Integrative clinical, hormonal, and molecular data associate with invasiveness in acromegaly: REMAH study.

INTRODUCTION: Growth hormone (GH)-secreting pituitary tumors (GHomas) are the most common acromegaly cause. At diagnosis, most of them are macroadenomas, and up to 56% display cavernous sinus invasion. Biomarker assessment associated with tumor growth and invasion is important to optimize their management. OBJECTIVES: The study aims to identify clinical/hormonal/molecular biomarkers associated with tumor size and invasiveness in GHomas and to analyze the influence of pre-treatment with somatostatin analogs (SSAs) or dopamine agonists (DAs) in key molecular biomarker expression. METHODS: Clinical/analytical/radiological variables were evaluated in 192 patients from the REMAH study (ambispective multicenter post-surgery study of the Spanish Society of Endocrinology and Nutrition). The expression of somatostatin/ghrelin/dopamine system components and key pituitary/proliferation markers was evaluated in GHomas after the first surgery. Univariate/multivariate regression studies were performed to identify association between variables. RESULTS: Eighty percent of patients harbor macroadenomas (63.8% with extrasellar growth). Associations between larger and more invasive GHomas with younger age, visual abnormalities, higher IGF1 levels, extrasellar/suprasellar growth, and/or cavernous sinus invasion were found. Higher GH1 and lower PRL/POMC/CGA/AVPR1B/DRD2T/DRD2L expression levels (P < .05) were associated with tumor invasiveness. Least Absolute Shrinkage and Selection Operator's penalized regression identified combinations of clinical and molecular features with areas under the curve between 0.67 and 0.82. Pre-operative therapy with DA or SSAs did not alter the expression of any of the markers analyzed except for DRD1/AVPR1B (up-regulated with DA) and FSHB/CRHR1 (down-regulated with SSAs). CONCLUSIONS: A specific combination of clinical/analytical/molecular variables was found to be associated with tumor invasiveness and growth capacity in GHomas. Pre-treatment with first-line drugs for acromegaly did not significantly modify the expression of the most relevant biomarkers in our association model. These findings provide valuable insights for risk stratification and personalized management of GHomas.

Predictors of biochemical response to somatostatin receptor ligands in acromegaly.

Although predictors of response to first-generation somatostatin receptor ligands (fg-SRLs), and to a lesser extent to pasireotide, have been studied in acromegaly for many years, their use is still not recommended in clinical guidelines. Is there insufficient evidence to use them? Numerous biomarkers including various clinical, functional, radiological and molecular markers have been identified. The first ones are applicable pre-surgery, while the molecular predictors are utilized for patients not cured after surgery. In this regard, factors predicting a good response to fg-SRLs are specifically: low basal GH, a low GH nadir in the acute octreotide test, T2 MRI hypointensity, a densely granulated pattern, high immunohistochemistry staining for somatostatin receptor 2 (SSTR2), and E-cadherin. However, there is still a lack of consensus regarding which of these biomarkers is more useful or how to integrate them into clinical practice. With classical statistical methods, it is complex to define reliable and generalizable cut-off values for a single biomarker. The potential solution to the limitations of traditional methods involves combining systems biology with artificial intelligence, which is currently providing answers to such long-standing questions that may eventually be finally included into the clinical guidelines and make personalized medicine a reality. The aim of this review is to describe the current knowledge of the main fg-SRLs and pasireotide response predictors, discuss their current usefulness, and point to future directions in the research of this field.

Primary Cilia as a Tumor Marker in Pituitary Neuroendocrine Tumors.

Pituitary neuroendocrine tumors (PitNETs) account for approximately 15% of all intracranial neoplasms. Although they usually appear to be benign, some tumors display worse behavior, displaying rapid growth, invasion, refractoriness to treatment, and recurrence. Increasing evidence supports the role of primary cilia (PC) in regulating cancer development. Here, we showed that PC are significantly increased in PitNETs and are associated with increased tumor invasion and recurrence. Serial electron micrographs of PITNETs demonstrated different ciliation phenotypes (dot-like versus normal-like cilia) that represented PC at different stages of ciliogenesis. Molecular findings demonstrated that 123 ciliary-associated genes (eg, doublecortin domain containing protein 2, Sintaxin-3, and centriolar coiled-coil protein 110) were dysregulated in PitNETs, representing the upregulation of markers at different stages of intracellular ciliogenesis. Our results demonstrate, for the first time, that ciliogenesis is increased in PitNETs, suggesting that this process might be used as a potential target for therapy in the future.

Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating.

Food is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional value; however, the cellular and molecular basis of macronutrient-specific reward circuits is poorly understood. Here, we monitor in vivo calcium dynamics to provide direct evidence of independent vagal sensing pathways for the detection of dietary fats and sugars. Using activity-dependent genetic capture of vagal neurons activated in response to gut infusions of nutrients, we demonstrate the existence of separate gut-brain circuits for fat and sugar sensing that are necessary and sufficient for nutrient-specific reinforcement. Even when controlling for calories, combined activation of fat and sugar circuits increases nigrostriatal dopamine release and overeating compared with fat or sugar alone. This work provides new insights into the complex sensory circuitry that mediates motivated behavior and suggests that a subconscious internal drive to consume obesogenic diets (e.g., those high in both fat and sugar) may impede conscious dieting efforts.

Lung UltrasouNd Guided surfactant therapy in preterm infants: an international multicenter randomized control trial (LUNG study).

BACKGROUND: The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group. METHODS/DESIGN: In this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks' gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group. DISCUSSION: Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022.

Circadian modulation of microglial physiological processes and immune responses.

Microglia is considered the central nervous system (CNS) resident macrophages that establish an innate immune response against pathogens and toxins. However, the recent studies have shown that microglial gene and protein expression follows a circadian pattern; several immune activation markers and clock genes are expressed rhythmically without the need for an immune stimulus. Furthermore, microglia responds to an immune challenge with different magnitudes depending on the time of the day. This review examines the circadian control of microglia function and the possible physiological implications. For example, we discuss that synaptic prune is performed in the cortex at a certain moment of the day. We also consider the implications of daily microglial function for maintaining biological rhythms like general activity, body temperature, and food intake. We conclude that the developmental stage, brain region, and pathological state are not the only factors to consider for the evaluation of microglial functions; instead, emerging evidence indicates that circadian time as an essential aspect for a better understanding of the role of microglia in CNS physiology.

Impact of Change in Body Composition during Follow-Up on the Survival of GEP-NET.

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous rare diseases causing malnutrition and cachexia in which the study of body composition may have an impact in prognosis. Aim: Evaluation of muscle and fat tissues by computed tomography (CT) at the level of the third lumbar (L3 level) at diagnosis and at the end of follow-up in GET-NET patients and their relationships with clinical and biochemical variables as predictors of survival. Methodology: Ninety-eight GEP-NET patients were included. Clinical and biochemical parameters were evaluated. Total body, subcutaneous, visceral and total fat areas and very low-density, low-density, normal density, high-density, very high-density and total muscle areas were obtained from CT images. Results: Body composition measures and overall mortality correlated with age, ECOG (Eastern Cooperative Oncology Group performance status) metastases, lactate dehydrogenase (LDH), albumin and urea levels. Although there was no relationship between body composition variables at diagnosis and overall and specific mortality, an increase in low-density muscle and a decrease in normal-density muscle during follow-up were independently correlated to overall (p <0.05) and tumor-cause mortality (p < 0.05). Conclusion: Although body composition measures obtained by CT at diagnosis did not impact survival of GEP-NET patients, a loss of good quality muscle during follow-up was associated with an increased overall and tumor-related mortality. Nutritional status should therefore be supervised by nutrition specialists and an increase in good quality muscle could improve prognosis.

Towards the development of an epitope-focused vaccine for SARS-CoV-2.

