Prognostic impact of tumor location and gene expression profile in sporadic desmoid tumor.

PURPOSE: Prognostic biomarkers remain necessary in sporadic desmoid tumor (DT) because the clinical course is unpredictable. DT location along with gene expression between thoracic and abdominal wall locations was analyzed. METHOD: Sporadic DT patients (GEIS Registry) diagnosed between 1982 and 2018 who underwent upfront surgery were enrolled retrospectively in this study. The primary endpoint was relapse-free survival (RFS). Additionally, the gene expression profile was analyzed in DT localized in the thoracic or abdominal wall, harboring the most frequent CTNNB1 T41A mutation. RESULTS: From a total of 454 DT patients, 197 patients with sporadic DT were selected. The median age was 38.2 years (1.8-89.1) with a male/female distribution of 33.5/66.5. Most of them harbored the CTNNB1 T41A mutation (71.6 %), followed by S45F (17.8 %) and S45P (4.1 %). A significant worse median RFS was associated with males (p = 0.019), tumor size ≥ 6 cm (p = 0.001), extra-abdominal DT location (p < 0.001) and the presence of CTNNB1 S45F mutation (p = 0.013). In the multivariate analysis, extra-abdominal DT location, CTNNB1 S45F mutation and tumor size were independent prognostic biomarkers for worse RFS. DTs harboring the CTNNB1 T41A mutation showed overexpression of DUSP1, SOCS1, EGR1, FOS, LIF, MYC, SGK1, SLC2A3, and IER3, and underexpression of BMP4, PMS2, HOXA9, and WISP1 in thoracic versus abdominal wall locations. CONCLUSION: Sporadic DT location exhibits a different prognosis in terms of RFS favoring the abdominal wall compared to extra-abdominal sites. A differential gene expression profile under the same CTNNB1 T41A mutation is observed in the abdominal wall versus the thoracic wall, mainly affecting the Wnt/ß-catenin, TGFß, IFN, and TNF pathways.

PARP inhibition with rucaparib alone followed by combination with atezolizumab: Phase Ib COUPLET clinical study in advanced gynaecological and triple-negative breast cancers.

BACKGROUND: Combining PARP inhibitors (PARPis) with immune checkpoint inhibitors may improve clinical outcomes in selected cancers. We evaluated rucaparib and atezolizumab in advanced gynaecological or triple-negative breast cancer (TNBC). METHODS: After identifying the recommended dose, patients with PARPi-naive BRCA-mutated or homologous recombination-deficient/loss-of-heterozygosity-high platinum-sensitive ovarian cancer or TNBC received rucaparib plus atezolizumab. Tumour biopsies were collected pre-treatment, during single-agent rucaparib run-in, and after starting combination therapy. RESULTS: The most common adverse events with rucaparib 600 mg twice daily and atezolizumab 1200 mg on Day 1 every 3 weeks were gastrointestinal effects, fatigue, liver enzyme elevations, and anaemia. Responding patients typically had BRCA-mutated tumours and higher pre-treatment tumour levels of PD-L1 and CD8 + T cells. Markers of DNA damage repair decreased during rucaparib run-in and combination treatment in responders, but typically increased in non-responders. Apoptosis signature expression showed the reverse. CD8 + T-cell activity and STING pathway activation increased during rucaparib run-in, increasing further with atezolizumab. CONCLUSIONS: In this small study, rucaparib plus atezolizumab demonstrated acceptable safety and activity in BRCA-mutated tumours. Increasing anti-tumour immunity and inflammation might be a key mechanism of action for clinical benefit from the combination, potentially guiding more targeted development of such regimens. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03101280).

Maintenance with mirvetuximab soravtansine plus bevacizumab vs bevacizumab in FRα-high platinum-sensitive ovarian cancer.

At first recurrence, platinum-sensitive ovarian cancer (PSOC) is frequently treated with platinum-based chemotherapy doublets plus bevacizumab, then single-agent bevacizumab. Most patients' disease progresses within a year after chemotherapy, emphasizing the need for novel strategies. Mirvetuximab soravtansine-gynx (MIRV), an antibody-drug conjugate, comprises a folate receptor alpha (FRα)-binding antibody and tubulin-targeting payload (maytansinoid DM4). In FRα-high PSOC, MIRV plus bevacizumab previously showed promising efficacy (objective response rate, 69% [95% CI: 41-89]; median progression-free survival, 13.3 months [95% CI: 8.3-18.3]; median duration of response, 12.9 months [95% CI: 6.5-15.7]) and safety. The Phase III randomized GLORIOSA trial will evaluate MIRV plus bevacizumab vs. bevacizumab alone as maintenance therapy in patients with FRα-high PSOC who did not have disease progression following second-line platinum-based doublet chemotherapy plus bevacizumab.Clinical Trial Registration: ClinicalTrials.gov ID: NCT05445778; GOG.org ID: GOG-3078; ENGOT.ESGO.org ID: ENGOT-ov76.

