bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of pre-treatment anxiety and depression on long term survival of prostate cancer patients treated radically with radiation and hormone therapy.
Authors: Jones Lauren , O'Cathail Micheal , Hosni Shaymaa Usama , Little Jessica , Cox Ashley , Fergusson Eamonn , Sundar Santhanam
Published: May 2019

e23087

Background: The evidence for effect of anxiety and depression on cancer survival rates is contradictory (Ref : Prostate-JCO 2014.32:2471, Breast-JCO 1987. 5:768, Lung-JPSM 2017.53:1057). We assessed the effect of prospectively collected HADS score (Hospital Anxiety and Depression Scale) on subsequent long term survival. Methods: After ethics approval & informed consent, 145 prostate cancer patients (pts) were enrolled, onto a QOL study. HADS questionnaire was prospectively completed at baseline & at 3 mths after start of androgen deprivation therapy (ADT). Survival data collected in Jan 2019. PATIENT CHARACTERISTICS: Median age 69 (range 50 to 78); T stage T2:63.5%, T3:28.4%. Gleason 7 in 53.4% and 8-10 in 39.2%; Median PSA 10.2 (0.3 to 102); Median testosterone 11.6 (0.6 to 26.7); ADT duration median 6 mths (2 to 60 mths); Median overall survival 10.11 yrs Results: At baseline, HADS anxiety scores normal (0-7) in 78%; abnormality mild (8-10) in 12%; moderate (11-14) in 6% and severe (15-21) in 2%.. At > 3 mths, respective anxiety scores (%) were 71.3, 17.5, 7.7 and 3.5. At baseline, HADS depression scores (%) were 91.2, 5.2, 1.4 and 0.7. At > 3 mths, respective depression scores were (%) 83.9, 11.2, 3.5 and 1.4 Although median survival was numerically lower in pts scoring high on HADS at baseline, the survival rates were not statistically significant on Log rank test. Moreover, on Cox regression analysis with Age, Gleason Score, T Stage, baseline PSA as co-variates, there was no increased hazard from higher HADS scores (Table). Conclusions: Biological factors probably outweigh the influence of psychological factors on overall survival. [Table: see text]
Is in vivo reflectance confocal microscopy a useful assessment tool in chemotherapy-induced peripheral neuropathy (CIPN)?
Authors: Ramnarine Sabrina , Rolke Roman , Dougherty Patrick M. , Williams Linda J , Alessi Fox Christi , Coleman Andrew , Fallon Marie T
Published: May 2019

e23088

Background: The lack of standardized diagnostic or assessment tools in CIPN pose an unmet need for objective and reliable measures. Advances in non-invasive, in vivo reflectance confocal microscopy (RCM) offer a painless method to identify markers of peripheral neuropathy such as loss of Meissner’s corpuscles (MC). This study aims to investigate the feasibility of RCM in CIPN by assessing MC density in healthy controls compared to cancer patients. Methods: RCM imaging (Vivascope 1500) was performed on the fingertip (digit V) to evaluate MC density in 45 healthy controls and 9 cancer patients prior to starting chemotherapy. Quantification was completed by two reviewers, one being blinded to achieve unbiased identification as the maximum MC count/6x6 mm image. Quantitative Sensory Testing (thermal and mechanical detection thresholds) along with the grooved pegboard test (sensorimotor function) were conducted for comparison with MC density. Spearman’s correlation coefficients were used to determine associations. Results: In healthy controls (25 females, 20 males; mean age 58.9, range 24-81 years), females exhibited a greater mean MC density compared with males (49.9 ± 7.1 MC vs 30.9 ± 4.2 MC; p = 0.03). Variances were observed across age range by decade (p < 0.0001). MC density was inversely correlated with mechanical detection (ρ = -0.51) and warm detection thresholds (ρ = -0.47) in contrast to cold pain threshold (ρ = 0.49). All correlations were significant (p < 0.01). Time to complete the grooved pegboard test correlated with MC density in the dominant hand (p = 0.02) and non-dominant hand (p < 0.01). Compared with age and gender matched controls, cancer patients had reduced MC density (22.0 ± 9.3 vs 35.4 ± 14.1; p = 0.03), mirroring deficits in cold detection threshold and the grooved pegboard test. Inter-rater reliability of MC density count showed an intraclass correlation of 0.96 (p < 0.0001). Conclusions: The findings from this study support the clinical utility of RCM in CIPN. Assessment of MC density using RCM may provide meaningful markers of sensory loss, sensorimotor function and an ability to detect possible subclinical deficits in patients at risk of CIPN prior to initiating chemotherapy.
Factors affecting sleep quality and its association to quality of life in adult Filipinos with cancer.
Authors: Gerona Amabelle Trina Borgonia , Baquilod Ryelene , Bernardo Deborah A. , De Guzman Roselle B.
Published: May 2019

