[Patient participation through active listening. About the remodeling of an extractions service]. / Participación del paciente a través de la escucha activa. A propósito de la remodelación de un servicio de extracciones.

BACKGROUND AND OBJECTIVE: From listening to patients there arises the possibility of improving both the care and the health infrastructure that users frequent. Our purpose of study was to explore the perception of users about the means and the care received involved in a hospital service through active listening, and to evaluate the satisfaction perceived after the opening of the renovated area. METHODS: A mixed methodology evaluative investigation was carried out within the context of the Extraction Service of the Costa del Sol Hospital, using qualitative methodology to assess the perception of users, and quantitative methodology through a satisfaction survey to identify the change after remodeling of the area. RESULTS: Through a qualitative approach, improvements have been identified in terms of the internal and external infrastructure of the center, highlighting the need to personalize spaces depending on the profile of the patient attended. In evaluating the impact after remodeling the area, patients have a higher overall satisfaction both from the healthcare professionals who attend them and from the healthcare center. CONCLUSIONS: Through the use of a mixed methodology, useful information has been incorporated for a project to improve a hospital infrastructure, and a subsequent evaluation of the positive impact on the satisfaction perceived by users after remodeling.

Síndrome de neurotoxicidad asociada a células inmunoefectoras: un enfoque terapéutico en el paciente crítico / Immune effector cell-associated neurotoxicity syndrome: A therapeutic approach in the critically ill

La inmunoterapia con células T modificadas con receptor quimérico antígeno-específico (chimeric antigen receptor conocida como [CAR-T]) está emergiendo como un tratamiento prometedor para enfermedades hematológicas. Así, las CAR-T dirigidas contra el complejo de diferenciación 19 han demostrado gran eficacia antitumoral contra neoplasias de células B resistentes a terapias convencionales. Sin embargo, la activación dirigida de la respuesta inmunitaria desata en ciertos casos complicaciones específicas graves y potencialmente mortales. Entre ellas cabe destacar el síndrome de liberación de citoquinas y el síndrome de toxicidad neurológica asociado a la terapia con células inmunoefectoras (Immune-effector cell associated neurotoxicity syndrome conocido como ICANS), siendo este último el objetivo de nuestra revisión. Aunque los mecanismos fisiopatológicos que conducen al ICANS son poco conocidos, existen factores clínicos y biológicos que aumentan el riesgo de desarrollo de neurotoxicidad asociada a la terapia CAR-T. El tratamiento se basa en medidas de monitorización y soporte, tratamiento con anticonvulsivantes, corticosteroides e ingreso en los servicios de medicina intensiva de forma precoz. Este artículo proporciona una revisión exhaustiva de la literatura disponible sobre el ICANS desde una perspectiva multidisciplinar, incluyendo recomendaciones de intensivistas, neurólogos y hematólogos formados en el cuidado de adultos críticamente enfermos (AU)

Immunotherapy with chimeric antigen-specific receptor modified T cells, known as CAR-T, is emerging as a promising approach to hematological malignancies. In this regard, CAR-T against human cluster of differentiation (CD) 19 has demonstrated antitumor efficacy in application to B cell neoplasms resistant to conventional therapy. However, activation of the immune system induces severe and specific complications which can prove life-threatening. These include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (known as ICANS) - the latter being the subject of the present review. Although the physiopathological mechanisms underlying ICANS are not well known, a number of clinical and biological factors increase the risk of developing neurotoxicity associated to CAR-T therapy. Treatment is based on close monitoring, measures of support, anticonvulsivants, corticosteroids, and early admission to intensive care. The present study offers a comprehensive review of the available literature from a multidisciplinary perspective, including recommendations from intensivists, neurologists and hematologists dedicated to the care of critically ill adults (AU)

Immune effector cell-associated neurotoxicity syndrome: A therapeutic approach in the critically ill.

