Práctica médica y sufrimiento espiritual (1a parte)

En el último decenio se ha visto en la literatura médica una profusión de artículos sobre la relación entre Religión o Vida Espiritual y Salud. Se ha determinado que no hay una relación causal entre estos dos aspectos de la vida humana, pero que existe evidencia científica sugestiva de una directa asociación de ambas: salud y espiritualidad están misteriosamente entrelazadas en la vida del individuo. El deba- te y la investigación continúan, como continúa la experiencia por parte del enfermo de un “sufrimiento espiritual” y la muchas veces vacilante actitud del médico de ofrecimiento de un “soporte espiritual”, pues no está seguro de que éste sea su papel. En esta primera parte se revisa la literatura científica reciente sobre el tema con el objeto de ofrecer una reflexión sobre esta realidad asistencial. La lectura crítica de estos artículos permite concluir que el médico debe ser más consciente del papel de la vida espiritual en la salud, particularmente en dos momentos: el primero durante su formación académica, sin descuidar la vertiente humanística de esta profesión; el segundo en cada acto médico, pues la atención de cada enfermo no pide la resolución de un problema, sino la sanación de un ser que sufre no únicamente en su realidad material.Over the past decade a large number of articles have appeared in the medical literature sharing a particular concern: what is the connection between spirituality and health? There seems to be one, but its nature is unknown. Research goes on, and in the meantime, our lack of knowledge takes its toll: on the one hand the patient experiences not just pain but also a kind of discomfort that has been termed 'spiritual suffering'; on the other hand the physician is willing to alleviate suffering but unsure of his or her role as a spiritual healer. After reviewing some of the most significant recently published studies, we wish to offer in this first part of a series a reflection that could be of some help to the practitioner. Our conclusion is that doctors should be more aware of the link between spiritual life and health, with consequences at two different stages: First, during their years of training in medical school, giving more attention to humanistic aspects of their formation. Second, in each of the medical acts, since when dealing with a patient we are not just trying to solve a problem, but to alleviate pain in a human being who transcends the purely material

Práctica médica y sufrimiento espiritual (2a parte)

En el último decenio se ha visto en la literatura médica una profusión de artículos sobre la relación entre Religión o Vida Espiritual y Salud. Se ha determinado que no hay una relación causal entre estos dos aspectos de la vida humana, pero que existe evidencia científica sugestiva de una directa asociación de ambas: salud y espiritualidad están misteriosamente entrelazadas en la vida del individuo. El debate y la investigación continúan, como continúa la experiencia por parte del enfermo de un “sufrimiento espiritual” y la muchas veces vacilante actitud del médico de ofrecimiento de un “soporte espiritual”, pues no está seguro de que éste sea su papel. En esta segunda parte se plantea que el sufrimiento espiritual puede y debe ser diagnosticado y convenientemente tratado. Esta reflexión nos lleva a sugerir un renovado interés por las materias humanísticas, en particular por la Antropología Filosófica. En cuanto a la práctica de la medicina sugerimos una valoración más cuidadosa de aspec- tos espirituales en los pacientes con trastornos más importantes, junto con la recomendación a todo el personal sanitario de procurar desarrollar un “Talento Clínico de Compasión”.Over the past decade a large number of articles have appeared in the medical literature sharing a particular concern: what is the connection between spirituality and health? There seems to be one, but its nature is unknown. Research goes on, and in the meantime, a toll is paid because of this ignorance: on the one hand the patient experiencing not just pain but also a kind of pain that has been termed 'spiritual suffering'; on the other hand the physician, willing to alleviate suffering but unsure of his role as a spiritual healer. In this second part of a series we hold that spiritual suffering may and ought to be diagnosed and treated. Also, this reflection encourages us to suggest a renewed interest in the humanistic disciplines, especifically in the philosophical anthropology. We believe that in medical practice an effort should be made by all caregivers to adequately assess the spiritual needs and sensibility of patients, while developing a clinical skill of compassion

