SOX11 is a novel binding partner and endogenous inhibitor of SAMHD1 ara-CTPase activity in mantle cell lymphoma.

The sterile alpha motif and histidine-aspartate (HD) domain containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara-C) resistance in several haematological malignancies. Targeting SAMHD1's ara-CTPase activity has recently been demonstrated to enhance ara-C efficacy in acute myeloid leukemia. Here, we identify the transcription factor SRY-related HMG-box containing protein 11 (SOX11) as a novel direct binding partner and first known endogenous inhibitor of SAMHD1. SOX11 is aberrantly expressed not only in mantle cell lymphoma (MCL), but also in some Burkitt lymphomas. Co-immunoprecipitation of SOX11 followed by mass spectrometry in MCL cell lines identified SAMHD1 as the top SOX11 interaction partner which was validated by proximity ligation assay. In vitro, SAMHD1 bound to the HMG box of SOX11 with low-micromolar affinity. In situ crosslinking studies further indicated that SOX11-SAMHD1 binding resulted in a reduced tetramerization of SAMHD1. Functionally, expression of SOX11 inhibited SAMHD1 ara-CTPase activity in a dose-dependent manner resulting in ara-C sensitization in cell lines and in a SOX11-inducible mouse model of MCL. In SOX11-negative MCL, SOX11-mediated ara-CTPase inhibition could be mimicked by adding the recently identified SAMHD1 inhibitor hydroxyurea. Taken together, our results identify SOX11 as a novel SAMHD1 interaction partner and its first known endogenous inhibitor with potentially important implications for clinical therapy stratification.

SOX11/PRDX2 axis modulates redox homeostasis and chemoresistance in aggressive mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an incurable B-cell neoplasm characterized by an aggressive behavior, short responses to conventional therapies and SOX11 overexpression, which is associated with aggressive disease features and inferior clinical outcome of patients. Oxidative stress is known to induce tumorigenesis and tumor progression, whereas high expression levels of antioxidant genes have been associated with chemoresistance in different cancers. However, the role of oxidative stress in MCL pathogenesis and the involvement of SOX11 regulating redox homeostasis in MCL cells are largely unknown. Here, by integrating gene set enrichment analysis of two independent series of MCL, we observed that SOX11+ MCL had higher reactive oxygen species (ROS) levels compared to SOX11- MCL primary tumors and increased expression of Peredoxine2 (PRDX2), which upregulation significantly correlated with SOX11 overexpression, higher ROS production and worse overall survival of patients. SOX11 knockout (SOX11KO) significantly reduced PRDX2 expression, and SOX11KO and PRDX2 knockdown (PRDX2KD) had increased ROS levels and ROS-mediated tumor cell death upon treatment with drugs, compared to control MCL cell lines. Our results suggest an aberrant redox homeostasis associated with chemoresistance in aggressive MCL through SOX11-mediated PRDX2 upregulation, highlighting PRDX2 as promising target for new therapeutic strategies to overcome chemoresistance in aggressive MCLs.

SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features.

SRY-related HMG-box gene 11 (SOX11) is a transcription factor overexpressed in mantle cell lymphoma (MCL), a subset of Burkitt lymphomas (BL) and precursor lymphoid cell neoplasms but is absent in normal B-cells and other B-cell lymphomas. SOX11 has an oncogenic role in MCL but its contribution to BL pathogenesis remains uncertain. Here, we observed that the presence of Epstein-Barr virus (EBV) and SOX11 expression were mutually exclusive in BL. SOX11 expression in EBV- BL was associated with an IG∷MYC translocation generated by aberrant class switch recombination, while in EBV-/SOX11- tumors the IG∷MYC translocation was mediated by mistaken somatic hypermutations. Interestingly, EBV- SOX11 expressing BL showed higher frequency of SMARCA4 and ID3 mutations compared to EBV-/SOX11- cases. By RNA-sequencing, we identified a SOX11-associated gene expression profile, with functional annotations showing partial overlap with the SOX11 transcriptional program of MCL. Contrary to MCL, no differences on cell migration or BCR signaling were found between SOX11- and SOX11+ BL cells. However, SOX11+ BL showed higher adhesion to VCAM-1 than SOX11- BL cell lines. Here we demonstrate that EBV- BL comprises two subsets of cases based on SOX11 expression. The mutual exclusion of SOX11 and EBV, and the association of SOX11 with a specific genetic landscape suggest a role of SOX11 in the early pathogenesis of BL.