Immunotherapy with chimeric antigen-specific receptor modified T cells, known as CAR-T, is emerging as a promising approach to hematological malignancies. In this regard, CAR-T against human cluster of differentiation (CD) 19 has demonstrated antitumor efficacy in application to B cell neoplasms resistant to conventional therapy. However, activation of the immune system induces severe and specific complications which can prove life-threatening. These include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (known as ICANS) - the latter being the subject of the present review. Although the physiopathological mechanisms underlying ICANS are not well known, a number of clinical and biological factors increase the risk of developing neurotoxicity associated to CAR-T therapy. Treatment is based on close monitoring, measures of support, anticonvulsivants, corticosteroids, and early admission to intensive care. The present study offers a comprehensive review of the available literature from a multidisciplinary perspective, including recommendations from intensivists, neurologists and hematologists dedicated to the care of critically ill adults.

Impact of the COVID-19 pandemic on the care of cancer patients in Spain.

BACKGROUND: Studies evaluating the effects of the COVID-19 pandemic on public healthcare systems are limited, particularly in cancer management. As no such studies have been carried out in Spain, our objective is to describe and quantify the impact of the COVID-19 pandemic on cancer patients in Spanish hospitals during the first wave of the pandemic. MATERIALS AND METHODS: This retrospective, multicenter, nationwide study collected information from hospital departments treating oncology patients. An electronic questionnaire comparing outcomes and management of oncohematological patients for the March-June 2019 and March-June 2020 periods was used. RESULTS: Information from 78 departments (36 tertiary hospitals) was analyzed. Forty-four departments implemented adapted protocols during March 2020. Most of these (n = 38/44; 86.4%) carried out COVID-19 triage, while 26 of 44 (59.1%) carried out onsite polymerase chain reaction tests for clinically suspected cases. A shift from in-person to telephone visits was observed in 43 of 44 (97.7%) departments. Comparing the March-June 2019 and March-June 2020 periods, the number of new patients decreased by 20.8% (from 160.2 to 126.4). Decreases were also seen in the mean number of total (2858.2 versus 1686.1) and cancer (465.5 versus 367.2) biopsies, as well as the mean number of bone marrow biopsies (30.5 versus 18.6). Concerning the number of patients visiting specific cancer care departments, a decrease from 2019 to 2020 was seen for mean number of chemotherapy treatments (712.7 versus 643.8) and radiation therapy (2169.9 versus 2139.9). Finally, a reduction from 2019 to 2020 of 12.9% (from 8.6 to 7.4) in the mean number of patients included in clinical trials was noted. CONCLUSIONS: This study provides the first comprehensive data concerning the impact of COVID-19 on cancer care in Spain. The pandemic caused a 20.8% decrease in newly diagnosed patients, which may impact future outcomes. Measures must be taken to ensure cancer management receives priority in times of healthcare emergencies.

Immune effector cell-associated neurotoxicity syndrome: A therapeutic approach in the critically ill. / Síndrome de neurotoxicidad asociada a células inmunoefectoras: un enfoque terapéutico en el paciente crítico.

Immunotherapy with chimeric antigen-specific receptor modified T cells, known as CAR-T, is emerging as a promising approach to hematological malignancies. In this regard, CAR-T against human cluster of differentiation (CD) 19 has demonstrated antitumor efficacy in application to B cell neoplasms resistant to conventional therapy. However, activation of the immune system induces severe and specific complications which can prove life-threatening. These include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (known as ICANS) - the latter being the subject of the present review. Although the physiopathological mechanisms underlying ICANS are not well known, a number of clinical and biological factors increase the risk of developing neurotoxicity associated to CAR-T therapy. Treatment is based on close monitoring, measures of support, anticonvulsivants, corticosteroids, and early admission to intensive care. The present study offers a comprehensive review of the available literature from a multidisciplinary perspective, including recommendations from intensivists, neurologists and hematologists dedicated to the care of critically ill adults.

ECO-SEOM-SEEO safety recommendations guideline for cancer patients receiving intravenous therapy.

