[Creutzfeldt-Jakob disease: Report of one case]. / Desafíos en el diagnóstico de enfermedad de Creutzfeldt-Jakob: Caso clínico.

Creutzfeldt-Jakob disease has a higher incidence in Chile than in other countries. The post mortem pathological characterization of brain tissue is necessary to reach a definitive diagnosis. We report a 73 years old man with a history compatible with of a rapidly progressive dementia, in which the first electroencephalographic study showed a pattern consistent with non-convulsive status epilepticus. Besides discarding this diagnosis, it was necessary to rule out other causes of rapidly progressive dementia such as Hashimoto encephalopathy. Finally, the sustained clinical deterioration with no response to anticonvulsants and corticosteroids, the imaging studies, a serial electroencephalographic monitoring study and the detection of 14-3-3 protein in cerebrospinal fluid were the keys to achieve the diagnosis of the disease.

Functional gap junctions accumulate at the immunological synapse and contribute to T cell activation.

Gap junction (GJ) mediates intercellular communication through linked hemichannels from each of two adjacent cells. Using human and mouse models, we show that connexin 43 (Cx43), the main GJ protein in the immune system, was recruited to the immunological synapse during T cell priming as both GJs and stand-alone hemichannels. Cx43 accumulation at the synapse was Ag specific and time dependent, and required an intact actin cytoskeleton. Fluorescence recovery after photobleaching and Cx43-specific inhibitors were used to prove that intercellular communication between T cells and dendritic cells is bidirectional and specifically mediated by Cx43. Moreover, this intercellular cross talk contributed to T cell activation as silencing of Cx43 with an antisense or inhibition of GJ docking impaired intracellular Ca(2+) responses and cytokine release by T cells. These findings identify Cx43 as an important functional component of the immunological synapse and reveal a crucial role for GJs and hemichannels as coordinators of the dendritic cell-T cell signaling machinery that regulates T cell activation.

Where did it hit harder? Understanding the geography of excess mortality during the COVID-19 pandemic.

The health impact of the COVID-19 pandemic across OECD (Organisation for Economic Co-operation and Development) and European regions has been strikingly uneven. In 2020, excess mortality rates in the hardest-hit regions were, on average, 17 percentage points higher than those in the least affected regions of the same country. This paper shows that low health system capacity, followed by population density, air pollution, the share of elderly people, and low institutional quality were associated with higher excess mortality during the first year of the pandemic. Finally, reduced home-to-work mobility, following governments' COVID-19 responses, was associated with lower excess mortality 2 months after implementation of the measures.

Habitat manipulation for sustainable management of Philaenus spumarius, the main vector of Xylella fastidiosa in Europe.

BACKGROUND: The unexpected Xylella fastidiosa (Xf) outbreak in Europe has led to aggressive management of the disease in recent years. As there is no cure for infected plants, management of vector populations is mandatory to contain the spread of Xf in infected areas. We aimed to assess the suitability of plant species commonly used as cover crops for the population growth of Philaenus spumarius L. (Aphrophoridae). Thus, we conducted a series of no-choice and multiple-choice assays to assess the oviposition preference of P. spumarius adults as well as the development and mortality rate of nymphs on 10 candidate plant species under laboratory and semi-field conditions. Our results will help to design ecological infrastructures, including a pull-push strategy for effective management of Xf vectors in olive groves. RESULTS: Results showed that Anthriscus cerefolium is a suitable plant to enhance oviposition but has a lethal effect on the first nymphal instars of P. spumarius. Moreover, Diplotaxis tenuifolia is not suitable for oviposition or nymphal development. Sinapis alba does not enhance oviposition but is suitable for nymphal development with a medium-high cumulative mortality of the nymphs. Conversely, adults and nymphs had a high preference and low mortality on Taraxacum officinale, and nymphs showed a medium-high preference on Lavandula angustifolia, suggesting that these two species should be avoided as ground cover plants on Xf-susceptible crops. CONCLUSION: The results obtained in our study open new ways to manage the vectors of Xf by using specific plant species as ground cover, which in turn will reduce the spread and prevalence of Xf. © 2022 Society of Chemical Industry.

Glyphosate Pollution Treatment and Microbial Degradation Alternatives, a Review.