Clinicopathological and Genomic Identification of Breast Cancers with No Impact on Mortality.

BACKGROUND: Implementing mammogram screening means that clinicians are seeing many breast cancers that will never develop metastases. The purpose of this study was to identify subgroups of breast cancer patients who did not present events related to long-term breast cancer mortality, taking into account diagnosis at breast screening, absence of palpability and axillary involvement, and genomic analysis with PAM50. PATIENTS AND METHODS: To identify them, a retrospective observational study was carried out selecting patients without any palpable tumor and without axillary involvement, and a genomic analysis was performed with PAM50. RESULTS: The probability of distant metastasis-free interval (DMFI) of 337 patients was 0.92 (95% CI, 0.90-0.93) at 20 years and 0.96 (95% CI, 0.92-1.00) in 95 patients (28%) with available PAM50 tests. In 22 (23.15%) luminal A tumors and in 9 (9.47%) luminal B tumors smaller than 1 cm, and in HER2 and basal type tumors, there were no metastatic events (20-year DMFI of 1.00). CONCLUSION: Patients with nonpalpable breast cancer found at screening with negative nodes are at very low risk. It is possible to identify subgroups without metastatic events by determining the intrinsic subtype and tumor size less than 1 cm. Therefore, de-escalation of treatment should be considered.

SOX11 is a novel binding partner and endogenous inhibitor of SAMHD1 ara-CTPase activity in mantle cell lymphoma.

ABSTRACT: Sterile alpha motif and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara-C) resistance in several hematological malignancies. Targeting SAMHD1's ara-CTPase activity has recently been demonstrated to enhance ara-C efficacy in acute myeloid leukemia. Here, we identify the transcription factor SRY-related HMG-box containing protein 11 (SOX11) as a novel direct binding partner and first known endogenous inhibitor of SAMHD1. SOX11 is aberrantly expressed not only in mantle cell lymphoma (MCL), but also in some Burkitt lymphomas. Coimmunoprecipitation of SOX11 followed by mass spectrometry in MCL cell lines identified SAMHD1 as the top SOX11 interaction partner, which was validated by proximity ligation assay. In vitro, SAMHD1 bound to the HMG box of SOX11 with low-micromolar affinity. In situ crosslinking studies further indicated that SOX11-SAMHD1 binding resulted in a reduced tetramerization of SAMHD1. Functionally, expression of SOX11 inhibited SAMHD1 ara-CTPase activity in a dose-dependent manner resulting in ara-C sensitization in cell lines and in a SOX11-inducible mouse model of MCL. In SOX11-negative MCL, SOX11-mediated ara-CTPase inhibition could be mimicked by adding the recently identified SAMHD1 inhibitor hydroxyurea. Taken together, our results identify SOX11 as a novel SAMHD1 interaction partner and its first known endogenous inhibitor with potentially important implications for clinical therapy stratification.

[Association between reproductive history, breast cancer subtype, and survival in premenopausal women]. / Asociación entre la historia reproductiva, el subtipo de cáncer de mama y la supervivencia de mujeres premenopáusicas.