The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as vaccines focused on the partial or total sequence of the Spike protein using different novel platforms such us RNA, DNA, proteins, and non-replicating viral vectors have been developed. The high global need for vaccines, now and in the future, and the emergence of new variants of concern still requires development of accessible vaccines that can be adapted according to the most prevalent variants in the respective regions. Here, we describe the immunogenic properties of a group of theoretically predicted RBD peptides to be used as the first step towards the development of an effective, safe and low-cost epitope-focused vaccine. One of the tested peptides named P5, proved to be safe and immunogenic. Subcutaneous administration of the peptide, formulated with alumina, induced high levels of specific IgG antibodies in mice and hamsters, as well as an increase of IFN-γ expression by CD8+ T cells in C57 and BALB/c mice upon in vitro stimulation with P5. Neutralizing titers of anti-P5 antibodies, however, were disappointingly low, a deficiency that we will attempt to resolve by the inclusion of additional immunogenic epitopes to P5. The safety and immunogenicity data reported in this study support the use of this peptide as a starting point for the design of an epitope restricted vaccine.

VIP/VPAC Axis Expression in Immune-Mediated Inflammatory Disorders: Associated miRNA Signatures.

Few studies have considered immune-mediated inflammatory disorders (IMID) together, which is necessary to adequately understand them given they share common mechanisms. Our goal was to investigate the expression of vasoactive intestinal peptide (VIP) and its receptors VPAC1 and VPAC2 in selected IMID, analyze the effect of biological therapies on them, and identify miRNA signatures associated with their expression. Serum VIP levels and mRNA of VPAC and miRNA expression in peripheral blood mononuclear cells were analyzed from 52 patients with psoriasis, rheumatoid arthritis, Graves' disease, or spondyloarthritis and from 38 healthy subjects. IMID patients showed higher levels of VIP and increased expression of VPAC2 compared to controls (p < 0.0001 and p < 0.0192, respectively). Receiver operating characteristic curve analysis showed that the levels of VIP or VPAC2 expression were adequate discriminators capable of identifying IMID. Treatment of IMID patients with anti-TNFα and anti-IL12/23 significantly affected serum VIP levels. We identified miRNA signatures associated with levels of serum VIP and VPAC2 expression, which correlated with IMID diagnosis of the patients. The results indicate that the expression of VIP/VPAC2 is able of identify IMIDs and open up a line of research based on the association between the VIP/VPAC axis and miRNA signatures in immune-mediated diseases.

Lung Ultrasound Scores Progress Differently in Extreme and Very Preterm Infants after Birth: A Multicentre Prospective Study.

INTRODUCTION: The lung ultrasound score (LUS) has been suggested to predict moderate-severe bronchopulmonary dysplasia (msBPD) in preterm infants. We aimed to assess LUS evolution after birth in preterm infants and the effect of gestational age. METHODS: This multicentre prospective observational study was performed with newborns born before 33 weeks of gestation. We created two groups: group 1 (23-27 weeks) and group 2 (28-32 weeks). We compared LUSs between the groups from birth until 36 weeks of postmenstrual age, and we estimated the LUS evolution in each group with a linear multilevel mixed-effects regression model. The effects of the need for surfactant or an msBPD diagnosis were also studied. RESULTS: We included 339 patients: 122 (36%) in group 1 and 217 (64%) in group 2. The infants in group 1 showed a steady progression in the LUS from birth until 4 weeks of age and a subsequent decrease; the infants in group 2 showed a progressive decrease in the LUS throughout the study. This progression varied significantly in the first weeks of life in infants who required surfactant at birth and after the first week of life in the patients diagnosed with msBPD. DISCUSSION/CONCLUSIONS: Extremely preterm infants showed persistently high LUSs during the first weeks of life, regardless of the progression to msBPD. In this group, the infants who did not require surfactant at birth exhibited an increase in their LUSs after the first week until their values were equal to the remaining infants in their group.

Optimization of the Rheological Properties of Self-Assembled Tripeptide/Alginate/Cellulose Hydrogels for 3D Printing.

