vanessa , Bruges Maya Ricardo Elias , Mantilla William Armando , Triana Ivan Camilo , Ramos Pedro , Aruachan Sandra , Quiroga Alicia , Munevar Isabel , Ortiz Juan , Llinas Nestor , Pinilla Paola , Vargas Henry , Idrobo Henry , Russi Noguera July Andrea , Manneh Kopp Ray , Rivas Giovanna Patricia , Gonzalez Florez Hector Alirio , Santa Daniel Andres , Insuasty Jesus , Lopes Gilberto
Published: June 2021

e18761

Background: Cancer has been described as a risk factor for worse prognosis in people with Covid-19. However, there are few studies informing on the characteristics of cancer patients that have asymptomatic SARS-cov2 infection. The ACHOCC-19 study included asymptomatic patients. Methods: Analytical cohort study of patients with cancer and SARS-cov2 infection in Colombia. From April 1 to October 31, 2020, we collected data on demographic and clinical variables related to cancer and COVID-19 infection. We describe the characteristics and outcomes of patients who had no symptoms of COVID19. Association between outcomes and prognostic variables was analyzed using logistic regression models. Results: We included 742 patients, of which 205 (27.6%) were asymptomatic. Of these 62.2% were older than 61 years, 66% were women, 1.42% were smokers. The most frequent malignancy was breast cancer (25%), followed by colon-rectum (14.6%), sarcoma/soft tissues (5.66%) and lung cancer (5.19%). Patients were more likely to be asymptomatic if they had fewer comorbidities (0-1 comorbidities: 84% asymptomatic, 2 comorbidities: 10.85%, more than 2 comorbidities: 5.15%). 90.5% lived in urban areas and 53.37% had low income. 35.4% of patients had metastatic disease, 8.7% had progressive cancer, 40% had stable disease or partial response. No patient had an ECOG PS of 4 or more, and only 1.91% had ECOG 3. In logistic regression analysis statistically significant associations for having symptomatic disease included: man, presence of 1, 2 or > 2 comorbidities, ECOG 1,2 or 3 and cancer in progression. On the other hand, the statistically significant ORs for having asymptomatic disease were age between 18 and 30 years old, cancer in remission and receiving non-cytotoxic treatment. Table sumarizes ORs and their respective 95% CIs of the variables adjusted in the logistic regression model. Conclusions: In our stumdy, cancer patients had a higher probability of asymptomatic COVID-19 infection if they were women, between the ages of 18 and 30 years, had cancer in remission , ECOG 0 and no comorbidities. This is the first cohort of patients with cancer and asymptomatic covid 19 with a significant sample size in Latin America.[Table: see text]
Insurance data of patients receiving sequential immune checkpoint inhibitors: A single center experience.
Authors: Awidi Muhammad , Ranjit Rojer , Connell Brendan James , Gil Brigitte , Dalbo Natalie , Maher Lewena , Daves Seanna , McDonald Stephanie , Tsoukas Philip , Voner Linda , Gunturu Krishna Soujanya
Published: June 2021

e18835

Background: Immune checkpoint inhibitors (ICI) up regulate T cell activity promoting tumor cell death and revolutionized modern oncology. The use and number of indications for ICI is growing at an unprecedented speed. Combination and sequential ICI therapies have been shown to be beneficial in certain types of cancer. There is no significant data to support non-FDA approved sequential use of ICI when patients develop toxicities or progression which could result in a significant financial burden on the patient and the health care system. We conducted a retrospective review of cancer patients receiving ICI at our institution and evaluated the insurance status of these patients who received sequential ICI. Methods: We retrospectively reviewed Oncology patients’ charts who received ICI between January 1, 2014 to December 18, 2018. We identified patients receiving sequential ICI, to be defined as patients who received a second ICI, following an initial ICI therapy. Insurance status was evaluated for patients receiving sequential therapy. Commercial insurance was defined as either private or non-Medicare/Medicaid. Results: Out of total 437 patients receiving ICI, 15 patients received sequential ICI. 11 patients were transitioned to a secondary ICI following disease progression (73%), three had immune related adverse events and one was switched per standard of care. Nine patients (60%) had commercial insurance and six patients (40%) had medicare/medicaid. Of those, one had urothelial carcinoma and was switched to pembrolizumab from atezolizumab due to disease progression. One patient had melanoma and received nivolumab following ipilimumab when data from the CHECKMATE 238 were published. Three patients with melanoma were transitioned from ipilimumab to nivolumab, two had disease progression and one had autoimmune dermatitis. Two patients had lung adenocarcinoma and were switched from nivolumab to pembrolizumab due to disease progression. One patient had small cell lung cancer and received pembrolizumab following nivolumab due to disease progression. One patient had squamous cell lung cancer and was switched to pembrolizumab from nivolumab following disease progression. Conclusions: With the rapid growth and advancement of ICI indications, there is limited data available on the benefits of sequential ICI to our patients in the clinical setting. We report a small percentage of oncology patients receiving sequential treatment with or without FDA approval and explore their insurance status. Majority of our patients who transitioned to a second ICI due to progression had commercial insurance. Larger prospective studies are needed to evaluate sequential ICI efficacy and tolerability and cost effectiveness.
Establishing a health economics and value unit at the Children’s Cancer Hospital–Egypt: Introducing a practical approach for evidence-based decision making.
Authors: Soliman Ranin , Tarek Nourhan , Samir Sandra , Okail Shimaa , Eweida Wael , Abouelnaga Sherif
Published: June 2021