BACKGROUND AND OBJECTIVE: Reproductive history influences breast cancer risk. We analysed its association with tumour subtype and survival in premenopausal women. PATIENTS AND METHODS: Retrospective, observational study of premenopausal women with stage I-III breast carcinoma in the last 20 years. Review of reproductive history, clinical data, and treatments in health records. RESULTS: In 661 premenopausal women (32.40% of 1377 total cases), median age was 47 years (19-53), menarche 12 (7-17), first delivery 28 (16-41) and number of deliveries 2 (0-9). One hundred and eleven (18.20%) were nulliparous. Three hundred and fifty-nine (58.80%) used natural lactation, with a median duration of 6 months. Anovulatory drugs were used by 271 (44.40%), with a median duration of 36 months. Associations were found between menarche <10 years and lower risk of luminal subtype (OR: 0.52, 95% CI: 0.28-0.94; P=.03), between menarche >11 years and lower risk of HER2 subtype (OR: 0.50, 95% CI: 0.26-0.97; P=.04) and between first birth >30 years and lower risk of triple negative subtype (OR: 0.40, 95% CI: 0.17-0.93; P=.03). The 20-year overall and disease-free survival probabilities were 0.80 (95% CI: 0.71-0.90) and 0.72 (95% CI: 0.64-0.79) respectively. Patients with ≥1 delivery had better overall survival than nulliparous patients (HR: 0.51, 95% CI: 0.27-0.96, P=.04). CONCLUSIONS: The findings suggest an association between age at menarche and age at first delivery and breast cancer subtype. Nulliparity is associated with worse survival.

PDZome-wide and structural characterization of the PDZ-binding motif of VANGL2.

VANGL2 is a core component of the non-canonical Wnt/Planar Cell Polarity signaling pathway that uses its highly conserved carboxy-terminal type 1 PDZ-binding motif (PBM) to bind a variety of PDZ proteins. In this study, we characterize and quantitatively assess the largest VANGL2 PDZome-binding profile documented so far, using orthogonal methods. The results of our holdup approach support VANGL2 interactions with a large panel of both long-recognized and unprecedented PDZ domains. Truncation and point mutation analyses of the VANGL2 PBM establish that, beyond the strict requirement of the P-0 / V521 and P-2 / T519 amino acids, upstream residues, including E518, Q516 and R514 at, respectively, P-3, P-5 and P-7 further contribute to the robustness of VANGL2 interactions with two distinct PDZ domains, SNX27 and SCRIBBLE-PDZ3. In agreement with these data, incremental amino-terminal deletions of the VANGL2 PBM causes its overall affinity to progressively decline. Moreover, the holdup data establish that the PDZome binding repertoire of VANGL2 starts to diverge significantly with the truncation of E518. A structural analysis of the SYNJ2BP-PDZ/VANGL2 interaction with truncated PBMs identifies a major conformational change in the binding direction of the PBM peptide after the P-2 position. Finally, we report that the PDZome binding profile of VANGL2 is dramatically rearranged upon phosphorylation of S517, T519 and S520. Our crystallographic approach illustrates how SYNJ2BP accommodates a S520-phosphorylated PBM peptide through the ideal positioning of two basic residues, K48 and R86. Altogether our data provides a comprehensive view of the VANGL2 PDZ network and how this network specifically responds to the post-translation modification of distinct PBM residues. These findings should prove useful in guiding future functional and molecular studies of the key PCP component VANGL2.

Palmitoylethanolamide shows limited efficacy in controlling cerebral cryptococcosis in vivo.

Cryptococcus neoformans (Cn) is an encapsulated neurotropic fungal pathogen and the causative agent of cryptococcal meningoencephalitis (CME) in humans. Recommended treatment for CME is Amphotericin B (AmpB) and 5-fluorocytosine (5-FC). Though effective, AmpB has displayed numerous adverse side effects due to its potency and nephrotoxicity, prompting investigation into alternative treatments. Palmitoylethanolamide (PEA) is an immunomodulatory compound capable of promoting neuroprotection and reducing inflammation. To investigate the efficacy of PEA as a therapeutic alternative for CME, we intracerebrally infected mice with Cn and treated them with PEA or AmpB alone or in combination. Our results demonstrate that PEA alone does not significantly prolong survival nor reduce fungal burden, but when combined with AmpB, PEA exerts an additive effect and promotes both survivability and fungal clearance. However, we compared this combination to traditional AmpB and 5-FC treatment in a survivability study and observed lower efficacy. Overall, our study revealed that PEA alone is not effective as an antifungal agent in the treatment of CME. Importantly, we describe the therapeutic capability of PEA in the context of Cn infection and show that its immunomodulatory properties may confer limited protection when combined with an effective fungicidal agent.

