Unlocking the Hidden Dimensions of Cancer Care: Cross-Cultural Adaptation and Feasibility Study of ESAS-FS, Assessing Spiritual Pain and Financial Distress in a Spanish-speaking Population with Advanced Cancer.

INTRODUCTION: Spiritual pain and financial distress are two important dimensions of cancer care that are often overlooked. Both dimensions can have a significant impact on the quality of life of patients with cancer and their families. METHODS: This study conducted a cross-cultural adaptation, feasibility study, and psychometric properties of the Edmonton Symptom Assessment System-Financial and Spiritual (ESAS-FS) in a Spanish-speaking population with advanced cancer. The ESAS-FS is a patient-reported outcome measure that assesses 12 symptoms, including spiritual pain and financial distress. RESULTS: In the cross-cultural adaptation process, the terms "spiritual pain" and "financial distress" were refined to "sufrimiento espiritual" and "preocupación por asuntos económicos" respectively, with strong professional consensus and high patients' acceptancy (relevant questions 80%, appropriate terms 91%). A cohort of 100 onco-hematologic patients revealed that 70% experienced spiritual pain (mean 2.9/10), while 49% reported financial distress (mean 2.2/10). Symptomatic analyses illustrated significant associations of spiritual pain with various symptoms like fatigue, drowsiness, and depression. Similarly, financial distress correlated notably with drowsiness, depression, and anxiety. Moreover, a distinct correlation was observed between spiritual pain and financial distress. CONCLUSION: The findings of this study suggest that the ESAS-FS is a valuable tool for assessing spiritual pain and financial distress in Spanish-speaking patients with advanced cancer. The tool can be used to identify patients who are experiencing these dimensions of distress and to provide them with appropriate care.

An analysis of the experiences of bereaved relatives and health care providers following palliative sedation: a study protocol for a qualitative international multicenter case study.

BACKGROUND: Patients at the end-of-life may experience refractory symptoms of which pain, delirium, vomiting and dyspnea are the most frequent. Palliative sedation can be considered a last resort option to alleviate one or more refractory symptoms. There are only a limited number of (qualitative) studies exploring the experiences of relatives of sedated patients and their health care professionals (HCPs). The aims of this study protocol are: 1) to elicit the experiences of bereaved relatives and health care professionals of patients treated with palliative sedation and 2) to explore the understanding of the decision-making process to start palliative sedation across care settings in 5 European countries. METHODS: This study protocol is part of the larger HORIZON 2020 Palliative Sedation project. Organisational case study methodology will be used to guide the study design. In total, 50 cases will be conducted in five European countries (10 per country). A case involves a semi-structured interview with a relative and an HCP closely involved in the care of a deceased patient who received some type of palliative sedation at the end-of-life. Relatives and health care professionals of deceased patients participating in a linked observational cohort study of sedated patients cared for in hospital wards, palliative care units and hospices will be recruited. The data will be analyzed using a framework analysis approach. The first full case will be analyzed by all researchers after being translated into English using a pre-prepared code book. Afterwards, bimonthly meetings will be organized to coordinate the data analysis. DISCUSSION: The study aims to have a better understanding of the experiences of relatives and professional caregivers regarding palliative sedation and this within different settings and countries. Some limitations are: 1) the sensitivity of the topic may deter some relatives from participation, 2) since the data collection and analysis will be performed by at least 5 different researchers in 5 countries, some differences may occur which possibly makes it difficult to compare cases, but using a rigorous methodology will minimize this risk.

Molecular analysis in cytological samples obtained by endobronchial or oesophageal ultrasound guided needle aspiration in non-small cell lung cancer.

