KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling

Killer-cell immunoglobulin-like receptors (KIR) are molecules expressed by the most important cells of the immune system for cancer immune vigilance, natural killer (NK) and effector T cells. In this manuscript we study the role that cytotoxic CD8+ T cells expressing KIR receptors could play in cancer immune surveillance. With this objective, frequencies of different KIR+ CD8+ T cell subsets are correlated with the overall survival of patients with melanoma, ovarian and bladder carcinomas. In addition, the gene expression profile of KIR+ CD8+ T cell subsets related to the survival of patients is studied with the aim of discovering new therapeutic targets, so that the outcome of patients with cancer can be improved. Killer-cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) and effector T cells. Although KIR+ T cells accumulate in oncologic patients, their role in cancer immune response remains elusive. This study explored the role of KIR+CD8+ T cells in cancer immunosurveillance by analyzing their frequency at diagnosis in the blood of 249 patients (80 melanomas, 80 bladder cancers, and 89 ovarian cancers), their relationship with overall survival (OS) of patients, and their gene expression profiles. KIR2DL1+ CD8+ T cells expanded in the presence of HLA-C2-ligands in patients who survived, but it did not in patients who died. In contrast, presence of HLA-C1-ligands was associated with dose-dependent expansions of KIR2DL2/S2+ CD8+ T cells and with shorter OS. KIR interactions with their specific ligands profoundly impacted CD8+ T cell expression profiles, involving multiple signaling pathways, effector functions, the secretome, and consequently, the cellular microenvironment, which could impact their cancer immunosurveillance capacities. KIR2DL1/S1+ CD8+ T cells showed a gene expression signature related to efficient tumor immunosurveillance, whereas KIR2DL2/L3/S2+CD8+ T cells showed transcriptomic profiles related to suppressive anti-tumor responses. These results could be the basis for the discovery of new therapeutic targets so that the outcome of patients with cancer can be improved

Home parenteral nutrition registry in Spain for the year 2010: NADYA-SENPE group

Objetivos: Comunicar los datos del Registro del Grupo NADYA SENPE de Nutrición Parenteral Domiciliaria NPD en España del año 2010. Material y métodos: Estudio descriptivo de la base de datos del Registro de ámbito nacional de NPD del grupo NADYA-SENPE (1 de enero de 2010 al 31 de diciembre de 2010). Para el cálculo de prevalencias se utilizó los últimos datos publicados por el Instituto Nacional de Estadística. Resultados: Se registraron 148 pacientes procedentes de 23 hospitales, 86 mujeres (58,11%) y 9 niños (6,08%). La edad media de los 139 pacientes adultos fue de 53,06 ± 15,41 años. La duración media de la NPD fue de 316,97 días/paciente. El diagnóstico más frecuente en los niños (menores de 14 años) fue intestino corto traumático con 5 casos (55,55%) y en los adultos la neoplasia en tratamiento paliativo 29 (19,59%). El motivo de la indicación de la NPD fue el síndrome de intestino corto en 74 ocasiones (47%). La vía de acceso más frecuentemente registrada fue el catéter tunelizado en 36 (22,78%) casos seguido del reservorio en 13 (8,23%) y otras vías en 3 ocasiones (1,90%). Se registraron 23 infecciones relacionadas con el catéter (82,14%), lo que representa 0,49/1000 días de NP y todas ellas ocurrieron en los adultos. A lo largo del año finalizaron 24 episodios de NPD, la causa más frecuente fue el paso a la vía oral en 12 episodios (50%). Se registró que los pacientes tenían una actividad normal en 70 episodios de NPD (44,30%) con una total autonomía en 88 de episodios (55,69%). Se identificaron 39 (24,68%) posibles candidatos para trasplante intestinal. Conclusiones: El número de pacientes registrados es discretamente inferior al del año anterior, aunque el número de hospitales participantes es el mismo. La complicación más frecuente sigue siendo la infección relacionada con el catéter aunque ha disminuido su incidencia respecto a años anteriores, presentándose la tasa más baja desde la creación del registro. Las diferencias en la participación en el registro observadas por Comunidades Autónomas lleva a plantear el desarrollo de estrategias de implementación del registro. Se observa un aumento progresivo de la duración de los días de NPD a lo largo de los años que hace pensar en la cronicidad de algunos pacientes, pero nos obliga a estudiar la existencia de un posible factor de confusión, en el caso de que existiera un olvido de cierre de algún episodio por lo que se hace necesario actualizar el registro con sistemas de alertas periódicas que faciliten la revisión de los pacientes incluidos y optimice la validez del registroObjectives: To report the Group Registry NADYASENPE data about home parenteral nutrition (HPN) in Spain in 2010. Material and methods: A descriptive study of the database of the national registry of HPN of NADYA-SENPE (December 10, 2009 to December 10, 2010). For the calculation of prevalence the latest data published by the Institute National Statistics Office (01/01/2009) was used. Results: There were registered 148 patients from 23 hospitals, 86 women (58.11%) and 9 children (6.08%). The average age of the 139 patients older than 14 years was 53.06 ± 15.41 years. The average duration of HPN was 316.97 days/patient. The most common diagnosis in those younger than 14 years was short bowel traumatic with 5 cases (55.55%) and in those older than 14 years, palliative care cancer with 29 cases (19.59%). The reason for the indication for HPN was short bowel syndrome in 74 cases (47%). The access via most frequently recorded was tunneled catheter in 36 cases (22.78%) followed by implanted port-catheters in 13 cases (8.23%) and other pathways in 3 cases (1.90%). There were 23 catheterrelated infections (82.14%) which represented 0.49 /1,000 days of PN, all of which occurred in cases older than 14 years. During the year 24 episodes of HPN ended, the most frequent cause was the transition to oral nutrition in 12 episodes (50%). It was reported that patients had a normal activity in 70 episodes of HPN (44.30%) with complete autonomy in 88 episodes (55.69%). Some patients 39 (24.68%) were potential candidates for intestinal transplantation. Conclusions: The number of registered patients is slightly lower than the previous year, although the number of participating hospitals is the same. The most frequent complication remains catheter-related infection but its incidence has decreased from previous years, presenting the lowest rate since the creation of the record. Differences in participation in the registry observed in the Autonomous Communities causes the development of implementation strategies. There is a gradual increase in day length of HPN over the years, which suggests the chronic treatments of some patients and obliges to study the existence of a possible confounding factor, in case there is an oversight of closing an episode. Therefore, it is necessary to update the registry with warning systems that facilitate periodic review of the patients and optimize the validity of registratio