Axillary management in patients with breast cancer and positive axilla at diagnosis. Experience in a Spanish university hospital with a 5-year follow-up.

Background: Axillary lymph node dissection (ALND) was the standard in breast cancer with axillary involvement until recently. Along with the number of metastatic nodes, axillary positivity was considered a main prognostic factor and scientific evidence shows that the administration of radiotherapy on ganglion areas decreases the risk of recurrence even in positive axilla. The objective of this study was to evaluate the axillary treatment in patients with positive axilla at diagnosis, the evolution of them over time, and to assess patient's follow-up with the aim of avoiding the morbidity associated with axillary dissection. Methods: A retrospective observational study of breast cancer patients diagnosed between 2010 and 2017 was performed. In total, 1,100 patients were studied, out of which 168 were women with clinically and histologically positive axilla at diagnosis. Seventy-six percent received primary chemotherapy and subsequent treatment with sentinel node biopsy, axillary dissection, or both. Patients with positive sentinel lymph node biopsy received either radiotherapy or lymphadenectomy depending on the year time they were diagnosed. Results: For 60 patients out of 168, neoadjuvant chemotherapy resulted in a complete pathological axillary response. Axillary recurrence was registered for six patients. No recurrence was detected in the biopsy group associated with radiotherapy. These results support the benefit of lymph node radiotherapy for patients with positive sentinel node biopsy after receiving primary chemotherapy. Conclusion: Sentinel node biopsy provides useful and reliable information about cancer staging and might prevent lymphadenectomy, leading to a decrease in morbidity. Pathological response to systemic treatment came out as the most important predictive factor of disease-free survival of breast cancer.

Percepciones sobre salud (física, mental y bucal) en un grupo de mujeres en situación de prostitución en la ciudad de Medellín

Introducción: las mujeres y las personas trans que han ejercido el trabajo sexual se encuentran vulneradas puesto que son víctimas de discriminación por su condición laboral, por su género y por los riesgos que acarrea esta labor, y esto impacta en su situación de salud. Este estudio tuvo como objetivo conocer las percepciones sobre salud (física, mental y bucal) en cuatro mujeres que ejercen la prostitución en Medellín, a partir de sus experiencias de vida y aquellas relacionadas con su contexto social. Métodos: se realizó una investigación cualitativa con enfoque etnográfico para analizar las situaciones mencionadas de acuerdo con el objetivo general. Se contó con la participación de cuatro mujeres: dos de nacionalidad venezolana y dos de nacionalidad colombiana; se llevaron a cabo entrevistas semiestructuradas. Se realizó análisis de contenido cualitativo, lo cual permitió la generación de cuatro categorías (salud mental, salud bucal, salud general y calidad de vida). Resultados: sus discursos permitieron elucidar la conexión entre las condiciones de vida y la situación de salud. La falta de oportunidades laborales, un proceso migratorio de profundos cambios económicos y sociales, y una Colombia con inequidades y barreras de acceso a servicios de salud y sociales, son procesos determinantes de orden general, particular y singular de las precarias condiciones de salud bucal y general. Conclusiones: la población participante se encuentra en situación de vulnerabilidad social y de salud, lo cual evidencia la necesidad de políticas públicas y estrategias basadas en la realidad social que contribuyan a generar equidad en salud.

Introduction: women and trans people who have engaged in sex work are triply vulnerable since they are victims of discrimination due to their employment status, their gender, and the risks that this work entails, this impacts their health situation. This study aimed to know the perceptions about health (physical, mental, and oral) of four women who work in prostitution in Medellin, based on their life experiences and those related to their social context. Methods: qualitative research with an ethnographic approach was conducted to analyze the situations mentioned. Four women participated, two Venezuelans and two Colombians, and semi-structured interviews were conducted. Qualitative content analysis was performed, which allowed the generation of four categories (mental health, oral health, general health, and quality of life). Results: her discourses made it possible to elucidate the connection between the living conditions and the health situation. Lack of job opportunities, a migratory process of profound economic and social changes, and a Colombia with inequities and barriers to access to health and social services are determining processes of a general and singular order of the precarious conditions of oral health and general. Conclusions: the participating population is in a situation of social and health vulnerability, which shows the need for public policies and strategies based on the social reality that contribute to generating equity in health.