INTRODUCTION: Cytological samples obtained by endobronchial ultrasound (EBUS) are capital for diagnosis, staging and molecular profile in non-small cell lung carcinoma (NSCLC). OBJECTIVE: To assess the success rate of complete, partial and individual of molecular analysis in samples obtained by EBUS-guided transbronchial needle aspiration (TBNA) and/or by oesophageal ultrasound-guided fine needle aspiration with an echobronchoscope (EUS-B-FNA) in patients with NSCLC. METHODS: Prospective study including 90 patients with non-squamous NSCLC, or non-smoking squamous. Cytological samples were classified into two groups. Group 1: PEN membrane slide and/or cell blocks for the determination of mutations of EGFR, KRAS, ERBB2 and BRAF. Group 2: silane coated slides or cell blocks for rearrangements of ALK, ROS1 and MET amplification. RESULTS: The success rate was 78.6% for 4 molecular alterations (EGFR, KRAS, ALK and ROS1), and 44% for 7 determinations. The individual success rate for EGFR was 97%, KRAS 96.3%, ALK 85%, ROS1 82.3%, ERBB2 71.4%, BRAF 67.7% and MET 81.1%. There were no significant differences (p=0.489) in the number of molecular analyses (1-3 vs. 4) in group 1, depending on the types of samples (cell block vs. PEN membrane slide vs. cell block and PEN membrane slide). CONCLUSIONS: In patients with NSCLC, the cytological material obtained by ultrasound-guided needle aspiration is sufficient for individual and partial molecular analysis in the vast majority of cases. Membrane slides such as cell blocks are valid samples for molecular analysis.

Evaluation of the intraoperative human papillomavirus test as a marker of early cure at 12 months after electrosurgical excision procedure in women with cervical high-grade squamous intraepithelial lesion: a prospective cohort study.

OBJECTIVE: To evaluate if the intraoperative human papillomavirus (IOP-HPV) test has the same prognostic value as the HPV test performed at 6 months after treatment of high-grade squamous intraepithelial lesion (HSIL) to predict treatment failure. DESIGN: Prospective cohort study. SETTING: Barcelona, Spain. POPULATION: A cohort of 216 women diagnosed with HSIL and treated with loop electrosurgical excision procedure (LEEP). METHODS: After LEEP, an HPV test was performed using the Hybrid Capture 2 system. If this was positive, genotyping was performed with the CLART HPV2 technique. The IOP-HPV test was compared with HPV test at 6 months and with surgical margins. MAIN OUTCOME MEASURE: Treatment failure. RESULTS: Recurrence rate of HSIL was 6%. There was a strong association between a positive IOP-HPV test, a positive 6-month HPV test, positive HPV 16 genotype, positive surgical margins and HSIL recurrence. Sensitivity, specificity, and positive and negative predictive values of the IOP-HPV test were 85.7, 80.8,24.0 and 98.8% and of the HPV test at 6 months were 76.9, 75.8, 17.2 and 98.0%. CONCLUSION: Intraoperative HPV test accurately predicts treatment failure in women with cervical intraepithelial neoplasia grade 2/3. This new approach may allow early identification of patients with recurrent disease, which will not delay the treatment. Genotyping could be useful in detecting high-risk patients. TWEETABLE ABSTRACT: IOP-HPV test accurately predicts treatment failure in women with CIN 2/3.

Impact of the baseline study with penile doppler ultrasound in patients with prostate cancer before radical prostatectomy. / Impacto del estudio basal con ecografía doppler en pacientes con cáncer de próstata previo a prostatectomía radical.

INTRODUCTION: Given the high prevalence of erectile dysfunction in male population between 40-70 years old and the effect of radical prostatectomy on this domain, it is important to perform a baseline study. MATERIAL AND METHODS: Prior radical prostatectomy, erectile function has been assessed prospectively in 112 prostate cancer patients using the erectile function (EF) domain of the International Index of Erectile Function (EF-IIEF), Erectile Hardness Score (EHS) and a penile doppler ultrasound (PDUS). Comorbidities and Charlson index were collected. The EORTC QLQ C-30 and PR-25 tests were administered. RESULTS: According to EF-IIEF questionnaire, 50.9% of patients showed normal EF and EHS grade 3-4 erection was achieved in the 75.9%. PDUS was normal only in 28.6% of patients and 51.8% showed arterial insufficiency. We found a significant association (P<.0001) between categorized EF-IIEF (normal, mild/moderate/severe) and the EHS value. Between PDUS (normal vs. pathologic) and EHS (3-4 vs. 1-2) statistically significant association (P=.005) was found. Just 35.3% of patients with EHS 3-4 showed normal PDUS. Correlation between the PDUS and the EF-IIEF (≥26 vs.<26) was statistically significant (P=.043). Moreover, only 38.6% of patients with EF-IIEF≥26 had a normal PDUS. CONCLUSIONS: In order to predict EF recovery after surgery, global assessment is required. Solely self-administered tests are not enough. In this baseline study, PDUS can play an important role.

