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The high prevalence of insomnia in cancer patients leads to a significant reduction in the quality of life of those affected. A detailed record of symptoms therefore plays an essential role for further course of treatment. Which screening instruments enable identification of cancer patients with insomnia is the subject of this single-arm nonrandomized study. During the data collection period, cancer patients meeting the following criteria: self-reported tiredness and/or trouble falling or staying asleep or sleeping too much in an electronic patient-reported outcome measurement were enrolled. For further analysis, focus was placed on the Patient Health Questionnaire Depression Scale (PHQ-8), the Minimal Documentation System (MIDOS2) and the Insomnia Severity Index (ISI). Frequency, correlation, and variance analyses were conducted to identify likely predictors of insomnia. Our findings indicate a closer correlation between the screening question pertaining to sleep disorders and the ISI, compared to the question on tiredness and the ISI. The initial recording of sleep-related parameters plays an essential role for cancer patients in order to identify and treat modifiable factors as promptly as possible. For an initial assessment, we recommend asking about trouble falling or staying asleep or sleeping too much. [ABSTRACT FROM AUTHOR]

Purpose: Patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC) have a dismal prognosis. The best strategies in these patients remain elusive. Against this background, we report the clinical course of patients with BRAFV600E-mutant mCRC to retrieve the best treatment strategy. Patients and methods: Clinico-pathological data were extracted from the electronic health records. Kaplan–Meier method was used to estimate overall (OS) and progression-free survival (PFS). Objective response rate (ORR) was assessed according to RECIST 1.1. Results: In total, 51 patients were enrolled. FOLFOXIRI was administered to 12 patients; 29 patients received FOLFOX or FOLFIRI as first-line treatment. Median OS was 17.6 months. Median PFS with FOLFOXIRI (13.0 months) was significantly prolonged (HR 0.325) as compared to FOLFOX/FOLFIRI (4.3 months). However, this failed to translate into an OS benefit (p = 0.433). Interestingly, addition of a monoclonal antibody to chemotherapy associated with superior OS (HR 0.523). A total of 64.7% patients received further-line therapy, which included a BRAF inhibitor in 17 patients. Targeted therapy associated with very favourable OS (25.1 months). Conclusion: Patients with BRAFV600E-mutated mCRC benefit from the addition of an antibody to first-line chemotherapy. Further-line treatment including a BRAF inhibitor has a dramatic impact on survival. [ABSTRACT FROM AUTHOR]