Neurotoxic/Neuroprotective Effects of Clozapine and the Positive Allosteric Modulator of mGluR2 JNJ-46356479 in Human Neuroblastoma Cell Cultures.

Current antipsychotics (APs) effectively control positive psychotic symptoms, mainly by blocking dopamine (DA) D2 receptors, but have little effect on negative and cognitive symptoms. Increased glutamate (GLU) release would trigger neurotoxicity, leading to apoptosis and synaptic pruning, which is involved in the pathophysiology of schizophrenia. New pharmacological strategies are being developed such as positive allosteric modulators (PAMs) of the metabotropic GLU receptor 2 (mGluR2) that inhibit the presynaptic release of GLU. We previously reported that treatment of adult mice with JNJ-46356479 (JNJ), a recently developed mGluR2 PAM, partially improved neuropathological deficits and schizophrenia-like behavior in a postnatal ketamine mouse model. In the present study, we evaluated, for the first time, the putative neuroprotective and antiapoptotic activity of JNJ in a human neuroblastoma cell line and compared it with the effect of clozapine (CLZ) as a clinical AP with the highest efficacy and with apparent utility in managing negative symptoms. Specifically, we measured changes in cell viability, caspase 3 activity and apoptosis, as well as in the expression of key genes involved in survival and cell death, produced by CLZ and JNJ alone and in combination with a high DA or GLU concentration as apoptosis inducers. Our results suggest that JNJ is not neurotoxic and attenuates apoptosis, particularly by decreasing the caspase 3 activation induced by DA and GLU, as well as increasing and decreasing the number of viable and apoptotic cells, respectively, only when cultures were exposed to GLU. Its effects seem to be less neurotoxic and more neuroprotective than those observed with CLZ. Moreover, JNJ partially normalized altered expression levels of glycolytic genes, which could act as a protective factor and be related to its putative neuroprotective effect. More studies are needed to define the mechanisms of action of this GLU modulator and its potential to become a novel therapeutic agent for schizophrenia.

Tumorigenic role of Musashi-2 in aggressive mantle cell lymphoma.

SOX11 overexpression has been associated with aggressive behavior of mantle cell lymphomas (MCL). SOX11 is overexpressed in embryonic and cancer stem cells (CSC) of some tumors. Although CSC have been isolated from primary MCL, their relationship to SOX11 expression and contribution to MCL pathogenesis and clinical evolution remain unknown. Here, we observed enrichment in leukemic and hematopoietic stem cells gene signatures in SOX11+ compared to SOX11- MCL primary cases. Musashi-2 (MSI2) emerged as one of the most significant upregulated stem cell-related genes in SOX11+ MCLs. SOX11 is directly bound to the MSI2 promoter upregulating its expression in vitro. MSI2 intronic enhancers were strongly activated in SOX11+ MCL cell lines and primary cases. MSI2 upregulation was significantly associated with poor overall survival independently of other high-risk features of MCL. MSI2 knockdown decreased the expression of genes related to apoptosis and stem cell features and significantly reduced clonogenic growth, tumor cell survival and chemoresistance in MCL cells. MSI2-knockdown cells had reduced tumorigenic engraftment into mice bone marrow and spleen compared to control cells in xenotransplanted mouse models. Our results suggest that MSI2 might play a key role in sustaining stemness and tumor cell survival, representing a possible novel target for therapeutic interventions in MCL.

