Pulmonologists' Opinion on the Use of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease Patients in Spain: A Cross-Sectional Survey.

Introduction: Identifying the variables that guide decision-making in relation to the use of inhaled corticosteroids (ICS) can contribute to the appropriate use of these drugs. The objective of this study was to identify the clinical variables that physicians consider most relevant for prescribing or withdrawing ICS in COPD. Methods: A cross-sectional survey was conducted in Spain from November 2020 to May 2021. Therapeutic decisions on the use of ICS in 11 hypothetical COPD patient profiles were collected using an online survey answered by specialists with experience in the management of patients with COPD. Mixed-effects logistic regression was used to analyze the impact of patients' characteristics in the therapeutic decision for prescribing ICS or proceeding to its withdrawal. Results: A total of 74 pulmonologists agreed to collaborate in the survey and answered the questionnaire. The results showed great variability, with only 2 profiles achieving consensus for starting or withdrawing the treatment. The frequency and severity of exacerbations influenced the decision to prescribe ICS in a dose-response fashion (1 exacerbation odds ratio (OR) = 1.86, 95% confidence interval (CI) 1.02 to 3.43, two exacerbations OR = 11.6, 95% CI: 4.47 to 30.2 and three OR = 123, 95% CI: 25 to 601). Similarly, increasing blood eosinophils and history of asthma were associated with ICS use. On the other hand, pneumonia reduced the probability of initiating treatment with ICS (OR = 0.54 [0.29 to 0.98]). Lung function and dyspnea degree did not influence the clinician's therapeutic decision. The results for withdrawal of ICS were similar but in the opposite direction. Conclusion: In accordance with guidelines, exacerbations, blood eosinophils and history of asthma or pneumonia are the factors considered by pulmonologist for the indication or withdrawal of ICS. However, the agreement in prescription or withdrawal of ICS when confronted with hypothetical cases is very low, suggesting a great variability in clinical practice.

Percepción de los usuarios sobre el acompañamiento del Servicio de Salud Mental del Hospital Infantil Dr. Robert Reid Cabral durante la pandemia de la COVID-19, entre diciembre del año 2020 y marzo del año 2021 / User's perception of the accompaniment by the Mental Health Service of the Dr. Robert Reid Cabral Children's Hospital during the COVID-19 pandemic, from December 2020 & March 2021

Introducción: a finales del año 2019 el mundo se enfrentó al SARS-CoV-2, coronavirus causante de la COVID-19 y declarada pandemia en marzo del 2020. En este contexto, los servicios de salud han necesitado reorganizar, diseñar estrategias o interrumpir sus servicios de rutina, y muchos dejaron de brindar atención a las personas en tratamiento contra enfermedades de salud mental y condiciones crónicas. Asimismo, muchos trabajadores de la salud que suelen brindar esta atención fueron redirigidos a la respuesta de COVID-19. Material y Métodos: se realizó un estudio observacional, descriptivo y transversal, con el objetivo de estudiar la percepción de los usuarios sobre el acompañamiento del Servicio de Salud Mental del Hospital Infantil Dr. Robert Reid Cabral durante la pandemia de la COVID-19, entre diciembre 2020 y marzo 2021. La población estuvo conformada por un total de 237 pacientes, de la cual un 19 % fue incluido en la investigación final. Discusión: más de la mitad de los usuarios del servicio de Salud Mental de nuestro Hospital percibió el acompañamiento recibido como bueno. Esto coincide con otros estudios internacionales que igualmente han utilizado herramientas como telesalud para mantener el contacto y la atención con los pacientes. No encontramos diferencias significativas en la cantidad de pacientes con contactos positivos confirmados entre sus convivientes y las alteraciones en los patrones de sueño, alimentación y conducta, en comparación con aquellos que no tuvieron un contacto positivo confirmado entre sus convivientes. Conclusiones: la oferta de acceso a servicios de salud a distancia resulta ser una buena alternativa para ofrecer a los pacientes y a sus familias, brindar una atención oportuna a los conflictos presentados, y, cuando es implementada apropiadamente, las familias beneficiadas perciben como bueno el servicio ofrecido.