Glyphosate is a broad-spectrum herbicide extensively used worldwide to eliminate weeds in agricultural areas. Since its market introduction in the 70's, the levels of glyphosate agricultural use have increased, mainly due to the introduction of glyphosate-resistant transgenic crops in the 90's. Glyphosate presence in the environment causes pollution, and recent findings have proposed that glyphosate exposure causes adverse effects in different organisms, including humans. In 2015, glyphosate was classified as a probable carcinogen chemical, and several other human health effects have been documented since. Environmental pollution and human health threats derived from glyphosate intensive use require the development of alternatives for its elimination and proper treatment. Bioremediation has been proposed as a suitable alternative for the treatment of glyphosate-related pollution, and several microorganisms have great potential for the biodegradation of this herbicide. The present review highlights the environmental and human health impacts related to glyphosate pollution, the proposed alternatives for its elimination through physicochemical and biological approaches, and recent studies related to glyphosate biodegradation by bacteria and fungi are also reviewed. Microbial remediation strategies have great potential for glyphosate elimination, however, additional studies are needed to characterize the mechanisms employed by the microorganisms to counteract the adverse effects generated by the glyphosate exposure.

[Validity of predictive power of the Adjusted Morbidity Groups (AMG) with respect to others population stratification tools.] / Validación del poder predictivo de los Grupos de Morbilidad Ajustada (GMA) respecto de otras herramientas de estratificación de la población.

OBJECTIVE: This work was performed in order to get objective elements of judgment that support the improvement of a national population morbidity grouper based in the Adjusted Morbidity Groups (AMG). The study compared the performance in terms of predictive power on certain health and resource outcomes, in between the AMG and several existing morbidity groupers (ACG®, Adjusted Clinical Groups and CRG®, Clinical Risk Group) used in some Autonomous Regions in Spain (Aragón, Canarias y Castilla y León). METHODS: Cross-sectional analytical study in entitled/insured population with respect to rights of healthcare. Predictive capacity of the complexity weight obtained with the different stratification tools in the first year of the study period was evaluated using a simple classification method that compares the areas under the curves ROC for the following outcomes that occurred in the second year of the study period: Probability of death; probability of having at least one urgent hospital admission; total number of visits to hospital emergencies; total number of visits to primary care; total number of visits to hospital care and spending in pharmacy. RESULTS: The results showed that AMG complexity weight were good predictors for almost all the analyzed outcomes (AUC ROC>0.7; p<0.05), for the different Autonomous Regions and compared to ACG® or CRG®. Only for the outcome of visits to hospital emergencies in Aragon and Canarias; and visits to specialized care in Aragon, the predictive power was weak for all the compared stratification tools. CONCLUSIONS: GMA® is a population stratification tool adequate and as useful as others existing morbidity groupers.

OBJETIVO: Este trabajo se realizó con el objetivo de conseguir elementos objetivos de juicio que apoyasen la evolución de un estratificador de la población nacional desarrollado en base a los Grupos de Morbilidad Ajustada (GMA). Para ello se validó el poder predictivo de esta herramienta de estratificación sobre determinadas variables de resultado, mediante comparación con otros estratificadores como ACG® (Adjusted Clinical Groups) y CRG® (Clinical Risk Group), utilizados en algunas comunidades autónomas (CCAA) como Aragón, Canarias y Castilla y León. METODOS: Se realizó un estudio analítico transversal en la población con derecho a la asistencia sanitaria. Se evaluó la capacidad predictiva del peso de complejidad obtenido con cada una de las herramientas de estratificación en el primer año, mediante un método de clasificación simple que comparó las áreas bajo las curvas ROC sobre las siguientes variables de resultado que sucedieron en el año siguiente: probabilidad de muerte; probabilidad de tener al menos un ingreso hospitalario urgente; número total de asistencias a urgencias hospitalarias; número total de visitas a Atención Primaria (AP); número total de consultas externas de Atención Hospitalaria (AH) y gasto farmacéutico. RESULTADOS: Los resultados obtenidos mostraron que los GMA® fueron buenos predictores de casi todas las variables analizadas (Resultados Curvas ROC AUC>0,7; p<0,05) para las distintas comunidades autónomas, al comparar con los ACG® o los CRG®. Únicamente para la variable de asistencia a urgencias hospitalarias en el caso de Aragón y Canarias, y las derivaciones a AH en el caso de Aragón, la capacidad predictiva no fue adecuada con ninguna de las herramientas de estratificación comparadas. CONCLUSIONES: La herramienta GMA® es un sistema de estratificación de la población adecuado y tan útil como otras alternativas existentes.