e23100

Background: Sleep disturbances are highly prevalent in cancer patients and may be attributable to factors including pain, treatment side effects and psychological factors. However, the relationship between sleep and cancer is bidirectional. There is substantial evidence that sleep disturbance is associated with many aspects of cancer treatment, morbidity, mortality and quality of life. This study evaluated sleep quality in adult Filipinos with cancer and determined the association of demographic characteristics and clinical features to sleep quality. Methods: This was a cross-sectional surveillance study conducted among adult Filipinos with cancer seen at the Ambulatory Care Unit of a tertiary hospital. Questionnaires were answered to assess subjective sleep quality, pain score and quality of life. Frequency and percentages were determined. Determination of factors affecting sleep quality was analyzed using univariate and multivariate statistics. Results: Of the 406 cancer patients studied, 80% were women and the mean age was 53 years old. Majority (62%) had breast cancer. Seventy-nine percent (79%) of the patients had a PSQI score of 5 or greater, indicating poor sleep quality. Sleep among participants was characterized by prolonged time to fall asleep and shortened sleep duration. Majority reported some degree of daytime dysfunction due to poor sleep. Age, gender and marital status did not appear to affect the quality of sleep. Among disease-related factors, presence of more advanced disease, increasing pain severity and treatment with chemotherapy and/or radiotherapy were demonstrated to lead to poorer sleep quality. Surprisingly, even patients who were not receiving any active therapies (on-going surveillance) complained of sleep disturbance. Upon further investigation, poor sleep quality was shown to predict a worse quality of life among the study participants. Conclusions: Overall, the quality of sleep among adult Filipinos with cancer is significantly impaired. In particular, presence of more advanced disease, treatment with chemotherapy and radiotherapy and moderate to severe pain significantly increase the risk of having poor sleep. In turn, disturbed sleep predicted a poorer quality of life. These findings support the need to include assessment of sleep quality for a more holistic approach to cancer care.
Are patients with advanced colon cancer availing of palliative care services?: Findings from a high-volume urban center.
Authors: Jamorabo Daniel S , Renelus Benjamin D , Kancharla Pragnan , Briggs William M
Published: May 2019

e23101

Background: Palliative care is integral to cancer treatment. Our goal was to investigate the factors associated with palliative care service involvement for hospitalized colon cancer patients. Methods: We carried out a retrospective study of all colon cancer patients diagnosed and hospitalized at our institution from 1/1/2010 through 12/31/2017. We identified 667 patients, including 370 women (55%). We used Fisher’s exact test to find statistically significant differences in proportions of patients seen by the palliative care service based on sex, race, cancer stage, surgical intervention, and chemotherapy administration. Results: We found that 561/667 (84%) colon cancer patients were not evaluated by the palliative care service (including 301 women; 54%) and that overall they were unlikely to have been evaluated regardless of sex, race, cancer stage, or chemotherapy (Table). Patients who underwent surgery were equally likely to be seen by the team as those who did not have surgery. We found that 53% (150/285) of patients with Stage III and IV disease received neither chemotherapy nor palliative care evaluation. Conclusions: The palliative care service is underutilized at our facility even when patients with advanced stage disease are hospitalized. Even when patients are not on chemotherapy, the palliative care service remains uninvolved. This may be due to inadequate staffing, misconceptions that providers and patients have about palliative care, or lack of coordination between inpatient and outpatient providers. We did not find that palliative care service utilization led to a statistically significant difference in survival, but their involvement is critical to helping address patients’ goals of care and symptoms. It is also instrumental to improving cancer patients’ quality of life both in the outpatient and inpatient setting, regardless of cancer stage or survival, as in our patient population. More effort is needed to include the palliative care service in the care of patients with advanced colon cancer. [Table: see text]
The efficacy and safety of exercise in metastatic solid cancer: A meta-analysis of randomized control trials.
Authors: Nadler Michelle , Saleh Ramy , Desnoyers Alexandra , Amir Eitan
Published: May 2019

e23107

Background: The prevalence of people living with metastatic solid cancers is increasing. Such patients can experience cancer-related fatigue, decreased physical function (PF), and poor quality of life (QoL). Exercise has been shown to improve these symptoms in the curative setting, but there is uncertainty about the efficacy and safety of exercise in patients with metastatic cancer. Methods: Studies were identified from 3 prior systematic reviews and updated using a search of PubMed. Included studies were prospective randomized controlled trials of any moderate/high intensity aerobic exercise or resistance training intervention versus control in patients with metastatic solid cancers. The mean score and standard deviation (SD) for validated outcome measures (QoL, PF, and fatigue) were extracted for intervention and control groups at baseline and post-intervention. The effect of exercise was evaluated as the pooled change between baseline and post-intervention comparing exercise and control groups. Analysis was performed using the Mann Whitney test. Results: Of 21 trials which met inclusion criteria, 7 were excluded due to incomplete data. Among patients with mean baseline scores, exercise was not associated with significant change in fatigue, PF or QoL, although improvement was noted in 6-minute walk test (6-MWT) (14.7 vs 27.4 meters). QoL scores showed non-significant improvement (0.4 vs 4.9). In those with baseline scores 2SD below mean, exercise provided clinically meaningful improvement in PF using two different subscales (0.44 vs 8.5 and -1.0 vs 5.1) and avoidance of decline in 6-MWT (-29.75 vs -0.38m), although these did not meet statistical significance. There was a statistical improvement in sit-to-stand at the mean and 2 SD below the mean (2.5 vs 6.5, p = 0.029) for both groups. Only 5 papers reported adverse events in a standardized fashion in both groups. No differences in falls, fractures, or pain were reported. Conclusions: In patients with metastatic solid cancers, exercise interventions are associated with clinically meaningful improvements in PF, and statistically improved sit-to-stand scores. The effects are seen in patients with baseline score at the mean or lower.
Breast cancer patients’ quality of life: Real-world data.
Authors: Kosmidis Paris A. , Athanasakou Barbara , Kosmidis Thanos
Published: May 2019

