Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity.

Diet-derived nutrients are inextricably linked to human physiology by providing energy and biosynthetic building blocks and by functioning as regulatory molecules. However, the mechanisms by which circulating nutrients in the human body influence specific physiological processes remain largely unknown. Here we use a blood nutrient compound library-based screening approach to demonstrate that dietary trans-vaccenic acid (TVA) directly promotes effector CD8+ T cell function and anti-tumour immunity in vivo. TVA is the predominant form of trans-fatty acids enriched in human milk, but the human body cannot produce TVA endogenously1. Circulating TVA in humans is mainly from ruminant-derived foods including beef, lamb and dairy products such as milk and butter2,3, but only around 19% or 12% of dietary TVA is converted to rumenic acid by humans or mice, respectively4,5. Mechanistically, TVA inactivates the cell-surface receptor GPR43, an immunomodulatory G protein-coupled receptor activated by its short-chain fatty acid ligands6-8. TVA thus antagonizes the short-chain fatty acid agonists of GPR43, leading to activation of the cAMP-PKA-CREB axis for enhanced CD8+ T cell function. These findings reveal that diet-derived TVA represents a mechanism for host-extrinsic reprogramming of CD8+ T cells as opposed to the intrahost gut microbiota-derived short-chain fatty acids. TVA thus has translational potential for the treatment of tumours.

Exceptional tumour responses to fasting-mimicking diet combined with standard anticancer therapies: A sub-analysis of the NCT03340935 trial.

BACKGROUND: Cyclic fasting or calorie-restricted, low-carbohydrate, low-protein diets, collectively referred to as fasting-mimicking diets (FMDs), demonstrated additive or synergistic antitumour effects when combined with chemotherapy, targeted therapies, or immunotherapy in several preclinical in vivo models, including murine models of breast cancer, lung cancer, and colorectal cancer. However, no data on the antitumour efficacy of cyclic FMD in patients with cancer have been published so far. Here, we aim at reporting on patients with advanced cancer achieving complete and long-lasting tumour remissions with cyclic FMD in combination with standard anticancer therapies in the context of the phase Ib NCT03340935 trial. PATIENTS AND METHODS: The NCT03340935 trial enrolled 101 patients with different tumour types, and it showed that a severely calorie-restricted FMD regimen is safe and feasible in patients with cancer receiving concomitant standard-of-care antineoplastic therapies. In addition, cyclic FMD resulted in positive metabolic and immunologic modifications, thus recapitulating the biological effects that in preclinical models were found to mediate the antitumour effects of fasting/FMD. RESULTS: Of the 101 patients enrolled in the NCT03340935 trial, we identified five patients with advanced, poor prognosis solid neoplasms (n = 1: extensive stage small cell lung cancer; n = 1: metastatic pancreatic adenocarcinoma; n = 1: metastatic colorectal cancer; n = 2: metastatic triple-negative breast cancer), who achieved complete and long-lasting tumour responses when treated with a combination of cyclic FMD and standard systemic treatments in the context of the NCT03340935 trial. CONCLUSION: These excellent responses prompt the initiation of clinical trials to investigate cyclic FMD in combination with standard antitumour therapies in specific clinical contexts.

Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations.

The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate diet regimen that mimics the metabolism of the fasting state to induce the production of ketone bodies. The KD has long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy and has increasingly garnered research attention rapidly in the past decade, subject to emerging evidence of the promising therapeutic potential of the KD for various diseases, besides epilepsy, from obesity to malignancies. In this review, we summarize the experimental and/or clinical evidence of the efficacy and safety of the KD in different diseases, and discuss the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels. We emphasize that the KD may function through multiple mechanisms, which remain to be further elucidated. The challenges and future directions for the clinical implementation of the KD in the treatment of a spectrum of diseases have been discussed. We suggest that, with encouraging evidence of therapeutic effects and increasing insights into the mechanisms of action, randomized controlled trials should be conducted to elucidate a foundation for the clinical use of the KD.