Introduction: At the end of 2019, the world faced SARS-CoV-2, the coronavirus that causes COVID-19, declared a pandemic in March 2020. In this context, health services have needed to reorganize, design strategies or interrupt their services routine, and many stopped providing care to people being treated for mental health illnesses and chronic conditions. Additionally, many healthcare workers who typically provide this care were redirected to the COVID-19 response. Material and methods: An observational, descriptive and cross-sectional study was carried out, with the aim of studying the perception of users about the follow-up of the Mental Health Service of the Dr. Robert Reid Cabral Children's Hospital during the COVID-19 pandemic, between December 2020 and March 2021. The population consisted of a total of 237 patients, of which 19% were included in the final investigation. Discussion: More than half of the users of the Mental Health service of our Hospital perceived the accompaniment received as good. This coincides with other international studies that have also used tools such as telehealth to maintain contact and care with patients. A single review study recorded the perception of the users interviewed towards the remote mental health care service, where they qualify it, in general terms, as good, which coincides with our results. We found no significant differences in the number of patients with confirmed positive contacts between their partners and alterations in sleep, eating and behavior patterns, compared to those who did not have a confirmed positive contact between their partners. A single review study recorded the perception of the users interviewed towards the remote mental health care service, where they qualify it, in general terms, as good, which coincides with our results. Conclusions: The offer of access to remote health services turns out to be a good alternative to offer patients and their families, provide timely attention to the conflicts presented, and, when properly implemented, the beneficiary families perceive the offered service as good.

In vivo phosphoproteomics reveals kinase activity profiles that predict treatment outcome in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) lacks prognostic and predictive markers. Here, we use high-throughput phosphoproteomics to build a functional TNBC taxonomy. A cluster of 159 phosphosites is upregulated in relapsed cases of a training set (n = 34 patients), with 11 hyperactive kinases accounting for this phosphoprofile. A mass-spectrometry-to-immunohistochemistry translation step, assessing 2 independent validation sets, reveals 6 kinases with preserved independent prognostic value. The kinases split the validation set into two patterns: one without hyperactive kinases being associated with a >90% relapse-free rate, and the other one showing ≥1 hyperactive kinase and being associated with an up to 9.5-fold higher relapse risk. Each kinase pattern encompasses different mutational patterns, simplifying mutation-based taxonomy. Drug regimens designed based on these 6 kinases show promising antitumour activity in TNBC cell lines and patient-derived xenografts. In summary, the present study elucidates phosphosites and kinases implicated in TNBC and suggests a target-based clinical classification system for TNBC.

[Complicated jejunoileal diverticular disease: a 12 cases' serie and literature review]. / Enfermedad diverticular yeyuno-ileal complicada tratada quirúrgicamente: serie de 12 casos y revisión de literatura.

OBJECTIVE: To perform a retrospective analysis of a series of complicated JID (jejunoileal diverticulitis) cases surgically treated in our service during the period from 2002 to 2015. MATERIALS AND METHODS: We treated 12 cases of jejunoileal complicated diverticulosis. 7 women and 5 men. The mean age was 76 years. The clinical presentation in all cases was acute abdominal pain, one with gastrointestinal bleeding. All cases had leukocytosis, neutrophilia and increased acute phase reactants. All patients underwent emergency abdominal CT. RESULTS: In 11 cases, there was consistency between imaging studies and surgical findings. Diverticula were located: jejunum (9) and ileum (3). Urgent exploratory laparotomy was always done and findings were: diverticular perforation with peritonitis (7 cases), diverticular perforation with abscess (4 cases) and in one case an ischemic area with diverticular perforation after embolization. Intestinal resection and anastomosis was performed in all cases. There were no patients, in which the diagnosis of diverticulosis jejunoileal was previously known. Complications were: Clavien I (2), Clavien IIIa (1), Clavien IVb (1), Clavien V (1). CONCLUSIONS: Jejunoileal diverticulitis is a rare entity, usually the first sign of onset of diverticular disease not previously known. Abdominal CT is of great diagnostic value. Resection of the affected segment is the treatment of choice.