Identification of oestrogen, progesterone receptor and human epidermal growth factor receptor 2 expression in mediastinal metastases of breast cancer obtained by endobronchial ultrasound-guided transbronchial needle aspiration.

BACKGROUND: In breast cancer patients, the expression statuses of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are crucial in the choice of treatment. Receptor expression in metastatic lesions can differ from the primary tumour. The aim of our study was to analyse the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to obtain samples allowing the identification of ER, PR and HER2 expression in patients with mediastinal metastases of breast cancer. PATIENTS AND METHODS: The clinical files of all patients with a final diagnosis of breast cancer mediastinal metastases diagnosed by EBUS-TBNA in our institution were retrospectively analysed. The ability of EBUS-TBNA to obtain samples that allowed hormone receptor and HER2 expression analysis was calculated. RESULTS: Twenty-four patients were included. ER, PR and HER2 assessments could be performed in 22, 20 and 22 patients, respectively. In 20 of the 24 patients it was possible to investigate all three types of receptor expression. In the remaining four cases, where ER, PR or HER2 expression tests could not be performed, it was due to a lack of tissue. In cases with adequate results for EBUS-TBNA and the primary tumour agreement was greater for ER (16/19) and HER2 (12/14) than PR (8/17). Based on receptor status, there was a change in the choice of treatment for five patients. CONCLUSION: In patients with breast cancer mediastinal metastases, ER, PR and HER2 expression can be assessed in samples obtained by EBUS-TBNA whenever a sufficient tissue sample is collected.

Integrated palliative care in Europe: a qualitative systematic literature review of empirically-tested models in cancer and chronic disease.

BACKGROUND: Integrated Palliative Care (PC) strategies are often implemented following models, namely standardized designs that provide frameworks for the organization of care for people with a progressive life-threatening illness and/or for their (in)formal caregivers. The aim of this qualitative systematic review is to identify empirically-evaluated models of PC in cancer and chronic disease in Europe. Further, develop a generic framework that will consist of the basis for the design of future models for integrated PC in Europe. METHODS: Cochrane, PubMed, EMBASE, CINAHL, AMED, BNI, Web of Science, NHS Evidence. Five journals and references from included studies were hand-searched. Two reviewers screened the search results. Studies with adult patients with advanced cancer/chronic disease from 1995 to 2013 in Europe, in English, French, German, Dutch, Hungarian or Spanish were included. A narrative synthesis was used. RESULTS: 14 studies were included, 7 models for chronic disease, 4 for integrated care in oncology, 2 for both cancer and chronic disease and 2 for end-of-life pathways. The results show a strong agreement on the benefits of the involvement of a PC multidisciplinary team: better symptom control, less caregiver burden, improvement in continuity and coordination of care, fewer admissions, cost effectiveness and patients dying in their preferred place. CONCLUSION: Based on our findings, a generic framework for integrated PC in cancer and chronic disease is proposed. This framework fosters integration of PC in the disease trajectory concurrently with treatment and identifies the importance of employing a PC-trained multidisciplinary team with a threefold focus: treatment, consulting and training.

Effects of dietary grape seed extract on growth performance, amino acid digestibility and plasma lipids and mineral content in broiler chicks.