PURPOSE: Cancer patients require implantation of venous access devices to meet their personalized therapeutic needs, which are often complex due to the nature of the medication and the disease status. Therefore, it is essential to have standardized protocols that guarantee the best results in health and patient safety. METHODS: To learn about the availability of protocols and aspects related to safety in clinical practice and to detect possible opportunities for improvement, a survey has been conducted in various Spanish hospitals, in addition to a review of the evidence regarding the various devices available and complications associated with the administration of chemotherapy. RESULTS: As a result of both analyses, the Foundation for Excellence and Quality in Oncology (ECO), the Spanish Society of Medical Oncology (SEOM), and the Spanish Society of Oncology Nursing (SEEO) have developed a catheter selection algorithm based on patient characteristics and treatment to facilitate the clinical decision-making process, as well as some recommendations aimed at ensuring patient safety and rational use of available resources. CONCLUSIONS: In conclusion, both the venous access catheter selection algorithm and the proposed recommendations aim to respond to the needs revealed in clinical practice and to become an integrable tool in electronic prescription systems to offer homogeneous criteria for action in cancer patients that require venous access, optimizing the use of available health resources with the highest safety and quality of life for the patient.

Creation Of The «Soludable¼ Sun Protection Accreditation Program For Schools. / Creación del distintivo Soludable: un modelo de certificación en fotoprotección para centros escolares.

INTRODUCTION: Sun exposure during childhood is the main risk factor for skin cancer in later life. School-based sun protection policies and practices have proven to be the most effective and cost-effective strategies for preventing skin cancer. OBJECTIVE: To develop a sun protection accreditation program known as «Soludable¼ (a play on the Spanish words sol [sun] and saludable [healthy]) to objectively identify schools that actively promote sun protection behaviors among students. METHODS: The consensus method used was a 2-round Delphi technique with input from a panel of experts. We then calculated the median scores for the importance and feasibility of each of the recommendations proposed and the level of complexity assigned to each recommendation by counting the percentage of experts who chose each difficulty category. RESULTS: The resulting accreditation model consists of 14 recommendations with corresponding evaluation criteria divided into 7 domains: 1) organizational leadership (5 recommendations), 2) effective communication (2 recommendations), 3) structural elements (2 recommendations), 4) training of professionals (1 recommendation), 5) school curriculum (1 recommendation), 6) behavioral models (2 recommendations), and 7) student habits (1 recommendation). A high level of agreement among experts was observed for all recommendations, in terms of both their perceived importance and feasibility and their categorization by levels of complexity. CONCLUSIONS: This is the first sun protection accreditation program developed for Spanish schools. Studies are needed to evaluate how this program is received and how it affects students' sun protection behaviors.

Correction to: Persistent major alopecia following adjuvant docetaxel for breast cancer: incidence, characteristics, and prevention with scalp cooling.

In the original publication of the article, Table 1 was published with incorrect caption and values. The Table 1 with corrected caption and values is given in this Correction.

Persistent major alopecia following adjuvant docetaxel for breast cancer: incidence, characteristics, and prevention with scalp cooling.

BACKGROUND: Persistent alopecia (PA) after docetaxel has been recently described. The aim of our study is to establish the incidence and characteristics of PA following adjuvant docetaxel for breast cancer (BC) and to test the ability of scalp cooling in prevention. PATIENTS AND METHODS: BC patients receiving adjuvant chemotherapy followed or not by endocrine therapy (and a control group receiving only endocrine therapy) were interviewed in a single institution at 1.5 to 5 years following primary diagnosis searching for PA. A confirmatory prevalence study was later performed in other two institutions. Finally, a prevention study using prophylactic scalp cooling (PSC) with ELASTO-GEL hypothermia caps in patients receiving adjuvant docetaxel was performed. RESULTS: In the initial prevalence study (492 patients), minor forms of PA (grade 1) were recorded with all chemotherapy regimens and aromatase inhibitors. Patients receiving docetaxel regimens at cumulative dose (CD) ≥ 400 mmg/m2 presented a significantly higher prevalence of grades 1 PA (33-52%) and 2 PA (5-12%). Prevalence of grade 2 PA with docetaxel CD ≥ 400 mmg/m2 was confirmed in two other institutions. Overall, grade 2 PA was seen in 10.06% (95% CI 7.36-13.61) of 358 patients with docetaxel regimens reaching CD ≥ 400 mmg/m2, but not in patients with lower docetaxel CD, other chemotherapy regimens, or endocrine therapy alone. In prevention trial, no grade 2 PA occurred among 116 patients receiving adjuvant docetaxel (≥ 400 mmg/m2) and PSC followed-up after a 96 months median time. PSC was well tolerated. No scalp relapses were seen among 30 patients (22% of all inclusions) having disease relapse. CONCLUSION: Adjuvant treatment with docetaxel (CD ≥ 400 mmg/m2) is associated with a significant rate of grade 2 PA, leading to wearing a wig, in around 10% of patients. This toxicity was completely prevented with scalp cooling. Clinical Trial Reference: NCT00515762.