3D printing is an emerging and powerful technique to create shape-defined three-dimensional structures for tissue engineering applications. Herein, different alginate-cellulose formulations were optimized to be used as printable inks. Alginate (Alg) was chosen as the main component of the scaffold due to its tunable mechanical properties, rapid gelation, and non-toxicity, whereas microcrystalline cellulose (MCC) was added to the hydrogel to modulate its mechanical properties for printing. Additionally, Fmoc-FFY (Fmoc: 9-fluorenylmethoxycarbonyl; F: phenylalanine; Y: tyrosine), a self-assembled peptide that promotes cell adhesion was incorporated into the ink without modifying its rheological properties and shear-thinning behavior. Then, 3D-printed scaffolds made of Alg, 40% of MCC inks and Fmoc-FFY peptide were characterized by scanning electron microscopy and infrared spectroscopy, confirming the morphological microstructure of the hydrogel scaffolds with edged particles of MCC homogeneously distributed within the alginate matrix and the self-assembly of the peptide in a ß-sheet conformation. Finally, the cytocompatibility of the scaffolds was tested in contact with the MG63 osteosarcoma cells, confirming the absence of cytotoxic components that may compromise their viability. Interestingly, MG63 cell growth was retarded in the scaffolds containing the peptide, but cells were more likely to promote adhesive interactions with the material rather than with the other cells, indicating the benefits of the peptide in promoting biological functionality to alginate-based biomaterials.

Injectable Tripeptide/Polymer Nanoparticles Supramolecular Hydrogel: A Candidate for the Treatment of Inflammatory Pathologies.

Supramolecular peptide-based hydrogels attract great attention in several fields, i.e., biomedicine, catalysis, energy, and materials chemistry, due to the noncovalent nature of the self-assembly and functional tunable properties defined by the amino acid sequence. In this work, we developed an injectable hybrid supramolecular hydrogel whose formation was triggered by electrostatic interactions between a phosphorylated tripeptide, Fmoc-FFpY (F: phenylalanine, pY: phosphorylated tyrosine), and cationic polymer nanoparticles made of vinylimidazole and ketoprofen (poly(HKT-co-VI) NPs). Hydrogel formation was assessed through inverted tube tests, and its fibrillary structure, around polymer NPs, was observed by transmission electron microscopy. Interestingly, peptide self-assembly yields the formation of nontwisted and twisted fibers, which could be attributed to ß-sheets and α-helix structures, respectively, as characterized by circular dichroism and infrared spectroscopies. An increase of the elastic modulus of the Fmoc-FFpY/polymer NPs hybrid hydrogels was observed with peptide concentration as well as its injectability property, due to its shear thinning behavior and self-healing ability. After checking their stability under physiological conditions, the cytotoxicity properties of these hybrid hydrogels were evaluated in contact with human dermal fibroblasts (FBH) and murine macrophages (RAW 264.7). Finally, the Fmoc-FFpY/polymer NPs hybrid hydrogels exhibited a great nitric oxide reduction (∼67%) up to basal values of pro-inflammatory RAW 264.7 cells, thus confirming their excellent anti-inflammatory properties for the treatment of localized inflammatory pathologies.

[Is juvenile gangrenous vasculitis of the scrotum an endemic disease of mediterranean countries? Review of global publications and description of a new case.] / ¿Es la vasculitis gangrenosa juvenil del escroto una enfermedad endémica de los países mediterráneos? Revisión de las publicaciones mundiales y descripción de un nuevo caso.

