Digging into phenotype change in mismatch repair deficient endometrial carcinoma and treatment with immune checkpoint inhibition, a case report.

•False negative cases for mismatch repair determination by immunohistochemistry may occur.•The mismatch repair phenotype in endometrial carcinoma impacts on therapeutic decision making.•Retesting for mismatch repair at relapse of endometrial carcinoma should be considered.

A Case of COL1A1-PDGFB Fusion Uterine Sarcoma.

COL1A1-PDGFB gene fusion uterine sarcoma is a recently described entity which shows some overlapping features with dermatofibrosarcoma protuberans. To date, only 4 cases have been reported in the literature. Due to its rarity, succinct clinicopathologic characteristics are yet to be established. We report a fifth case initially mistaken as a uterine fibroid which histologically proved to be a CD34 + high-grade spindle cell proliferation which on fluorescence in situ hybridization analysis displayed COL1A1-PDGFB gene rearrangement. With this case description we hope to raise awareness and aid in the characterization of this emerging entity.

Prevalence of Anal High-Risk Human Papilloma Virus Infection and Abnormal Anal Cytology among Women Living with HIV.

Background: Women living with human immunodeficiency virus (HIV), WLWHs, are at high risk of developing anal cancer associated with high-risk human papilloma virus infection (HR-HPV). We analyzed the prevalence of anal HR-HPV infection and abnormal anal cytology in a cohort of WLWHs and assessed the risk factors for anal HR-HPV infection. Methods: We present a single-center, observational cross-sectional study. WLWHs who underwent anal cytology and anal human papilloma virus (HPV) testing were selected. High-resolution anoscopy was performed in cases of abnormal anal cytology. All suspicious lesions were biopsied. A univariate and multivariate logistic regression model was used to analyze risk factors for abnormal anal screening. The results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Results: In total, 400 WLWHs were studied. Of them, 334 met the eligibility criteria and were enrolled in the study. Abnormal anal cytology was detected in 39.5% of patients, and anal HR-HPV in 40.1%, with HPV 16 in 33 (26.6%) of them. Concomitant HR-HPV cervical infection was the only independent risk factor for HR-HPV anal infection (OR 1.67 95% CI, p < 0.001). Conclusions: WLWHs have a high prevalence of HR-HPV anal infection and anal cytologic abnormalities. HR-HPV cervical infection is the main predictor of HR-HPV anal infection.

Píldoras formativas para mejorar la educación enfermera sobre programación temprana / Educational pills to improve nursing education on early programming

Introducción: La obesidad infantil ha sido declarada la epidemia del siglo XXI. La programación temprana es un elemento esencial que debe utilizarse para prevenir enfermedades no transmisibles. Las enfermeras están en una posición única para aplicar este concepto, pero no está incluido en su educación. Objetivos: El desarrollo, implementación y evaluación del uso de píldoras educativas que se ofrecen a los estudiantes de enfermería para mejorar su conocimiento sobre la programación temprana. Metodología: Se trata de una investigación cuasi-experimental. Es un estudio pre/post con seguimiento longitudinal. Para la recolección de datos, se diseñaron tres cuestionarios de desarrollo propio para medir el nivel de conocimiento, la intención de actuar y la satisfacción con la metodología. El nivel de conocimiento y la intención de actuar se midieron antes y después de la intervención para ver el efecto de la intervención. Se midió la satisfacción con la metodología y los recursos utilizados después de la intervención. La población incluida en este estudio son los estudiantes de enfermería de primer y segundo año matriculados en dos asignaturas diferentes en el curso 2019/2020. Se estima que el tamaño de la población es de 200 estudiantes. Se ha organizado el proceso en tres etapas definidas: etapa inicial, etapa de elaboración y etapa de implementación. Resultados: Se han observado diferencias significativas en todos los parámetros medidos. Conclusiones: La intervención ha mejorado el conocimiento de las futuras enfermeras sobre la programación temprana, ha aumentado la intención de actuar y los estudiantes encuentran esta metodología adecuada para su formación. (AU)