e18859

Background: Health Economics is a multi-disciplinary practice that recently gained recognition in healthcare management systems. Value-based healthcare (VBHC) focuses on improving patient outcomes while using fewer healthcare resources. Integrating the principles of health economics and VBHC are essential to better inform decision-making based on evidence, especially in resource-limited settings, that need ultimate efficiency in managing resources. Egypt has the highest second estimated number of incident childhood cancer cases in the Eastern Mediterranean Region (EMR), based on GLOBOCAN 2020. Thus, childhood cancer in Egypt is an urging priority due to the large number of patients, limited resources, and poor outcomes. There is a need to optimize resource use and promote value in care delivery for childhood cancer care in Egypt, based on real-world evidence. Methods: This work aims to highlight the role of establishing a health economics and value (HEV) unit at the Children’s Cancer Hospital 57357 –Egypt (CCHE), to improve care and outcomes for children with cancer efficiently. CCHE is a not-for profit pediatric oncology center, treating around 50–60% of childhood cancers across Egypt free of charge. Results: The HEV unit was established in 2017 as a sub-function of the upper management at the hospital. The core mission of the unit is to translate health economics and VBHC concepts into practice to promote evidence-based decision-making, through applying the following functions and activities: monitoring trends in childhood cancer survival, resource use, and costs; applying health economic evaluation tools such as cost-effectiveness analysis (CEA) and multi-criteria decision analysis (MCDA); applying time-driven activity based costing (TDABC); implementing VBHC on a disease- and a hospital-level; monitoring costs and benchmarking. Some of these functions/activities reflect on operational processes such as integrating the CEA tools within the hospital procedures to maximize value of money spent; and restructuring hospital-wide cost centers for accurate costs reporting. Capacity building is also an important pillar in the unit’s framework, where the unit team conducts internal and external training sessions and workshops to spread the knowledge about health economics, VBHC, and evidence-based healthcare. Conclusions: The HEV unit at CCHE presents a unique model of applying health economics and value-based healthcare at a micro level in a pediatric oncology center in Egypt. This is a novel approach for healthcare management in Egypt and making informed decisions based on real-world evidence.
Co-occurring alteration of NOTCH and DDR pathways serve as novel predictor to efficacious immunotherapy in NSCLC.
Authors: Zhang Zhimin , Gu Yanyan , Su Xiaona , Bai Jing , Guan Wei , Ma Jungang , Luo Jia , He Juan , Zhang Bicheng , Geng Mingying , Xia Xuefeng , Guan Yan-Fang , Shen Cheng , Chen Chuan
Published: June 2021

e21106

Background: Although immune checkpoint inhibitors (ICIs) have shown remarkable benefit for treatment of advanced non-small lung cancer (NSCLC), only a minority of patients can achieve durable responses and the majority produce an ultra-rapid progressive disease. Methods: Here, we collected the availably published datasets and mined the determinants of response to immunotherapy on pathway levels. 106 NSCLC patients treated with immunotherapy were combined from Rizvi et. al and Hellman et. al studies (whole exon sequencing) as the discovery dataset. Two independent validation datasets were comprised of the MSKCC cohort (targeted sequencing) and data by Anagnostou and colleagues (whole exon sequencing). The Cancer Genome Atlas (TCGA) somatic mutation and gene expression data were applied to explore the immunobiology features. Results: In the first combined cohort, we detected NOTCH pathway altered in 71% patients with durable clinical benefit (DCB) while only 36% among no durable benefit (NDB) (p = 0.005). Compared to NDB group, co-occurrence of NOTCH and at least two DDR (co-DDR) pathway was discovered in DCB group and contributed to a prolonged progression-free survival (PFS) [ 22.1 vs 3.6 months, p < 0.0001, HR, 0.34, 95% confidence interval (CI), 0.2-0.59]. In two independent datasets, co-occurrence of NOTCH+/co-DDR+ was also validated to be a better immunotherapy efficacy [ Cohort 2: 13 vs 6 months, p = 0.034, HR, 0.55, 95% CI, 0.31-0.96 ; Cohort 3: 21 vs 11 months, p = 0.067, HR, 0.45, 95% CI, 0.18-1.1 ]. By analyzing TCGA cohort, we found patients with coexisting NOTCH and co-DDR pathway had a higher TMB, more infiltration of CD4+T cells. Conclusions: Overall, co-occurrence of NOTCH and co-DDR pathway reflect a better immunotherapy efficacy in advanced NSCLC. This genomic predictor show promise in stratifying patients that suit for immunotherapy for future clinical practice.
Genomic analysis of primary malignant melanoma of the esophagus.
Authors: Li Jingjing , Yan Shi , Guan Wenyan , Xiao Xiao , Liu Bing , Wang Changxi , Yu Zicheng , Ma Yuanyuan , Wu Nan
Published: June 2021