INTRODUCTION AND OBJECTIVES: Juvenile gangrenous vasculitis of the scrotum was described by the Girona dermatologist Joaquín Piñol Aguadéin 1973. The objectives of this article are to review the world publications and provide a clinical case of this disease between urological and/or dermatological. MATERIAL AND METHODS: A review of juvenile gangrenous vasculitis of the scrotum between 1973 and 2019 is carried out and a new clinical case is contributed. The identification of articles in Medline was carried outwith MeSH terms "juvenile gangrenous vasculitis scrotum" and in Google with "juvenile gangrenous vasculitisscrotum". Ten clinical-epidemiological variables were studied in the articles: year, source, authors, number of cases, age, previous pharyngo-tonsillitis, biopsy of the lesion, treatment, days to healing, city and country. The results of the variables were analyzed with descriptive statistics. A new clinical case is described. RESULTS: We found 26 world references, 18 of them Spanish, corresponding to 24 publications and 2 conference papers with a total of 29 patients. The meanage of the patients was 23.6 years. The treatments used were exeresis of the lesion (23%), cephalosporins and/or corticoids i.v. (15.3%), tetracyclines, ciprofloxacin or oral amoxicillin-clavulanate (15.3%), local cure and oral corticoids (11.5%) and mupirocin or topical tetracyclines (7.6%). Healing took place in an average of 21 days. The cities with the most cases reported were Barcelona with 11 (37.9%) and Pontevedra with 2 (6.8%). By country, Spain contributed 22 cases (75.8%) and Chile, Argentina, Portugal, Italy, Tunisia, Turkey and Great Britainthe remaining 7 cases (24.1%). CONCLUSIONS: Juvenile gangrenous vasculitis of the scrotum is a benign entity with a self-limiting course. The process is preceded by pharyngo-tonsillitis in about half of the patients. The results of the study confirm the endemic nature of the disease in Mediterranean countries, including Spain.

INTRODUCCIÓN Y OBJETIVOS: La vasculitis gangrenosa juvenil del escroto fue descrita por el dermatólogo gerundense Joaquín Piñol Aguadé en1973. Los objetivos de este artículo son realizar una revisión de las publicaciones mundiales y aportar un caso clínico de esta enfermedad a caballo entre urológica y/o dermatológica.MATERIAL Y MÉTODOS: Se realiza una revisión sobre la vasculitis gangrenosa juvenil del escroto entre 1973 y 2019 y se aporta un nuevo caso clínico. La identificación de artículos en Medline se llevó a cabo con términos MeSH en inglés "juvenile gangrenous vasculitis scrotum" y en Google con "vasculitis gangrenosa juvenil del escroto". En los artículos se ha estudiado 10 variables clínico-epidemiológicas: año, fuente, autores, nº decasos, edad, faringoamigdalitis previa, biopsia de la lesión, tratamiento, días hasta curación, ciudad y país. Los resultados de las variables se analizaron con estadísticas descriptivas. Se describe un nuevo caso clínico.RESULTADOS: Hemos encontrado 26 referencias mundiales que correspondían a 24 publicaciones y 2 comunicaciones a congresos con un total de 29 pacientes. La edad media de los pacientes fue 23,6 años. Los tratamientos empleados fueron exéresis de la lesión (23%), cefalosporinas y/o corticoides i.v (15,3%), tetraciclinas, ciprofloxacino o amoxicilina-clavulánico orales (15,3%), cura local y corticoides orales (11,5%) y mupirocinao tetraciclinas tópicas (7,6%). La curación se produjo en una media de 21 días. Las ciudades con más casos aportados fueron Barcelona con 11 (37,9%) y Pontevedra con 2 (6,8%). Por países España aporta 22 casos (75,8%) y Chile, Argentina, Portugal, Italia, Túnez, Turquía, Gran Bretaña los 7 casos restantes (24,1%).CONCLUSIONES: La vasculitis gangrenosa juvenil del escroto es una entidad benigna de curso autolimitado. El proceso viene precedido de faringoamigdalitis en cerca de la mitad de los pacientes. Los resultados del trabajo confirman el carácter endémico de la enfermedad en los países mediterráneos entre los que destaca España.

The Predictive Value of Lung Ultrasound Scores in Developing Bronchopulmonary Dysplasia: A Prospective Multicenter Diagnostic Accuracy Study.

