Long-Term Survival and Immune Response Dynamics in Melanoma Patients Undergoing TAPCells-Based Vaccination Therapy.

Cancer vaccines present a promising avenue for treating immune checkpoint blockers (ICBs)-refractory patients, fostering immune responses to modulate the tumor microenvironment. We revisit a phase I/II trial using Tumor Antigen-Presenting Cells (TAPCells) (NCT06152367), an autologous antigen-presenting cell vaccine loaded with heat-shocked allogeneic melanoma cell lysates. Initial findings showcased TAPCells inducing lysate-specific delayed-type hypersensitivity (DTH) reactions, correlating with prolonged survival. Here, we extend our analysis over 15 years, categorizing patients into short-term (<36 months) and long-term (≥36 months) survivors, exploring novel associations between clinical outcomes and demographic, genetic, and immunologic parameters. Notably, DTHpos patients exhibit a 53.1% three-year survival compared to 16.1% in DTHneg patients. Extended remissions are observed in long-term survivors, particularly DTHpos/M1cneg patients. Younger age, stage III disease, and moderate immune events also benefit short-term survivors. Immunomarkers like increased C-type lectin domain family 2 member D on CD4+ T cells and elevated interleukin-17A were detected in long-term survivors. In contrast, toll-like receptor-4 D229G polymorphism and reduced CD32 on B cells are associated with reduced survival. TAPCells achieved stable long remissions in 35.2% of patients, especially M1cneg/DTHpos cases. Conclusions: Our study underscores the potential of vaccine-induced immune responses in melanoma, emphasizing the identification of emerging biological markers and clinical parameters for predicting long-term remission.

The importance of compassionate care / A importância do cuidado humanizado na Odontologia

Recently, studies have highlighted the importance of compassionate care in healthcare. Not only does it improve patient outcomes and satisfaction, but it also improves the healthcare providers' overall well-being. Furthermore, it helps streamline the healthcare system by shortening hospital stays and rates or readmittance. Unfortunately, patients report that they feel there is a lack of compassionate care provided to them, thus shedding light on the compassion crisis. The compassion crisis seems to have its roots in healthcare professional education, as evidenced by the high levels of burnout experienced by students, particularly in dental students. Compassion training, however, not only equips healthcare professionals with strategies to more effectively treat their patients, but also with coping mechanisms to better handle the stressors of their profession. Dentistry is no exception and has some unique barriers to care as well such as communication, the physical barrier during treatment. This further highlights the importance of compassionate care while providing treatment. Implementing compassionate care to be taught in school will improve patient outcomes and provider well-being (AU)

Recentemente, estudos destacaram a importância da empatia na área da saúde. A empatia não só melhora resultados e satisfação do paciente, mas também melhora o bem-estar dos profissionais de saúde. Além disso, ajuda a diminuir o custo do sistema de saúde ao reduzir as internações hospitalares e as taxas de reinternação. Infelizmente, os pacientes relatam que sentem falta de empatia, levando a uma atual crise de falta de empatia nos servicos de saúde. A crise da falta de empatia parece ter suas raízes na formação dos profissionais de saúde, como evidenciado pelos altos níveis de burnout experimentados pelos alunos, principalmente em estudantes de Odontologia. Treinamento para empatia, no entanto, não apenas prepara os profissionais de saúde com estratégias para tratar de forma mais eficaz seus pacientes, mas também com mecanismos de enfrentamento para lidar melhor com os fatores de estresse da profissão. A Odontologia não é exceção e tem algumas barreiras específicas, como a comunicação, que fica comprometida durante o tratamento odontológico. Isso destaca ainda mais a importância da empatia durante o tratamento. Ensinando empatia nos cursos de Odontologia melhorará os resultados para os pacientes e o bem-estar dos profissionais. (AU)

Ackonc-AWA: A multi-species animal welfare assessment protocol for wild animals under human care to overcome the use of generic welfare checklists.