e21515

Background: Primary malignant melanoma of the esophagus (PMME) is an exceedingly rare disease but behave more aggressively and have a poorer prognosis. No specific histopathological classification and therapy strategies have been established for this type of disease due to lack of both tumor biological and genetics perception to PMME. Methods: We performed whole exome sequencing on 29 dissections including 23 primary tumors and 6 metastatic lymph nodes from 18 PMME patients. The genetic characteristics including somatic mutations and copy number variation (CNV) of PMME were compared to 398 skin cutaneous melanoma (SKCM), 67 mucosal melanoma (MM) and 79 uveal melanoma (UVM). Using multi-region sequencing, we reconstructed the phylogenetic structure and inferred the evolutionary mode. Results: We found that PMME/MM have similar genomic patterns to SKCM but distinct from UVM. Frequently mutated driver genes such as MUC16, BRAF, NRAS, NF1, KMT2C, POLE, PTPRT, RANBP2 appeared in both SKCM and PMME/MM cohorts. Of note, pathway enrichment analysis using identified driver genes revealed that melanoma pathway and MAPK signaling pathway were among the top affected pathways in MM/PMME as well as in SKCM. UVR-associated single base substitution signature 7 (SBS7) was not a dominant signature (median: 0.17, range:0̃0.79) in PMME/MM but 99 percent (89/90) of them do have it. An overall concordant trend in genome instability was found between PMME and SKCM. Significant CNV events at arm level showed the similar changes in PMME and SKCM, including amplification regions of 1q, 6p, 7p, 8q, 15q, 20p and deletion of 10p, 10q, 11p. CDKN2A loss appeared as a shared focal event by PMME and SKCM. To elucidate the evolution trajectory of spatially separated samples, we also performed multi-region sequencing, and the phylogenetic analysis suggested that whole genome doubling (WGD) was an early and clonal event, which preceded the majority of somatic mutations and CNV. Most driver genes such as NF1, RANBP2 and MUC16 mutated after WGD except TP53. Above findings suggested that WGD might be capable of promoting ongoing genome instability and shaping the evolution in PMME. Moreover, parallel evolution of RANBP2 was recurrently observed indicating the existence of constraints and selection. Conclusions: Our data showed that PMME/MM exhibited genetic features very similar to SKCM so it might not be excluded from treatments currently used for common SKCM.
Metastatic site-specific utilization and outcome of immunotherapy in stage IV melanoma: A national perspective.
Authors: Cao Lifen , Bliggenstorfer Jonathan T. , Towe Christopher W. , Mangla Ankit , Miller Megan E. , Rothermel Luke
Published: June 2021

e21525

Background: Metastatic melanoma is an aggressive disease with a rapid systemic dissemination. We evaluated the effect of metastatic sites on the utilization immunotherapy and survival outcomes in stage IV melanoma. Methods: The National Cancer Database from 2010-2017 was queried for stage IV melanoma. Those with missing relevant data were excluded. Patients were grouped into five categories based on metastatic sites: lung metastasis only, brain metastasis only, liver metastasis only, bone metastasis only and multiple sites metastasis. Multivariable logistic regression was used to predict use of immunotherapy. Effects of immunotherapy on overall survival were assessed using Kaplan-Meier curves and Cox proportional hazards model. Results: A total 12, 315 were included in the study, among whom 2206 (17.9%) had lung metastasis only, 1,873 (15.2%) had brain metastasis only, 785 (6.4%) had liver metastasis only, 662 (5.4%) had bone metastasis only and 5,983 (48.6%) presented with multiple metastatic sites. Surgery at primary site was performed in 34.3% of patients with bone metastasis (p<0.001), and radiation therapy was delivered to 69.2% patients with brain metastasis (p<0.001). Site of metastatic disease was associated with immunotherapy utilization, with multiple sites (OR = 1.149, p=0.012), and distant lymph nodes (OR=2.867, p<0.001) demonstrating the strongest association, while patients with oligo brain metastasis were less likely to receive immunotherapy (OR = 0.486, p<0.001). Immunotherapy is associated with superior survival among metastatic melanoma patients (HR=0.433, P<0.001). The Kaplan-Meier curves showed the median overall survival among the immunotherapy group was 33.7 months for lung metastasis (vs. 13.4 months without immunotherapy, HR=0.633, p<0.001), 25 months for brain metastasis (vs. 6.7 months without immunotherapy, HR=0.447, P<0.001), 16.8 months for liver metastasis (vs. 4.2 months without immunotherapy, HR=0.449, P<0.001), 18.3 months in bone metastasis (vs. 7.6 months without immunotherapy, HR=0.615, p<0.001) and 12.1 months in multiple metastasis (vs. 3.8 months without immunotherapy, HR=0.338, p<0.001). Conclusions: Utilization of immunotherapy is influenced by location of metastatic disease in stage IV melanoma. Overall survival is improved for patients treated with immunotherapy.[Table: see text]
Analysis of metastatic melanoma treated with immune checkpoint inhibitors and the rates of adverse events of colitis and hepatitis.
Authors: Horan Emily , Arneil Melissa , Xu Wen , Atkinson Victoria
Published: June 2021