Background: Childhood obesity has been declared the epidemic of the 21st century. Early programming is an essential element that should be used to prevent non-communicable diseases. Nurses are uniquely positioned to apply this concept, but it is not included in their education. Objectives: The development, implementation and evaluation of the use of educational pills offered to nurse students to improve their knowledge of early programming. Methodology: This is quasi-experimental research. It is a pre/post study with a longitudinal follow-up. For data collection, three self-developed questionnaires were designed to measure the level of knowledge, intention to act and satisfaction with the methodology. The level of knowledge and the intention to act were measured before and after the intervention to see the intervention's effect. Satisfaction with the methodology and resources used was measured after the intervention. The population included in this study is the first-year and second-year nursing students enrolled in two different subjects in the academic year 2019/2020. The population size is estimated to be 200 students. We have organised the process into three defined stages: the initial stage, elaboration stage and implementation stage. Results: Significant differences have been observed in all the measured parameters. Conclusions: The intervention has improved the knowledge of future nurses about early programming and has increased the intention of nurses to act. Students find this methodology suiTable for their training. (AU)

The Effect of Play on Pain and Anxiety in Children in the Field of Nursing: A Systematic Review.

PROBLEM: The role of play in the reduction of anxiety and pain and in the improvement of behaviours and overall wellbeing in children in the field of nursing care in hospital settings. ELIGIBILITY CRITERIA: Studies published during the period 2014-2019 including original articles in English, Spanish and Portuguese. Databases consulted: SCOPUS, MEDLINE/PubMed, WoS, and CUIDEN (Nursing database in Spanish). SAMPLE: Seventeen relevant records were selected. After critical reading using the CASPe (Critical Appraisal Skills Programme in Spanish) instrument, 7 articles were rejected and 10 were finally selected. RESULTS: Each of eight studies showed significant evidence for the role of therapeutic play in the reduction of anxiety and pain and in the overall wellbeing of paediatric patients. IMPLICATIONS: This review aimed to critically assess and synthesize the existing empirical evidence on the contributions of therapeutic play interventions for reducing anxiety, pain and improving the overall wellbeing of paediatric patients. CONCLUSIONS: Based on these findings, it may be safe to say that therapeutic play interventions are effective in reducing the negative emotional manifestations of children, decreasing preoperative anxiety and pain, improving compliance with the induction of anaesthesia and reducing anxiety and postoperative pain. There is also evidence that dramatic puppetry is an effective preoperative care and preparation strategy for reducing anxiety in children undergoing surgery.

Orientaciones formativas para un cuidado humanizado en enfermería: una revisión integrativa de la literatura / Training guidelines for humanised nursing care: an integrative literature review

INTRODUCCIÓN: La comunicación y la relación interpersonal son los elementos más esenciales para un cuidado humanizado. El establecimiento de una relación más allá de la atención física a través de la humanización de las acciones en el plan de cuidados, favorece el proceso de recuperación; sin embargo, tanto en la formación como en la práctica enfermera se mantiene la inercia de un enfoque técnico y neopositivista, dejando de lado tales aspectos. OBJETIVO: Aportar conocimientos más específicos sobre la importancia de situar y orientar los cuidados de la enfermería desde una proyección biopsicosocial, con un enfoque humanizado, poniendo especial énfasis en las competencias comunicativas y relaciones interpersonales como elementos esenciales. METODOLOGÍA: Revisión bibliográfica integrativa, con análisis crítico de la literatura consultada, que incluye artículos originales y de revisión publicados en castellano, portugués e inglés de 2013 a 2018. Para la búsqueda se han consultado las bases de datos SciELO, MEDLINE/Pubmed, Web of Science y CUIDEN. RESULTADOS: Se han extraído cuatro categorías de análisis que dan como resultado 1) las habilidades comunicativas y emocionales como elementos esenciales del cuidado humanizado, 2) la necesaria capacitación emocional y comunicativa en la formación de enfermería, 3) otros factores que contribuyen a un cuidado humanizado y 4) cambios metodológicos y recursos pedagógicos para la capacitación comunicativa y emocional de docentes, alumnado y profesionales de enfermería. CONCLUSIONES: Se reclama la necesidad de incorporar, de manera más pedagógica y profunda, programas formativos en competencias emocionales y de comunicación en enfermería para un cuidado humanizado