Leucine-Rich Diet Improved Muscle Function in Cachectic Walker 256 Tumour-Bearing Wistar Rats.

Skeletal muscle atrophy occurs in several pathological conditions, such as cancer, especially during cancer-induced cachexia. This condition is associated with increased morbidity and poor treatment response, decreased quality of life, and increased mortality in cancer patients. A leucine-rich diet could be used as a coadjutant therapy to prevent muscle atrophy in patients suffering from cancer cachexia. Besides muscle atrophy, muscle function loss is even more important to patient quality of life. Therefore, this study aimed to investigate the potential beneficial effects of leucine supplementation on whole-body functional/movement properties, as well as some markers of muscle breakdown and inflammatory status. Adult Wistar rats were randomly distributed into four experimental groups. Two groups were fed with a control diet (18% protein): Control (C) and Walker 256 tumour-bearing (W), and two other groups were fed with a leucine-rich diet (18% protein + 3% leucine): Leucine Control (L) and Leucine Walker 256 tumour-bearing (LW). A functional analysis (walking, behaviour, and strength tests) was performed before and after tumour inoculation. Cachexia parameters such as body weight loss, muscle and fat mass, pro-inflammatory cytokine profile, and molecular and morphological aspects of skeletal muscle were also determined. As expected, Walker 256 tumour growth led to muscle function decline, cachexia manifestation symptoms, muscle fibre cross-section area reduction, and classical muscle protein degradation pathway activation, with upregulation of FoxO1, MuRF-1, and 20S proteins. On the other hand, despite having no effect on the walking test, inflammation status or muscle oxidative capacity, the leucine-rich diet improved muscle strength and behaviour performance, maintained body weight, fat and muscle mass and decreased some protein degradation markers in Walker 256 tumour-bearing rats. Indeed, a leucine-rich diet alone could not completely revert cachexia but could potentially diminish muscle protein degradation, leading to better muscle functional performance in cancer cachexia.

Estudio en vida real de un suplemento oral enriquecido con ácidos grasos w-3 en pacientes ambulatorios oncológicos: efecto sobre la calidad de vida y los parámetros nutricionales / Real-world study in oncological outpatients of an oral supplement enriched with w-3 fatty acids — effect on quality of life and nutritional parameters

Antecedentes: los pacientes oncológicos son un grupo de alto riesgo nutricional. Los suplementos orales nutricionales (SON) pueden ayudar a mejorar su situación nutricional. Objetivo: el objetivo de nuestro estudio fue evaluar en un estudio en vida real la efectividad sobre los parámetros nutricionales y la calidad de vida de un SON enriquecido con ω-3 en pacientes ambulatorios oncológicos. Material y métodos: se reclutaron 35 pacientes oncológicos ambulatorios que recibieron 2 SON al día. Se realizaron: valoración bioquímica y antropométrica, impedanciometría, encuesta nutricional, test Malnutrition Universal Screening Tool (MUST) y test de calidad de vida EQ5D, antes y a los 3 meses de intervención. Resultados: la edad media fue de 65,4 ± 10,7 años (18 mujeres/17 hombres). La cumplimentación media del grupo fue de un 81,7 ± 7,2 %. Durante la intervención aumentaron los niveles de proteínas totales (1,5 ± 0,2 g/dl; p = 0,01), albúmina (0,9 ± 0,1 mg/dl; p = 0,04) y transferrina (53,9 ± 21,1 mg/dl; p = 0,02). Al inicio del estudio, un 100 % de los pacientes presentaban en el test MUST la categoría de alto riesgo nutricional. Tras la intervención, un 34,3 % (n = 12) presentaban la categoría de bajo riesgo nutricional, un 51,4 % (n = 18) presentaban en el test MUST la categoría de moderado riesgo nutricional, y solo un 14,3 % (n = 5) presentaban la categoría de alto riesgo nutricional; previamente, el 100 % de los pacientes tenían la categoría alto riesgo (p = 0,02). La puntuación total del test de calidad de vida aumentó significativamente (0,51 ± 0,06 vs. 0,84 ± 0,03 puntos; p = 0,01), mejorando cualitativamente las 5 dimensiones. Conclusiones: la utilización de un SON enriquecido con ω-3 en pacientes oncológicos ambulatorios en condiciones de vida real muestra un efecto beneficioso sobre los parámetros nutricionales y la calidad de vida. (AU)