Quality of life and cost-effectiveness analysis of topical tranexamic acid and fibrin glue in femur fracture surgery

Background: we assessed quality of life (QoL) of patients undergoing surgery for proximal femur fracture and performed a cost-effectiveness analysis of haemostatic drugs for reducing postoperative bleeding. Methods: we analysed data from an open, multicentre, parallel, randomized controlled clinical trial (RCT) that assessed the efficacy and safety of tranexamic acid (TXA group) and fibrin glue (FG group) administered topically prior to surgical closure, compared with usual haemostasis methods (control group). For this study we conducted a cost-effectiveness analysis of these interventions from the Spanish Health System perspective, using a time horizon of 12 months. The cost was reported in $US purchasing power parity (USPPP). We calculated the incremental cost-effectiveness ratio (ICER) per QALY (quality-adjusted life-year). Results: we included 134 consecutive patients from February 2013 to March 2015: 42 patients in the TXA group, 46 in the FG group, and 46 in the control group. Before the fracture, EuroQol visual analogue scale (EQ-VAS) health questionnaire score was 68.6. During the 12 months post-surgery, the intragroup EQ-VAS improved, but without reaching pre-fracture values. There were no differences between groups for EQ-VAS and EuroQol 5 dimensions 5 levels (EQ-5D-5L) health questionnaire score, nor in hospital stay costs or medical complication costs. Nevertheless, the cost of one FG treatment was significantly higher (399.1$USPPP) than the cost of TXA (12.9 $USPPP) or usual haemostasis (0$USPPP). When comparing the cost-effectiveness of the interventions, FG was ruled out by simple dominance since it was more costly (13,314.7 $USPPP) than TXA (13,295.2$USPPP) and less effective (utilities of 0.0532 vs. 0.0734, respectively). TXA compared to usual haemostasis had an ICER of 15,289.6 $USPPP per QALY). Conclusions: there were no significant differences between the intervention groups in terms of postoperative changes in QoL. However, topical TXA was more cost-effective than FG or usual haemostasis

KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling

Killer-cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) and effector T cells. Although KIR+ T cells accumulate in oncologic patients, their role in cancer immune response remains elusive. This study explored the role of KIR+CD8+ T cells in cancer immunosurveillance by analyzing their frequency at diagnosis in the blood of 249 patients (80 melanomas, 80 bladder cancers, and 89 ovarian cancers), their relationship with overall survival (OS) of patients, and their gene expression profiles. KIR2DL1+ CD8+ T cells expanded in the presence of HLA-C2-ligands in patients who survived, but it did not in patients who died. In contrast, presence of HLA-C1-ligands was associated with dose-dependent expansions of KIR2DL2/S2+ CD8+ T cells and with shorter OS. KIR interactions with their specific ligands profoundly impacted CD8+ T cell expression profiles, involving multiple signaling pathways, effector functions, the secretome, and consequently, the cellular microenvironment, which could impact their cancer immunosurveillance capacities. KIR2DL1/S1+ CD8+ T cells showed a gene expression signature related to efficient tumor immunosurveillance, whereas KIR2DL2/L3/S2+CD8+ T cells showed transcriptomic profiles related to suppressive anti-tumor responses. These results could be the basis for the discovery of new therapeutic targets so that the outcome of patients with cancer can be improved.This research was funded by the Spanish Ministry of Economy—Institute of Health Carlos III (PI1302297), Fundación Mutua Madrileña (AP74392010), and Fundación Séneca de la Agencia de Ciencia y Tecnología, Región de Murcia, (20812-PI-18). M.V. Martínez-Sánchez was funded by the Asociación Pablo Ugarte (APU).Ye