Most patients with ovarian cancer are initially treated with platinum-based chemotherapy. If the cancer reappears/recurs after more than 6 months following this therapy, it is called platinum-sensitive ovarian cancer (PSOC). Patients with PSOC usually receive additional platinum-based chemotherapy along with bevacizumab, a drug that reduces tumor growth by decreasing its blood supply. If patients improve or are stable on this therapy, they are usually kept on bevacizumab alone for 'maintenance therapy'. Unfortunately, this maintenance therapy does not work long-term in all patients, so better long-term treatments are needed. The GLORIOSA (NCT05445778) clinical trial will compare maintenance therapy with bevacizumab alone to maintenance therapy with bevacizumab plus a drug called mirvetuximab soravtansine-gynx (MIRV) to determine which therapy leads to better results in patients with PSOC. MIRV is made up of an antibody that binds to a specific protein (folate receptor alpha [FRα]) on cancer cells to directly deliver a cancer-killing drug. MIRV received US FDA approval to be used as a therapy for patients with ovarian cancer who are resistant to platinum-based chemotherapy and express high levels of FRα. The GLORIOSA trial will study maintenance therapy with MIRV plus bevacizumab in patients with PSOC who have not had cancer progression after second-line platinum-based chemotherapy plus bevacizumab, and whose cancer expresses high amounts of FRα. The main purpose of this trial is to determine if MIRV plus bevacizumab leads to better patient survival and decreases cancer growth and spread when compared with bevacizumab alone.

Performance of the Idylla microsatellite instability test in endometrial cancer.

CONTEXT: DNA mismatch repair (MMR) deficiency (dMMR) testing is now recommended in endometrial cancer. Defect identification in the molecules participating in this pathway, or the presence of microsatellite instability, are commonly employed for this purpose. Novel methods are continuously evolving to report dMMR/microsatellite instability and to easily perform routine diagnoses. OBJECTIVE: The main aim of this study was to compare the concordance of the Idylla microsatellite instability test for the identification of dMMR endometrial cancer samples defined by immunohistochemistry and MMR genomic status. DESIGN: We applied the Idylla MSI test to 126 early-stage endometrial cancer cases with MMR testing by immunohistochemistry and genomic characterization (methylation in MLH1 and sequence alterations in MLH1, PMS2, MSH2 and MSH6). Individual markers and overall specific performance indicators were explored. RESULTS: The Idylla platform achieved a higher global concordance rate with MMR genomic status than with immunohistochemistry (75 % and 66 %, respectively). Sensitivity and specificity are also higher (75 % vs 66 % and 96 % vs 90 %, respectively). Clustering analysis split the patients into 2 well-differentiated clusters, the pMMR and the dMMR group, represented by MLH1/PMS2 loss and the MLH1 methylated promoter. Overall, immunohistochemistry and MMR genomic status identified more dMMR cases than did the Idylla test, although correlations were improved with a modified Idylla test cut-off. CONCLUSIONS: Performance of the Idylla test was better correlated with MMR genomic status than MMR immunohistochemistry status, which improved with a modified test cut-off. Further studies are needed to confirm the cut-off accuracy.

Periosteal Ewing Sarcoma with Distant Metastases: Report of Two Patients and Review of the Literature.

Periosteal Ewing sarcoma (ES) is an exceedingly rare topographic subtype of the ES. To our knowledge, only 60 patients have been reported in the medical English language literature. It predominantly affects men in the second decade of life and arises in the long tubular bone diaphysis. PES rarely develops distant metastases. We report two patients of this rare ES location that were found on the distal tibial shaft and proximal femoral diaphysis of a 21-year-old man and an 8-year-old boy, respectively. Both patients were treated with neoadjuvant chemotherapy, wide resection, and adjuvant chemotherapy. One of our patients had lung metastases at the time of diagnosis and died 5 years later. The other patient presented intramedullary humeral bone metastasis 19 years after diagnosis. There has been no evidence of disease in the 26 years of follow-up. Close follow-up of periosteal ES is recommended because distant metastases may exceptionally occur, even several years after diagnosis.