e23115

Background: CareAcross is a digital platform dedicated to support, inform and engage with cancer patients. It also collects medical and other data, and generates real world evidence. Methods: In an effort to collect and analyze information from breast cancer patients regarding side effects in relation to their treatments and supplements intake, we contacted 4837 patients in the UK, Germany, France, Spain and Italy. 474 had triple negative breast cancer (TNBC) and the remaining 4363 other breast cancer subtypes (non-TNBC). All data was collected anonymously, with strong privacy and security controls. Results: Different regimens were given either as adjuvant or as systemic treatments. AC treatment was given to 9% of TNBC vs 4% of non-TNBC patients; FEC-T to 20% vs 13%, FEC to 10% vs 8%, taxanes to 37% vs 20% and platinum-based chemotherapy to 12% vs 2%, respectively. Among non-TNBC patients, 12% received Trastuzumab and 53% received hormonal treatment. Eighty four TNBC and 696 non-TNBC patients were asked regarding side effects as well as vitamins and supplements intake. Among them, 76 TNBC patients reported an average of 2.8 side effects (95% CI 1.0-8.0) vs 577 non-TNBC patients reporting an average of 2.8 side effects (95% CI 1.0-13.0); p < 0.92. Similarly, an average of 5.0 vitamins and supplements was reported by 64 TNBC patients (95% CI 10.0-17.0) and an average of 3.8 was reported by 555 non-TNBC patients (95% CI 1.0-29.0); p < 0.023. Toxicity and supplements are tabulated below. Conclusions: The real world evidence obtained through an international analysis shows that TNBC patients receive more toxic treatments due to the aggressive disease, as expected. However, TNBC patients experience similar toxicities with non-TNBC patients, but their consumption of vitamins and supplements is much higher. [Table: see text]
A large multicenter, randomized, double-blind, crossover study in healthy volunteers, comparing pharmacokinetics and pharmacodynamics of Sandoz proposed biosimilar pegfilgrastim with European and United States reference pegfilgrastim.
Authors: Otto Gordon P. , Nakov Roumen , Schussler Steven , Schier-Mumzhiu Stefanie , Schelcher Celine , Koch Sven D. , Skerjanec Andrej , Wang Jessie , Krendyukov Andriy , Bellon Anne
Published: May 2019

e23118

Background: Similarity of the pharmacokinetic (PK)/pharmacodynamic (PD) profiles of Sandoz proposed biosimilar pegfilgrastim and EU-reference biologic was confirmed in a pivotal Phase I study. In order to confirm PK/PD similarity to the US reference biologic, and to bridge between the two references, a 3-way study was conducted. Methods: A randomized, double-blind, single-dose, 3-treatment, 6-sequence crossover Phase I study was performed in healthy volunteers (HVs) to demonstrate similarity in PK, PD, safety and immunogenicity between Sandoz proposed biosimilar, US reference, and EU reference pegfilgrastim administered subcutaneously (6 mg/0.6 mL) in each treatment period. The primary objective was to demonstrate PK (AUC0-inf, AUC0-last, Cmax) and PD similarity (ANC AUEC0-last, ANC Emax). The study was powered (90%) to achieve confidence intervals (CIs) within biosimilarity margins 0.8─1.25 in pairwise comparisons. Secondary objectives were additional PK/PD parameters, safety and immunogenicity. Results: The study included 577 male and female HVs. PK and PD similarity were demonstrated between Sandoz proposed biosimilar and US reference (Table), as well as EU reference and between both reference biologics since the 90% CIs of the geometric mean ratios were contained within the pre-defined margins of 0.80‒1.25. Safety, immunogenicity and secondary PK/PD parameters were also similar across treatment groups. Conclusions: This large randomized, double-blind, single-dose, 3-treatment, 6-sequence crossover study demonstrated PK and PD similarity between Sandoz proposed biosimilar, US reference and EU reference pegfilgrastim with similar safety, local tolerability and immunogenicity. Clinical trial information: 2016-003549-27. [Table: see text]
The effect of sukshma vyayama joint loosening yoga on aromatase inhibitor-induced arthralgia (AI) in breast cancer patients: A feasibility study conducted on Facebook.
Authors: Leibel L. Leigh , Metri Kashinath G. , Prasad Rajendra , Mears J. Gregory
Published: May 2019

e23129

Background: AI therapy causes joint pain in up to half of women, and up to 20% become non-compliant with treatment due to pain and discomfort. This pilot study investigated the efficacy of sukshma vyayama in improving AI-induced joint pain and evaluated the feasibility of delivering the intervention on Facebook. Methods: Breast cancer patients undergoing treatment with AI's with self-reported arthralgia were recruited via an IRB-approved announcement posted in two closed breast cancer support groups on Facebook to participate in a yoga study delivered on Facebook. Participants completed BPI, DASH, PRAI and WOMAC questionnaires before and after the study. Intervention consisted of 12 joint loosening exercises performed in a chair, once daily for 12 minutes, Monday-Friday for 4 weeks. Asynchronous video demonstrations were available in a secret Facebook group and viewing confirmed by typing "done" (time-stamped) in comments. Results: 200 women responded. 38 met the inclusion criteria/consent, 26 completed the online consent, interventions and pre/post questionnaires. Paired simple t tests results showed significant (P < 0.05) improvement in all the pain measures and quality of life parameters after yoga intervention compared to baseline. Conclusions: This study provides the first evidence that it is feasible to teach sukshma vyayama to patients on Facebook and that the intervention significantly improves AI-induced arthralgia. Teaching yoga via social media may provide better access to this therapeutic modality to patients at all points in the cancer care continuum globally. [Table: see text]
Mortality results from an oral oncolytic symptom management trial.
Authors: Vachon Eric , Champion Victoria
Published: May 2019