Background: cancer patients are a group at high nutritional risk. Oral nutritional supplementation (ONS) can improve nutritional status. Objective: the objective of our study was to evaluate the effectiveness on nutritional parameters and quality of life of a ω-3-enriched ONS in oncology outpatients in a real-world study. Material and methods: a total of 35 outpatient cancer patients who received 2 ONS per day were recruited. Chemistry, anthropometric, impedance measurement, nutritional survey, malnutrition universal screening tool (MUST) test, and EQ5D quality of life test were all used before and after 3 months of intervention. Results: mean age was 65.4 ± 10.7 years (18 females/17 males). Mean completion of the group was 81.7 ± 7.2 %. During the intervention, total protein (1.5 ± 0.2 g/dL; p = 0.01), albumin (0.9 ± 0.1 mg/dL; p = 0.04), and transferrin (53.9 ± 21.1 mg/dL; p = 0.02) levels increased. At the beginning of the study, 100 % of the patients were in the high nutritional risk category according to MUST. After the intervention, 34.3 % (n = 12) were in the low nutritional risk category, 51.4 % (n = 18) in the moderate nutritional risk category, and only 14.3 % (n = 5) in the category of high nutritional risk; previously, 100 % of patients had high nutritional risk (p = 0.02). The total score in the quality of life test increased significantly (0.51 ± 0.06 vs 0.84 ± 0.03 points; p = 0.01), with improvement in 5 dimensions. Conclusions: the use of a ω-3-enriched ONS in a real-world study with cancer outpatients showed a beneficial effect on nutritional parameters and quality of life. (AU)

Perioperative NSAIDs and Long-Term Outcomes After cancer Surgery: a Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: This review investigated the use of perioperative non-steroidal anti-inflammatory drugs (NSAIDs) and long-term outcomes in cancer surgery patients, and whether this is dependent on cancer type, type of NSAID and timing of administration. FINDINGS: Perioperative NSAID use was found to be associated with longer disease-free survival (hazard ration, HR = 0.84 (95% CI, 0.73-0.97)) and overall survival (HR = 0.78 (95% CI, 0.64-0.94)). No difference was found between different types of NSAID for disease-free survival, although in overall survival ketorolac use was significant (HR = 0.63 (95% CI, 0.42-0.95)). Analysis on the timing of NSAID administration found no subgroup to be associated with cancer outcomes. The cancer-type analysis found an association with outcomes in breast and ovarian cancers. However, the level of certainty remains very low, mostly due to the heterogeneity and the retrospective nature of most studies. Perioperative NSAID use may be associated with increased disease-free and overall survival after cancer surgery. This may be dependent on the type of cancer and type of NSAID, and further research is needed to support this. These data may inform future prospective trials, which are needed to determine the clinical impact, as well as optimal NSAID regimen.

Redox regulation by carotenoids: Evidence and conflicts for their application in cancer.

Carotenoids have been constantly investigated since the early fifty for their chemical, biochemical and biological properties being presence in foods. Among the more than 1100 carotenoids synthesized by plants and microorganisms, approximately 50 are present in the human diet, and about 20 can be detected in human blood and tissues. Review articles that discuss the anticancer and cancer preventing activity of phytochemicals have often in common the difficulty to find a coherency between the results deriving from experimental studies and the controversial or weak clinical indications arising from epidemiological and interventional studies. In this scenario, the class of carotenoids does not represent an exception. In fact, according with World Cancer Research Fund, strong evidence exists that high-dose supplementation of ß-carotene increases the risk of lung cancer, while for other types of cancer, the protective or harmful effects of food-containing carotenoids or carotenoid supplements have been considered limited, suggestive or unlikely. The analysis of the mechanistic evidence is complicated by the double nature of carotenoids being molecules acting either as antioxidant or pro-oxidant compounds. The present review analyzes the ambiguity and the unexpected results deriving from the epidemiological and interventional studies and discusses how the effects of carotenoids on cancer risk can be explained by understanding their capacity to modulate the cellular antioxidant response, depending on the concentration applied and the cellular metabolism. In the final part, a new global approach is proposed to study the contribution of carotenoids, but also of other phytochemicals, to disease prevention, including cancer.