Characterisation of new in vitro models and identification of potentially active drugs in angiosarcoma.

Angiosarcoma is a rare soft tissue sarcoma originating from endothelial cells. Given that current treatments for advanced disease have shown limited efficacy, alternative therapies need to be identified. In rare diseases, patient-derived cell models are crucial for screening anti-tumour activity. In this study, cell line models were characterised in 2D and 3D cultures. The cell lines' growth, migration and invasion capabilities were explored, confirming them as useful tools for preclinical angiosarcoma studies. By screening a drug library, we identified potentially effective compounds: 8-amino adenosine impacted cell growth and inhibited migration and invasion at considerably low concentrations as a single agent. No synergistic effect was detected when combining with paclitaxel, gemcitabine or doxorubicin. These results suggest that this compound could be a potentially useful drug in the treatment of AGS.

Progression-free survival and safety at 3.5 years of follow-up: results from the randomized phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer - a plain language summary.

What is this summary about? This PLSP provides a short summary of an original scientific article that presented results from the PRIMA study after 3.5 years of follow-up time. The original article was published in the European Journal of Cancer in 2023.The PRIMA study included adult patients with newly diagnosed advanced high-risk ovarian cancer whose tumors shrunk or became undetectable after treatment with chemotherapy with or without surgery. The PRIMA study evaluated how well the drug niraparib, also known as Zejula, worked at delaying or preventing ovarian cancer from coming back (recurring) or getting worse (progressing) compared with placebo (a substance with no effects that a doctor gives to a patient instead of a drug). The first results from the PRIMA study were published in 2019, when patients had participated in the PRIMA study for about 1.2 years.The article this PLSP is based on reports longer-term data from the PRIMA study, when patients had participated in the PRIMA study for about 3.5 years. Patients were monitored (or followed) for a longer time to understand how well niraparib continued to work and to evaluate whether the safety of niraparib changed with additional time being monitored.What were the results? Patients who took niraparib had more time before their cancer came back or got worse than patients who took placebo. In terms of safety, no new types of side effects with niraparib treatment were observed with additional time being monitored as part of the PRIMA study.What do the results mean? These results support that niraparib remains an important treatment option to help delay the cancer from coming back or getting worse in patients with newly diagnosed advanced ovarian cancer that responded to initial treatment.Clinical Trial Registration: NCT02655016 (PRIMA study) (ClinicalTrials.gov).

Prevalencia y factores asociados al consumo de marihuana en universitarios de Colombia en el año 2016

Introducción: El consumo de marihuana toma un singular interés en el contexto de la universidad y en los universitarios, pues su uso podría ser parte de las relaciones sociales con sus pares. Objetivo: Describir la prevalencia y examinar los factores asociados al consumo de marihuana durante los últimos treinta días en estudiantes universitarios de Colombia durante 2016. Método: Estudio transversal analítico. Se realizó un análisis con 9555 universitarios colombianos. Fue considerado como consumidor de marihuana el universitario que manifestó haberla consumido durante los últimos treinta días. Se tomaron como variables de interés el sexo, la edad, la percepción de la situación económica, los problemas académicos y disciplinarios en la secundaria y las características de control parental. Para el análisis se reportó la prevalencia de la marihuana por cada una de las características estudiadas. Las asociaciones fueron estimadas a través de modelos lineales generalizados, tales análisis se ajustaron por el factor de expansión. Resultados: Se halló que el 9,7 % (IC 95 % 9,1 %- 10,4 %) había consumido marihuana en los últimos treinta días; los hombres (OR 2,23 IC95 % 1,92 - 2,59), aquellos que acusaron no tener control parental sobre los amigos (OR 2,32 IC95 % 1,58- 3,41) y que confesaron haber tenido problemas disciplinarios en la secundaria (OR 3,35 IC95 % 2,67-4,19), mostraron asociación con el consumo de marihuana. Conclusiones: La prevalencia de consumo de marihuana en estudiantes universitarios es elevada con respecto a otros países de la región. Destacan características como la presencia de problemas académicos o disciplinarios en la secundaria, así como un pobre control parental; ellas mostraron que tenían mayor relación con el consumo de marihuana entre los universitarios indagados.