Persistent effects of pre-Columbian plant domestication on Amazonian forest composition.

The extent to which pre-Columbian societies altered Amazonian landscapes is hotly debated. We performed a basin-wide analysis of pre-Columbian impacts on Amazonian forests by overlaying known archaeological sites in Amazonia with the distributions and abundances of 85 woody species domesticated by pre-Columbian peoples. Domesticated species are five times more likely than nondomesticated species to be hyperdominant. Across the basin, the relative abundance and richness of domesticated species increase in forests on and around archaeological sites. In southwestern and eastern Amazonia, distance to archaeological sites strongly influences the relative abundance and richness of domesticated species. Our analyses indicate that modern tree communities in Amazonia are structured to an important extent by a long history of plant domestication by Amazonian peoples.

Responsiveness of the Spanish Version of the "Skin Cancer Index".

Background. Skin Cancer Index (SCI) is a specific questionnaire measuring health related quality of life (HRQL) in patients with cervicofacial non-melanoma skin cancer (CFNMSC). The original scale has recently been adapted and validated into Spanish. Objectives. Evaluate the responsiveness of the Spanish version of SCI. Methods. Patients with CFNMSC candidate for surgical treatment were administered the questionnaire at time of diagnostic (t0), 7 days after surgery (t1), and 5 months after surgery (t2). The scale and subscales scores (C1: social/appearance, C2: emotional) were then evaluated. Differences between t0-t1, t1-t2, and t0-t2 were determined and a gender-and-age segmented analysis was performed. Results. 88 patients, 54.8% male, mean age 62.5 years, completed the study. Differences between t0-t1 and t1-t2 scores were statistically significant (p < 0.05). The lowest values were found at time of diagnosis and postsurgery. Women and patients under 65 years showed the lowest values at the three times. Limitations. Concrete geographic and cultural area. Clinical and histological variables are not analysed. Conclusions. Our results confirm responsiveness of the Spanish version of the SCI. Further development of the instrument in Spanish-speaking countries and populations will make it possible to extend worldwide research and knowledge horizons on skin cancer.

Breast cancer dissemination promoted by a neuregulin-collagenase 3 signalling node.

Advances in the treatment of breast cancer have resulted in increased survival. However, in the metastatic setting, the disease remains incurable. Therefore, understanding of the mechanisms that promote dissemination of breast cancer cells may favor the development of novel therapeutic strategies to fight those tumors. Here, we show that the ErbB ligands, Neuregulins (NRGs), promote metastatic dissemination of breast cancer cells by switching on a kinase-metalloproteinase network. Clinicopathological analyses demonstrated that NRG expression in breast tumors associated to lymph node invasion and poor patient outcome. Preclinical in vivo analyses showed that NRG expression favored in situ tumor growth, local spreading and metastatic dissemination. Genomic, biochemical and functional studies identified matrix metalloproteinases, particularly stromelysin 2 and collagenase 3, as key mediators of the NRG-induced dissemination properties of breast cancer cells. Mechanistic analyses demonstrated that NRG augmented metalloproteinase expression through a route controlled by ERK1/2 kinases. ERK1/2 increased collagenase 3 expression by controlling the activity of an SBF1-related transcription factor. In conclusion, we describe a pathway linked to breast cancer dissemination. The clinical availability of agents that target some of the components of this signalling pathway suggests that patients with tumors fed by NRGs or other factors able to activate the ERK-Collagenase 3 route may benefit from agents that act on that signalling axis.

In vivo murine model of acquired resistance in myeloma reveals differential mechanisms for lenalidomide and pomalidomide in combination with dexamethasone.