Introduction: Maintaining a high level of animal welfare is essential in zoos, sanctuaries and aquaria for ethical, legislative and functional reasons. Therefore, it is necessary to have welfare assessment protocols that can be incorporated into daily management programs. Currently, there are different approaches to assessing animal welfare in zoos. Those that can be applied to multiple species consist of checklists or qualitative assessments, with limitations, especially regarding the lack of guidance in the selection and interpretation of indicators. Validated protocols also exist, but they are for very few wild species. This study aimed to develop, test in the field, and describe an animal welfare assessment protocol for wild animals under human care, that can be applied to multiple species, intended to overcome the use of generic welfare checklists and offer an alternative to challenging and time consuming species-specific tools. Methods: The development process consisted of the elaboration of a protocol, substantiated by published literature on zoo animal welfare and multidisciplinary focus group work, and its on-field feasibility test. This was performed on 14 species of different taxa housed in an Argentinian zoo. The protocol was structured in two forms: an initial form to serve as scan using various animal-based (ABM), resource-based (RBM), and management-based measurements (MBM), and a follow-up form using exclusively ABM. The protocol also included a user's manual with information about preliminary preparation, equipment required, steps from arrival until completion, and details on how to assess each indicator. The scoring method consisted in rating each indicator on a 3-point scale. Results: 23 ABM, 19 RBM, and three MBM were tested and selected to integrate Ackonc-AWA, a multidimensional protocol covering the five animal welfare domains and applicable to multiple species. Discussion: This protocol was entirely developed in Spanish and can be applied noninvasively and at a low cost, which constitute features of high relevance for Latin America. Further applications of the described welfare assessment tool in other species and different institutional contexts will reinforce the validation of the proposed measurements and allow the systematic and routine evaluation of animal welfare in zoos.

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. Special article: compassionate use and clinical trial on CAR-T cells.

There are only two ways for a patient to gain access to treatment with an experimental product, such as CAR-T cells: participate in a clinical trial or receive a product in a compassionate basis. In the first case, the main beneficiary is society itself, which may in turn obtain a new treatment paradigm for a specific disease. In the second case, the use of a medicinal product has the objective of care in benefit of patients in grave clinical condition, for which no approved medicinal products exist, or for which all the possibilities for benefit from standard therapies have been exhausted. The CAR-T cell therapy may be included in one or the other types of access. The compassionate use is not a specific type of clinical research and should therefore not have its use appreciated by a research ethics committee, but rather by the medical ethics committee at the institution where the treatment will take place and by the regulatory agency.

Compassionate Engagement and Action in the Education for Health Care Professions: A Cross-Sectional Study at an Ecuadorian University.

Objective: This study aimed at exploring the compassion attitudes and needs for awareness and training related to a compassionate approach for Medicine, Nursing, and Psychology students, as well as for the academic and administration personnel from the Universidad Técnica Particular de Loja (UTPL, Ecuador) Health Sciences area. Methods: A cross-sectional observational study, based on a self-administered questionnaire through a sample of 788 UPTL students. STROBE guidelines were followed and applied. Results: A positive correlation was found between life engagement and compassion for others, from others, and self-compassion. The Nursing students were those who reported having previous experiences of contact with people with an advanced disease or in an end-of-life situation and having received some type of training compared to Medicine and Psychology students and lecturers (faculty members). Differences were found on the "self-compassion" and "compassion for others" subscales, noting a higher level of compassion among Psychology students. Conclusions: To implement the philosophy of compassionate universities it is necessary to design trainings that include the students, the faculty members, and the administrative staff, centered on sensitization and training about assistance, care, and accompaniment at the end of life, as well as cultivating compassion in the workplace.

The High "Cost" of Experimental Drugs Obtained Through Health Litigation in Brazil.