Introduction: The consumption of marijuana takes on a singular interest in the context of the university and university students, because its use could be a part of relationships with their peers. Objective: To describe the prevalence and examine the factors associated with marijuana use during the last thirty days, in university students in Colombia, during the year 2016. Method: Cross-sectional analytical study. An analysis was carried out with 9555 Colombian university students. The university student who stated that he had used it during the last thirty (30) days was considered a marijuana user. The studied variables were sex, age, perception of the economic situation, academic and disciplinary problems in high school, and the characteristics of parental control. For analysis, the prevalence of marijuana was reported for each of the characteristics studied. The associations were estimated through generalized linear models; all analyzes were adjusted by the expansion factor. Results: It was found that 9.7% (95% CI 9.1%-10.4%) had used marijuana in the last thirty days; men (OR 2.23 CI95% 1.92 - 2.59), those who reported not having parental control over friends (OR 2.32 CI95% 1.58-3.41) and who confessed to having had disciplinary problems in high school (OR 3.35 CI95% 2.67-4.19) were associated with marijuana use. Conclusions: The prevalence of marijuana use in university students is high, compared to other countries in the region. They highlight characteristics such as the presence of academic or disciplinary problems in high school, as well as poor parental control; they showed that they had a greater relationship with the use of marijuana among the university students surveyed.

Evaluación del frenillo lingual en neonatos. Una revisión sistemática / Evaluation of the lingual frenulum in neonates. A Systematic Review

Introducción: el objetivo de esta revisión es responder al interrogante: ¿cuál es la metodología más eficaz de evaluación de frenillo lingual en neonatos? Bajo los pará-metros de objetividad, claridad y validación. Métodos: el estudio se realizó a través de una revisión sistemática, llevada a cabo con metodología Cochrane, en la que se utilizaron los descriptores de evaluación, frenillo lingual, anquiloglosia y recién nacido, y ejecutado en los bancos de datos Pubmed, Science Direct, Scielo. Para analizar el nivel de evidencia y grado de reco-mendación clínica, se tuvo en cuenta la clasificación GRADE y CEBM de Oxford. Resultados: por medio de la revisión se encontraron 2 evaluaciones y un tamizaje específicamente para recién nacidos, que evalúa de los 0 a los 30 días, los cuales se validan por medio de estudios de especificidad. Análisis y discusión: se identificó que los principales parámetros para diagnosti-car una alteración en el frenillo lingual son la anatomía y su funcionalidad. Conclusiones: según los estudios encontrados sí existe un método eficaz para el diagnóstico del frenillo lingual en neonatos.

Introduction: the objective of this review is to answer the question: What is the most effective methodology for assessing lingual frenulum in neonates? Under the parameters of objectivity, clarity and validation. Methods: the study was conducted through a systematic review carried out using the Cochrane methodology, in which the evaluation descriptors, lingual frenulum, ankyloglossia, and newborn were used, and developed in the Pubmed, Science Direct and Scielo data banks. To analyze the level of evidence and degree of clinical recom-mendation, the GRADE and CEBM classification of Oxford was taken into account. Results: through the review we found 2 evaluations and a screening specifically for new-borns that evaluates from 0 to 30 days, which are validated through specificity studies.Analysis and discussion: it was identified that the main parameters to diagnose an alteration in the lingual frenum are its anatomy and functionality. Conclusions: according to the studies found, there is an effective method for the diagnosis of the lingual frenulum in neonates.

Evaluación de anquiloglosia y lactancia materna en lactantes de 0 a 24 meses / Evaluation of ankyloglossia and breastfeeding in 0-24-month infants / Avaliação da anquiloglossia e da amamentação em lactentes de 0 a 24 meses

Introducción. La anquiloglosia es una condición limitante que en algunos casos no interfiere en la lactancia y genera adaptaciones anatomofisiológicas del frenillo al seno materno, el cual se presenta más elástico y menos fibroso. El objetivo fue establecer si existe relación entre las alteraciones del frenillo lingual y la lactancia materna. Materiales y métodos. Investigación descriptiva correlacional de corte transversal. La población objeto de estudio fue evaluada mediante el Protocolo de evaluación del frenillo de la lengua con puntuación para bebés. Resultados. Se identificó un 29% de prevalencia en las alteraciones del frenillo lingual. La anatomofisiología del frenillo y la succión son dependientes y estadísticamente significantes. Conclusiones. La lactancia materna y la anatomofisiología del frenillo lingual alterado, conocido como anquiloglosia, guardan una fuerte relación de dependencia, ya que ante la presencia de anquiloglosia no se produce un agarre adecuado del pezón en la cavidad oral. No obstante, en algunos casos se ha comprobado que los lactantes realizan procesos de adaptación para suplir las dificultades en la movilidad lingual y alimentarse.