Enfermedad diverticular yeyuno-ileal complicada tratada quirúrgicamente: serie de 12 casos y revisión de literatura / Complicated jejunoileal diverticular disease: a 12 cases' serie and literature review

Objetivo: Realizar un análisis retrospectivo de una serie de casos de diverticulitis yeyuno-ileal complicadas tratadas quirúrgicamente en nuestro servicio durante el periodo comprendido entre los años 2002 al 2015. Materiales y métodos: Se trató quirúrgicamente 12 casos de diverticulosis yeyuno-ileal complicadas, 7 mujeres y 5 varones. La edad media fue 76 años. La presentación clínica en todos los casos fue dolor abdominal agudo, uno de ellos con hemorragia digestiva. Todos presentaron leucocitosis, neutrofilia y aumento de reactantes de fase aguda. A todos los pacientes se les realizó TAC abdominal urgente. Resultados: En 11 casos hubo congruencia entre estudio de imagen y hallazgos quirúrgicos. La localización de los divertículos fue yeyuno (9) e íleon (3). Siempre se realizó laparotomía exploradora urgente encontrándose perforación diverticular con peritonitis (7 casos), perforación diverticular con absceso (4 casos) y en un caso un área isquémica con perforación diverticular tras embolización. Se realizó siempre resección intestinal y anastomosis. En ningún caso se conocía previamente el diagnóstico de diverticulosis yeyuno-ileal. Nuestras complicaciones fueron: Clavien I (2), Clavien IIIa (1), Clavien IVb (1), Clavien V (1). Conclusiones: La diverticulitis yetuno-ileal es una entidad infrecuente, suele ser la forma de debut de una enfermedad diverticular no conocida previamente. El TAC abdominal es de gran utilidad diagnóstica. La resección del segmento afecto es el tratamiento de elección

Objective: To perform a retrospective analysis of a series of complicated JID (jejunoileal diverticulitis) cases surgically treated in our service during the period from 2002 to 2015. Materials and methods: We treated 12 cases of jejunoileal complicated diverticulosis. 7 women and 5 men. The mean age was 76 years. The clinical presentation in all cases was acute abdominal pain, one with gastrointestinal bleeding. All cases had leukocytosis, neutrophilia and increased acute phase reactants. All patients underwent emergency abdominal CT. Results: In 11 cases, there was consistency between imaging studies and surgical findings. Diverticula were located: jejunum (9) and ileum (3). Urgent exploratory laparotomy was always done and findings were: diverticular perforation with peritonitis (7 cases), diverticular perforation with abscess (4 cases) and in one case an ischemic area with diverticular perforation after embolization. Intestinal resection and anastomosis was performed in all cases. There were no patients, in which the diagnosis of diverticulosis jejunoileal was previously known. Complications were: Clavien I (2), Clavien IIIa (1), Clavien IVb (1), Clavien V (1). Conclusions: Jejunoileal diverticulitis is a rare entity, usually the first sign of onset of diverticular disease not previously known. Abdominal CT is of great diagnostic value. Resection of the affected segment is the treatment of choice

Adenoma hepático malignizado en varones: presentación de 2 casos / Malignant liver adenoma in men: report of 2 cases

No disponible

"Ancient" schwannoma localizado en el músculo psoas / "Ancient" schwannoma in the psoas muscle

No disponible

Osteonecrosis maxilar asociada a infección por Actinomyces y tratamiento con bifosfonatos / Actinomyces and bisphosphonate-related osteonecrosis of the jaw

Objetivo. Describir anatomopatológicamente la osteonecrosis maxilar asociada a tratamiento con bifosfonatos y su asociación con infección por Actinomyces spp. Material y método. Se seleccionaron casos con diagnóstico clinicopatológico de necrosis maxilar o mandibular en las bases de datos de los hospitales de La Paz y de Guadalajara. Resultados. Se hallaron 16 casos con constatación anatomopatológica de necrosis ósea maxilomandibular e infección por Actinomyces. En 13 casos se informó de tratamiento con bifosfonatos. Un caso correspondió a osteorradionecrosis infectada. En 2 casos no se informó de tratamiento alguno. Conclusiones. Este cuadro es poco frecuente y suele sospecharse clínicamente, pero es relativamente desconocido para patólogos generales. Constantemente se asocia a infección por Actinomyces spp, que probablemente influya en la patogenia del proceso(AU)

Objetive. To describe pathological features in bisphosphonate-related osteonecrosis of the jaw and Actinomyces spp. infection. Materials and method. All cases, from both our hospitals, with a clinicopathological diagnosis of osteonecrosis of the jaw were reviewed. Results. Sixty cases of osteonecrosis of the jaw and Actinomyces infection are reported. Thirty cases were treated with bisphosphonate, 2 cases were untreated, and one case corresponded to infected osteoradionecrosis. Conclusion. This is a rare disease that is detected usually by clinicians but pathologists should be aware of it. It is constantly associated with, and probably caused by, Actinomyces spp. infection(AU)

Study of EWS/FLI-1 rearrangement in 18 cases of CK20+/CM2B4+ Merkel cell carcinoma using FISH and correlation to the differential diagnosis of Ewing sarcoma/peripheral neuroectodermal tumor.