BACKGROUND: Different lung ultrasound (LUS) scanning protocols have been used, and the results in terms of diagnostic accuracy are heterogeneous. RESEARCH QUESTIONS: What is the diagnostic accuracy of the LUS score to predict moderate to severe bronchopulmonary dysplasia (msBPD)? Does scanning of posterior lung fields improve the diagnostic accuracy? STUDY DESIGN AND METHODS: This was a multicenter prospective, observational study in six centers. Two LUS aeration scores, one involving only anterolateral lung fields and the other adding the posterior fields were obtained at birth, on the third day of life (DOL), on the seventh DOL, on the 14th DOL, and on the 21st DOL. The diagnostic accuracy of both scores to predict msBPD was assessed at each time point. RESULTS: Eight hundred thirty-two LUS examinations in 298 infants were included. Both LUS score using anterolateral and posterior fields and LUS score using only anterolateral fields showed a similar moderate diagnostic accuracy to predict msBPD on the third DOL (area under the receiver operating characteristic curve [AUC] 95% CI, 0.68-0.85 vs 0.68-0.85; P = .97), seventh DOL (AUC 95% CI, 0.74-0.85 vs 0.74-0.84; P = .26), and 21st DOL (AUC 95% CI, 0.72-0.86 vs 0.74-0.88; P = .17). The LUS score using anterolateral and posterior fields was slightly more accurate at 14th DOL (AUC 95% CI, 0.69-0.83 vs 0.66-0.80; P = .01). A cutoff of 8 points in the LUS score using only anterolateral fields on the seventh DOL provided a sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 70%, 79%, 3.3, and 0.38, respectively, to predict msBPD. Adding gestational age (GA) and sex improved the discriminative value without significant differences compared with a predictive model based on multiple clinical variables: AUC 95% CI, 0.77-0.88 vs 0.80-0.91 (P = .52). INTERPRETATION: The LUS score is able to predict msBPD from the third DOL with a moderate diagnostic accuracy. Scanning posterior lung fields slightly improved diagnostic accuracy only at the 14th DOL. Adding GA and sex improves the diagnostic accuracy of the LUS scores. The LUS score is useful to stratify BPD risk early after birth.

LAT-1 and GLUT-1 Carrier Expression and Its Prognostic Value in Gastroenteropancreatic Neuroendocrine Tumors.

Cancer cells develop mechanisms that increase nutrient uptake, including key nutrient carriers, such as amino acid transporter 1 (LAT-1) and glucose transporter 1 (GLUT-1), regulated by the oxygen-sensing Von Hippel Lindau-hypoxia-inducible factor (VHL-HIF) transcriptional pathway. We aimed to analyze these metabolic players in gastroenteropancreatic neuroendocrine tumors (GEP-NET) and correlate them with tumor malignancy and progression. LAT-1, GLUT-1, and pVHL expression was analyzed in 116 GEP-NETs and 48 peritumoral tissue samples by immunohistochemistry. LAT-1 was stably silenced using specific shRNA in the human NET BON cell line. LAT-1 expression was significantly increased in tumor tissue compared to non-tumor tissue in both gastrointestinal (67% vs. 44%) and pancreatic NETs (54% vs. 31%). Similarly, GLUT-1 was substantially elevated in gastrointestinal (74% vs. 19%) and pancreatic (58% vs. 4%) NETs. In contrast, pVHL expression was decreased (85% vs. 58%) in pancreatic NETs. Tumors with metastases at diagnosis displayed increased LAT-1 and GLUT-1 and decreased pVHL expression (p < 0.001). In accordance with these data, silencing LAT-1 curtailed cell proliferation in BON cells. These findings suggest that specific mechanisms that increase nutrient uptake, such as LAT-1 and GLUT-1, are increased in GEP-NETs, whereas pVHL is decreased. These markers might be related to the proliferation and metastatic capacity of these tumors.

[Androgen deprivation therapy in advanced prostate cancer. Multicenter study.] / Terapia de deprivación androgénica en cáncer de próstata avanzado. Estudio multicéntrico.