Relationship between glycemic control and chronic obstructive pulmonary disease in patients with type 2 diabetes: A nested case-control study.

AIMS: To evaluate the relationship between glycemic control and plasma glycated hemoglobin (HbA1c) levels in patients with type 2 diabetes mellitus (T2D) and the risk of chronic obstructive pulmonary disease (COPD). METHODS: We conducted a population-based, retrospective, nested, case-control study involving 124,876 patients with DM2 from the Canary Islands, Spain. From the cohort, we selected all COPD cases and, for each case, five control subjects who were COPD free. We analyzed the association between glycemic control, HbA1c level and incident COPD. RESULTS: A total of 1320 incidence cases of COPD (1.06%) were identified and matched individually with 6600 controls according to age and sex. After multivariate adjustment, the COPD risk increased among patients with poor glycemic control compared to patients with good glycemic control [HbA1c levels <7% (53 mmol/mol)] (OR 1.18; 95% CI: 1.03-1.36). In comparison with patients exhibiting HbA1c levels <7% (53 mmol/mol), the risk of COPD was higher among people with HbA1c levels of 7-8% (53-64 mmol/mol) (OR 1.24; 95% CI: 1.05-1.47) and 8-9% (64-75 mmol/mol) (OR 1.31; 95% CI: 1.04-1.66). CONCLUSIONS: Poor glycemic control reveals a weak association with increased risk of COPD in T2D patients.

[Comparison of predictive models for the selection of high-complexity patients]. / Comparación de modelos predictivos para la selección de pacientes de alta complejidad.

OBJECTIVE: To compare the concordance of complexity weights between Clinical Risk Groups (CRG) and Adjusted Morbidity Groups (AMG). To determine which one is the best predictor of patient admission. To optimise the method used to select the 0.5% of patients of higher complexity that will be included in an intervention protocol. METHOD: Cross-sectional analytical study in 18 Canary Island health areas, 385,049 citizens were enrolled, using sociodemographic variables from health cards; diagnoses and use of healthcare resources obtained from primary health care electronic records (PCHR) and the basic minimum set of hospital data; the functional status recorded in the PCHR, and the drugs prescribed through the electronic prescription system. The correlation between stratifiers was estimated from these data. The ability of each stratifier to predict patient admissions was evaluated and prediction optimisation models were constructed. RESULTS: Concordance between weights complexity stratifiers was strong (rho = 0.735) and the correlation between categories of complexity was moderate (weighted kappa = 0.515). AMG complexity weight predicts better patient admission than CRG (AUC: 0.696 [0.695-0.697] versus 0.692 [0.691-0.693]). Other predictive variables were added to the AMG weight, obtaining the best AUC (0.708 [0.707-0.708]) the model composed by AMG, sex, age, Pfeiffer and Barthel scales, re-admissions and number of prescribed therapeutic groups. CONCLUSIONS: strong concordance was found between stratifiers, and higher predictive capacity for admission from AMG, which can be increased by adding other dimensions.

Extracellular adenosine promotes cell migration/invasion of Glioblastoma Stem-like Cells through A3 Adenosine Receptor activation under hypoxia.

Glioblastoma (GBM) is the brain tumor with the worst prognosis composed of a cell subpopulation called Glioblastoma Stem-like Cells (GSCs) responsible for tumor recurrence mediated by cell invasion. GSCs persist in a hypoxic microenvironment which promotes extracellular adenosine production and activation of the A3 Adenosine Receptor (A3AR), therefore, the aim of this study was to determine the role of extracellular adenosine and A3AR on GSCs invasion under hypoxia. GSCs were obtained from a U87MG cell line and primary cultures of GBM patients, and then incubated under normoxia or hypoxia. Gene expression was evaluated by RNAseq, RT-qPCR, and western blot. Cell migration was measured by spreading and transwell boyden chamber assays; cell invasion was evaluated by Matrigel-coated transwell, ex vivo brain slice, and in vivo xenograft assays. The contribution of A3AR on cell migration/invasion was evaluated using the A3AR antagonist, MRS1220. Extracellular adenosine production was higher under hypoxia than normoxia, mainly by the catalytic action of the prostatic acid phosphatase (PAP), promoting cell migration/invasion in a HIF-2-dependent process. A3AR blockade decreased cell migration/invasion and the expression of Epithelial-Mesenchymal Transition markers. In conclusion, high levels of extracellular adenosine production enhance cell migration/invasion of GSCs, through HIF-2/PAP-dependent activation of A3AR under hypoxia.