Polyphenols are chemically and biologically active compounds. Grape seed extracts (GSEs) have been widely used as a human food supplement for health promotion and disease prevention. However, there is little information regarding its application in animal feeds. An experiment was conducted to investigate the effect of inclusion of GSE at 0.025, 0.25, 2.5 and 5.0 g/kg in a wheat soya bean control diet on growth performance, protein and amino acid (AA) digestibility and plasma lipid and mineral concentrations in broiler chickens at 21 days of age. Performance was not affected by dietary treatment except in the case of birds fed the diet with the highest GSE concentration, which showed a worsening of weight gain and feed conversion. Apparent ileal digestibility (AID) of protein was significantly reduced in the birds fed the highest concentration of GSE, which also had a reduction on the AID of arginine, histidine, phenylalanine, cystine, glutamic acid and proline compared with those fed control diet. The inclusion of graded concentration of GSE in the chicken diets caused a significant linear decrease in the concentrations of plasma copper, iron and zinc. Plasma cholesterol, triglycerides and lipoproteins (high-density lipoprotein, low-density lipoprotein and very-low-density lipoprotein) concentrations were not affected by dietary GSE. In conclusion, this study demonstrated that incorporation of GSE in chicken diets up to 2.5 g/kg had no adverse effect on growth performance or protein and AA digestibility. Feed conversion was reduced and growth rate was retarded, when chickens were fed 5 g/kg of GSE. This study also indicated that grape polyphenols reduce the free plasma minerals.

Effects of dietary polyphenol-rich grape products on intestinal microflora and gut morphology in broiler chicks.

Grapes have high amounts of phenolic compounds, which can modulate the gut activity as well as modify the structure and function of the gastrointestinal tract. The microbiological activity of avoparcin, grape pomace concentrate, and grape seed extract was evaluated in an in vitro study. An in vivo experiment was also conducted to study the effect of the inclusion of grape pomace concentrate and grape seed extract in the diet of broiler chicks on performance, intestinal microflora (by cultured and terminal restriction fragment length polymorphism methodology), and gut morphology at 21 d of age. Dietary treatments included an antibiotic-free diet (CON), a positive control (AVP; 50 mg/kg of avoparcin), and antibiotic-free diets containing grape pomace concentrate (GPC; 60 g/kg) or grape seed extract (GSE; 7.2 g/kg). Performance was not affected by dietary treatment except in the case of birds fed the GSE diet, which showed decreased weight gain. In the ileal content, birds fed CON and GSE diets had the highest populations of Lactobacillus. Compared with the CON diet, the AVP, GPC, and GSE diets increased the populations of Enterococcus and decreased the counts of Clostridium in the ileal content. In the cecal digesta, birds fed GPC and GSE diets had higher populations of Escherichia coli, Lactobacillus, Enterococcus, and Clostridium than birds in any other treatment group. Animals fed GPC and GSE diets showed a higher biodiversity degree than those fed control diets. The frequency of detection of several potential phenol-degrading bacteria as well as unidentified and uncultured organisms was increased in animals fed GPC and GSE diets. Birds fed the CON diet had longer villi and deeper crypt depth than birds in any other treatment group. The highest villi height:crypt depth ratio corresponded to birds fed GPC and AVP diets and the lowest to those fed CON and GSE diets. In conclusion, dietary polyphenol-rich grape products modify the gut morphology and intestinal microflora and increase the biodiversity degree of intestinal bacteria in broiler chicks.

Barriers to the development of palliative care in Western Europe.

UNLABELLED: The Eurobarometer Survey of the EAPC Task Force on the Development of Palliative Care in Europe is part of a programme of work to produce comprehensive information on the provision of palliative care across Europe. AIM: To identify barriers to the development of palliative care in Western Europe. METHOD: A qualitative survey was undertaken amongst boards of national associations, eliciting opinions on opportunities for, and barriers to, palliative care development. By July 2006, 44/52 (85%) European countries had responded to the survey; we report here on the results from 22/25 (88%) countries in Western Europe. ANALYSIS: Data from the Eurobarometer Survey were analysed thematically by geographical region and by the degree of development of palliative care in each country. RESULTS: From the data contained within the Eurobarometer, we identified six significant barriers to the development of palliative care in Western Europe: (i) lack of palliative care education and training programmes; (ii) lack of awareness and recognition of palliative care; (iii) limited availability of/knowledge about opioid analgesics; (iv) limited funding; (v) lack of coordination amongst services; and (vi) uneven palliative care coverage. CONCLUSION: Findings from the EAPC Eurobarometer Survey suggest that barriers to the development of palliative care in Western Europe may differ substantially from each other in both their scope and context and that some may be considered to be of greater significance than others. A number of common barriers to the development of the discipline do exist and much work still remains to be done in the identified areas. This paper provides a road map of which barriers need to be addressed.