e21591

Background: Immune checkpoint inhibitors (CPI) are widely used in metastatic melanoma (MM), where it has markedly improved survival outcomes. ICI induced autoimmune adverse reactions (irAE) manifest in all organ systems and are due to over-activation of the immune system. Clinically relevant irAE are colitis and hepatitis as drivers of morbidity and mortality. Methods: Data was collected from a single centre (Princess Alexandra Hospital) from the electronic medical records system and immunotherapy prescribing software. Patient demographics, treatments, complications and outcomes were recorded from 2016-2019. Eligible patients had to have received immunotherapy (pembrolizumab, ipilimumab, or nivolumab) and experienced colitis or hepatitis toxicity. Trial patients were excluded. Results: The cohort of 337 patients who had received immune therapy, 18% (n = 61) had hepatitis or colitis, mean age was 56 years, 64% male. The majority were stage 4d 28% (n = 17). Braf wildtype accounted for 56% (n = 34). The highest rates of irAE occurred on combination ipilimumab and nivolumab 56% (n = 34), 10% nivolumab (n = 6), 3% (n = 2) ipilimumab, and 31% (n = 19) pembrolizumab monotherapy. Colitis affected 61% of patients (n = 37), 30% (n = 18) were grade 3 severity. Hepatitis affected 48% (n = 29), 18% (n = 32) were grade 1. The majority required oral steroids (80%, n = 49), followed by intravenous steroids (51%, n = 31), infliximab (18%, n = 11) and mycophenolate in 5% (n = 3). Hospitalisation occurred in 56% (n = 34), 20% (n = 12) requiring treatment cessation. Progressive disease occurred in 62% (n = 38), and 13% (n = 8) had a complete response. Conclusions: The findings of this analysis mirror current literature with immunotherapies used, rates and severity of irAE. The management of irAE also aligned with current guidelines. Further research is required to investigate patient factors increasing the risk of developing irAE, and ideal treatment regimens. Analysing this large cohort, the incidence of toxicity was 17%, predominantly colitis followed by hepatitis. Patients were severely impacted requiring significant interventions to manage toxicity, hospitalisation and morbidity.
An oncopalliative expertise unit in a French comprehensive cancer center: Experience at one year.
Authors: Mateus Christine , Vigouret-Viant Laurence , Voisin Sabine , Laurent Sophie , Renard Perrine , Sampetrean Anda , Pavliuc Elena , Scotte Florian , Dauchy Sarah
Published: June 2021

e24077

Background: Anticipation of palliative care improves advanced cancer patients quality of life and may increase survival. It has also been associated with health costs reduction. However it is made difficult by societal taboos and reluctance of patients and caregivers to talk about therapeutic limitations and end of life. Methods: In a large French Comprehensive Cancer Center (CCC), the causes for both emergency consultations and medical hospitalizations have been analyzed, showing that repeated hospitalizations are more frequent when the level of care complexity increases and when the therapeutic project is unclear. Considering the European and international experiences of acute palliative care unit (APCU), we decided to create an APCU with reinforced onco-palliative expertise. This Onco-Palliative Expertise Unit (OPEU) main objective, besides treating refractory symptoms is to allow oncologists, palliative care specialists, pts and relatives to discuss together in order to redefine the therapeutic project. Results: One year after opening, this 10-bed unit has received 251 patients in 314 stays. 53% came directly from the home, 46% were already being followed by our palliative care team. After an average length of stay of 11.6 days, discharge was distributed between return home (41%), a palliative care unit (26%), death (22%) and other oncology units, or other hospitals (11%). At the opening, refractory symptoms were the most frequent reason for hospitalization (67% of stays). For the first 6 months period to the second one, discussing the therapeutic project increased from 23% to 34% of the hospitalization causes in the OPEU, showing the appropriation of this unit by the oncologists. A discussion about the project was carried out for almost all stays. On admission, specific cancer treatment was ongoing for 56% of stays. After assessment and multidisciplinary discussion, 49% of them decided to stop chemotherapy. Conversely, the start or resumption of treatment was recommended for 9% of stays without specific treatment on admission. The OPEU is a decompression chamber in the pt care pathway, which allows a multidisciplinary analysis of the pt’s condition on a single unit and leads to a quick and more appropriate therapeutic decision. Of the 251 pts hospitalized, only 19% were readmitted to hospital during the same one-year period, mainly for refractory symptoms. Conclusions: The creation of an OPEU in a CCC allows getting around the taboo of palliative care. It supports the dialogue between the oncologist and the pt, allows the pt to make the therapeutic project evolve toward a life project, avoiding costly unreasonable obstinacy.
Rescue-free laxation response with methylnaltrexone treatment in cancer patients with opioid-induced constipation: The impact of baseline ECOG status.
Authors: Boniol Scott , Slatkin Neal E. , Stambler Nancy , Israel Robert J.
Published: June 2021