BACKGROUND: Brazilian patients have legal right to access unlicensed medicines undergoing clinical research, if there is evidence of efficacy and safety. This study investigated the occurrence of serious adverse events related to very high-cost medicines from clinical studies, expanded access and compassionate use programs, obtained by patients though health litigation. METHODS: A descriptive study using secondary data investigated unlicensed medicines obtained through lawsuits from 2010 to 2017, costing more than 1 million Brazilian reais (BRL), adjusted by the Brazilian Consumer Index to July 2017. Data sources were the Brazilian Health Surveillance Agency Registry (DATAVISA) and Adverse Events in Clinical Studies (NotivisaEC) Databases. Medicines were categorized by the Anatomical Therapeutic Chemical classification to level 03 and events by the WHO Adverse Drug Reaction Terminology. The study received ethical approval by the University of Brasilia Institutional Research Board. RESULTS: In the period, 812 drugs were obtained through litigation, and of these, 78 exceeded cost of 1 million BRL; 44 of them presented reports of 1,248 serious adverse events. Total Brazilian Government expenditure with these drugs was 3.2 billion BRL. Class L04A (n=7) showed greater expenditures (over 1.8 billion BRL). One hundred ninety-six deaths occurred and L01X was the most involved category (49.5%). Most other serious events (n=419) and sequelae (n=10) were related to L01X. CONCLUSION: Very high-cost drugs paid for by the government and obtained through health litigation presented deaths and serious adverse events in expanded access and compassionate use programs in Brazil.

Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program.

BACKGROUND: CIGB-247 is a cancer therapeutic vaccine that uses as antigen a variant of human vascular endothelial growth factor (VEGF) mixed with the bacterially-derived adjuvant VSSP. CIGB-247 has been already evaluated in two phase I clinical trials (CENTAURO and CENTAURO-2), showing to be safe and immunogenic in advanced cancer patients selected under well-defined and controlled clinical conditions. Surviving patients were submitted to monthly re-immunizations and some of them showed objective clinical benefits. Based on these results, a compassionate use program (CUP) with CIGB-247 was initiated for patients that did not meet the strict entry criteria applied for the CENTAURO and CENTAURO-2 clinical trials, but could potentially benefit from the application of this cancer therapeutic vaccine. RESULTS: Polyclonal IgM, IgA and IgG antibodies specific for VEGF were detected by ELISA in serum samples from patients vaccinated with 400 µg of antigen combined with 200 µg of VSSP. Polyclonal antibody response showed no cross reactivity for other VEGF family member molecules like VEGF-C and VEGF-D. Serum from immunized individuals was able to block the binding of VEGF to its receptors VEGFR2 and VEGFR1. IgG fraction purified from immune sera shared the aforementioned characteristics and also inhibited the interaction between VEGF and the therapeutic recombinant antibody bevacizumab, an anti-angiogenic drug approved for the treatment of different tumors. No serious adverse events attributable to CIGB-247 have been documented yet in participants of the CIGB-247 CUP. The present paper is a first report of our findings concerning the humoral response and safety characteristics in treated CIGB-247 CUP cancer patients. The study has provided the unique opportunity of not only testing CIGB-247 in a broader clinical spectrum sample of Cuban cancer patients, but also within the context of the day-to-day clinical practice and treatment settings for these diseases in Cuban medical institutions. CONCLUSIONS: The CIGB-247 CUP has demonstrated that immunization and follow-up of a variety of cancer patients, under day-to-day clinical practice conditions in several Cuban medical institutions, replicate our previous findings in clinical trials: CIGB-247 is safe and immunogenic.

Highlights of key initiatives 2017-2018

This document highlights the major achievement of the Ministry of Health for the period 2017-2018. Contains information about compassionate care, the strengthening of the health system , treatment of non-communicable, combating communicable diseases, protecting the health of mothers and children and rehabilitation and new investment in critical health infrastructure.

Empathy is a Stable Predictor of Compassionate Emotions Independent of an Attribution of Responsibility Manipulation / La empatía es un predictor estable de emociones compasivas independiente de una manipulación de atribución de responsabilidad

ABSTRACT The goal of the present research was to investigate if individual differences in empathy and personal distress were stable predictors of compassionate emotions and whether these emotions, in turn, mediate the effect of attribution on prosocial propensity. We formulated four hypotheses to be tested concerning direct and indirect effects between the variables in our model. 627 participants, mainly female (N = 408), were randomly assigned to one of two conditions in which we manipulated the attribution of responsibility of a target person (uncontrollability x controllability). Our results corroborated totally or partially all four hypotheses, indicating that empathy was a stable predictor of compassionate emotions and that these emotions mediated the effect of attribution on prosocial propensity. Notably, we found that empathy was an even stronger predictor of compassionate emotions compared to the attribution that participants made. We found evidence corroborating the assumption that these prosocial individual differences measures can predict the tendency to actually experience compassionate emotions in different situations. Thus, we conclude that the comprehension of prosocial decision-making and attribution processes underlying prosocial situations must take into account individual differences as antecedents of compassionate emotions.

