Análisis y caracterización clínica, patológica y molecular de pacientes con sospecha de poliposis colónica hereditaria

[ES] La investigación establece como hipótesis: La poliposis gastrointestinal es un problema clínico común en el que aún no se ha encontrado un consenso sobre el mejor manejo de los pacientes con un moderado número de pólipos y sin variante patogénica germinal identificada. Los síndromes hereditarios de poliposis son entidades poco frecuentes, genética y clínicamente heterogéneas, con características que, a menudo, solapan uno o más de los distintos síndromes, y en las que la identificación de su causa genética repercute favorablemente en el pronóstico y vigilancia de los afectados. Y, agrupar y analizar las características clínicas, patológicas, familiares y moleculares de pacientes con sospecha de poliposis hereditaria e intentar correlacionarlas en distintos grupos o entidades ya conocidas supone un reto, dado que, la clasificación de los pólipos y de las poliposis ha cambiado a lo largo de los años. Merece una reflexión y análisis de los individuos estudiados con sospecha de poliposis, pero sin identificar la causa genética, incorporando un análisis exhaustivo de todas las variables e incorporando un estudio molecular innovador. El principal objetivo de este proyecto es: Analizar las características clínicas, patológicas, moleculares y familiares de los pacientes con sospecha de poliposis adenomatosa familiar estudiados en la Unidad de Consejo Genético del Complejo Asistencial Universitario de Salamanca (CAUSA). Como objetivos específicos se encuentran: 1. Analizar la frecuencia de detección de Síndromes de Poliposis Adenomatosa Colónica Familiar mediante el uso de criterios clínicos. 2. Análisis de la correlación genotipo-fenotipo en pacientes con Poliposis Colónica Familiar. 3. Caracterización clínica, patológica y molecular de los pacientes con sospecha de poliposis hereditaria y estudio genético no informativo para los genes APC y MUTYH. Búsqueda de otros genes potencialmente implicados

Sarcoidosis and sacroiliitis, a case report

Producción CientíficaSarcoidosis is amultisystem disorder of unknown etiology characterized by the presence of non-caseating granulomas in the organs affected. Sarcoid arthropathy is a rare manifestation, and sacroiliitis is an unusual first manifestation of the disorde

Immune system disorders, cancer and viral infections: A new treatment opportunity for the immune checkpoint inhibitors

Producción CientíficaThe relationship between viral infections and cancer is well known and has been established for decades. Multiple tumours are generated from alterations secondary to viral infections 2 resulting from a dysregulation of the immune system in many cases. Certain causal relationships, such as that between the Epstein–Barr virus (EBV) in nasopharyngeal cancer or hepatitis C and B viruses in hepatocarcinoma, have been clearly established, and their implications for the prognosis and treatment of solid tumours are currently unknown. Multiple studies have evaluated the role that these infections may have in the treatment of solid tumours using immunotherapy. A possible relationship between viral infections and an increased response to immune checkpoint inhibitors (ICIs) has been established at a theoretical level in solid neoplasms, such as EBV-positive cavum cancer and human papillomavirus (HPV)-positive and oropharyngeal cancer. These could yield a greater response associated with the activation of the immune system secondary to viral infection, the consequence of which is an increase in survival in these patients. That is why the objective of this review is to assess the different studies or clinical trials carried out in patients with solid tumours secondary to viral infections and their relationship to the response to ICIs

Resistance to immune checkpoint inhibitors secondary to myeloid-derived suppressor cells: A new therapeutic targeting of haematological malignancies

Producción CientíficaMyeloid-derived suppressor cells (MDSCs) are a set of immature myeloid lineage cells that include macrophages, granulocytes, and dendritic cell precursors. This subpopulation has been described in relation to the tumour processes at different levels, including resistance to immunotherapy, such as immune checkpoint inhibitors (ICIs). Currently, multiple studies at the preclinical and clinical levels seek to use this cell population for the treatment of different haematological neoplasms, together with ICIs. This review addresses the different points in ongoing studies of MDSCs and ICIs in haematological malignancies and their future significance in routine clinical practice

[EMBARGADO HAST DIC 2021]Antimicrobial effect of nanostructured membranes for guided tissue regeneration: an in vitro study

Objective:The purpose of this in vitrostudy was to evaluate the antibacterial effect ofanovel non-resorbable, bioactive polymeric nanostructuredmembrane(NMs), whendoped with zinc, calcium and doxycycline.Methods:A validated in vitrosubgingival biofilm model with six bacterial species (Streptococcus oralis, Actinomyces naeslundii, Veillonela parvula, Fusobacterium nucleatum, Porphyromonas gingivalis andAggregatibacter actinomycetemcomitans)was used. The experimental NMs, with and without beingdoped with doxycycline, calcium and zinc,were placed on hydroxyapatite (HA) discs. As positive control membranes, commercially available dense polytetrafluoroethylene (d-PTFE) membranes were used and,as negative controls,the HA discs without any membrane.The experimental, positive and negative control discs were exposed to a mixed bacterial suspension, at 37ºC under anaerobic conditions,during 12, 24, 48 and 72 hours. The resulting biofilms were analyzed through scanning electron microscopy(SEM),to study their structure,andby quantitative polymerase chain reaction (qPCR),to assess the bacterialload,expressed as colony forming units (CFU) per mL. Differences between experimental and control groups were evaluated with the general linear model and the Bonferroni adjustment. Results:As shown by SEM, all membrane groups,except the NMswith doxycycline,resulted in structured biofilms from 12 to 72 hours. Similarly, only the membranes loaded with doxycycline demonstrated a significant reduction in bacterial load during biofilm development,when compared with the control groups (p<0.001).Significance:Doxycycline-doped nanostructured membranes have an impact onbiofilm growth dynamics by significant reducing the bacterial load.This work was supported by the Ministry of Economy and Competitiveness (and European Regional Development Fund [Project MAT2017-85999-PMINECO/AEI/FEDER/UE] and University of Granada Research and Transfer Program