Merkel cell carcinoma (MCC) and primary cutaneous Ewing sarcoma/primitive neuroectodermal tumors (PCES/PNET) pose a challenging morphologic differential diagnosis. Approximately 90% of Ewing sarcoma/primitive neuroectodermal tumors (PNETs) have a specific translocation, t(11;22) (q24;q12). The EWS-friend leukemia integration-1 (FLI-1) fusion results in FLI-1 overexpression. EWS/FLI-1 rearrangement has been suggested as a useful tool in the diagnosis of PCES/PNET. In contrast, Merkel cell polyomavirus was found to be an infective agent related to the pathogenesis of MCC. Merkel cell polyomavirus can be immunohistochemically detected with the antibody CM2B4. To the best of our knowledge, there is no case of any cytokeratin (CK)20-/CM2B4+ PNET. The goal of our study was to investigate whether EWS/FLI-1 rearrangement was present in cases of MCC. We have studied 18 cases of MCC. To make sure that the cases investigated by fluorescent in situ hybridization were genuine MCC, we considered only CK20+/CM2B4+ cases. Six cases met this criterion. EWS/FLI-1 rearrangement was not evidenced in any of the 18 cases (including the 6 "genuine" cases of MCC). Although our findings were somewhat expected, we think that they fill a gap in the literature: the confirmation that MCC is devoid of the EWS/FLI-1 rearrangement.

The immunohistochemical profile of Spitz nevi and conventional (non-Spitzoid) melanomas: a baseline study.

Several isolated markers have been proposed to aid in differential diagnostic of difficult melanocytic lesions, albeit none has been shown to be definitive in differentiating Spitz nevus from melanoma. This study proposes a wide panel of 22 markers having important functions in different biological functions (cell cycle, apoptosis, DNA repair proteins and membranous receptors) to provide a combination of proteins associated with either benign or malignant phenotype. Using tissue microarrays, we compared protein expression profiles in 28 typical Spitz nevi and 62 primary vertical growth phase non-spitzoid melanomas. Most of the significant differences were linked to cell-cycle deregulation such as overexpression of cyclin D1 and p21 in Spitz nevi compared with non-spitzoid melanomas (74 vs 16% and 91 vs 27%, respectively) and mitotic rate including Ki-67, highly expressed in deep areas of non-spitzoid melanomas (37%), whereas it is not expressed in Spitz nevi (0%), topoisomerase IIalpha (79% in non-spitzoid melanomas vs 15% in Spitz nevi) and nuclear survivin (69% in melanomas vs 0% in Spitz nevi). A combination of biological markers differentially expressed in Spitz nevi from non-spitzoid melanomas is defined, thus providing a potential tool for histopathological differential diagnostic between Spitz nevus and melanoma. Nevertheless, more studies including atypical Spitz nevi and spitzoid melanomas are necessary to further establish a reliable panel to differentiate among difficult cases.

MAP17 enhances the malignant behavior of tumor cells through ROS increase.

Tumorigenesis occurs when the mechanisms involved in the control of tissue homeostasis are disrupted and cells stop responding to physiological signals. Therefore, genes capable of desensitizing tumoral cells from physiological signals may provide a selective advantage within the tumoral mass and influence the outcome of the disease. We undertook a large-scale genetic screen to identify genes able to alter the cellular response to physiological signals and provide selective advantage once tumorigenesis has begun. We identified MAP17, a small 17 kDa non-glycosylated membrane protein previously identified by differential display being over-expressed in carcinomas. Tumor cells that over-express MAP17 show an increased tumoral phenotype with enhanced proliferative capabilities both in presence or absence of contact inhibition, decreased apoptotic sensitivity and increased migration. MAP17-expressing clones also grow better in nude mice. The increased malignant cell behavior induced by MAP17 are associated with an increase in reactive oxygen species (ROS) production, and the treatment of MAP17-expressing cells with antioxidants results in a reduction in the tumorigenic properties of these cells. Treatment of melanoma cells with inhibitors of Na+-coupled co-transporters lead to an inhibition of ROS increase and a decrease in the malignant cell behavior in MAP17-expressing clones. Finally, we show that MAP17-dependent ROS increase and tumorigenesis are dependent on its PDZ-binding domain, since disruption of its sequence by point mutations abolishes its ability to enhance ROS production and tumorigenesis. Our work shows the tumorigenic capability of MAP17 through a connection between Na+-coupled co-transporters and ROS.