Melanocortin 1 receptor is expressed by uveal malignant melanoma and can be considered a new target for diagnosis and immunotherapy.

PURPOSE: Uveal melanoma is the most common primary malignant ocular cancer in adults. This tumor has a distinct expression pattern of markers compared with cutaneous melanoma. MC1R is under study as a potential target for antitumor immunity. Because of the potential immunogenicity of MC1R, it is important to evaluate its expression on uveal melanomas. METHODS: Two novel monoclonal antibodies (MP1.1C11 and MP1.1B7) were used to examine the expression of MC1R in uveal melanomas. Tissue samples obtained from 17 patients were analyzed for expression of MC1R by immunohistochemistry. Additionally, uveal melanoma cell lines were treated with proinflammatory cytokines, after which MC1R cell surface expression was analyzed by flow cytometry. RESULTS: Results demonstrated that MC1R is expressed by uveal melanoma to a significantly greater extent than other melanoma markers. With the use of MP1.1C11 or MP1.1B7, MC1R was detected in 95% of the tested melanoma tissues, including one liver metastasis. In contrast, MART-1, S100-specific protein, and gp-100 were only expressed by 66%, 33%, and 67% of the analyzed samples, respectively. Results also demonstrated that even though MC1R is mainly located intracellularly, its cell surface expression can be promoted by cytokines such as IFN-gamma, TNF-alpha, IL-4, and IL-10. CONCLUSIONS: These observations support the inclusion of MC1R in the panel of markers for the diagnosis of uveal melanoma. Therapeutic use of MC1R-specific antibodies targeting cytokine-induced MC1R potentially requires expression of the target molecule on the surfaces of tumor cells. Data presented here support MC1R as a new marker and a putative therapeutic target for uveal melanoma.

The connection between nursing diagnosis and the use of healthcare resources. / Relación entre diagnósticos de enfermería y uso de recursos sanitarios.

AIM: The health service invests up to 75% of its resources on chronic care where the focus should be on caring rather than curing. Nursing staff focuses their work on such care. Care requires being redorded in health histories through the standardized languages. These records enable useful analyses to organisational and healthcare decision-making. Our proposal is to know the association of between nursing diagnosis and a higher total expenditure on health. METHOD: An observational cross-sectional analytical study was performed based on data from electronic health records in Primary Care (Drago-AP), hospital discharges (CMBD-AH) and prescriptions (REC-SCS) of patients over 50 from 2012-2013 in the Canary Islands. A descriptive, bivariate and multivariate analysis was undertaken to create a predictive model on the use of resources. INDEPENDENT VARIABLES: Sociodemographic (age, sex, type of health-care affiliation, type of prescription charge) and nursing diagnosis (ND) recorded in late 2012. Dependent variables: Resources consumed in 2013. RESULTS: 582,171 patients met the criteria for inclusion. 53.0% of them were women with an average age of 64.3 years (SD 10.8years). 53.2% were pensioners. 49% of the included population had an ND, with an average of 2.1ND per patient. The average costs per patient were 1824.62€ (with a median of 827.5€) 25 and 27 percentiles of 264.1€ and 1824.7€, respectively. The bivariate analysis showed a significant correlation between these expenses and all the demographic variables; the expenses increased when a nursing diagnosis has been made (Spearman's rank=0.37: the more diagnoses, the more expenses). In the multivariate analysis, a first linear regression with the sociodemographic variables as independent variables explains 13.7% of the variability of the logarithm of the full costs (R2=0.137). If we add to this model the presence of nursing diagnoses, the explanatory capacity reaches 19.77% (R2=0.1977). CONCLUSION: Compared with a model that only consists of sociodemographic variables, nursing diagnoses can enhance the explanatory capacity of the use of healthcare resources.

The role of regulatory T lymphocytes in the induced immune response mediated by biological vaccines.