Immunohistochemical Assessment of the P53 Protein as a Predictor of Non-Small Cell Lung Cancer Response to Immunotherapy.

Determining predictive biomarkers for immune checkpoint inhibitors (ICIs) is a current challenge in oncology. Previous studies on non-small cell lung cancer (NSCLC) have shown how TP53 gene mutations are correlated with different responses to ICIs. Strong and diffuse immuno-expression of p53 by immunohistochemistry (IHC) is interpreted as a likely indicator of a TP53 gene mutation. We aimed to assess the p53 protein expression via IHC in NSCLC as a predictive biomarker of the response to ICIs. This was a retrospective hospital-based study of patients with NSCLC treated with Nivolumab in the University Hospital of Salamanca. All diagnostic biopsies were studied via IHC (measuring p53 protein expression, peroxidase anti-peroxidase immunohistochemistry technique using Leica BOND Polymer development kits). Survival analysis was performed by subgroups of expression of p53 and other factors using the Kaplan-Meier estimator and Cox proportional-hazards model. Seventy-three patients were included (59 men and 14 women). The median age was 68 (44-84) years. Thirty-six biopsies were adenocarcinoma, 34 were squamous, and three were undifferentiated. In 41 biopsies (56.2%), the cellular expression of p53 was A trend toward a greater response to ICIs was observed in the PFS and OS of patients with high expression of p53 by IHC (TP53 mutation), especially in the PD-L1 negative adenocarcinoma subgroup. These results will make it possible to make future modifications to the clinical guidelines of NSCLC according to the expression of p53

Influence of DNA Mismatch Repair (MMR) System in Survival and Response to Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC): Retrospective Analysis

Mutations in the mismatch repair (MMR) system predict the response to immune checkpoint inhibitors (ICIs) like colon or gastric cancer. However, the MMR system&rsquo;s involvement in non-small cell lung cancer (NSCLC) remains unknown. Addressing this issue will improve clinical guidelines in the case of mutations in the main genes of the MMR system (MLH1, MSH2, MSH6, and PMS2). This work retrospectively assessed the role that these gene mutations play in the response to and survival of ICIs in NSCLC. Patients with NSCLC treated with nivolumab as the second-line treatment in the University Hospital of Salamanca were enrolled in this study. Survival and response analyses were performed according to groups of MMR system gene expression (MMR expression present or deficiency) and other subgroups, such as toxicity. There was a statistically significant relationship between the best response obtained and the expression of the MMR system (p = 0.045). The presence of toxicity grade &ge; 3 was associated with the deficiency expression of MMR (dMMR/MSI-H) group (p = 0.022; odds ratio = 10.167, 95% confidence interval (CI) 1.669&ndash;61.919). A trend towards greater survival and response to ICIs was observed in NSCLC and dMMR. Assessing the genes in the MMR system involved in NSCLC is key to obtaining personalized immunotherapy treatments

Response to Treatment with an Anti-Interleukin-6 Receptor Antibody (Tocilizumab) in a Patient with Hemophagocytic Syndrome Secondary to Immune Checkpoint Inhibitors

Background. Immunotherapy represents one of the fundamental treatments in the management of some types of cancer, especially malignant melanoma. Toxicity derived from increased immune system activity can manifest in multiple organs and systems. We present a case of hematological toxicity, manifested as hemophagocytic syndrome (HPS), which was successfully treated with an anti-interleukin-6 antibody (tocilizumab). Case Report. This case presents a 75-year-old woman diagnosed with metastatic choroidal melanoma, refractory to several lines of treatment. After the failure of the previous lines, ipilimumab was started. After the third dose, she developed grade 2 thrombocytopenia and anemia accompanied by elevated levels of ferritin, triglycerides, and decreased fibrinogen. Hemophagocytosis was observed in the bone marrow biopsy, and a PET-CT showed splenomegaly with increased metabolism. Treatment was based on high doses of corticosteroids and tocilizumab. Four days after the start of treatment, progressive clinical and analytical improvement was observed, achieving total remission of the condition. Discussion. HPS induced by immunotherapy is due to an immunorelated cytokine storm syndrome (CSS). The administration of the anti-interleukin-6 receptor antibody drug acted on this cytokine cascade, leading to stabilization and subsequent remission. For this reason, the use of tocilizumab should be part of the immunotherapy-induced HPS treatment algorithm