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies.

As a multifactorial disease, treatment of cancer depends on understanding unique mechanisms involved in its progression. The cancer stem cells (CSCs) are responsible for tumor stemness and by enhancing colony formation, proliferation as well as metastasis, and these cells can also mediate resistance to therapy. Furthermore, the presence of CSCs leads to cancer recurrence and therefore their complete eradication can have immense therapeutic benefits. The present review focuses on targeting CSCs by natural products in cancer therapy. The growth and colony formation capacities of CSCs have been reported can be attenuated by the dietary agents. These compounds can induce apoptosis in CSCs and reduce tumor migration and invasion via EMT inhibition. A variety of molecular pathways including STAT3, Wnt/ß-catenin, Sonic Hedgehog, Gli1 and NF-κB undergo down-regulation by dietary agents in suppressing CSC features. Upon exposure to natural agents, a significant decrease occurs in levels of CSC markers including CD44, CD133, ALDH1, Oct4 and Nanog to impair cancer stemness. Furthermore, CSC suppression by dietary agents can enhance sensitivity of tumors to chemotherapy and radiotherapy. In addition to in vitro studies, as well as experiments on the different preclinical models have shown capacity of natural products in suppressing cancer stemness. Furthermore, use of nanostructures for improving therapeutic impact of dietary agents is recommended to rapidly translate preclinical findings for clinical use.

[Real-world study in oncological outpatients of an oral supplement enriched with ω-3 fatty acids - effect on quality of life and nutritional parameters]. / Estudio en vida real de un suplemento oral enriquecido con ácidos grasos ω-3 en pacientes ambulatorios oncológicos: efecto sobre la calidad de vida y los parámetros nutricionales.

INTRODUCTION: Background: cancer patients are a group at high nutritional risk. Oral nutritional supplementation (ONS) can improve nutritional status. Objective: the objective of our study was to evaluate the effectiveness on nutritional parameters and quality of life of a ω3-enriched ONS in oncology outpatients in a real-world study. Material and methods: a total of 35 outpatient cancer patients who received 2 ONS per day were recruited. Chemistry, anthropometric, impedance measurement, nutritional survey, malnutrition universal screening tool (MUST) test, and EQ5D quality of life test were all used before and after 3 months of intervention. Results: mean age was 65.4 ± 10.7 years (18 females/17 males). Mean completion of the group was 81.7 ± 7.2 %. During the intervention, total protein (1.5 ± 0.2 g/dL; p = 0.01), albumin (0.9 ± 0.1 mg/dL; p = 0.04), and transferrin (53.9 ± 21.1 mg/dL; p = 0.02) levels increased. At the beginning of the study, 100 % of the patients were in the high nutritional risk category according to MUST. After the intervention, 34.3 % (n = 12) were in the low nutritional risk category, 51.4 % (n = 18) in the moderate nutritional risk category, and only 14.3 % (n = 5) in the category of high nutritional risk; previously, 100 % of patients had high nutritional risk (p = 0.02). The total score in the quality of life test increased significantly (0.51 ± 0.06 vs 0.84 ± 0.03 points; p = 0.01), with improvement in 5 dimensions. Conclusions: the use of a ω3-enriched ONS in a real-world study with cancer outpatients showed a beneficial effect on nutritional parameters and quality of life.