[Coordinating efforts in complex clinical cases: added value of palliative care at a university teaching hospital]. / La coordinación de esfuerzos en casos clínicos complejos: un valor añadido de cuidados paliativos en un hospital universitario.

Palliative care is generally understood on caring for terminal patients in chronic settings but more recently these units are developing also in acute care settings or university hospitals as consultants teams. We report the case of a complex patient with rectal adenocarcinoma and four problems of difficult approach: uncontrolled neuropathic pain despite opioids treatment, systemic infection, depression with intense demoralisation and open surgery wound. We show the measures adopted and how an excellent inter-departmental collaboration under the co-ordination of palliative medicine consultant team helped to resolve the untenable situation.

The management of constipation in palliative care: clinical practice recommendations.

Constipation is one of the most common problems in patients receiving palliative care and can cause extreme suffering and discomfort. The aims of this study are to raise awareness of constipation in palliative care, provide clear, practical guidance on management and encourage further research in the area. A pan-European working group of physicians and nurses with significant experience in the management of constipation in palliative care met to evaluate the published evidence and produce these clinical practice recommendations. Four potentially relevant publications were identified, highlighting a lack of clear, practical guidance on the assessment, diagnosis and management of constipation in palliative care patients. Given the limited data available, our recommendations are based on expert clinical opinion, relevant research findings from other settings and best practice from the countries represented. Palliative care patients are at a high risk of constipation, and while general principles of prevention should be followed, pharmacological treatment is often necessary. The combination of a softener and stimulant laxative is generally recommended, and the choice of laxatives should be made on an individual basis. The current evidence base is poor and further research is required on many aspects of the assessment, diagnosis and management of constipation in palliative care.

Effect of grape pomace concentrate and vitamin E on digestibility of polyphenols and antioxidant activity in chickens.

Grape pomace provides a rich source of polyphenols that have the capacity to act as powerful antioxidants. An experiment was conducted to study the effect of inclusion of grape pomace concentrate (GPC) at levels of 15, 30, and 60 g/kg and alpha-tocopheryl acetate (200 mg/kg) in broiler chicks (21 to 42 d of age) on performance; digestive organ sizes; protein; fat; hydrolyzable polyphenol and condensed tannin digestibilities; the anti-oxidant activity of diet, serum, ileal content, and excreta; and the susceptibility to oxidation of breast meat during refrigerated storage. The inclusion of GPC did not affect the performance; the apparent ileal digestibility of CP; the relative abdominal fat, liver, pancreas, and spleen weight; and the relative intestinal length. Fat digestibility was reduced in birds fed control and GPC diets compared with birds fed vitamin E. Ileal and fecal digestibility of hydrolyzable polyphenols and condensed tannins reached values in a range of 56 to 73% and 14 to 47%, respectively. The GPC diets reduced ileal and fecal digestibility of hydrolyzable polyphenols. Antioxidant activity in GPC diet, ileal content, and excreta [2, 2-azinobis (3-ethilenzotiazolin)-6-sulfonate method] and GPC diet (ferric antioxidant power method) exhibited higher scavenging free radical capacity than control and vitamin E diets. The lipid oxidation in breast meat was lower in the birds fed the supplemented vitamin E diet than the control diet after 1, 4, and 7 d of refrigerated storage. Oxidative stability in breast meat at 1, 4, and 7 d of storage was equivalent in GPC diets compared with the vitamin E diet. In conclusion, the inclusion of GPC (up to 60 g/kg) did not impair chicken growth performance, digestive organ sizes, and protein digestibility. Hydrolyzable polyphenols were more bioavailable than condensed tannins. Antioxidant activity in diet, excreta, ileal content, and breast muscle were increased in GPC diets. The GPC supplementation was equally as effective in antioxidant potential as vitamin E. On the basis of these observations, we concluded that GPC could be a new source of antioxidant in animal nutrition.