MAP17 overexpression is a common characteristic of carcinomas.

We undertook a large-scale genetic screen to identify genes able to alter the cellular response to physiological signals and provide selective advantage once tumorigenesis has begun. We identified MAP17, a small 17 kDa non-glycosylated membrane protein previously identified, being overexpressed in carcinomas. We found that MAP17 is overexpressed in a great variety of human carcinomas. Immunohistochemical analysis of MAP17 during cancer progression shows, at least in prostate and ovarian carcinomas, that overexpression of the protein strongly correlates with tumoral progression (P < 0.0001). Many tumor cells also express MAP17 and its expression does not correlate with expression of SCL, a neighbor gene reported to be co-expressed in some hematopoietic cell lines. SCL neither is expressed in most MAP17-positive tumors, indicating the independent transcription of MAP17, at least in carcinomas. We cloned 5' genomic region to MAP17 and described the minimal promoter necessary to produce independent activation of MAP17. Moreover, we have found that MAP17 promoter is activated by oncogenes. Taken together, our data show an independent activation of MAP17 promoter that can be driven by oncogenes and that might explain the common overexpression of MAP17 in human carcinomas.

A high-throughput study in melanoma identifies epithelial-mesenchymal transition as a major determinant of metastasis.

Metastatic disease is the primary cause of death in cutaneous malignant melanoma (CMM) patients. To understand the mechanisms of CMM metastasis and identify potential predictive markers, we analyzed gene-expression profiles of 34 vertical growth phase melanoma cases using cDNA microarrays. All patients had a minimum follow-up of 36 months. Twenty-one cases developed nodal metastatic disease and 13 did not. Comparison of gene expression profiling of metastatic and nonmetastatic melanoma cases identified 243 genes with a >2-fold differential expression ratio and a false discovery rate of <0.2 (206 up-regulated and 37 down-regulated). This set of genes included molecules involved in cell cycle and apoptosis regulation, epithelial-mesenchymal transition (EMT), signal transduction, nucleic acid binding and transcription, protein synthesis and degradation, metabolism, and a specific group of melanoma- and neural-related proteins. Validation of these expression data in an independent series of melanomas using tissue microarrays confirmed that the expression of a set of proteins included in the EMT group (N-cadherin, osteopontin, and SPARC/osteonectin) were significantly associated with metastasis development. Our results suggest that EMT-related genes contribute to the promotion of the metastatic phenotype in primary CMM by supporting specific adhesive, invasive, and migratory properties. These data give a better understanding of the biology of this aggressive tumor and may provide new prognostic and patient stratification markers in addition to potential therapeutic targets.

Mst1, RanBP2 and eIF4G are new markers for in vivo PI3K activation in murine and human prostate.

Phosphatidylinositol 3-kinases (PI3Ks) constitute important regulators of signaling pathways. The PIK3CA gene encoding the p110-alpha catalytic subunit represents one of the highly mutated oncogenes identified in human cancer. Here, we report new markers for in vivo PI3K activation in prostate. To that end, we used a transgenic mouse line, which expresses a constitutively active p110-alpha subunit in the epithelial cells of the prostate. The activity of the PI3K pathway in the prostate was proven by assessing the phosphorylation of the PI3K direct target AKT1 and of the mTOR target eukaryotic translation initiation factor 4G (eIF4G). To establish also transcriptional ('late') targets of the PI3K pathway, we tested two genes, Mst1 and RanBP2, which we recently described as transcriptional targets of the growth factor platelet-derived growth factor-beta. We show that the levels of both proteins are elevated in transgenic animals. Additionally, we describe that the phosphorylation of AKT and eIF4G, as well as the elevation of the Mst1 and RanBP2 protein levels, can be inhibited in vivo in transgenic animals by the PI3K inhibitor LY294002. Finally, we performed human tissue microarray experiments with the four markers. Since they define overlapping but not identical subsets of the tested tissue panel, a combination of all four markers might lead to a more accurate diagnosis of the status of the PI3K-signaling cascade in cancer patients.