e23139

Background: Although mortality rates have declined, cancer remains the second leading cause of death in the United States. There has been an increase in prescriptions of oral oncolytic agents (OOA), which are typically prescribed to late stage patients as third or fourth line therapy. Because of this, death rates are higher among these patients and may impact attrition rates in OOA intervention trials. For researchers working with late stage patients, attrition by mortality should be considered when determining sample size. The purpose of this report is to identify the mortality incidence and its related factors in a symptom management randomized controlled trial (RCT). Methods: A total of 272 cancer patients newly prescribed OOAs (136 males, 136 females) were entered into the 12-week, multi-site RCT after signing written consent. Hospice patients were ineligible. Patients were randomized to experimental (n = 137) and control (n = 135) groups, with experimental group receiving an automated phone adherence intervention and a Symptom Management Toolkit (SMT). Data were gathered through recruitment site screening, patient interviews, medical record audits (MRA), and obituary searches at 6 months post-enrollment. A multiple logistic regression model was used to test the effect of concurrent intravenous chemotherapy, age, sex, intervention group, OOA class, comorbidities, and emergency room and hospital visits on death. Hematologic patients (n = 26) were excluded as none died, resulting in multicollinearity. Results: Fifteen patients (6%) died during the 12 week study period, while 34 (14%) died during the 6 months after enrollment. ER visits ( p .02), cardiovascular disease ( p.05), and depression ( p .01) were significantly associated with death 6 months from enrollment. Fifty-seven (23%) patients reported visiting the ER and 68 (28%) patients had a hospital stay during the study period. Conclusions: As would be hypothesized, adverse events and comorbidities were associated with death in this RCT. Mortality was similar by intervention group. Behavioral trials, even those lasting six months, should estimate attrition rates considering death and/or entry into hospice. Adequate planning in sampling will be critical for success in these types of trials. Clinical trial information: NCT02043184.
Effect of free amino acids mix with medium triglycerides and Withania somnifera on cancer cachexia.
Authors: Gaddam Kalyan R , Shambaugh Shawn C. , Kanamori David E. , Rustagi Pradip K. , Ng Richard Kim-Thean , Bell Susana , Desai Ajay , Gorla Giridhar R. , Cartmell Alan D. , Patel Rishi
Published: May 2019

e23140

Background: Cancer cachexia is a multifactorial syndrome involving systemic inflammation, negative protein and energy balance, and involuntary loss of lean muscle mass. It not only adversely affects quality of life but also leads to poor responses to chemotherapy and reduced survival rates. Conventional nutritional support has not been successful in cancer cachexia and most commercially available formulas have shown little to no effect on cancer cachexia. This study assessed nutritional benefits of E2 Energy, an amino acid (AA) supplement powder enriched with branched-chain AAs, medium-chain triglycerides, and Withania somnifera, on body weight, lean muscle mass, and cancer-related piper fatigue score. Methods: This prospective, open-label preliminary feasibility study was conducted in patients receiving active treatment for cancer (e.g. chemotherapy, radiation, targeted therapy, or hormone therapy) with documented evidence of significant weight loss. Patients were evaluated at baseline and at the end of treatment (12 weeks) for lean muscle mass as measured by bioimpedance analysis, body weight, C-reactive protein (CRP), serum albumin, fatigue as measured by Piper Fatigue Scale (PFS), and proinflammatory cytokines (IL-1, IL-2, IL-6, and TNF-α). Being a pilot study, enrollment was restricted to approximately 30 patients with focus on descriptive statistics rather than formal tests of hypotheses. Results: We analyzed data of 15 patients who completed at least 6 weeks of treatment. Treatment with AA powder increased lean muscle mass in 12 (80%) patients. Similarly, PFS scores improved in 14 (93.33%) patients. Overall, in 6 patients (40%), body weight either remained stable or increased from baseline values. Six patients presented abnormal cytokine levels at baseline; however, their results at follow-up were unavailable, thus making interpretation inconclusive. Conclusions: Treatment with AA powder supplement may prevent loss in lean muscle mass, reduce fatigue, and curtail weightloss. However, these results must be substantiated in large well-designed (randomized) studies.
An observational study to evaluate the potential of Onlife to improve chemotherapy-induced peripheral neuropathy: Final results of the STEFANO trial.
Authors: Zaiss Matthias R. , Uhlig Jens , Zahn Mark-Oliver , Decker Thomas , Lehmann Helmar C. , Harde Johanna , Vannier Corinne , Hogrefe Cathrin , Marschner Norbert
Published: May 2019