Immunotherapy has become a novel therapeutic alternative for various kinds of tumours. Recently, we have finalized the first phase I clinical study in Chile for the treatment of advanced malignant melanoma, using dendritic cells (DCs) loaded with allogeneic melanoma cell lysate. This study included 20 patients and the obtained results, pioneer in Latin America, showed that DC-based immunotherapy is innocuous, even provided in combination with IL-2. In addition, immunological responses were detected in 50% of the treated patients, establishing a positive correlation between the delayed type hypersensitivity (DTH) reaction, which indicates induction of in vivo immunological memory, and patients surviving. Nevertheless, objective clinical responses in vaccinated patients are still insufficient. Only sporadic objective metastasis regressions have been registered and an important proportion of the treated patients did not respond, or their responses were weak. Several strategies have been described to be used by tumours to escape from the immune response. Actually, we have demonstrated that IL-10 inhibits antigen presentation in melanoma, reducing tumour sensitivity to melanoma-specific cytotoxic T lymphocytes (CTLs). Regulation of the immunological response by inhibitory cells could be another possible cause of clinical unresponsiveness. Lately, the existence of subpopulations of regulatory T lymphocytes (RTL) able to limit the immune response in a specific form has been established, specially inhibiting the proliferation and activity of CD4+ and CD8+ effector T lymphocytes. These cellular subpopulations, mostly CD4+/CD25+/Foxp3+ T lymphocytes (Treg) of thymic origin, or TR1 lymphocytes able to release IL-10, and tumour growth factor beta (TGF-beta) producing TH3 lymphocytes, would be accumulated in the body during tumour growth, inhibiting the immune response. In relation to RTL and cancer, evidence indicates that Treg cell numbers are increased in blood and other tissues in different types of cancer. Additionally, it has been demonstrated that in patients with refractory metastatic melanoma, the adoptive transference of anti-tumour CD8+ T lymphocytes after non-myeloablative chemotherapy was able to induce important tumour regressions that would be due to elimination of RTL populations. Additionally, chemotherapeutical drugs like decarbazine, besides their effect on tumour proliferation, also have an immunosuppressive effect on T lymphocyte populations, as well as on accumulated RTL. In this article, a novel strategy for the study of RTL is proposed, including potential therapeutic innovations, which is being pioneered in current clinical trials.

Effectiveness and cost-effectiveness of knowledge transfer and behavior modification interventions in type 2 diabetes mellitus patients--the INDICA study: a cluster randomized controlled trial.

BACKGROUND: Type 2 diabetes mellitus is a chronic disease whose health outcomes are related to patients and healthcare professionals' decision-making. The Diabetes Intervention study in the Canary Islands (INDICA study) aims to evaluate the effectiveness and cost-effectiveness of educational interventions supported by new technology decision tools for type 2 diabetes patients and primary care professionals in the Canary Islands. METHODS/DESIGN: The INDICA study is an open, community-based, multicenter, clinical controlled trial with random allocation by clusters to one of three interventions or to usual care. The setting is primary care where physicians and nurses are invited to participate. Patients with diabetes diagnosis, 18-65 years of age, and regular users of mobile phone were randomly selected. Patients with severe comorbidities were excluded. The clusters are primary healthcare practices with enough professionals and available places to provide the intervention. The calculated sample size was 2,300 patients. Patients in group 1 are receiving an educational group program of eight sessions every 3 months led by trained nurses and monitored by means of logs and a web-based platform and tailored semi-automated SMS for continuous support. Primary care professionals in group 2 are receiving a short educational program to update their diabetes knowledge, which includes a decision support tool embedded into the electronic clinical record and a monthly feedback report of patients' results. Group 3 is receiving a combination of the interventions for patients and professionals. The primary endpoint is the change in HbA1c in 2 years. Secondary endpoints are cardiovascular risk factors, macrovascular and microvascular diabetes complications, quality of life, psychological outcomes, diabetes knowledge, and healthcare utilization. Data is being collected from interviews, questionnaires, clinical examinations, and records. Generalized linear mixed models with repeated time measurements will be used to analyze changes in outcomes. The cost-effectiveness analysis, from the healthcare services perspective, involves direct medical costs per quality-adjusted life year gained and two periods, a 'within-trial' period and a lifetime Markov model. Deterministic and probabilistic sensitivity analyses are planned. DISCUSSION: This ongoing trial aims to set up the implementation of evidence-based programs in the clinical setting for chronic patients. TRIAL REGISTRATION: Clinical Trial.gov NCT01657227.