e24083

Background: Opioid-induced constipation (OIC) is a common side effect of opioid treatment for cancer-related pain. Methylnaltrexone (MNTX) is a peripherally active µ-opioid receptor antagonist indicated for OIC that does not affect opioid central analgesia. We assessed if baseline Eastern Cooperative Oncology Group (ECOG) status impacted the rescue-free laxation (RFL) responses among cancer patients with OIC treated with repeated doses of MNTX. Methods: This pooled post hoc analysis from 2 randomized, placebo-controlled, institutional review board–approved clinical studies included cancer patients with OIC (study 302, NCT00402038; study 4000, NCT00672477). Study 302 compared subcutaneous MNTX 0.15 mg/kg vs placebo and study 4000 compared body weight‒based subcutaneous MNTX 8 mg (38–< 62 kg) or 12 mg (³ 62 kg) vs placebo. The data were stratified by baseline ECOG status (< 2 vs ≥ 2). Endpoints included the number of patients with RFL responses within 4 hours after ≥ 2 of the first 4 doses and the number of patients with RFL response within 4 hours of treatment for patients who received all 7 doses. Results: The intent-to-treat analysis included 43 patients with an ECOG < 2 (placebo = 20; MNTX = 23) and 187 patients with an ECOG ≥ 2 (placebo = 94; MNTX = 93). Those with an ECOG < 2 were younger (mean age 58 vs 65 years), predominantly male (60.5% vs 51.3%), and used a higher daily dose of oral morphine equivalent (190.7 vs 180.0 mg/d) compared with those with an ECOG ≥ 2. Cancer patients with an ECOG < 2 treated with MNTX had a significantly greater RFL response within 4 hours after ≥ 2 of the first 4 doses compared with placebo (56.5% vs 5.0%, P = 0.0003). Similar results were reported for patients with an ECOG ≥ 2 (57.0% vs 5.3%, P < 0.0001). Compared with placebo, the MNTX group had a greater proportion of patients with an RFL response, whether they had at least 1 RFL response or up to 7 RFL responses out of 7 doses, with significant treatment differences with each additional RFL per 7 doses among cancer patients with an ECOG ≥ 2 (Table). Conclusions: RFL response rates in cancer patients were significantly greater in the MNTX group vs the placebo group regardless of baseline ECOG status; responses were similar between the 2 groups despite a higher daily dose of opioids in the group with an ECOG > 2. Clinical trial information: NCT00402038; NCT00672477. [Table: see text]
Development and Evaluation of Deep Learning-based Automated Segmentation of Pituitary Adenoma in Clinical Task
Authors: Wang He , Zhang Wentai , Li Shuo , Fan Yanghua , Feng Ming , Wang Renzhi
Published: June 2021

Context

The resection plan of pituitary adenoma (PA) needs preoperative observation of the sellar region. Radiomics prediction requires high-quality segmentations. Manual delineation is time-consuming and subject to rater variability.

Objective

This work aims to create an automated segmentation method for the sellar region, several tools to extract invasiveness-related features, and evaluate their clinical usefulness by predicting the tumor consistency.

Methods

Patients included were diagnosed with pituitary adenoma at Peking Union Medical College Hospital. A deep convolutional neural network, called gated-shaped U-net (GSU-Net), was created to automatically segment the sellar region into 8 classes. Five magnetic resonance imaging (MRI) features were extracted from the segmentation results, including tumor diameters, volume, optic chiasma height, Knosp grading system, and degree of internal carotid artery contact. The clinical usefulness of the proposed methods was evaluated by the diagnostic accuracy of the tumor consistency.

Results

A total of 163 patients with confirmed pituitary adenoma were included as the first group and were randomly divided into a training data set and test data set (131 and 32 patients, respectively). Fifty patients with confirmed acromegaly were included as the second group. The Dice coefficient of pituitary adenoma in important image slices was 0.940. The proposed methods achieved accuracies of more than 80% for the prediction of 5 invasive-related MRI features. Methods derived from the automatic segmentation showed better performance than original methods and achieved areas under the curve of 0.840 and 0.920 for clinical models and radiomics models, respectively.