e23143

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, long-term side effect of many antineoplastic agents and has a detrimental impact on patients (pts)’ quality of life and functional activities of daily living. Currently, preventive measures and treatment options for CIPN are quite limited. OnLife is a dietary supplement that contains a patented mixture of fatty acids with anti-inflammatory, neuroprotective and antinociceptive properties. Methods: The STEFANO study – an observational, prospective, two-cohort, multicenter study of dietary supplementation – was designed to evaluate the potential of OnLife to improve CIPN in adult pts with completed neo-/adjuvant chemotherapy and manifest CIPN (grade 1-3) (Cohort A: colon cancer, oxaliplatin-containing therapy; cohort B: breast cancer, paclitaxel therapy). Pts received OnLife for 3 months. The primary objective – assessment of changes in CIPN – was evaluated by comparing the severity of sensory and motor CIPN according to CTCAE v4.03 before, during and after treatment with OnLife. Secondary endpoints included patient-reported experience of symptoms and functional limitations related to CIPN. Descriptive statistics were used to analyze data. Results: In total, 75 breast cancer pts with paclitaxel-induced and 71 colon cancer pts with oxaliplatin-induced peripheral neuropathy, respectively, received OnLife. Based on physician-rated CTCAE grades, 21.3% of breast cancer pts and 12.7% of colon cancer pts had a sustained improvement of sensory CIPN after OnLife treatment. Concerning motor CIPN, the proportions were 12.0% and 9.9%, respectively. According to patient-reported outcomes, 45.3% of breast cancer pts and 23.9% of colon cancer pts had less symptoms and functional limitations related to sensory CIPN after OnLife treatment. Concerning motor CIPN, the proportions were 32.0% and 22.5%, respectively. Conclusions: STEFANO provides indications of the potential of OnLife to reduce severity of objective and subjective CIPN-related symptoms. Therefore, it is a promising agent to meet the unmet medical need of management options for patients with established CIPN. Clinical trial information: NCT03065478.
Physical activity platform to improve bone health in cancer survivors.
Authors: Skinner Cathy
Published: May 2019

TPS11632

Background: Cancer treatment-induced bone loss and the subsequent risk of fractures in both men and women is a significant burden on national health care. US cancer survivors will reach 18 million by 2022 and by 2025 and the projected burden of osteoporosis is $25.3B. Cancer patients treated with medications that lower hormone levels face an increased risk of fractures. Clinical studies report that moderate-intensity resistance exercises prevent a decline in bone health in female cancer survivors, and that strength training may reduce complications such as fatigue, muscle wasting, and bone loss. Unfortunately, only a small percentage of female cancer survivors engage in and adhere to a strength training exercise routine. Several factors account for this low level of engagement such as poor awareness of the benefits of exercise, lack of motivation, and the lack of affordable and easily accessible exercise programs designed for cancer survivors. Internet-based self-managed programs of exercises and guidance can potentially address these problems, and can be scaled for broader dissemination. Methods: The Thrivors platform seeks to shift the current paradigm of poor adherence to exercise by providing an affordable and accessible means of improving outcomes for cancer survivors. Thrivors plus Bone Health (Thrivors+BH), will be a first-of-its-kind offering of clinically validated bone health exercises that can be customized to a cancer survivor's pain and energy levels, with several novel interactive feedback features. The product has supportive modules for connecting with a community of other users, mindfulness training, nutritional advice and educational information. The Thrivors platform is scalable, device-agnostic, and allows analysis of de-identified usage data. The two versions of the platform will be deployed in a 20-week, two-arm randomized controlled trial of 50 breast cancer survivors. Adherence to exercise sessions (primary outcome) and platform usage will be measured by platform software, while user engagement (secondary outcomes) will be assessed by surveys. Differences between primary and secondary outcomes for the control and intervention groups will be evaluated. Usage statistics, motivational responses and user feedback will be used to further refine platform features and content. Clinical trial information: NCT03651037.
Prospective study of germline and somatic alterations for early onset lung cancer patients (EOLUNG MASTER protocol).
Authors: Jove Maria , Gausachs Mireia , Bosch-Barrera Joaquim , Carcereny Costa Enric , Teule Alex , Izquierdo Angel , Navarro Matilde , Palmero Ramon , Vilariño Noelia , Ruffinelli Jose Carlos , Sais Elia , Moran Teresa , Estival Anna , Fina Claudia , Brunet Joan , Capella Gabriel , Lazaro Conxi , Nadal Ernest
Published: May 2019

TPS9122

Background: Lung cancer (LC) is a rare disease among young adults. Polymorphisms in genes involved in carcinogenic metabolism of tobacco and/or xenobiotic metabolism have been identified in those patients. The growing use of next generation sequencing (NGS) unravelled germline mutations in genes associated with hereditary cancer in patients with LC. However, germline DNA mutations have not been systematically studied in young adults with LC. Early onset LC patients are likely to harbor actionable somatic mutations. Broad hybrid NGS can identify actionable genomic alterations in LC patients deemed driver negative by routine molecular analysis. Trial Design: This is a multicentre, prospective, single-cohort study to determine whether young patients with LC harbor germline mutations and to evaluate the impact of NGS using Foundation One platform on the therapeutic options and overall survival for this specific patient population. Major inclusion criteria: 1) patients already or newly diagnosed of non-small cell lung cancer at any stage at age < 51; 2) to have sufficient tumor sample to perform standard molecular diagnosis ( EGFR/ALK/ROS1/BRAF); 3) to provide written informed consent for the study. Methods: After signing the informed consent form, family history of cancer and smoking history will be collected and a peripheral blood sample will be obtained. Germline targeted sequencing will be carried out in our centre using a customized hereditary cancer panel (I2HCP) of 136 genes designed to cover the coding exons and intron-exon boundaries of genes associated with moderate or high risk of hereditary cancer. Patients with clinical criteria for hereditary cancer or harboring pathogenic or probably pathogenic germline alteration will be referred to the genetic counselling unit. Patients will follow the usual clinical pathway for biomarker analysis and in case of remaining tumour material it will be used for conducting comprehensive genomic profiling through Foundation One platform. When tumour material available will not be sufficient to perform NGS, a tumour re-biopsy will be considered. Enrolment begun on June 2018 and, to date, a total of 41 patients have been included in the study.
MS201944-0170: A phase IIa study to investigate the clinical activity and safety of avelumab in combination with cetuximab plus gemcitabine and cisplatin in patients with advanced squamous NSCLC.
Authors: Ciardiello Fortunato , Dols Manuel Cobo , Juan Vidal Oscar , Paz-Ares Luis G. , de Castro Carpeño Javier , Felip Enriqueta , Campelo Rosario Garcia , Losonczy Gyorgy , Szalai Zsuzsanna , Vicente David , Schröder Andreas , Beier Frank , Bhandge Prasad , Galffy Gabriella
Published: May 2019