Melanocortin 1 Receptor-derived peptides are efficiently recognized by cytotoxic T lymphocytes from melanoma patients.

BACKGROUND: Melanocortin 1 Receptor (MC1R) is expressed in a majority of melanoma biopsies and cell lines. We previously demonstrated that three hydrophobic low-affinity HLA-A2-restricted MC1R-derived peptides: MC1R291-298, MC1R244-252 and MC1R283-291 can elicit cytotoxic T-lymphocytes (CTL) responses from normal donor peripheral blood lymphocytes (PBL). Moreover, peptide-specific CTL recognized a panel of MHC-matched melanomas, demonstrating that human melanoma cell lines naturally present MC1R epitopes. However, the natural presence of MC1R-specific T cells in melanoma patient's tumour and blood remains unknown. METHODS: The presence of anti-MC1R specific CD8(+) T cells was established in a population of melanoma-specific T cells derived from peripheral blood mononuclear cells (PBMC) and tumour-infiltrating lymphocytes (TIL) from HLA-A2(+) melanoma patients. RESULTS: CTLs specific for the three MC1R-derived peptides that lysed allogeneic HLA-A2(+)MC1R(+) melanomas were elicited from PBMC, demonstrating the existence of an anti-MC1R T cell repertoire in melanoma patients. Moreover, TILs also recognized MC1R epitopes and HLA-A2(+) melanoma cell lines. Finally, HLA-A2/MC1R244-specific CD8(+) T cell clones derived from TILs and a subset of MC1R291 specific TILs were identified using HLA-A2/MC1R tetramers. CONCLUSION: Our results demonstrate that MC1R-derived peptides are common immunogenic epitopes for melanoma-specific CTLs and TILs, and may thus be useful for the development of anti-melanoma immunotherapy.

Desafíos en el diagnóstico de enfermedad de Creutzfeldt-Jakob: caso clínico / Creutzfeldt-Jakob disease: report of one case

Creutzfeldt-Jakob disease has a higher incidence in Chile than in other countries. The post mortem pathological characterization of brain tissue is necessary to reach a definitive diagnosis. We report a 73 years old man with a history compatible with of a rapidly progressive dementia, in which the first electroencephalographic study showed a pattern consistent with non-convulsive status epilepticus. Besides discarding this diagnosis, it was necessary to rule out other causes of rapidly progressive dementia such as Hashimoto encephalopathy. Finally, the sustained clinical deterioration with no response to anticonvulsants and corticosteroids, the imaging studies, a serial electroencephalographic monitoring study and the detection of 14-3-3 protein in cerebrospinal fluid were the keys to achieve the diagnosis of the disease.

Heat-shock induction of tumor-derived danger signals mediates rapid monocyte differentiation into clinically effective dendritic cells.

PURPOSE: This study characterizes, biologically and clinically, a novel type of dendritic cells (DC) produced in the short term and called tumor antigen-presenting cells (TAPCells). In particular, we identified factors present in a lysate derived from heat-shocked allogeneic melanoma cells (TRIMEL) that are associated with TAPCells' enhanced capability to induce CD8(+) T-cell responses in vitro and in vaccinated melanoma patients. EXPERIMENTAL DESIGN: First, extensive phenotypic and functional characterization of TAPCells was performed, followed by vaccination of 45 melanoma patients with four doses of TAPCells over a period of 2 months. Specific delayed-type hypersensitivity (DTH) reaction was analyzed posttreatment and correlated with overall survival rates. Furthermore, heat-shock (HS)-induced factors present in TRIMEL and their effects on DC activation were identified and studied. RESULTS: TRIMEL induced a committed, mature, DC-like phenotype in TAPCells and effectively activated melanoma-specific CD4(+) and CD8(+) T cells. Clinically, 64% of vaccinated patients showed positive DTH reaction against TRIMEL, and this was associated with improved overall survival. HS treatment of tumor cells increased calreticulin (CRT) plasma membrane translocation and induced the release of high-mobility group box 1 proteins (HMGB1). Both CRT and HMGB1 mobilization were associated with enhanced TAPCells' maturation and antigen (Ag) cross-presentation, respectively. DTH infiltration analysis revealed the presence of CD8(+)/CD45RO(+) T cells, thus confirming TAPCells' ability to cross-present Ags in vivo. CONCLUSIONS: Our results indicate that lysates derived from heat-shocked tumor cells are an optimal source of tumor-associated Ags, which are crucial for the generation of DCs with improved Ag cross-presentation capacity and clinically effective immunogenicity.