Time-course of c-Jun N-terminal kinase activation after cerebral ischemia and effect of D-JNKI1 on c-Jun and caspase-3 activation.

The c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in ischemic brain injury. The d-retro-inverso form of c-Jun N-terminal kinase-inhibitor (D-JNKI1), a cell-permeable inhibitor of JNK, powerfully reduces neuronal death induced by permanent and transient ischemia, even when administered 6 h after the ischemic insult, offering a clinically relevant window. We investigated the JNK molecular cascade activation in rat cerebral ischemia and the effects of D-JNKI1 on this cascade. c-Jun activation starts after 3 h after ischemia and peaks at 6 h in the ischemic core and in the penumbra at 1 h and at 6 h respectively. The 6 h c-Jun activation peak correlates well with that of P-JNK. We also examined the activation of the two direct JNK activators, MAP kinase kinase 4 (MKK4) and MAP kinase kinase 7 (MKK7). MKK4 showed the same time course as JNK in both core and penumbra, reaching peak activation at 6 h. MKK7 did not show any significant increase of phosphorylation in either core or penumbra. D-JNKI1 markedly prevented the increase of P-c-Jun in both core and penumbra and powerfully inhibited caspase-3 activation in the core. These results confirm that targeting the JNK cascade using the TAT cell-penetrating peptide offers a promising therapeutic approach for ischemia, raising hopes for human neuroprotection, and elucidates the molecular pathways leading to and following JNK activation.

Effect of dietary grape pomace and vitamin E on growth performance, nutrient digestibility, and susceptibility to meat lipid oxidation in chickens.

Grape pomace (GP) is a source of polyphenols with powerful antioxidant capacity. An experiment was conducted to investigate the effect of inclusion of GP at levels of 5, 15, and 30 g/kg and alpha-tocopheryl acetate (200 mg/kg) in a corn-soybean basal diet on growth performance, protein and amino acid digestibilities; antioxidant activity of diet, serum and excreta, lipid oxidation of breast and thigh meats during refrigerated storage, and liver vitamin E concentration. Growth performance and protein and amino acid digestibilities were not affected among the different treatments. Total intake and digestibility of extractable polyphenols in the birds fed the GP diet were increased compared with birds fed supplemented and unsupplemented vitamin E diets. Antioxidant activity in vitamin E and GP diets and excreta exhibited higher scavenging free radical capacity than the control diet using 3-ethylbenzthiazoline-6-sulfonic acid and ferric reducing antioxidant power methods. Lipid oxidation (malondialdehyde concentration) in breast and thigh meats was lower in the birds fed the supplemented vitamin E diet than the control diet after 1, 4, and 7 d of refrigerated storage. Results showed a linear reduction of lipid oxidation in breast and thigh meats at 4 and 7 d with increasing content of GP in the diet. Oxidative stability in breast and thigh meats at 1, 4, and 7 d of storage was equivalent or less effective in GP diets compared with the vitamin E diet. A linear increase was observed in liver alpha-tocopherol concentration with increasing content of GP in the diet, but it was inferior to the supplemented vitamin E diet. In conclusion, the results showed that a dietary inclusion rate up to 30 g/kg of GP did not impair chickens growth performance and protein and amino acids digestibilities and increased antioxidant activity in diet and excreta. Grape pomace and vitamin E diets reduced the lipid oxidation of meat during refrigerated storage and increased liver alpha-tocopherol concentration, although these effects were greater, in some cases, by adding vitamin E to the diet.