Purpose: Systemic-inflammatory response parameters (SIR) are known prognostic markers in different tumour entities, but have not been evaluated in patients with iCCA treated with systemic chemotherapy. Therefore, we evaluated the impact of different SIR markers on the clinical course of patients with advanced iCCA treated at our center. Methods: SIR markers were retrospectively evaluated in 219 patients with iCCA at the West-German-Cancer-Center Essen from 2014 to 2019. Markers included neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), CRP, and the modified Glasgow-Prognostic-Score (mGPS), which were correlated with clinico-pathological findings, response to chemotherapy (ORR), progression-free (PFS) and overall survival (OS) using Kaplan–Meier analyses, and Cox proportional models. Results: Median overall survival (OS) of the entire cohort was 14.8 months (95% CI 11.2–24.4). Median disease-free survival (DFS) in 81 patients undergoing resection was 12.3 months (95% CI 9.7–23.1). The median OS from start of palliative CTX (OSpall) was 10.9 months (95% 9.4–14.6). A combined Systemic Inflammatory Score (SIS) comprising all evaluated SIR markers correlated significantly with ORR, PFS, and OSpall. Patients with a high SIS (≥ 2) vs. SIS 0 had a significantly inferior OSpall (HR 8.7 95% CI 3.71–20.38, p < 0.001). Multivariate analysis including known prognostic markers (ECOG, CA19-9, LDH, and N- and M-status) identified the SIS as an independent prognostic factor. Conclusions: Inflammatory markers associate with inferior survival outcomes in patients with iCCA. A simple SIS may guide treatment decisions in patients treated with systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The effect of the duration of an educational rotation presented at a palliative care unit on the palliative care knowledge gain and the increase of palliative care self-efficacy expectations are unclear. Methods: This national prospective multicenter pre–post survey conducted at twelve German University Comprehensive Cancer Centers prospectively enrolled physicians who were assigned to training rotations in specialized palliative care units for three, six, or twelve months. Palliative care knowledge [in %] and palliative care self-efficacy expectations [max. 57 points] were evaluated before and after the rotation with a validated questionnaire. Results: From March 2018 to October 2020, questionnaires of 43 physicians were analyzed. Physicians participated in a 3- (n = 3), 6- (n = 21), or 12-month (n = 19) palliative care rotation after a median of 8 (0–19) professional years. The training background of rotating physicians covered a diverse spectrum of specialties; most frequently represented were medical oncology (n = 15), and anesthesiology (n = 11). After the rotation, median palliative care knowledge increased from 81.1% to 86.5% (p <.001), and median palliative care self-efficacy expectations scores increased from 38 to 50 points (p <.001). The effect of the 12-month rotation was not significantly greater than that of the 6-month rotation. Conclusion : An educational rotation presented in a specialized palliative care unit for at least six months significantly improves palliative care knowledge and palliative care self-efficacy expectations of physicians from various medical backgrounds. [ABSTRACT FROM AUTHOR]

Purpose: Despite that early integration of palliative care is recommended in advanced cancer patients, referrals to outpatient specialised palliative care (SPC) frequently occur late. Well-defined referral criteria are still missing. We analysed indicators associated with early (ER) and late referral (LR) to SPC of an high volume outpatient unit of a comprehensive cancer center. Methods: Characteristics, laboratory parameters and symptom burden of 281 patients at first SPC referral were analysed. Timing of referral was categorized as early, intermediate and late (> 12, 3–12 and < 3 months before death). Ordinal logistic regression analysis was used to identify factors related to referral timing. Kruskal–Wallis test was used to determine symptom severity and laboratory parameter in each referral category. Results: LRs (50.7%) had worse scores of weakness, loss of appetite, drowsiness, assistance of daily living (all p < 0.001) and organisation of care (p < 0.01) in contrast to ERs. The mean symptom sum score was significantly higher in LRs than ERs (13.03 vs. 16.08; p < 0.01). Parameters indicative of poor prognosis, such as elevated LDH, CRP and neutrophil-to-lymphocyte ratio (NLR) (p < 0.01) as well as the presence of ascites (p < 0.05), were significantly higher (all p < 0.001) in LRs. In univariable analyses, psychological distress (p < 0.05) and female gender (p < 0.05) were independently associated with an ER. Conclusion: A symptom sum score and parameters of poor prognosis like NLR or LDH might be useful to integrate into palliative care screening tools. [ABSTRACT FROM AUTHOR]