Conclusion

The proposed methods could automatically segment the sellar region and extract features with high accuracy. The outstanding performance of the prediction of the tumor consistency indicates the methods’ clinical usefulness for supporting neurosurgeons in judging patients’ conditions, predicting prognosis, and other downstream tasks during the preoperative period.
Women With Polycystic Ovary Syndrome Have an Increased Risk of Major Cardiovascular Events: a Population Study
Authors: Berni Thomas R , Morgan Christopher L , Rees D Aled
Published: June 2021

Context

The effects of polycystic ovary syndrome (PCOS) on cardiovascular morbidity and mortality are unclear.

Objective

This work aims to establish the relative risk of myocardial infarction (MI), stroke, angina, revascularization, and cardiovascular mortality for women with PCOS.

Methods

Data were extracted from the Clinical Practice Research Datalink Aurum database. Patients with PCOS were matched to controls (1:1) by age, body mass index (BMI) category, and primary care practice. The primary outcome was the time to major adverse cardiovascular event (MACE); a composite end point incorporating MI, stroke, angina, revascularization and cardiovascular mortality. Secondary outcomes were the individual MACE end points.

Results

Of 219 034 individuals with a diagnosis of PCOS, 174 660 (79.7%) met the eligibility criteria and were matched. Crude rates of the composite end point, MI, stroke, angina, revascularization, and cardiovascular mortality were respectively 82.7, 22.7, 27.4, 32.8, 10.5, and 6.97 per 100 000 patient-years for cases, and 64.3, 15.9, 25.7, 19.8, 7.13, and 7.75 per 100 000 patient-years for controls. In adjusted Cox proportional hazard models (CPHMs), the hazard ratios (HRs) were 1.26 (95% CI, 1.13-1.41), 1.38 (95% CI, 1.11-1.72), 1.60 (95% CI, 1.32-1.94), and 1.50 (95% CI, 1.08-2.07) for the composite outcome, MI, angina, and revascularization, respectively. In a time-dependent CPHM, weight gain (HR 1.01; 1.00-1.01), prior type 2 diabetes mellitus (T2DM) (HR 2.40; 1.76-3.30), and social deprivation (HR 1.53; 1.11-2.11) increased risk of progression to the composite end point.

Conclusion

The risk of incident MI, angina, and revascularization is increased in young women with PCOS. Weight and T2DM are potentially modifiable risk factors amenable to intervention.
RNA-binding proteins regulate aldosterone homeostasis in human steroidogenic cells
Authors: Fu Rui , Wellman Kimberly , Baldwin Amber , Rege Juilee , Walters Kathryn , Hirsekorn Antje , Riemondy Kent , E. Rainey William , Mukherjee Neelanjan
Published: June 2021

Angiotensin II (AngII) stimulates adrenocortical cells to produce aldosterone, a master regulator of blood pressure. Despite extensive characterization of the transcriptional and enzymatic control of adrenocortical steroidogenesis, there are still major gaps in the precise regulation of AngII-induced gene expression kinetics. Specifically, we do not know the regulatory contribution of RNA-binding proteins (RBPs) and RNA decay, which can control the timing of stimulus-induced gene expression. To investigate this question, we performed a high-resolution RNA-seq time course of the AngII stimulation response and 4-thiouridine pulse labeling in a steroidogenic human cell line (H295R). We identified twelve temporally distinct gene expression responses that contained mRNA encoding proteins known to be important for various steps of aldosterone production, such as cAMP signaling components and steroidogenic enzymes. AngII response kinetics for many of these mRNAs revealed a coordinated increase in both synthesis and decay. These findings were validated in primary human adrenocortical cells stimulated ex vivo with AngII. Using a candidate screen, we identified a subset of RNA-binding protein and RNA decay factors that activate or repress AngII-stimulated aldosterone production. Among the repressors of aldosterone were BTG2, which promotes deadenylation and global RNA decay. BTG2 was induced in response to AngII stimulation and promoted the repression of mRNAs encoding prosteroidogenic factors indicating the existence of an incoherent feedforward loop controlling aldosterone homeostasis. These data support a model in which coordinated increases in transcription and decay facilitate the major transcriptomic changes required to implement a prosteroidogenic expression program that actively resolves to prevent aldosterone overproduction.
Μιχαήλ Ψελλός και δαιμονολογία
Authors: Κοκοτσάκη Αρχόντισσα
Published: June 2021