Introduction. Ankyloglossia appears as a limiting condition, in some cases it does not interfere with lactation, presenting anatomophysiological adaptations of the frenulum to the mother's breast; it is more elastic and less fibrous. The objective was to establish whether there is a relationship between lingual frenulum alterations and breastfeeding. Methods. Cross-sectional correlational descriptive research. The population under study was evaluated through the "Protocol for evaluating the frenulum of the tongue with scores for babies". Results. A 29% prevalence of alterations in the lingual frenulum was identified, the anatomophysiology of the frenulum and suction are dependent and statistically significant. Conclusions. Breastfeeding and the anatomophysiology of the altered lingual frenulum known as ankyloglossia are strongly dependent, since in the presence of ankyloglossia there is not an adequate grip of the nipple in the oral cavity; however, in some cases it has been It has been proven that infants carry out adaptation processes in order to compensate for difficulties in tongue mobility and feeding.

Introdução. A anquiloglossia é uma condição limitante que em alguns casos não interfere na lactação e gera adaptações anatomofisiológicas do frênulo à mama da mãe, que é mais elástica e menos fibrosa. O objetivo foi estabelecer se existe relação entre as alterações do frênulo lingual e a amamentação. Materiais e métodos. Pesquisa descritiva e correlacional de corte transversal. A população em estudo foi avaliada por meio do protocolo de avaliação do frênulo da língua com pontuação para bebês. Resultados. Identificou-se prevalência de 29% nas alterações do frênulo lingual. A anatomofisiologia do frênulo e da sucção são dependentes e estatisticamente significativas. Conclusões. A amamentação e a anatomofisiologia do frênulo lingual alterado, conhecido como anquiloglossia, apresentam forte relação de dependência, visto que na presença de anquiloglossia não há pega adequada do mamilo na cavidade oral. No entanto, em alguns casos, descobriu-se que os bebês realizam processos de adaptação para superar as dificuldades de mobilidade da língua e alimentação.

Asociaciones entre clase social e hipoacusia laboral / Associations between social class and labor hipoacusia

Introducción: la exposición a ruidos forma parte de nuestros hábitos cotidianos, culturales y de ocio. En el entorno de trabajo aparecen diferentes sonidos que puedenser perjudiciales para los oídos. El presente escrito trata de identificar la influencia que existe entre clase social e hipoacusia laboral en trabajadores de la ciudad de Cú-cuta, en edades comprendidas entre los 17 y los 70 años. Métodos: observacional, analítico y transversal; la población estudiada incluyó tra-bajadores del sector público y privado del municipio de Cúcuta, a quienes se les reali-zó un examen audiométrico ocupacional por parte del programa de Fonoaudiología. Resultados: se encontró que la mayoría de los trabajadores, un 54.05%, pertenece a una clase social baja; el 65% se expone a ruido en el trabajo, el 60% no utiliza ele-mentos de protección personal y el 30% presenta hipoacusia.Análisis y discusión: hay una asociación significativa entre la actividad laboral y la actividad extra laboral del grupo etario. Predomina el sexo masculino con una representación del 63%. Esto puede explicarse dado el contexto cultural en el que se realizó el estudio.Conclusiones: en Colombia, existe escasa información sobre la relación entre clase social e hipoacusia laboral. Se debe realizar un análisis de segregación socio-espacial tanto de los hogares como de la enfermedad, para así determinar qué enfermedades se asocian con la actividad laboral

Introduction: exposure to noise is part of our daily, cultural and leisure habits. In the work environment different sounds can be harmful to the ears. The present text tries to identify the influence that exists between social class and work-related hearing loss in the city of Cúcuta, aged between 17 and 70 years Methods: It is observational, analytical and cross-sectional. The studied population consisted of individuals working in the public and private sector of the municipality of Cúcuta. They underwent an occupational audiometric examination by the Speech-Audiology program.Results: It was determined that most of the workers, 54.05%, are members of a low social class; 65% of workers are exposed to noise at work, 60% of workers do not use personal protection elements and 30% of evaluated workers have hearing loss. Analysis and discussion: there is a significant association between work activity and non-work activity of the age group, predominant in males with a representation of 63%, this can be explained given the cultural context in which the study was conducted. Conclusions: in Colombia, there is little information on social class and work-related hearing loss. An analysis of socio-spatial segregation of both households and the disease must be carried out in order to determine which diseases are associated to work activity