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Purpose: Physical activity (PA) is recommended to improve advanced cancer patients' (ACP) physical functioning, fatigue, and quality of life. Yet, little is known about ACPs' attitude towards PA and its influence on fatigue and depressiveness over a longer period. This prospective, non-interventional cohort study examined ACPs' fatigue, depression, motivation, and barriers towards PA before and after 12 months of treatment among ACP Methods: Outpatients with incurable cancer receiving treatment at a German Comprehensive Cancer Center reporting moderate/severe weakness/tiredness during self-assessment via MIDOS II were enrolled. Fatigue (FACT-F), depression (PHQ-8), cancer-related parameters, self-assessed PA behavior, motivation for and barriers against PA were evaluated (T0). Follow-up data was acquired after 12 months (T1) using the same questionnaire. Results: At follow-up, fatigue (p=0.017) and depressiveness (p=0.015) had increased in clinical relevant extent. Physically active ACP did not show significant progress of FACT-F (p=0.836) or PHQ-8 (p=0.799). Patient-reported barriers towards PA remained stable. Logistic regression analyses identified motivation as a positive predictor for PA at both time points (T0, β=2.152, p=0.017; T1, β =2.264, p=0.009). Clinically relevant depression was a negative predictor for PA at T0 and T1 (T0, β=−3.187, p=0.044; T1, β=−3.521, p=0.041). Conclusion: Our findings emphasize the importance of psychological conditions in physical activity behavior of ACP. Since psychological conditions seem to worsen over time, early integration of treatment is necessary. By combining therapy approaches of cognitive behavioral therapy and exercise in interdisciplinary care programs, the two treatment options might reinforce each other and sustainably improve ACPs' fatigue, physical functioning, and QoL. Trial registration: German Register of Clinical Trials, DRKS00012514, registration date: 30.05.2017 [ABSTRACT FROM AUTHOR]

This document is an abstract from the Journal of Clinical & Translational Science. It includes summaries of three research projects. The first project examines the efficacy of FOXA2 as a biomarker in advanced prostate cancer samples. The second project assesses the labeling of drugs approved for Type 2 Diabetes for the inclusion of geriatric sub-population data. The third project investigates the effects of dihydroxyacetone (DHA), a combustion product of electronic cigarettes, on cardiac-specific injury through metabolic and mitochondrial imbalances. The abstract provides objectives, methods, and anticipated results for each project, highlighting the need for further research and consideration of diverse populations. [Extracted from the article]

Purpose: The prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains dismal. New cytotoxic agents such as nab-paclitaxel and liposomal irinotecan (nal-Iri) have extended the armamentarium of therapeutic options in the last years. Nowadays, sequential therapeutic strategies with moderately toxic chemotherapeutic protocols can be administered to the patients. However, prognostic and predictive biomarkers are still missing to identify those patients, which profit most from a "continuum of care" concept rather than receiving intensive first-line protocols such as FOLFIRINOX. To this end, we retrospectively evaluated the impact of the systemic inflammation as one essential hallmark of cancer in patients with advanced PDAC treated with sequential systemic. Methods: A cohort of 193 PDAC patients treated at our center from January 2005 to August 2011 were retrospectively evaluated for the following systemic inflammatory response (SIR) markers: neutrophil–lymphocyte ratio (NLR), lymphocyte–monocyte ratio (LMR) C-reactive protein (CRP), and the modified Glasgow Prognostic Score (mGPS). SIR markers were correlated with clinico-pathological findings, response to chemotherapy and overall survival (OS) using Kaplan–Meier curves and Cox proportional models. Results: All evaluated SIR markers were significantly associated with OS in patients with metastatic disease but not in patients with locally advanced PDAC. Interestingly, all SIR markers were only prognostic in patients not receiving antibiotics as surrogate marker for systemic bacterial infections. Based on the evaluated SIR markers, we propose a new Systemic Inflammation Score (SIS), which significantly correlated with reduced OS (HR: 3.418 (1.802–6.488, p < 0.001)) and the likelihood of receiving further-line systemic therapies (p = 0.028). Conclusion: Routinely assessed SIR biomarkers have potential to support therapeutic decision making in patients with metastatic PDAC. [ABSTRACT FROM AUTHOR]