INTRODUCCIÓN: Antecedentes: los pacientes oncológicos son un grupo de alto riesgo nutricional. Los suplementos orales nutricionales (SON) pueden ayudar a mejorar su situación nutricional. Objetivo: el objetivo de nuestro estudio fue evaluar en un estudio en vida real la efectividad sobre los parámetros nutricionales y la calidad de vida de un SON enriquecido con ω-3 en pacientes ambulatorios oncológicos. Material y métodos: se reclutaron 35 pacientes oncológicos ambulatorios que recibieron 2 SON al día. Se realizaron: valoración bioquímica y antropométrica, impedanciometría, encuesta nutricional, test Malnutrition Universal Screening Tool (MUST) y test de calidad de vida EQ5D, antes y a los 3 meses de intervención. Resultados: la edad media fue de 65,4 ± 10,7 años (18 mujeres/17 hombres). La cumplimentación media del grupo fue de un 81,7 ± 7,2 %. Durante la intervención aumentaron los niveles de proteínas totales (1,5 ± 0,2 g/dl; p = 0,01), albúmina (0,9 ± 0,1 mg/dl; p = 0,04) y transferrina (53,9 ± 21,1 mg/dl; p = 0,02). Al inicio del estudio, un 100 % de los pacientes presentaban en el test MUST la categoría de alto riesgo nutricional. Tras la intervención, un 34,3 % (n = 12) presentaban la categoría de bajo riesgo nutricional, un 51,4 % (n = 18) presentaban en el test MUST la categoría de moderado riesgo nutricional, y solo un 14,3 % (n = 5) presentaban la categoría de alto riesgo nutricional; previamente, el 100 % de los pacientes tenían la categoría alto riesgo (p = 0,02). La puntuación total del test de calidad de vida aumentó significativamente (0,51 ± 0,06 vs. 0,84 ± 0,03 puntos; p = 0,01), mejorando cualitativamente las 5 dimensiones. Conclusiones: la utilización de un SON enriquecido con ω-3 en pacientes oncológicos ambulatorios en condiciones de vida real muestra un efecto beneficioso sobre los parámetros nutricionales y la calidad de vida.

Ketogenic Diet for Cancer: Critical Assessment and Research Recommendations.

Despite remarkable improvements in screening, diagnosis, and targeted therapies, cancer remains the second leading cause of death in the United States. It is increasingly clear that diet and lifestyle practices play a substantial role in cancer development and progression. As such, various dietary compositions have been proposed for reducing cancer risk and as potential adjuvant therapies. In this article, we critically assess the preclinical and human trials on the effects of the ketogenic diet (KD, i.e., high-fat, moderate-to-low protein, and very-low carbohydrate content) for cancer-related outcomes. The mechanisms underlying the hypothesized effects of KD, most notably the Warburg Effect, suggest that restricting carbohydrate content may impede cancer development and progression via several pathways (e.g., tumor metabolism, gene expression). Overall, although preclinical studies suggest that KD has antitumor effects, prolongs survival, and prevents cancer development, human clinical trials are equivocal. Because of the lack of high-quality clinical trials, the effects of KD on cancer and as an adjunctive therapy are essentially unknown. We propose a set of research recommendations for clinical studies examining the effects of KD on cancer development and progression.

The impact of physiological metabolite levels on serine uptake, synthesis and utilization in cancer cells.

Serine is a non-essential amino acid that is critical for tumour proliferation and depletion of circulating serine results in reduced tumour growth and increased survival in various cancer models. While many cancer cells cultured in a standard tissue culture medium depend on exogenous serine for optimal growth, here we report that these cells are less sensitive to serine/glycine depletion in medium containing physiological levels of metabolites. The lower requirement for exogenous serine under these culture conditions reflects both increased de novo serine synthesis and the use of hypoxanthine (not present in the standard medium) to support purine synthesis. Limiting serine availability leads to increased uptake of extracellular hypoxanthine, sparing available serine for other pathways such as glutathione synthesis. Taken together these results improve our understanding of serine metabolism in physiologically relevant nutrient conditions and allow us to predict interventions that may enhance the therapeutic response to dietary serine/glycine limitation.