[Gastrointestinal stromal tumors. Review of 15 patients]. / Tumores gastrointestinales estromales (GIST): experiencia del Servicio de Cirugía del Hospital Clínico de la Universidad de Chile entre 1999 y 2005.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most common mesenchymatous tumors of the digestive tract. The pathological diagnosis is based on microscopy and immunohistochemistiy. AIM: To review the experience of our surgical unit in patients with GIST MATERIAL AND METHODS: Review of medical records of 15 patients (aged 66+/-13 years, 11 women), with a pathological diagnosis of GIST, treated between 1999 and 2005. RESULTS: The main presenting symptoms were melena in 40%, hematemesis in 20%, abdominal pain in 60% and anemia in 13%. In only one patient, the tumor appeared as an incidentaloma. All patients underwent upper gastrointestinal endoscopy A CAT scan was done in 87%, a barium swallow in 60% and a digestive endosonography in 20%. Thirteen tumors were located in the stomach and two in the small bowel. Mean tumor diameter was 5.3+/-1.7 cm. Surgical management was a tumor resection in 40%, a partial gastrectomy in 27%, a total gastrectomy in 20% and an intestinal excision in the rest. Mean hospital stay was 6.9+/-4.2 days. No postoperative complications were recorded. CONCLUSIONS: The main clinical presentation of GIST in this retrospective series was an upper gastrointestinal bleeding. Surgical treatment was devoid of complications.

Functional gap junctions facilitate melanoma antigen transfer and cross-presentation between human dendritic cells.

Previously, we found that human dendritic cells (hDCs) pulsed with a melanoma cell lysate (MCL) and stimulated with TNF-alpha (MCL/TNF) acquire a mature phenotype in vitro and are able to trigger tumor-specific immune responses when they are used in melanoma immunotherapy in patients. In this study, we describe that MCL/TNF induces gap junction (GJ)-mediated intercellular communications and promotes melanoma Ag transfer between ex vivo produced hDCs from melanoma patients. hDCs also exhibit increased expression of the GJ-related protein connexin 43, which contributes to GJ plaque formation after MCL/TNF stimulation. The addition of GJ inhibitors suppresses intercellular tumor Ag transfer between hDCs, thus reducing melanoma-specific T cell activation. In summary, we demonstrate that MCL/TNF-stimulated hDCs can establish functional GJ channels that participate in melanoma Ag transfer, facilitating Ag cross-presentation and an effective dendritic cell-mediated melanoma-specific T cell response. These results suggest that GJs formed between hDCs used in cancer vaccination protocols could be essentials for the establishment of a more efficient antitumor response.

Tumores gastrointestinales estromales (GIST): Experiencia del Servicio de Cirugía del Hospital Clínico de la Universidad de Chile entre 1999 y 2005 / Gastrointestinal stromal tumors: Review of 15 patients

Background: Gastrointestinal stromal tumors (GIST) are the most common mesenchymatous tumors of the digestive tract. The pathological diagnosis is based on microscopy and immunohistochemistiy. Aim: To review the experience of our surgical unit in patients with GIST Material and methods: Review of medical records of 15 patients (aged 66+13 years, 11 women), with a pathological diagnosis of GIST, treated between 1999 and 2005. Results: The main presenting symptoms were melena in 40 percent, hematemesis in 20 percent, abdominal pain in 60 percent and anemia in 13 percent. In only one patient, the tumor appeared as an incidentaloma. All patients underwent upper gastrointestinal endoscopy A CAT scan was done in 87 percent, a barium swallow in 60 percent and a digestive endosonography in 20 percent. Thirteen tumors were located in the stomach and two in the small bowel. Mean tumor diameter was 5.3+1.7 cm. Surgical management was a tumor resection in 40 percent, a partial gastrectomy in 27 percent, a total gastrectomy in 20 percent and an intestinal excision in the rest. Mean hospital stay was 6.9+4.2 days. No postoperative complications were recorded. Conclusions: The main clinical presentation of GIST in this retrospective series was an upper gastrointestinal bleeding. Surgical treatment was devoid of complication.