Objective: In addition to question prompts for information transfer, we also used prompts to facilitate the expression of emotions. Our aim was to investigate how a question prompt list (QPL) is accepted by patients and whether it enhances interactional empowerment of the patients in the consultation with the radio-oncological treatment team before the beginning of radiotherapy.Methodology: Adult cancer patients before the beginning of radiotherapy were randomly assigned to the intervention group (IG) or control group (CG). The patients in the IG received a QPL with predefined subsets and subject areas. After the physician's consultation, both groups completed a self-developed, content validated questionnaire on interactional empowerment. The IG evaluated the QPL using a self-developed instrument.Result: A total of 279 adult cancer patients participated in the study (IG n = 139/CG n = 140). The participants of the IG reported a significantly higher interactional empowerment compared with those of the CG (t(277) = - 2.71, p = .007, 95% CI [- 1.61, - 0.26], d = 0.29). 60.4% of the IG agreed "rather" or "very" that they used the QPL in consultation with the medical team.Conclusion: The QPL used in the consultation improved the self-assessed competence for interaction with the medical team and strengthened the interactional empowerment. The QPL was well accepted by the patients and is to be introduced into a routine as a practicable and simple instrument in the future. The support of patients in addressing concerns and fears is an important innovation. [ABSTRACT FROM AUTHOR]

Background: In order to counteract fatigue, physical activity (PA) is recommended for all stages of cancer. However, only few advanced cancer patients (ACP) are physically active. Quantitative data with high numbers of ACP reporting barriers to PA are missing. This study aimed to identify barriers to PA in ACP with tiredness/weakness and investigate their motivation towards it. Methods: Outpatients with metastatic cancer receiving cancer care at a German Cancer Center reporting moderate/severe tiredness/weakness during self-assessment (MIDOS II) were enrolled. We assessed Fatigue-(FACF-F) and Depression (PHQ8) Scores, demographics, cancer-specific parameters, motivation for PA, physical, psychological and social barriers. Results: 141 of 440 eligible patients (32.0%) with different diagnoses agreed to participate. Patients frequently reported "I feel weakened due to my tumor therapy" (n = 108; 76.6%), physical symptoms (tiredness, weakness, dyspnea, joint-problems, pain, nausea [n = 107; 75.9%]) and fatigue (n = 99; 70.2%) as barriers to PA. However, no significant group differences regarding these barriers were found between physically active and inactive patients. Social barriers were rarely chosen. Motivated patients were 5.6 times more likely to be physically active (p < 0.001), also motivation turned out to be the strongest predictor for a physically active behavior (β = 1.044; p = 0.005). Motivated attitude towards PA was predicted by fatigue (β = − 2.301; p = 0.008), clinically relevant depression (β = − 1.390, p = 0.039), knowledge about PA and quality of life (QoL) (β = 0.929; p = 0.002), PA before diagnosis (β = 0.688; p = 0.005 and Interest in exercise program (β = 0.635; p = 0.008). Conclusion: "I feel weakened due to my tumor therapy" is the most reported barrier to PA among both, physically and inactive patients. Motivation for PA is the strongest predictor of performing PA. Interest in PA, knowledge about PA/QoL and PA before diagnosis are main predictors of a motivated attitude. Absence/presence of social barriers did not associate with motivation, fatigue and depression proved to be a negative predictor. Programs including information, motivational counseling and individualized training should be offered for ACP to overcome barriers and reduce fatigue. Trial registration: German Register of Clinical Trials DRKS00012514, registration date: 30.5.2017. [ABSTRACT FROM AUTHOR]

The parsnip webworm, Depressaria pastinacella, is restricted to two hostplant genera containing six structurally diverse furanocoumarins. Of these, imperatorin is detoxified by a specialized cytochrome P450, CYP6AB3. A previous whole‐larva transcriptome analysis confirmed the presence of nine transcripts that belong to the CYP6AE subfamily. Here, by examining midgut‐specific gene expression patterns we determined that CYP6AE89 transcripts were highly expressed and furanocoumarin‐inducible. Computer docking and energy‐minimization of a CYP6AE89 model with all six furanocoumarins showed that 5‐methoxylated bergapten and 8‐methoxylated xanthotoxin had the smallest distances from the heme to the proton‐donor residue in the catalytic I‐helix, and that the 5,8‐dimethoxylated isopimpinellin and bergapten had the smallest energy‐minimized distance from the heme oxygen to the furan ring double bond. To evaluate this prediction, we expressed the CYP6AE89 protein in an Escherichia coli system, and used it to detect high catalytic activity against the two mono‐methoxylated linear furanocoumarins – bergapten and xanthotoxin – and weak activity against isopimpinellin. Thus, CYP6AE89, like CYP6AB3, is probably specialized for detoxifying only a subset of hostplant furanocoumarins. A maximum‐likelihood tree built with six representative lepidopterans with manually annotated cytochrome P450s shows that CYP6AE89 may have evolved much faster than the other CYP6AE proteins, possibly indicative of host selection pressure. [ABSTRACT FROM AUTHOR]