Non Coding RNAs as Regulators of Wnt/ß-Catenin and Hippo Pathways in Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy histologically characterized by the replacement of myocardium by fibrofatty infiltration, cardiomyocyte loss, and inflammation. ACM has been defined as a desmosomal disease because most of the mutations causing the disease are located in genes encoding desmosomal proteins. Interestingly, the instable structures of these intercellular junctions in this disease are closely related to a perturbed Wnt/ß-catenin pathway. Imbalance in the Wnt/ß-catenin signaling and also in the crosslinked Hippo pathway leads to the transcription of proadipogenic and profibrotic genes. Aiming to shed light on the mechanisms by which Wnt/ß-catenin and Hippo pathways modulate the progression of the pathological ACM phenotype, the study of non-coding RNAs (ncRNAs) has emerged as a potential source of actionable targets. ncRNAs comprise a wide range of RNA species (short, large, linear, circular) which are able to finely tune gene expression and determine the final phenotype. Some share recognition sites, thus referred to as competing endogenous RNAs (ceRNAs), and ensure a coordinating action. Recent cancer research studies regarding the key role of ceRNAs in Wnt/ß-catenin and Hippo pathways modulation pave the way to better understanding the molecular mechanisms underlying ACM.

Maternal Supplementation with Polyphenols and Omega-3 Fatty Acids during Pregnancy: Prenatal Effects on Fetal Fatty Acid Composition in the Iberian Pig.

Intrauterine Growth Restriction (IUGR) is a major problem in pig production and different strategies, mainly maternal supplementation with different agents, are currently being studied. The combination of hydroxytyrosol and n3-PUFA seems to be a promising treatment to counteract IUGR, since the combination may help improve n3-PUFA composition and lower the inflammatory status of IUGR piglets. The aim of the present study is to determine the effects of a maternal supplementation, from day 35 to day 100 of pregnancy, with linseed oil and hydroxytyrosol on the fetal FA composition. The results showed higher n3 levels, including eicosapentaenoic and docosahexaenoic FA in the offspring from treated gilts, which showed lower n6-PUFA/n3-PUFA (n6/n3) ratios. Saturated and monounsaturated fatty acids were also affected by treatment, especially in the muscle and brain. Thus, a maternal supplementation with linseed oil and hydroxytyrosol affected the fetal FA tissue composition, which could have implications in pig production due to the improvement of the piglets' health status.

Polyphenols and IUGR Pregnancies: Effects of the Antioxidant Hydroxytyrosol on the Hippocampus Proteome in a Porcine Model.

Supplementation of a mother's diet with antioxidants such as hydroxytyrosol (HTX) has been proposed to ameliorate the adverse phenotypes of foetuses affected by intrauterine growth restriction (IUGR). Our previous studies showed, in a porcine model of IUGR, an effect of maternal HTX supplementation on the neurotransmitter profile of several brain areas and the morphology of the hippocampus in 100 days old foetuses. The present study analyzed the impact of maternal HTX supplementation on the hippocampus proteome at this foetal age by TMT10plex labelling. Eleven differentially abundant proteins were identified by comparing both conditions, and eight of them downregulated and three upregulated in the HTX-treated group. The downregulated proteins were mainly involved in protein synthesis and RNA metabolism and may explain the differences in neuron differentiation in the HTX-treated group. The upregulated proteins were related to cell detoxification and could represent a potential mechanism to explain the neuroprotective effect of HTX.

Novel indolic AMPK modulators induce vasodilatation through activation of the AMPK-eNOS-NO pathway.

Endothelial adenosine monophosphate-activated protein kinase (AMPK) plays a critical role in the regulation of vascular tone through stimulating nitric oxide (NO) release in endothelial cells. Since obesity leads to endothelial dysfunction and AMPK dysregulation, AMPK activation might be an important strategy to restore vascular function in cardiometabolic alterations. Here, we report the identification of a novel AMPK modulator, the indolic derivative IND6, which shows affinity for AMPKα1ß1γ1, the primary AMPK isoform in human EA.Hy926 endothelial cells. IND6 shows inhibitory action of the enzymatic activity in vitro, but increases the levels of p-Thr174AMPK, p-Ser1177eNOS and p-Ser79ACC in EA.Hy926. This paradoxical finding might be explained by the ability of IND6 to act as a mixed-type inhibitor, but also to promote the enzyme activation by adopting two distinct binding modes at the ADaM site. Moreover, functional assays reveal that IND6 increased the eNOS-dependent production of NO and elicited a concentration-dependent vasodilation of endothelium-intact rat aorta due to AMPK and eNOS activation, demonstrating a functional activation of the AMPK-eNOS-NO endothelial pathway. This kinase inhibition profile, combined with the paradoxical AMPK activation in cells and arteries, suggests that these new chemical entities may constitute a valuable starting point for the development of new AMPK modulators with therapeutic potential for the treatment of vascular complications associated with obesity.