TPS9123

Background: Preclinical studies have demonstrated that cetuximab plus chemotherapy results in immunogenic cell death and an increase in CD8+ T cells in the tumor microenvironment. Avelumab (an anti–PD-L1 antibody) has previously shown antitumor activity in NSCLC. We hypothesize that the combination of cetuximab with platinum-based chemotherapy and avelumab may have synergistic antitumor activity. Methods: This phase IIa, single-arm, multicenter study is investigating the clinical activity and safety of avelumab in combination with cetuximab plus gemcitabine and cisplatin in patients with advanced squamous NSCLC who are treatment naive in the advanced setting (NCT03717155). Eligibility criteria include histologically confirmed stage IV, metastatic or recurrent NSCLC with squamous histology, with no prior systemic therapy for metastatic NSCLC, no prior therapy with any antibody/drug targeting T-cell coregulatory proteins, and ECOG PS of 0 to 1. Patients with a tumor harboring an activating EGFR mutation or ALK rearrangement are excluded. Patients will receive doublet chemotherapy (cisplatin 75 mg/m2 on day 1, gemcitabine 1250 mg/m2 on days 1 and 8), cetuximab on days 1 (250 mg/m2) and 8 (500 mg/m2), and avelumab 800 mg on days 1 and 8 for a total of four 3-week cycles. Thereafter, avelumab (800 mg) and cetuximab (500 mg/m2) will be administered as maintenance treatment Q2W until disease progression, unacceptable toxicity, or withdrawal. Enrollment in a safety run-in, which will evaluate the safety and tolerability of avelumab in combination with cetuximab plus gemcitabine and cisplatin, is planned for the first 6 patients. Enrollment began on October 30, 2018. Study enrollment will continue until approximately 40 evaluable patients have been recruited. The primary endpoint is confirmed best overall response per RECIST 1.1 by investigator assessment. Secondary endpoints include safety (NCI CTCAE v5.0) and tolerability of the combination, duration of response, survival, and tumor biomarkers. The study is ongoing at sites in Hungary and Spain. Clinical trial information: NCT03717155.
CLARITY-BPA: Bisphenol A or Propylthiouracil on Thyroid Function and Effects in the Developing Male and Female Rat Brain
Authors: Bansal Ruby , Zoeller R Thomas
Published: May 2019

The CLARITY-BPA experiment, a large collaboration between the National Institute of Environmental Health Sciences, the National Toxicology Program, and the US Food and Drug Administration, is designed to test the effects of bisphenol A (BPA) on a variety of endocrine systems and end points. The specific aim of this subproject was to test the effect of BPA exposure on thyroid functions and thyroid hormone action in the developing brain. Timed-pregnant National Center for Toxicological Research Sprague-Dawley rats (strain code 23) were dosed by gavage with vehicle control (0.3% carboxymethylcellulose) or one of five doses of BPA [2.5, 25, 250, 2500, or 25,000 µg/kg body weight (bw) per day] or ethinyl estradiol (EE) at 0.05 or 0.50 µg/kg bw/d (n = 8 for each group) beginning on gestational day 6. Beginning on postnatal day (PND) 1 (day of birth is PND 0), the pups were directly gavaged with the same dose of vehicle, BPA, or EE. We also obtained a group of animals treated with 3 ppm propylthiouracil in the drinking water and an equal number of concordant controls. Neither BPA nor EE affected serum thyroid hormones or thyroid hormone‒sensitive end points in the developing brain at PND 15. In contrast, propylthiouracil (PTU) reduced serum T4 to the expected degree (80% reduction) and elevated serum TSH. Few effects of PTU were observed in the male brain and none in the female brain. As a result, it is difficult to interpret the negative effects of BPA on the thyroid in this rat strain because the thyroid system appears to respond differently from that of other rat strains.
The Low-Dose ACTH Test: Usefulness of Combined Analysis of Serum and Salivary Maximum Cortisol Response in Pediatrics
Authors: Vaiani Elisa , Lazzati Juan Manuel , Ramirez Pablo , Costanzo Mariana , Gil Silvia , Dratler Gustavo , Zaidman Veronica , Chaler Eduardo , Belgorosky Alicia
Published: May 2019

Context

The low-dose (1 µg) ACTH test (LDT) is widely used to assess central adrenal insufficiency (CAI); however, the serum cortisol cutoff value is controversial. Salivary cortisol (SC) may be a more accurate measurement for CAI.

Objective

To assess a new maximum cutoff value of serum cortisol after LDT in pediatric patients, taking into account serum and SC measurements.

Design and Setting

Prospective study in a pediatric tertiary referral center.