RESUMEN El objetivo de la presente investigación fue evaluar si las diferencias individuales en empatía y angustia personal eran predictores estables de emociones compasivas y si estas emociones a su vez median el efecto de la atribución sobre la propensión prosocial. Hemos formulado cuatro hipótesis que se someterán a prueba por medio de los efectos directos e indirectos entre las variables del modelo. 627 participantes, principalmente mujeres (N = 408), fueron asignados aleatoriamente a una de las condiciones en las que manipulamos la atribución de responsabilidad (incontrolabilidad x controlabilidad). Nuestros resultados corroboraron total o parcialmente las cuatro hipótesis, indicando que la empatia es un predictor estable de emociones compasivas y que estas emociones mediaron el efecto de la atribución sobre la propensión prosocial. Es importante destacar que encontramos que la empatia fue un predictor aún más fuerte de emociones compasivas en comparación con la atribución que los participantes hicieron. Encontramos evidencias que corroboran el supuesto de que estas medidas de las diferencias individuales prosociales pueden predecir la tendencia a experimentar emociones compasivas en diferentes situaciones y concluimos que la comprensión de los procesos de toma de decisiones y de atribución prosociales subyacentes a las situaciones prosociales debe tener en cuenta las diferencias individuales como antecedentes de emociones compasivas.

Nivel de orientación empática en los estudiantes de terapia física y rehabilitación de una universidad estatal / Level of empathic orientation in students of physical therapy and rehabilitation of a state university

Objetivo: Determinar el nivel de orientación empática en los estudiantes de Terapia Física y Rehabilitación de la Universidad Nacional Mayor de San Marcos, 2016. Materiales y métodos: Estudio de enfoque cuantitativo de tipo descriptivo-observacional, prospectivo, con diseño no experimental de corte transversal. Realizado en 134 estudiantes de Terapia Física y Rehabilitación del 2do al 5to año de carrera de la Escuela Académico Profesional de Tecnología Médica de la UNMSM; se empleó la Escala de Empatía Médica de Jefferson (EEMJ). Resultados: En general se obtuvo una puntuación media de 114.60±14.424, que corresponde a un nivel alto de orientación empática. Cualitativamente esta categoría está representada por el 85.1%. Respecto a las dimensiones, se obtuvieron puntuaciones medias de "Toma de perspectiva" (61.33, nivel alto [91.0%]), "Atención por compasión" (41.16, nivel alto [82.8%]) y "Capacidad de Ponerse en el Lugar del Paciente" (12.38, nivel medio [61.2%]). No hay diferencias significativas en general ni en las dimensiones según sexo y según edad (p>0.05), pero sí se encuentran diferencias significativas según año de carrera. Conclusión: Los estudiantes de Terapia Física y Rehabilitación de la Universidad Nacional Mayor de San Marcos, presentan del 3er, 4to y 5to año respecto al 2do año de carrera (p≤0.05) una orientación empática favorable; específicamente se muestran prestos a la comprensión de los sentimientos de los pacientes y en poner atención a las experiencias personales de los pacientes como medio terapéutico