Clinicopathological characteristics and survival results of patients with ultralow risk breast cancer. / Características clínico-patológicas y supervivencia de pacientes con cáncer de mama de riesgo muy bajo.

BACKGROUND AND OBJECTIVE: To identify subgroups with good progress over an extended period, we used diagnostic screening, tumour palpability, tumour phenotype, and node involvement. PATIENTS AND METHODS: We identified patients with good progress by means of a descriptive, observational and retrospective study. RESULTS: Of 746 patients diagnosed with node-negative breast cancer between 2001 and 2015: 110 (14.75%) had non-palpable screening-diagnosed tumours; 88 (80%) were endocrine-sensitive, 10 (9.10%) were triple-negative and 11 (10%) were HER2. Only 3 patients developed metastases, and there were 4 deaths: 2 from breast cancer and 2 from other causes. The distant recurrence-free interval (DRFI) was 95.60%: 100% in 34 endocrine-sensitive histological grade 1 (equivalent to luminal A) tumours, and 94.40% (95% CI 86.76-102.04) in 54 grade 2-3 (luminal B) tumours. In triple-negative and HER2 cases, it was 100%. In tumours <1 cm it was 100%, and >1 cm it was 95.50% (95% CI 79.42-100.98). CONCLUSIONS: Patients with non-palpable tumours detected by mammogram screening have ultralow risk. The good progress in the luminal A, triple-negative, HER2, and less than 1 cm subgroups may explain the efficacy of the treatment but it also makes them candidates to de-escalation of their treatment.

Satisfacción en los servicios de salud sexual y reproductiva: perspectiva de jóvenes. Medellín-Colombia / Satisfaction in Sexual and Reproductive Health Services: Youth Perspective. Medellín-Colombia / Satisfação nos serviços de saúde sexual e reprodutiva: perspectiva de jovens. Medellín-Colômbia

Resumen Objetivo: comprender la satisfacción en jóvenes de Medellín, Colombia, frente a los servicios de salud sexual y reproductiva ofertados en la Ciudad durante el período 2014-2015. Metodología: estudio cualitativo que utilizó la teoría fundada como método y el interaccionismo simbólico como perspectiva teórica. Para la recolección de información se realizaron nueve entrevistas en profundidad y un grupo focal con jóvenes entre 14 y 25 años, usuarios de los servicios de salud para jóvenes en la ciudad de Medellín. Resultados: la manera de ofrecer la atención y las características actitudinales del prestador del servicio son vitales para el logro de la satisfacción y la adhesión al servicio de asesoría en salud sexual y reproductiva. La escucha activa, el respeto, la construcción de confianza y la información diversa y sin tabúes, son fundamentales para responder a las necesidades de la población joven y generar un vínculo joven-prestador. Conclusión: para los jóvenes, la satisfacción y la adherencia a los servicios de salud están íntimamente ligados a la construcción de un vínculo de confianza con el servicio y con el prestador del servicio a partir de compartir y conversar lo que se vive, se piensa y se siente cotidianamente, promoviendo conciencia de autocuidado, actitudes críticas y reflexivas frente a la toma de decisiones.

Abstract Objective: To understand the satisfaction level of young people from Medellin, Colombia, about the sexual and reproductive health services offered in the City during the 2014-2015 period. Methodology: qualitative study that used grounded theory as a method and symbolic interactionism as a theoretical perspective. The collection of information was carried out by applying nine in-depth interviews and one focus group with young people between 14 and 25 years old, users of health services for young people in the city of Medellin. Results: The way of offering care and the attitudinal characteristics of the service provider are vital for achieving satisfaction and adherence to the sexual and reproductive health advisory service. Active listening, respect, trust building and diverse taboofree information is essential to respond to the needs of the young population and generate a young-provider bond. Conclusion: for young people, satisfaction and adherence to health services are intimately linked to building a bond of trust with the service and with the service provider based on sharing and talking about what is experienced, what is thought and what is felt on a daily basis, promoting awareness of self-care, critical and thoughtful attitudes towards decision-making.