Nutraceuticals and their role in tumor angiogenesis.

Angiogenesis plays a pivotal role in cancer initiation, maintenance, and progression. Diet may inhibit, retard or reverse these processes affecting angiogenesis (angioprevention). Nutraceuticals, such as omega-3 fatty acids, amino acids, proteins, vitamins, minerals, fibers, and phenolic compounds, improve health benefits as they are a source of bioactive compounds that, among other effects, can regulate angiogenesis. The literature concerning the pro-angiogenic and/or anti-angiogenic nutraceuticals and the possible activated pathways in cancer and other non-neoplastic diseases by in vivo and in vitro experiments are reviewed.

Efficacy and safety of BNT162b2 vaccination in patients with solid cancer receiving anticancer therapy - a single centre prospective study.

AIM: Patients with cancer are at an increased risk for severe coronavirus disease of 2019, thus data on the safety and efficacy of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We conducted this prospective study of patients with cancer vaccinated with BNT162b2 and monitored for antibody response and safety. The aim was to evaluate the rate of seropositivity and define predictors for non-reactive immune response. Furthermore, we evaluated the frequency and the severity of adverse events. METHODS: The study included patients with solid tumours undergoing anticancer treatment and immunocompetent health-care workers serving as controls. Serum titres of the receptor-binding domain (RBD) immunoglobulin G (IgG) and neutralising antibodies were measured 2-4 weeks after each vaccine dose. RESULTS: The analysis included 129 patients, of which 70.5% patients were metastatic. Patients were treated with chemotherapy (55%), immunotherapy (34.1%), biological agents (24.8%), hormonal treatment (8.5%) and radiotherapy (4.6%), that were given either alone or in combinations. The seropositivity rate among patients with cancer and controls was 32.4% versus 59.8% (p < 0.0001) after the first dose and 84.1% versus 98.9% (p < 0.0001) after the second dose, respectively. Median RBD-IgG titre was lower among patients than controls (p < 0.0001). Patients who were seronegative after the second dose had significantly more comorbidities than that with patients with seropositivity (77.8% vs 41.1%, respectively, p = 0.0042). CONCLUSION: Adequate antibody response after BNT162b2 vaccination was achieved after two doses but not after one dose, in patients with cancer vaccinated during anticancer therapy.

Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges.

The immune cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted rapidly evolving attention as a cancer treatment modality because of its competence to selectively eliminate tumor cells without instigating toxicity in vivo. TRAIL has revealed encouraging promise in preclinical reports in animal models as a cancer treatment option; however, the foremost constraint of the TRAIL therapy is the advancement of TRAIL resistance through a myriad of mechanisms in tumor cells. Investigations have documented that improvement of the expression of anti-apoptotic proteins and survival or proliferation involved signaling pathways concurrently suppressing the expression of pro-apoptotic proteins along with down-regulation of expression of TRAILR1 and TRAILR2, also known as death receptor 4 and 5 (DR4/5) are reliable for tumor cells resistance to TRAIL. Therefore, it seems that the development of a therapeutic approach for overcoming TRAIL resistance is of paramount importance. Studies currently have shown that combined treatment with anti-tumor agents, ranging from synthetic agents to natural products, and TRAIL could result in induction of apoptosis in TRAIL-resistant cells. Also, human mesenchymal stem/stromal cells (MSCs) engineered to generate and deliver TRAIL can provide both targeted and continued delivery of this apoptosis-inducing cytokine. Similarly, nanoparticle (NPs)-based TRAIL delivery offers novel platforms to defeat barricades to TRAIL therapeutic delivery. In the current review, we will focus on underlying mechanisms contributed to inducing resistance to TRAIL in tumor cells, and also discuss recent findings concerning the therapeutic efficacy of combined treatment of TRAIL with other antitumor compounds, and also TRAIL-delivery using human MSCs and NPs to overcome tumor cells resistance to TRAIL.