Hematopoetic stem cell transplantation for solid tumors in Europe

Background: Hematopoetic stem cell transplants (HSCT) are discussed as treatment options for patients with solid tumors. Transplant numbers have changed substantially over the last decade, few controlled studies are available and different opinions prevail. Objective information on current practice is needed. Patients and methods: Data from 27 902 HSCT for solid tumors (2% allogeneic, 98% autologous), collected by the European Group for Blood and Marrow Transplantation (EBMT) activity survey from 1991 to 2002 were used to assess trends, transplant rates and coefficient of variation of transplant rates in Europe. Results: Transplant numbers increased from 536 in 1991 to 4154 in 1997 and decreased to 1913 in 2002. Indications were neuroblastoma (2504 HSCT; 9%), glioma (662 HSCT; 2%), soft tissue sarcoma (1253 HSCT; 4%), germ cell cancer (3291 HSCT; 12%), breast cancer (13 524 HSCT; 48%), Ewing's sarcoma (1896 HSCT; 7%), lung cancer (387 HSCT; 1%), ovarian cancer (845 HSCT; 3%) and other solid tumors (3540 HSCT; 14%). Allogeneic cells were used in <20 cases up to 1997; since then allogeneic HSCT increased to 159 in 2002, mainly for renal cell carcinoma. Low coefficients of variation in transplant rates (<60%) are observed for Ewing's sarcoma (<56.5%), suggesting consensus for this indication. Conclusions: These data give an overview on current practice of HSCT for solid tumors in Europe. They provide objective information for health-care providers and patient counsellin

Il-15 enhances the persistence and function of bcma-targeting car-t cells compared to il-2 or il-15/il-7 by limiting car-t cell dysfunction and differentiation

Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the treatment of B-lymphoid malignancies. For multiple myeloma (MM), B-cell maturation antigen (BCMA)-targeted CAR-T cells have achieved outstanding complete response rates, but unfortunately, patients often relapse within a year of receiving the therapy. Increased persistence and reduced dysfunction are crucial features that enhance the durability of CAR-T cell responses. One of the factors that influence CAR-T cell in vivo longevity and loss of function, but which has not yet been extensively studied for BCMA-directed CAR-T cells, are the cytokines used during their production. We here compared the impact of IL-2, IL-15 and a combination of IL-15/IL-7 on the phenotype and function of ARI2h, an academic BCMA-directed CAR-T cell that is currently being administered to MM patients. For this study, flow cytometry, in vitro cytotoxicity assays and analysis of cytokine release were performed. In addition, ARI2h cells expanded with IL-2, IL-15, or IL-15/IL-7 were injected into MM tumor-bearing mice to assess their in vivo efficacy. We demonstrated that each of the cytokine conditions was suitable for the expansion of ARI2h cells, with clear in vitro activity. Strikingly, however, IL-15-produced ARI2h cells had improved in vivo efficacy and persistence. When explored further, it was found that IL-15 drove a less-differentiated ARI2h phenotype, ameliorated parameters related to CAR-T cell dysfunction, and lowered the release of cytokines potentially involved in cytokine release syndrome and MM progression. Moreover, we observed that IL-15 was less potent in inducing T cell senescence and DNA damage accumulation, both of which may contribute to an unfavorable CAR-T cell phenotype. These findings show the superiority of IL-15 to IL-2 and IL-15/IL-7 in the quality of anti-BCMA CAR-T cells, particularly their efficacy and persistence, and as such, could improve the duration of responses if applied to the clinical production of CAR-T cells for patients