Resumo Objetivo: compreender a satisfação em jovens de Medellín, Colômbia, frente aos serviços de saúde sexual e reprodutiva ofertados na Cidade durante o período 2014-2015. Metodologia: estudo qualitativo que utilizou a teoria fundada como método e o interaccionismo simbólico como perspectiva teórica. Para a colheita de informação foram feitas nove entrevistas em profundidade e um grupo focal com jovens entre 14 e 25 anos, usuários dos serviços de saúde para jovens na cidade de Medellín. Resultados: a maneira de oferecer a atenção e as características atitudinais do prestador do serviço são vitais para o logro da satisfação a adesão ao serviço de assessoria em saúde sexual e reprodutiva. A escuta ativa, o respeito, a construção de confiança e a informação diversa e sem tabus, são fundamentais para responder às necessidades da população jovem e gerar um vínculo jovem-prestador. Conclusão: para os jovens, a satisfação e a aderência aos serviços de saúde estão intimamente ligados à construção de um vínculo de confiança com o serviço e com o prestador do serviço a partir de compartir e conversar o que se vive, se pensa e se sente cotidianamente, promovendo consciência de autocuidado, atitudes críticas e reflexivas frente à toma de decisões.

Calidad de vida relacionada con la salud y percepción de amenaza de la enfermedad en pacientes con enfermedad renal crónica avanzada

Introducción: la enfermedad renal crónica avanzada (ERCA) puede impactar notablemente la calidad de vida relacionada con la salud (CVRS) de las personas que la padecen. Además, la percepción sobre lo amenazante que es esta enfermedad para su vida puede impactar notablemente la salud física y emocional de los pacientes. Objetivos: valorar la CVRS y la percepción de amenaza de la enfermedad en pacientes con ERCA y evaluar las asociaciones entre las variables de estudio. Materiales y métodos: estudio transversal realizado en 70 pacientes (80 % varones) de entre 38 y 88 años (M=68,88; DT=9,98) mediante dos instrumentos: el cuestionario de calidad de vida en enfermedad renal versión abreviada (KDOQL-SF36) y el cuestionario de percepción de amenaza de enfermedad (BIPQ). Se realizó un análisis descriptivo de los datos mediante el programa estadístico SPSS 26.0 y usando los estadísticos pruebas t, d de Cohen y correlaciones de Pearson. Resultados: los participantes mostraron una gran afectación de su CVRS y una percepción negativa de la enfermedad, siendo los peores indicadores los encontrados en mujeres. Una peor percepción de la enfermedad se asoció con mayor afectación de la CVRS. Conclusiones: la percepción de los pacientes sobre su salud puede afectar la adherencia terapéutica, por lo que es necesario implementar programas de intervención que incidan en ella y favorezcan la salud física y mental de los pacientes.

Theoretical framework: advanced chronic kidney disease (AKD) can have a significant impact on patients' health-related quality of life (HRQOL). However, a patient's perception of how life-threatening the disease is can have a significant impact on his or her physical and emotional health. Aim: to assess HRQoL and perceived threat of disease in patients with ACKD and to evaluate the associations between the variables under study. Methods: 70 patients (80 % male), between 38-88 years old (M=68.88; DT= 9.98) were evaluated by means of: the Quality of Life in Kidney Disease Shortened Version Questionnaire (KDOQL-SF36) and the Perception of Threatening Disease Questionnaire (BIPQ). Descriptive analyses, Cohen's t, d tests and Pearson's correlations were performed. Results: patients showed a great affectation of their HRQOL and a negative perception of the disease. Women had worse HRQoL and disease perception indicators. A worse perception of the disease was associated with a greater impairment of HRQOL. Conclusions: patients' perception of their health may affect their therapeutic adherence, so intervention programs are needed to influence it and favour the patient's physical and mental health.