Association between the dietary regimen and infection-related complications in neutropenic high-risk patients with cancer.

BACKGROUND: Many haematology/oncology departments still provide a germ-free diet for neutropenic patients (neutropenic diet, ND) to minimise pathogen exposure, even though evidence on benefits is missing. We analysed the effects of a standard diet (SD) in neutropenic high-risk patients with cancer while focussing on infection-related outcomes. PATIENTS AND METHODS: Based on the Cologne Cohort of Neutropenic Patients, we conducted a propensity score-matched case-control study in haematological/oncological patients with a period of neutropenia longer than five days treated at our department between January 2004 and December 2012 (implementation of SD in January 2008). We assessed the association between an SD and selected infection-related end-points in an adjusted multivariable regression model and time-to-event analysis. RESULTS: In total, 2086 neutropenic episodes (1043 per diet group) were included into analysis. The median days of neutropenia were 9 (interquartile range 7-16). The adjusted multivariable model revealed no association between the SD and severity and persistence of fever, death within 28 days, antibiotic treatment and weight loss >3 kg and a non-significant adjusted association between SD and duration of antibiotic treatment and blood stream infections. There was a significant association between SD and incidence of diarrhoea (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.45-0.68; P < 0.001), nausea (OR, 0.53; 95% CI, 0.43-0.66; P < 0.001) and weight loss >1 kg (OR, 0.93; 95% CI, 0.89-0.98; P = 0.002) with fewer events in SD than in the ND group. The hazard ratios of SD for the analysed end-points were non-significant. CONCLUSION: In our study, the implementation of an SD for high-risk neutropenic patients with cancer was safe regarding infection-related end-points.

Análisis de las intervenciones nutricionales en el proceso asistencial del paciente oncológico en Andalucía: el proyecto NOA / Analysis of nutritional interventions in the care process of oncological patients in Andalusia - The NOA project

Introducción: la desnutrición en los pacientes oncológicos puede conllevar una reducción de la calidad de vida del paciente y un aumento de la morbimortalidad y de los costes sanitarios asociados. Objetivos: analizar las intervenciones nutricionales en las diferentes fases del proceso oncológico, integrando las necesidades de los pacientes y las de los profesionales sanitarios. Material y métodos: se utilizaron técnicas de Design Thinking para abordar el análisis de la situación actual e identificar los aspectos clave. Participaron 13 profesionales de 8 centros sanitarios (endocrinología y nutrición, oncología médica y radioterápica, atención primaria (AP), enfermería y dietética) públicos de Andalucía. Resultados: no se realiza cribado nutricional de forma sistemática en las diferentes fases del proceso oncológico, y no existe consenso universal en los protocolos de actuación e intervención nutricional. Existe un cumplimiento generalizado de los circuitos y tiempos de derivación de los procesos seleccionados. En la fase terapéutica se dispone de la posibilidad de consultar a la Unidad de Nutrición Clínica y Dietética (UNCYD) y el 75 % disponen de protocolos específicos de derivación. La enfermera gestora de casos está presente en todos los hospitales y en AP. El acceso del paciente al psicólogo del centro era posible en el 87 % de los hospitales. Escasa participación de la UNCYD en los Comités de Tumores (solo en el 25 % de los centros). En todos los centros existe algún tipo de colaboración y apoyo de las asociaciones de pacientes y de la Escuela de Pacientes, especialmente en las fases terapéuticas y de control y seguimiento. Conclusiones: se observan variaciones entre los diferentes hospitales y territorios de Andalucía, tanto en la disposición de medios y estructuras como en las actividades y procedimientos. Se han seleccionado y priorizado puntos clave para mejorar la atención nutricional en oncología. (AU)