Working Hypothesis

The combined analysis of serum and SC response to LDT might improve LDT for CAI diagnosis.

Participant and Outcome Measurement

A total of 145 pediatric patients underwent LDT. Serum and SC levels were measured. A central adrenal sufficient (CAS) response was established according to the reference serum cortisol cutoff value of ≥497 nmol/L.

Results

The LDT study showed central adrenal sufficiency in 72 patients and CAI in 73 patients. Considering the lower quartile of maximum SC value (21 nmol/L) in the CAS group, an intermediate CAI (InCAI) group and a real CAI (RCAI) group were defined. Regarding the median maximum value of serum cortisol levels in the InCAI group, a new serum cortisol cutoff value of 450 nmol/L was established. Furthermore, 91% of the patients in the RCAI group were below this cutoff value.

Conclusion

The combined evaluation of maximum serum and SC levels to LDT might be useful to define an InCAI group and to avoid unnecessary hormone replacement therapy. However, rigorous patient follow-up is required
VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle
Authors: Figeac Nicolas , Mohamed Abdalla D. , Sun Congshan , Schönfelder Martin , Matallanas David , Garcia-Munoz Amaya , Missiaglia Edoardo , Collie-Duguid Elaina , De Mello Vanessa , Pobbati Ajaybabu V. , Pruller Johanna , Jaka Oihane , Harridge Stephen D. R. , Hong Wanjin , Shipley Janet , Vargesson Neil , Zammit Peter S. , Wackerhage Henning
Published: May 2019

VGLL proteins are transcriptional co-factors that bind TEAD family transcription factors to regulate events ranging from wing development in fly, to muscle fibre composition and immune function in mice. Here, we characterise Vgll3 in skeletal muscle. We found that mouse Vgll3 was expressed at low levels in healthy muscle but that its levels increased during hypertrophy or regeneration; in humans, VGLL3 was highly expressed in tissues from patients with various muscle diseases, such as in dystrophic muscle and alveolar rhabdomyosarcoma. Interaction proteomics revealed that VGLL3 bound TEAD1, TEAD3 and TEAD4 in myoblasts and/or myotubes. However, there was no interaction with proteins from major regulatory systems such as the Hippo kinase cascade, unlike what is found for the TEAD co-factors YAP (encoded by YAP1) and TAZ (encoded by WWTR1). Vgll3 overexpression reduced the activity of the Hippo negative-feedback loop, affecting expression of muscle-regulating genes including Myf5, Pitx2 and Pitx3, and genes encoding certain Wnts and IGFBPs. VGLL3 mainly repressed gene expression, regulating similar genes to those regulated by YAP and TAZ. siRNA-mediated Vgll3 knockdown suppressed myoblast proliferation, whereas Vgll3 overexpression strongly promoted myogenic differentiation. However, skeletal muscle was overtly normal in Vgll3-null mice, presumably due to feedback signalling and/or redundancy. This work identifies VGLL3 as a transcriptional co-factor operating with the Hippo signal transduction network to control myogenesis.
Comprehensive analysis of genes contributing to euryhalinity in the bull shark, Carcharhinus leucas; Na+-Cl− co-transporter is one of the key renal factors up-regulated in acclimation to low-salinity environment in bull sharks, but not in houndsharks, Triakis scyllium
Authors: Imaseki Itaru , Wakabayashi Midori , Hara Yuichiro , Watanabe Taro , Takabe Souichirou , Kakumura Keigo , Honda Yuki , Ueda Keiichi , Murakumo Kiyomi , Matsumoto Rui , Matsumoto Yosuke , Nakamura Masaru , Takagi Wataru , Kuraku Shigehiro , Hyodo Susumu
Published: May 2019

Most of the cartilaginous fishes live principally in seawater (SW) environments, while a limited number of species including the bull shark, Carcharhinus leucas, inhabit both SW and freshwater (FW) environments during their life cycle. Euryhaline elasmobranchs maintain high internal urea and ion levels even in FW environments, but little is known about the osmoregulatory mechanisms that enable them to maintain internal homeostasis in hypoosmotic environments. In the present study, we focused on the kidney because this is the only organ that can excrete excess water from the body in a hypoosmotic environment. We conducted a transfer experiment of bull sharks from SW to FW and performed differential gene expression analysis between the two conditions using RNA-seq. A search for genes up-regulated in the FW-acclimated bull shark kidney indicated that the expression of the Na+-Cl− cotransporter (NCC; Slc12a3) was ten times higher in the FW-acclimated fish compared to that in SW fish. In the kidney, apically-located NCC was observed in the late distal tubule and in the anterior half of collecting tubule where basolateral Na+/K+-ATPase was also expressed, implying that these segments contribute to NaCl reabsorption from the filtrate for diluting the urine. This expression pattern was not observed in the houndshark, Triakis scyllium, that had been transferred to 30% SW; this species cannot survive in FW environment. The salinity transfer experiment combined with a comprehensive gene screening approach demonstrates that NCC is a key renal protein that contributes to the remarkable euryhaline ability of the bull shark.
Dynamic optimization: search for absolute extrema
Authors: Орел Евгений , Orel Evgeniy , Орел Ольга , Orel Ol'ga
Published: May 2019