INTRODUCTION: Communication and interpersonal relationships are the most essential elements of humanised care. The process of recovery is fostered by establishing relationships outside of physical care through the humanisation of actions in the care plan. However, in both nursing training and nursing practice, the inertia of a technical and neo-positivist approach persists and such aspects are therefore neglected. OBJECTIVE: To provide more specific knowledge on the importance of considering nursing care from a biopsychosocial perspective, with a humanised approach, placing special emphasis on communicative skills and interpersonal relationships as essential elements. METHODS: An integrative literature review, with a critical analysis of the literature consulted, including original articles and reviews published in Spanish, Portuguese, and English from 2013 to 2018. The SciELO, MEDLINE/PubMed, Web of Science, and CUIDEN databases were searched. RESULTS: The following four categories emerged from this analysis: 1) communicative and emotional skills as essential elements of humanised care; 2) the necessary emotional and communicative training in nursing education; 3) other factors contributing to humanised care; and 4) methodological changes and pedagogical resources for the communicative and emotional training of lecturers, students, and nursing professionals. CONCLUSIONS: There is a need to develop, in a more pedagogical and profound way, training programmes in nursing on emotional skills and communication for humanised care

New case of secondary bladder amyloidosis with massive hematuria-role of intravesical instillations with dimethyl sulfoxide.

Secondary bladder amyloidosis is a rare condition with less than 60 cases published in the world. It is usually secondary to chronic inflammatory processes such as rheumatologic diseases. Hematuria is its predominant and most important symptom, and usually occurs after a bladder catheterization. The diagnostic confirmation is made through a pathological and immunohistochemical study. The treatment must be staggered from less to more invasive. Our objectives are to present a new case of secondary bladder amyloidosis in a woman with a history of chronic bronchiectasis after tuberculosis and frequent super infections, whose main manifestation was a massive hematuria, and review this rare pathology. We have obtained very good initial results using intravesical instillations with dimethyl sulfoxide (DMSO) with complete resolution of the hematuria, the patient remaining asymptomatic for 6 months. After that, there was a recurrence of the hematuria that was treated with embolization of the hypogastric arteries, with good results. We can conclude that, despite being a rare condition, we must consider secondary bladder amyloidosis in patients who have already been diagnosed with systemic amyloidosis and/or chronic pathologies who develop hematuria after bladder catheterization. Based on our experience, instillations with dimethyl sulfoxide are a safe option and provide a quick and temporary resolution of hematuria symptoms.

Multiplatform plasma fingerprinting in cancer cachexia: a pilot observational and translational study.

BACKGROUND: Cachexia is a metabolic syndrome that affects up to 50-80% of cancer patients. The pathophysiology is characterized by a variable combination of reduced food intake and abnormal metabolism, including systemic inflammation and negative protein and energy balance. Despite its high clinical significance, defined diagnostic criteria and established therapeutic strategies are lacking. The 'omics' technologies provide a global view of biological systems. We hypothesize that blood-based metabolomics might identify findings in cachectic patients that could provide clues to gain knowledge on its pathophysiology, and eventually postulate new therapeutic strategies. METHODS: This is a cross-sectional observational study in two cohorts of cancer patients, with and without cachexia. Patients were consecutively recruited from routine clinical practice of a General Oncology Department at '12 de Octubre' University Hospital. Selected clinical and biochemical features were collected. Blood metabolite fingerprinting was performed using three analytical platforms, gas chromatography coupled to mass spectrometry (GC-MS), capillary electrophoresis coupled to mass spectrometry (CE-MS), and liquid chromatography coupled to mass spectrometry (LC-MS). Besides, we performed pathway-based metabolite analyses to obtain more information on biological functions. RESULTS: A total of 15 subjects were included in this study, 8 cachectic and 7 non-cachectic patients. Metabolomic analyses were able to correctly classify their samples in 80% (GC-MS), 97% (CE-MS), 96% [LC-MS (positive mode)], and 89% [LC-MS (negative mode)] of the cases. The most prominent metabolic alteration in plasma of cachectic patients was the decrease of amino acids and derivatives [especially arginine, tryptophan, indolelactic acid, and threonine, with 0.4-fold change (FC) compared with non-cachectic patients], along with the reduction of glycerophospholipids [mainly lysophosphatidylcholines(O-16:0) and lysophosphatidylcholines(20:3) sn-1, FC = 0.1] and sphingolipids [SM(d30:0), FC = 0.5]. The metabolite with the highest increase was cortisol (FC = 1.6). Such alterations suggest a role of the following metabolic pathways in the pathophysiology of cancer cachexia: arginine and proline metabolism; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; lysine degradation; aminoacyl-tRNA biosynthesis; fatty acid elongation in mitochondria; tricarboxylic acids cycle; among others. CONCLUSIONS: These findings suggest that plasma amino acids and lipids profiling has great potential to find the mechanisms involved in the pathogenesis of cachexia. Metabolic profiling of plasma from cancer patients show differences between cachexia and non-cachexia in amino acids and lipids that might be related to mechanisms involved in its pathophysiology. A better understanding of these mechanisms might identify novel therapeutic approaches to palliate this unmet medical condition.