The development of resistance to therapy is unavoidable in the history of multiple myeloma patients. Therefore, the study of its characteristics and mechanisms is critical in the search for novel therapeutic approaches to overcome it. This effort is hampered by the absence of appropriate preclinical models, especially those mimicking acquired resistance. Here we present an in vivo model of acquired resistance based on the continuous treatment of mice bearing subcutaneous MM1S plasmacytomas. Xenografts acquired resistance to two generations of immunomodulatory drugs (IMiDs; lenalidomide and pomalidomide) in combination with dexamethasone, that was reversible after a wash-out period. Furthermore, lenalidomide-dexamethasone (LD) or pomalidomide-dexamethasone (PD) did not display cross-resistance, which could be due to the differential requirements of the key target Cereblon and its substrates Aiolos and Ikaros observed in cells resistant to each combination. Differential gene expression profiles of LD and PD could also explain the absence of cross-resistance. Onset of resistance to both combinations was accompanied by upregulation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway and addition of selumetinib, a small-molecule MEK inhibitor, could resensitize resistant cells. Our results provide insights into the mechanisms of acquired resistance to LD and PD combinations and offer possible therapeutic approaches to addressing IMiD resistance in the clinic.

A Spanish version of the Skin Cancer Index: a questionnaire for measuring quality of life in patients with cervicofacial nonmelanoma skin cancer.

INTRODUCTION: The Skin Cancer Index (SCI) is the first specific patient-reported outcome measure for patients with cervicofacial nonmelanoma skin cancer. To date, only the original English version has been published. OBJECTIVES: To develop a Spanish version of the SCI that is semantically and linguistically equivalent to the original, and to evaluate its measurement properties in this different cultural environment. MATERIAL AND METHODS: A cross-sectional study was conducted of the cultural adaptation and empirical validation of the questionnaire, analysing the psychometric properties of the new index at different stages. RESULTS: Of 440 patients recruited to the study, 431 (95%) completed the Spanish version of the SCI questionnaire, in a mean time of 6·3 min (SD 2·9). Factor analysis of the scale revealed commonality and loading values of < 0·5 for three of the 15 items. The remaining 12 items converged into two components: appearance/social aspects (seven items) and emotional aspects (five items). Both domains presented a high level of internal consistency, with Cronbach's alpha values above 0·8. The convergent-discriminant validity analysis produced correlations higher than 0·3 for the mental component of the Short Form Health Survey-12v2 Health Questionnaire (correlation coefficient 0·39) and the Dermatology Quality of Life Index (correlation coefficient -0·30). In the test-retest, nine of the 12 items produced a weighted kappa value exceeding 0·4, and for the remaining three items, the absolute agreement percentage exceeded 60%. CONCLUSIONS: The Spanish version of the SCI quality of life scale has been satisfactorily adapted and validated for use in Spanish-speaking countries and populations.

Active kinase profiling, genetic and pharmacological data define mTOR as an important common target in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer. Despite response to chemotherapy, relapses are frequent and resistance to available treatments is often seen in the metastatic setting. Therefore, identification of new therapeutic targets is required. With this aim, we have profiled the activation status of 44 receptor tyrosine kinases (RTKs) and their major signaling pathways in patient-derived TNBC tumors. Frequent co-activation of several RTKs as well as the extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) and mammalian target of rapamycin (mTOR) routes was found. Pharmacologic targeting of the activated kinases indicated that agents that attack the mTOR route are more potent and efficient antitumoral treatments than agents targeting RTKs. mTOR signals through two multiprotein complexes, mTORC1 and mTORC2. We used a genetic approach to explore the contribution of each of the two mTOR branches to the regulation of cell number of TNBC cells. RNA interference experiments indicated that mTORC1 predominated over mTORC2 in the control of TNBC cell proliferation. Moreover, RNA interference of mTOR had a superior antiproliferative action than separately acting on mTORC1 or mTORC2. To analyze the relevance of mTOR targeting in vivo, we used mice with TNBC. Treatment of these mice with BEZ235, a drug that targets mTOR, slowed tumor growth. Mechanistically, BEZ235 delayed cell cycle progression without affecting cell viability. Our results show that TNBCs are particularly sensitive to inhibition of the mTOR pathway, and indicate that mTOR targeting may be a more efficient anti-TNBC therapy than exclusively acting on the mTORC1 branch of the pathway. This is relevant as most mTOR inhibitors used in the clinic act on mTORC1. Collectively with the fact that BEZ235 synergized with drugs commonly used in the treatment of TNBC, our data support the clinical development of agents that act on mTOR as a therapy for this disease.