The book is intended for those who are interested in the search for global (absolute) extremum in the problems of optimal control and
adjacent sections of mathematics. This is the extreme required in most applications related to Economics, Finance, artificial intelligence and robotics. Considered as methods that use necessary and sufficient conditions for an extremum, direct methods of optimization. The book is provided with numerous examples and drawings. It will be of interest to mathematicians, specialists in business and engineering, as well as students studying models and methods of dynamic optimization.
Long-term financial policy of the organization
Authors: Карпова Елена , Karpova Elena , Усенко Анастасия , Usenko Anastasiya , Кочановская Ольга , Kochanovskaya Olga , Коновалов Александр , Konovalov Aleksandr
Published: May 2019

Consider the directions of the long-term financial policy of the organization, financial support, sources of financing, capital structure and dividend policy, planning and forecasting framework. Examples of business situations appropriate to the topics studied,there are questions forself-study, and a Glossary.
For university students studying in the fields of study "Economics" and "Management". It is interesting to teachers of economic universities, as well as employees of the financial services business organizations
Teaching about Leadership or Teaching through Leadership?
Authors: Seger Jan , Bergsten Urban
Published: May 2019

This article is based on experiences and convictions from teaching leadership to students on the university and college levels. Teaching through leadership rather than about leadership is advocated. Student learning and facilitator teaching are contrasted. Leadership is viewed more as a mutual relationship rather than certain personality traits of the leader. The importance of understanding group processes is stressed.
Influences of Theory and Practice in the Development of Servant Leadership in Students
Authors: Massey Jennifer , Sulak Tracey , Sriram Rishi
Published: May 2019

This paper explores the extent to which the leadership knowledge, skills, and abilities of upper-year student leaders on one private, United States college campus developed as a consequence of their education and experience as an extended orientation leader. Findings reveal that compared to leadership education in the classroom, leadership development is limited by experiences that do not include intentional reflection. We identify key elements in pedagogical frameworks that support and impede the leadership development of students and propose strategies to enhance the learning outcomes established for leadership development.
Cultivating Self-Awareness with Team-Teaching: Connections between Classroom Learning and Experiential Learning
Authors: Polk Denise M.
Published: May 2019

The Honors College program prepares leaders for the 21st century to become forces for positive change through problem-solving, scholarship, service, teamwork, and leadership. Its structure involves nine sequenced courses familiarizing students with challenges facing communities. Courses are team-taught by professors in different disciplines to highlight the diversity in applying concepts across contexts. This paper offers an examination of the connections for cultivating self-awareness through team-teaching in the classroom and experiential learning.
Outside the Comfort Zone: Strategies for Developing Emotionally Intelligent Leaders
Authors: Liepold Michael J. , Rasmussen Catherine M. , Boyce Kim , Poskas Denise Trudeau
Published: May 2019

A recent study of the Minnesota Agriculture and Rural Leadership (MARL) program set out to determine the relationship between andragogical program design and increased levels of emotional intelligence (EI). Members of two cohorts in the MARL leadership development program received different levels of focused effort, peer coaching, individual action plans, disorienting dilemmas, self-reflection, and training in the area of emotional intelligence. We examined four years of data, including participants’ results on the Bar-On Emotional Quotient Inventory (EQ-i) before and after undergoing leadership development training, as well as their individual reflections on the EI components of their training. The intention is that this research will encourage practices that seek to increase emotional intelligence in leaders.
Organizational Climate of the Association of Leadership Educators
Authors: Moore Lori , McKim Billy , Bruce Jackie
Published: May 2019

Without feedback from members and former members, professional organizations run the risk of being stalemated. This study sought to explore perceptions of current and former members of the Association of Leadership Educators (ALE) related to the organization and the climate within the organization. No statistical differences were found in the perceptions of dues paying and non-dues paying members related to the climate of ALE as measured by the Team Climate Inventory (TCI); however, perceptions of both groups were fairly neutral. Open-ended questions were asked to elaborate, enhance, and clarify findings. Five themes emerged as successes achieved by ALE including the members, the ALE annual conference, information and idea sharing, networking, and the Journal of Leadership Education. Five themes also emerged as challenges facing the organization including a lack of direction or identity, recruitment and retention issues, lack of cohesion, lack of communication, and lack of participation.
LEADERSHIP DEVELOPMENT: Three programs that maximize learning over time
Authors: Roupnel Servane , Rinfre Natalie , Grenier Jennifer
Published: May 2019

In order to respond to the many challenges that confront them, organizations must assist their leaders to develop their personal and professional strengths. The development of leaders and leadership involves more than just the development of knowledge and must become an integral part of the organizational culture so as to also develop know-how and soft skills. Accordingly, programs have been created that are based on collaborative learning and the contextualization of the various issues demanding resolution, all with a view to developing leadership capable of surpassing the limitations of current management methods. To demonstrate how these programs can influence leadership, this article proposes a theoretical review of leadership, viewed as an ongoing process and then presents three proven development programs: coaching, mentoring and action learning.
Modeling Youth Leadership: An Integration of Personality Development Theories and Ethics
Authors: Sherif Victoria
Published: May 2019

Although youth leadership has been well described within the literature, the dearth of theoretically derived models that specifically reflect ethics and comprehensive nature of youth development still remains. The purpose of this article is to synthesize the existing youth leadership research and theories of personality development to propose a model of youth leadership. The resulting model includes 5 major interconnected components, such as cognitive, socio-emotional, motivational, behavioral, and ethical. As part of the model, ethics is suggested as a core of youth leadership and its development. The model can be used to inform planning of contextually reflective leadership education, specific curriculum and developmental interventions.