Introduction: malnutrition in cancer patients can lead to a reduction in patient quality of life, increased morbidity and mortality, and associated healthcare costs. Objective: to analyze nutritional interventions in the different phases of the oncological process, integrating the needs of patients and those of healthcare professionals. Material and methods: "Design Thinking" techniques were used to address the analysis of the current situation and identify key aspects. Thirteen professionals from 8 public health centers (endocrinology and nutrition, medical and radiotherapy oncology, primary care (PC), nursing and dietetics) participated in the study. Results: nutritional screening is not carried out in a systematic way in the different phases of the oncological process, and there is no universal consensus on the protocols for action and nutritional intervention. A wide compliance with the pathways and referral times of the selected processes has been observed. In the therapeutic phase, there is the possibility of consulting the Clinical Nutrition and Dietetics Unit (UNCYD) and 75 % have specific referral protocols. The nurse case manager is present in all hospitals and in PC. Patient access to the center psychologist was possible in 87 % of the hospitals. Participation of the UNCYD in Tumor Committees was low (only in 25 % of the centers). In all centers there is some kind of collaboration and support by patient associations and the School of Patients, especially in the therapeutic and the control and follow-up phases. Conclusions: variations are observed between the different hospitals and areas in Andalusia, both in terms of means and structures and in activities and procedures. Key points have been selected and prioritized to improve nutritional care in oncology. (AU)

Modulation of Gut Microbiota to Enhance Effect of Checkpoint Inhibitor Immunotherapy.

Accumulating evidence demonstrated the crucial role of gut microbiota in many human diseases, including cancer. Checkpoint inhibitor therapy has emerged as a novel treatment and has been clinically accepted as a major therapeutic strategy for cancer. Gut microbiota is related to cancer and the effect of immune checkpoint inhibitors (ICIs), and supplement with specific bacterial species can restore or enhance the responses to the ICIs. Namely, specified bacteria can serve as the biomarkers for distinguishing the patient who will respond to ICIs and determine the effectiveness of ICIs, as well as predicting the efficacy of checkpoint inhibitor immunotherapy. Regardless of the significant findings, the relationship between gut microbiota and the effect of ICIs treatment needs a more thorough understanding to provide more effective therapeutic plans and reduce treatment complication. In this review, we summarized the role of gut microbiota played in immune system and cancer. We mainly focus on the relationship between gut microbiota and the checkpoint inhibitor immunotherapy.

Modifiable and Non-Modifiable Risk Factors for Atherothrombotic Ischemic Stroke among Subjects in the Malmö Diet and Cancer Study.

Risk factors for ischemic stroke is suggested to differ by etiologic subtypes. The purpose of this study was to examine the associations between modifiable and non-modifiable risk factors and atherothrombotic stroke (i.e., excluding cardioembolic stroke), and to examine if the potential benefit of modifiable lifestyle factors differs among subjects with and without predisposing comorbidities. After a median follow-up of 21.2 years, 2339 individuals were diagnosed with atherothrombotic stroke out of 26,547 study participants from the Malmö Diet and Cancer study. Using multivariable Cox regression, we examined non-modifiable (demographics and family history of stroke), semi-modifiable comorbidities (hypertension, dyslipidemia, diabetes mellitus and atherosclerotic disease), and modifiable (smoking, body mass index, diet quality, physical activity, and alcohol intake) risk factors in relation to atherothrombotic stroke. Higher age, male gender, family history of stroke, and low educational level increased the risk of atherothrombotic stroke as did predisposing comorbidities. Non-smoking (hazard ratio (HR) = 0.62, 95% confidence interval (CI) 0.56-0.68), high diet quality (HR = 0.83, 95% CI 0.72-0.97) and high leisure-time physical activity (HR = 0.89, 95% CI 0.80-0.98) decreased the risk of atherothrombotic ischemic stroke independent of established risk factors, with non-significant associations with body mass index and alcohol intake. The effect of the lifestyle factors was independent of predisposing comorbidities at baseline. The adverse effects of several cardiovascular risk factors were confirmed in this study of atherothrombotic stroke. Smoking cessation, improving diet quality and increasing physical activity level is likely to lower risk of atherothrombotic stroke in the general population as well as in patient groups at high risk.