Objectives: Rehabilitation for patients with rheumatic diseases improves both illness representations (IR) and clinical outcomes such as pain and physical functioning (PF). However, it is unclear whether IR may affect and, in turn, are affected by pain and PF. In this study, we examined both between-person associations and within-person associations between IR and pain/PF over time on three measurement occasions. Furthermore, cross-lagged relationships were examined. Design and main outcome measures: This secondary analysis is based on data from N = 186 patients with rheumatic diseases. Data on pain, PF and IR were assessed using self-report questionnaires at the beginning, the end and three months after a 3-week inpatient rehabilitation. Methods: To separate between- and within-person level, data were analysed using random-intercept cross-lagged panel models. Results: On both the between-person level (r = |0.21| − |0.44|) and the within-person level (r = |0.15| − |0.46|), pain and PF were related to cognitive and emotional IR. In addition, we found within-person bidirectional cross-lagged effects between emotional IR and PF. Conclusion: IR show complex relationships with pain and PF. Improving PF might improve subsequent illness-related emotional distress and vice versa. [ABSTRACT FROM AUTHOR]

Introduction: Patients (pts) with locally advanced (LAPC) or metastatic pancreatic ductal adenocarcinoma (mPDAC) have a dismal prognosis. Recently, new combination chemotherapies such as FOLFIRINOX and nab-paclitaxel/gemcitabine have demonstrated superiority over gemcitabine monotherapy. However, a substantial proportion of pts cannot tolerate these intensive front-line protocols. Moreover, the long-term superiority of multiagent protocols over less intensive strategies remains to be shown. To provide a benchmark for future studies, we analyzed the outcome of patients with LAPC or mPDAC treated at the West German Cancer Center before the FOLFIRINOX/nab-paclitaxel + gemcitabine era.Methods: This retrospective analysis included 201 consecutive pts with LAPC and mPDAC treated between 2007 and 2011. Efficacy parameters were correlated with type of chemotherapy, number of treatment lines and clinicopathological parameters.Results: Gemcitabine monotherapy was given as first-line therapy in 51.1%, whereas 48.9% received combination chemotherapies such as gemcitabine/oxaliplatin or FOLFOX. Patients received a median of two lines of treatment, with 54.8% receiving second-line and 37.9% receiving third- and further-line therapies. There was no significant difference between gemcitabine monotherapy and combination therapies. Despite moderate activity of first-line treatment, median overall survival for LAPC was 11.3 months and 8.7 months for mPDAC. Multivariate analysis identified age and number of treatment lines as prognostic markers.Conclusion: The long-term outcome of unselected pts with LAPC and mPDAC treated before the introduction of aggressive multiagent chemotherapy protocols compares favorably with the results of contemporary benchmark trials. This suggests a multifactorial benefit from interdisciplinary care provided over sequential treatment lines at high volume expert centers. [ABSTRACT FROM AUTHOR]