Poor outcome of patients with COVID-19 after CAR T-cell therapy for B-cell malignancies: results of a multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Càncer hematològic; Malalties infecciosesCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cáncer hematológico; Enfermedades infecciosasCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Haematological cancer; Infectious diseasesCOVID-19 is posing a significant threat to health in vulnerable patients, such as immunocompromised patients. For hematopoietic cell transplantation (HCT) recipients and patients with hematologic malignancies it is known that COVID-19 leads to severe morbidity and high mortality as compared to the general population [1–3]. For patients treated with Chimeric Antigen Receptor T-cell (CAR-T-cell) therapy for B-cell malignancies however, descriptions of the clinical course and outcome are still limited to small case series and case reports [4–8]. CAR-T-cell therapy recipients are believed to be at high risk of poor outcomes from COVID-19 due to their severely immunocompromised state, caused by prior lymphodepleting immunochemotherapy and CAR-T-cell therapy related side effects such as B-cell depletion, hypogammaglobulinemia, and cytopenias. In order to rapidly inform the medical field on the impact of COVID-19 on CAR-T-cell therapy recipients, the EBMT Infectious Diseases Working Party and the EHA Lymphoma Group joined forces and present the clinical course of COVID-19 in the largest European cohort to date

CAR-T Cell Therapy: A Door Is Open to Find Innumerable Possibilities of Treatments for Cancer Patients

Seven years ago a chronic lymphocytic leukemia patient was for the first time successfully treated with chimeric antigen receptor (CAR)-modified T cells (CAR-T cells) to target CD19 overexpression in tumor cells. This was the beginning of the development of a new type of immunotherapy treatment in cancer patients. Since then, identification of novel antigens expressed in tumor cells and optimization of both CAR constructs and protocols of administration have opened up new avenues for the successful treatment of other hematological malignancies. However, research still continues to avoid some problems such as toxicities associated with the treatment and to find strategies to avoid tumor cell immune evasion mechanisms. On the other hand, for solid tumors, CAR-T therapy results are still in an early phase. In contrast to hematological malignancies, the complex tumor heterogeneity of solid tumors has led to the research of novel and challenging strategies to improve CAR-T cell activity. Here, we will review the main clinical results obtained with CAR-T cells in hematological malignancies, specifically focusing on CAR-T-19 and CAR-T against B-cell maturation antigen (CAR-T-BCMA). Moreover, we will mention the main problems that decrease CAR-T cell activity in solid tumors and the strategies to overcome them. Finally, we will present some of the first clinical results obtained for solid tumors

Noninvasive characterization of the healthy human manubrium using di use optical spectroscopies

The abnormal, uncontrolled production of blood cells in the bone marrow causes hematological malignancies which are common and tend to have a poor prognosis. These types of cancers may alter the hemodynamics of bone marrow. Therefore, noninvasive methods that measure the hemodynamics in the bone marrow have a potential impact on the earlier diagnosis, more accurate prognosis, and in treatment monitoring. In adults, the manubrium is one of the few sites of bone marrow that is rich in hematopoietic tissue and is also relatively superficial and accessible. To this end we have combined time resolved spectroscopy and diffuse correlation spectroscopy to evaluate the feasibility of the noninvasive measurement of the hemodynamics properties of the healthy manubrium in 32 subjects. The distribution of the optical properties (absorption and scattering) and physiological properties (hemoglobin concentration, oxygen saturation and blood flow index) of this tissue are presented as the first step toward investigating its pathology.Peer ReviewedPostprint (author's final draft

development of adaptive immune effector therapies in solid tumors

Abstract State-of-the-art treatment strategies have drastically ameliorated the outcome of patients affected by cancer. However, resistant and recurrent solid tumors are generally nonresponsive to conventional therapies. A central factor in the sequence of events that lead to cancer is an alteration in antitumor immune surveillance, which results in failure to recognize and eliminate the transformed tumor cell. A greater understanding of the dysregulation and evasion of the immune system in the evolution and progression of cancer provides the basis for improved therapies. Targeted strategies, such as T-cell therapy, not only generally spare normal tissues, but also use alternative antineoplastic mechanisms that synergize with other therapeutics. Despite encouraging success in hematologic malignancies, adaptive cellular therapies for solid tumors face unique challenges because of the immunosuppressive tumor microenvironment, and the hurdle of T-cell trafficking within scarcely accessible tumor sites. This review provides a brief overview of current cellular therapeutic strategies for solid tumors, research carried out to increase efficacy and safety, and results from ongoing clinical trials