Objective: To determine the level of empathic orientation in students of Physical Therapy and Rehabilitation of Universidad Nacional Mayor de San Marcos (UNMSM), 2016. Materials and methods: A quantitative descriptive-observational prospective non-experimental cross-sectional study performed in 134 second- to fifth-year students of Physical Therapy and Rehabilitation at Escuela Académico Profesional de Tecnología Médica of UNMSM. The Jefferson Scale of Empathy (JSE) was used. Results: In general, a mean score of 114.60 ± 14.424 was obtained, corresponding to a high level of empathic orientation. This category is qualitatively represented by 85.1%. Regarding the dimensions, mean scores were obtained in "Perspective Taking" (61.33, high level [91.0%]), "Compassionate Care" (41.16, high level [82.8%]) and "Standing in the Patient's Shoes" (12.38, mean level [61.2%]). There were no significant differences neither in general terms nor in gender and age (p>0.05), but there were significant differences in the year of the career. Conclusion: Third, fourth and fifth-year students of Physical Therapy and Rehabilitation of Universidad Nacional Mayor de San Marcos have a favorable empathic orientation compared to second-year students (p≤0.05). They specifically show willingness to understand patients' feelings and pay attention to patients' personal experiences as therapeutic means

Ministry of Health Annual report 2016-2017: Highlights of key initiatives

This document highlights the major achievement of the Ministry of Health for the period 2016-2017. Contains information about compassionate care, the strengthening of the health system , treatment of non-communicable diseases, combating communicable diseases, protecting the health of mothers and children, rehabilitation and new investment in critical health infrastructure.

Conceptual clarifications regarding Chilean Act 20850 on public funding of high-cost diseases.

In 2015, Chile enacted the 20850 law, providing public funds for rare and costly diseases that demanded high diagnostic and therapeutic expenditures. The law modifies the Chilean Sanitary Code regulation of research with human beings, aiming at the protection of subjects by securing post-investigational medical benefits and insurance coverage for damage imputable to the research they participated in. Due to ambiguous phrasing, a polemic rose for fear that these protective measures applied to all clinical research, although a careful reading of the law in its context clearly suggests that it refers to phase I therapeutic trials. This paper stresses the distinction between compassionate use and genuine phase I/II therapeutic trials aimed at both pharmacodynamics and an intended therapeutic effect for severe and progressive diseases that are therapeutically orphaned, emphasizing the ethical and medical duty of providing post-trial beneficial medication.

En 2015 se publica en Chile la Ley 20850, cuyo objetivo declarado es el financiamiento público de enfermedades raras y de aquellas de alto costo diagnóstico y terapéutico. Inserto en la ley hay un articulado a introducir en el Código Sanitario, que exige de las investigaciones clínicas que mantengan los beneficios médicos determinados por el estudio, para los pacientes investigados, por todo el tiempo que sea médicamente necesario; amparado por extensos seguros para cubrir eventuales complicaciones y efectos indeseados. La redacción de la ley había motivado intensas polémicas, debido a su imprecisa redacción que permite interpretar que la protección exigida es extensible a todo estudio clínico; siendo que la lectura atenta y el contexto de este articulado claramente lo refieren a terapias experimentales. Este artículo distingue entre uso compasivo y terapias experimentales genuinas, que enlazan Fase I (delimita dosis máximas no tóxicas en individuos sanos) y Fase II (estudia efectividad en pequeños grupos de pacientes), investigando tanto farmacodinamia como efectos terapéuticos para enfermedades graves, en deterioro progresivo y huérfanas de tratamiento, con el objetivo ético y médico de la disponibilidad de efectos benéficos, más allá de terminado el estudio.

Responses towards a dying adult group member in a wild New World monkey.

Compassionate caretaking behaviour towards dying adult group members has been reported as being unique to humans and chimpanzees. Here we describe in detail the reaction of a wild dominant male common marmoset, a neotropical primate, to the accidental death of the dominant female of its group. The male exhibited behaviours towards the dying female that resembled those of chimpanzees and humans. The long-term relationship between the dominant pair (which lasted at least 3.5 years) and their social status in the group may have contributed to the male's behavioural response. The male prevented young individuals from approaching the dying female, behaviour previously observed in chimpanzees. The data provide an interesting insight into compassionate caretaking behaviours in New World primates as well as the pair-bond systems of common marmosets. These are rare observations, and thus their detailed descriptions are essential if we are to create a comparative and enhanced understanding of human and nonhuman primate thanatology.