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In insects, cytochrome P450 monooxygenases (P450s) contribute to phytochemical and pheromone clearance in chemoreception and xenobiotic detoxification in food processing. In eusocial species, P450 expression varies with anatomy and age-related behaviour. Adult honeybees ( Apis mellifera) possess appendages differentially equipped for chemoreception; antennae and prothoracic and mesothoracic legs assess food and pheromone signals whereas metathoracic legs transport pollen over long distances. Newly eclosed bees and nurses remain in the hive and neither gather nor process food, whereas foragers collect pollen and nectar, thereby encountering phytochemicals. To understand the functions of cytochrome P450, family 4, subfamily G, polypeptide 11 ( CYP4G11) in the honeybee genome, we compared its expression relative to worker age and task to expression of cytochrome P450, family 9, subfamily Q, polypeptides ( CYP9Qs) known to metabolize xenobiotics. That CYP4G11 is highly expressed in forager antennae and legs, with highest expression in prothoracic and mesothoracic legs, is consistent with chemosensory perception, whereas weak expression of CYP4G11 in nurses suggests that it may process primarily exogenous rather than endogenous chemical signals. By contrast, and consistent with xenobiotic detoxification, the three CYP9Q transcripts were almost undetectable in newly eclosed workers and highest in foragers, with maximal expression in the metathoracic legs that closely contact pollen phytochemicals. These CYP4G11 expression patterns suggest a role in processing environmental signals, particularly those associated with food. [ABSTRACT FROM AUTHOR]

Cobalt oxide nanomaterials show high activity in several catalytic reactions thereby offering the potential to replace noble metals in some applications. We have developed a well-defined model system for partially reduced cobalt oxide materials aiming at a molecular level understanding of cobalt-oxide-based catalysis. Starting from a well-ordered Co3O4(111) film on Ir(100), we modified the surface by deposition of metallic cobalt. Growth, structure, and adsorption properties of the cobalt-modified surface were investigated by scanning tunneling microscopy (STM), low-energy electron diffraction (LEED), and infrared reflection absorption spectroscopy (IRAS) using CO as a probe molecule. The deposition of a submonolayer of cobalt at 300 K leads to the formation of atomically dispersed cobalt ions distorting the surface layer of the Co3O4 film. Upon annealing to 500 K the Co ions are incorporated into the surface layer forming ordered two-dimensional CoO islands on the Co3O4 grains. At 700 K, Co ions diffuse from the CoO islands into the bulk and the ordered Co3O4(111) surface is restored. Deposition of larger amounts of Co at 300 K leads to formation of metallic Co aggregates on the dispersed cobalt phase. The metallic particles sinter at 500 K and diffuse into the bulk at 700 K. Depending on the degree of bulk reduction, extended Co3O4 grains switch to the CoO(111) structure. All above structures show characteristic CO adsorption behavior and can therefore be identified by IR spectroscopy of adsorbed CO. [ABSTRACT FROM AUTHOR]

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Background:We sought to examine whether mitotic count (MC) and the amount of viable tumour (VT) following neoadjuvant systemic chemotherapy (SC) for primary, localised, high-grade soft tissue sarcoma (STS) correlate with prognosis.Methods:Retrospective analysis of 57 patients who underwent SC involving a combination of an anthracycline and an alkylating agent, followed by surgical resection between 2001 and 2011.Results:The amount of VT after chemotherapy was significantly associated with disease-specific survival (DSS) and event-free survival (EFS). Patients with <10% VT had a DSS of 94% at 5 years, compared with 61% for patients with ⩾10% VT (P=0.033); EFS was 75%, compared with 48% (P=0.030). Patients with an MC of ⩾20/10 high power fields (HPF) after chemotherapy had a significantly lower DSS (33% vs 84% at 5 years, P<0.001) and EFS (40% vs 63% at 5 years, P=0.019) than patients with an MC of <20/10 HPF.Conclusions:The MC and the amount of VT after neoadjuvant therapy for primary, localised, high-grade STS appear to correlate with prognosis. If these results are validated prospectively, then they could provide a rational for the design of neoadjuvant treatment modification/escalation studies, analogue to the EURAMOS-1 trial for bone sarcomas. [ABSTRACT FROM AUTHOR]

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Copyright of Der Schmerz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)