Η παρούσα διατριβή ασχολείται με τις δαιμονολογικές πεποιθήσεις του Μιχαήλ Ψελλού (1017-1090;). Ο Ψελλός έζησε στην Κωνσταντινούπολη. Ήταν πολύ καλός γνώστης της αρχαίας ελληνικής φιλοσοφίας. Επιχείρησε να εξετάσει την κοσμολογία, συσχετίζοντας την με τα χριστιανικά πιστεύω. Αυτή η περίοδος χαρακτηρίστηκε από την έντονη παρουσία της Χριστιανικής πίστης και η Εκκλησία ήταν αποφασισμένη να βρίσκεται στο κέντρο της κοινωνικής και της πνευματικής ζωής. Παράλληλά, οι διανοούμενοι της εποχής αντιλήφθηκαν την επιστήμη κάτω από το πρίσμα της Αρχαίας φιλοσοφίας και ο Νεοπλατωνισμός επηρέασε βαθιά τον τρόπο εξέτασης της Θεολογίας. Ο Ψελλός επηρεάστηκε σε μεγάλο βαθμό από την Πλατωνική παράδοση και τον Νεοπλατωνισμό, εντούτοις, στην διάρκεια της εξέτασης απέρριψε δοξασίες που δεν είχαν συνάφεια με τον Χριστιανισμό. Επιπρόσθετα, ήταν εξαίρετος μελετητής των αρχαίων θρησκειών, του μυστικισμού και της αλχημείας. Ως βυζαντινός διανοούμενος άφησε μια τεράστια κληρονομιά και το έργο του επηρέασε σημαντικά τους Ευρωπαίους συγγραφείς της Αναγέννησης. Σημαντικός αριθμός αρχαίων ελληνικών κειμένων διασώθηκε χάρη στο μεταφραστικό έργο του Ψελλού. Η αυθεντική μορφή της φιλοσοφικής πραγματείας De Operatione Daemonum (περί ενεργείας δαιμόνων) βασίζεται σε μια παρισινή έκδοση του G. Gaulmin Gautier και η λατινική εκδοχή του De Daemonibus δημοσιεύθηκε από τον Pierre Morel (1577). Μπορεί η απόδοση της πραγματείας στον Ψελλό να έχει αμφισβητηθεί από τους σύγχρονους μελετητές, ωστόσο, η πραγματεία παραμένει να είναι ένα πολύτιμο εγχειρίδιο για την δαιμονολογική σκέψη στην Ανατολική Βυζαντινή Αυτοκρατορία.
Ορισμοί εκπαιδευτικών προσχολικής ηλικίας για τον αναστοχασμό
Authors: Κοκκόση Αγγελική , Πούλου Μαρία , Κουστουράκης Γεράσιμος , Χανιωτάκης Νικόλαος
Published: June 2021

Το εν λόγω άρθρο μελετά τους ορισμούς των εκπαιδευτικών προσχολικής ηλικίας για τον αναστοχασμό. Σύμφωνα με τη βιβλιογραφία ο αποτελεσματικός εκπαιδευτικός θα πρέπει να έχει την ικανότητα να αναστοχάζεται για όσα διαδραματίζονται στο πλαίσιο του σχολείου. Ο αναστοχασμός βοηθάει τους εκπαιδευτικούς να αντιληφθούν τη σύνθετη φύση της διδασκαλίας και των σχολικών τάξεων. Σκοπός της παρούσας εργασίας είναι να μελετηθούν οι ορισμοί των εκπαιδευτικών προσχολικής ηλικίας για τον αναστοχασμό μέσα από τη χρήση ημερολογίου αναστοχασμού Στο κομμάτι του σχεδιασμού των ερευνητικών εργαλείων και της ανάλυσής τους ακολουθήθηκε η έρευνα μεικτών μεθόδων με στόχο να εξασφαλιστεί μια πληρέστερη κατανόηση του ζητήματος που εξετάζεται. Η έρευνα διήρκησε τέσσερις εβδομάδες και συμμετείχαν 47 εκπαιδευτικοί προσχολικής ηλικίας που υπηρετούν σε δημόσια νηπιαγωγεία της Δυτικής Ελλάδας. Οι ορισμοί των εκπαιδευτικών προσχολικής ηλικίας για τον αναστοχασμό αντλήθηκαν με τη χρήση ενός εβδομαδιαίου ημερολόγιου αναστοχασμού. Για την ανάλυση των δεδομένων χρησιμοποιήθηκε το λογισμικό ποιοτικής ανάλυσης NVivo-8 και το στατιστικό πακέτο SPSS. Από τα αποτελέσματα της μελέτης φάνηκε ότι η χρήση ενός εβδομαδιαίου ημερολογίου αναστοχασμού επηρεάζει τις αντιλήψεις των εκπαιδευτικών προσχολικής ηλικίας σχετικά με το τι είναι ο αναστοχασμός. Οι ορισμοί που αναφέρουν οι συμμετέχοντες όσο περνούν οι εβδομάδες συμπλήρωσης του ημερολογίου αναστοχασμού εμπεριέχουν όλο και περισσότερα στοιχεία από τον επιστημονικό ορισμό του Dewey για τον αναστοχασμό.
Video games Squared. Espacios heterotópicos y videojuegos en la era del audiovisual
Authors: Barros Grela Eduardo , Cancelo López Pablo , Vélez Barreiro Marco
Published: June 2021