Mechanistic added value of a trans-Sulfonamide-Platinum-Complex in human melanoma cell lines and synergism with cis-Platin.

BACKGROUND: Cisplatin is a potent antitumor agent. However, toxicity and primary and secondary resistance are major limitations of cisplatin-based chemotherapy, leading to therapeutic failure. We have previously reported that mono-sulfonamide platinum complexes have good antitumor activity against different tumoral cell lines and with a different and better cytotoxic profile than cisplatin. Besides, N-sulfonamides have been used extensively in medicinal chemistry as bactericides, anticonvulsant, inhibitors of the carbonic anhydrase, inhibitors of histone deacetylases, and inhibitors of microtubule polymerization, among others. METHODS: We aimed to compare the cytotoxic effects of cisplatin and a trans-sulfonamide-platinum-complex (TSPC), in two human melanoma cell lines that differ in their TP53 status: SK-MEL-5, TP53 wild type, and SK-MEL-28, TP53 mutated. We performed cytotoxicity assays with both drugs, alone and in combination, cell cycle analyses, western blotting and immunoprecipitation, and fluorescence immunocytochemistry. RESULTS: TSPC had similar antiproliferative activity than cisplatin against SK-MEL-5 (3.24 ± 1.08 vs 2.89 ± 1.12 µM) and higher against SK-MEL-28 cells (5.83 ± 1.06 vs 10.17 ± 1.29 µM). Combination of both drugs inhibited proliferation in both cell lines, being especially important in SK-MEL-28, and showing a synergistic effect. In contrast to cisplatin, TSPC caused G1 instead G2/M arrest in both cell lines. Our present findings indicate that the G1 arrest is associated with the induction of CDKN1A and CDKN1B proteins, and that this response is also present in melanoma cells containing TP53 mutated. Also, strong accumulation of CDKN1A and CDKN1B in cells nuclei was seen upon TSPC treatment in both cell lines. CONCLUSIONS: Overall, these findings provide a new promising TSPC compound with in vitro antitumor activity against melanoma cell lines, and with a different mechanism of action from that of cisplatin. Besides, TSPC synergism with cisplatin facilitates its potential use for co-treatment to reduce toxicity and resistance against cisplatin. TSPC remains a promising lead compound for the generation of novel antineoplastic agent and to explore its synergism with other DNA damaging agents.

¹H, ¹³C and ¹5N backbone and side-chain chemical shift assignments of the free and bound forms of the human PTPN11 second SH2 domain.

Src homology 2 (SH2) domains have an important role in the regulation of protein activity and intracellular signaling processes. They are geared to bind to specific phosphotyrosine (pY) motifs, with a substrate sequence specificity depending on the three amino acids immediately C-terminal to the pY. Here we report for the first time the (1)H, (15)N and (13)C backbone and side-chain chemical shift assignments for the C-terminal SH2 domain of the human protein tyrosine phosphatase PTPN11, both in its free and bound forms, where the ligand in the latter corresponds to a specific sequence of the human erythropoietin receptor.