La paradigmática consolidación del software de entretenimiento en el siglo XXI y el desarrollo de la tecnología —y de la industria— en el ámbito de los videojuegos ha dado lugar a nuevas formas de narración que implican una nueva conceptualización de la cultura y de los esquemas literarios tradicionales. En este artículo se propone una aproximación crítica al estudio de los videojuegos como elementos discursivos con una narratividad propia, y se formula una metodología basada en un triple enfoque: una reflexión teórica sobre la problemática actual del formato digital del videojuego como narrativa; una contextualización histórica del desarrollo del videojuego desde sus inicios hasta la actualidad; y un enfoque analítico que estudia la aplicabilidad de las reflexiones teóricas sobre el videojuego aplicadas al ámbito de la pedagogía.
La Evolución de las “Stammbildungen” o Formaciones de Raíces en las Arqui-/ Protolenguas Germánicas y Románicas: teoretización sobre el concepto “Verwandte Sprachen”
Authors: Castro Moreno Carmen Cayetana
Published: June 2021

The proof of genetic relation between two or more languages is considered to be valid, if there are sufficient common characteristics and the following two reasons for such similarity can be excluded: (1) The similarities grew in each language independently; (2) The similarity are product of contact between the observed languages or even of the relations to a third one. The question whether these causes of exclusion are reasonable and sufficient will be object of our linguistic discussion. We will compare new tendencies as well in Romania as in Germania as the main concepts of rootformation in the frame of language evolution. Keywords: Relationship, doubtful loans, orthographic adjustments, secondary structures and confixes Resumen: La prueba de si dos o más lenguas están genéticamente emparentadas entre sí se considera válida, siempre que las lenguas presenten abundantes características comunes, pudiendo ser excluidas las siguientes causas de semejante parentesco: (1) los parentescos han surgido en cada lengua de forma independiente; (2) los parentescos se han originado por contacto de las lenguas en cuestión, respectivamente en relación con una tercera lengua. El planteamiento de si esos motivos son razonables o no para su exclusión, será objeto de nuestra discusión lingüística. Serán comparadas tanto las nuevas tendencias en la Romania y en la Germania como las consiguientes concepciones principales de la formación de raíces en el marco de la evolución de la lengua.
La metáfora selvática. Una aproximación a los códigos simbólicos de The Asphalt Jungle de William R. Burnett
Authors: Mármol Carlos
Published: June 2021

This work analyzes the process of metaphorical construction in the novel The Asphalt Jungle, by W.R. Burnett, and his later cinematographic version directed by John Huston, who uses elements of the own literary story to change the terms of the original story to provide it with a new meaning. This process of metaphorical adaptation shows the extraordinary symbolic capacity of the literature and the film noir. Key words: Hard-boiled. William R. Burnett, metaphorical construction, John Huston, United States, Film noir.
Kurt Vonnegut’s Quest for Identity
Authors: Martín Párraga Javier
Published: June 2021

he present paper analyzes Kurt Vonnegut’s complex national roots, since he was an American citizen with a clearly German background who was deprived of any German education during his childhood and, consequently, had to discover the country of his ancestors when he was fighting the Nazis during World War II. Thus, his roots become an everlasting source of influence for Vonnegut. Obviously, and taking into account his rejection of Barthes’ concept of “the death of the author”, Vonnegut’s quest for roots will become a recurring element from his first literary adventures to the last published more mature novels.The main focus of the paper will be centered on how, even without a rich German education, Germany will play a fundamental role throughout the novelist’s whole corpus. In order to achieve this goal, I have examined both Vonnegut’s biography as well as his literary corpus (including fictional and non-fictional Works), together with the many interviews he gave during his long and complex literary career.
Von Wacken und Klötzen kulturelle Aspeke der Bibelübersetzung als Herausforderung für die kommunikative Aquivalenz
Authors: Jung Linus
Published: June 2021

Toe article explores the relationship between cultural aspects and communicative equivalence in the bible translation. In a first step, it describes the principie characteristics of the bible text and the possible difficulties in the cultural transfer. In the case of bible translation, the source and target cultures are separated by such a huge cultural, temporal, and geograplúcal gap that the relationship between the two texts does not seem to be allowing us any specification of communicative equivalence. Toe article tries to give an answer to this question. Af ter elaborating a dynarnic definition of the communicative equivalence concept, the author discusses various translations of Mt 5, 41.
Trading Places in New Zealand two women's literary search for self-realization overseas
Authors: Maver Igor
Published: June 2021

Toe paper compares sorne of the possíble reasons for the radical change of locale and overseas travel far away from home in the case of the New Zealand writer Katherine Mansfield and especially the Slovenian author Alma Maximiliana Karlin in the early twentieth-century, which shows an interesting parallelism and search for the 'othemess' of experience beyond their respective homelands. If Mansfield decided to leave New Zealand for London to study, and for the second time to avoid the provincial climate at home, then the Slovenian travel writer Alma Karlin decided to leave Europe for Asia and New Zealand at roughly the same time as Mansfield arrived in the modemist literary Bloomsbury area in London. Toe publication of Mansfield's famous collection, I11e Carden Parti; and Other Ston·es (1922), and Karlin's travel book, Solitan; Journey (Die Einsame Weltreise, 1929), almost coincided, although the two women authors never met.