OBJECTIVES: Advanced prostate cancer (PC) is a frequent entity. The objectives of this paper are the presentation of a sample of patients with PC undergoing treatment with androgen deprivation therapy (ADT) in usual clinical practice and the determination of parameters associated with the development of resistance to castration (CRPC). MATERIAL AND METHODS: Multicenter, observational, retrospective study that analyzes patients treated with ADT from January 2016 to January 2017. Descriptive analysis of the most relevant clinical variables and univariante analysis and progression times by Kaplan-Meier test. RESULTS: Sample of 952 patients. At PC diagnosis median age 74 years. Median PSA at PC diagnosis 23 ng/ml, when begining ADT 20.2 ng/ml. 80.2% of patients were biopsied at PC diagnosis: 28.2% Gleason score group 1, 38.7% groups 2 and 3 and 33.1% groups 4 and 5. Initial treatment of PC: 75.9% ADT, radical prostatectomy 8.4% and radiotherapy 15.1%. Of the 952 patients, 281 (29.6%) fulfilled CRPC criteria.In this group 21.7% achieved undetectable PSA (group in which it was 59.9%. Increased probability of progression to CRPC in: PSA >30ng/ml at PC diagnosis (p=0.000, OR 2.78), Gleason score group 4-5 (p=0.000, OR 2.33), and not to reach undetectable PSA after ADT (p <0.001, OR 3.32). The initial ADT group presents progression to metastatic CRPC more rapidly in unfavourable histology and when not reached undetectable PSA after ADT. CONCLUSIONS: We present a sample of patients with advanced PC in treatment with ADT that shows heterogeneity in usual clinical practice. In our sample, elevated PSA at PC diagnosis, unfavorable histology and failure to achieve a PSA<0.1 ng/ml after ADT is presented as an indicator of progression to the CRPC stage.

OBJETIVO: El cáncer de próstata (CP) avanzado es una entidad frecuente. Los objetivos de este trabajo son la presentación de una serie de pacientes con CP en tratamiento con Terapia de Deprivación Androgénica (TDA) en práctica clínica habitual y la determinación de parámetros asociados al desarrollo de resistencia a la castración (CPRC).MATERIAL Y MÉTODOS: Estudio multicéntrico,  observacional, retrospectivo que analiza pacientes tratados con TDA desde enero 2016 hasta enero 2017. Análisis descriptivo de las variables clínicas más relevantes, análisis univariante y supervivencia libre de progresión mediante test Kaplan-Meier. RESULTADOS: Muestra 952 pacientes. Al diagnóstico del CP edad mediana 74 años. Mediana de PSA al diagnóstico de CP 23 ng/ml, al inicio TDA 20,2 ng/ml. El 80,2% de pacientes tenían biopsia al diagnóstico del CP: 28,2% grado pronóstico Gleason grupo 1, 38,7% grados 2 y 3 y 33,1% grados 4 y 5. Tratamiento inicial del CP: 75,9% TDA, prostatectomía radical 8,4% y radioterapia 15,1%.De los 952 pacientes, 281 (29,6%) cumplían criterios de CPRC. En este grupo el 21,7% alcanzó PSA indetectable (<0,1 ng/ml) con la TDA 20,2  frente al grupo no CPRC en el que lo alcanzaron el 59,9%. Encontramos mayor probabilidad de progresión a CPRC en pacientes con PSA al diagnóstico de CP >30 ng/ml (p=0,000, OR 2,78), grado pronóstico Gleason grupos 4-5 (p=0,000, OR 2,33) y en aquellos que no alcanzan PSA indetectable tras TDA (p<0,01, OR 3,32) variables que se relacionan con los tiempos de progresión a CPRC y especialmente al estadio metastásico. CONCLUSIONES: Se presenta una serie de pacientes CP avanzado en tratamiento con TDA que muestra heterogeneidad de características y de manejo según práctica clínica habitual. En nuestra serie el PSA elevado al diagnóstico, histología desfavorable y no alcanzar un PSA<0,1 ng/ml tras la TDA se presentan como indicadores de progresión a estadio CPRC.

[Video game cable in urethral meatus with ball retained in bladder. First case in the world.] / Cable de videojuego en meato uretral con ovillo retenido en vejiga. Primer caso mundial.

INTRODUCTION AND OBJECTIVES: Urethral-vesical and bladder foreign bodies by electric cables are the most uncommon. The objectives of this article are to present the first worldwide case of urethro-vesical foreign body by the cable of a video game and to review the 5 Spanish publications. CLINICAL CASE: 14-year-old male attending the emergency department for urethral cable retention, urethralgia, hypogastric pain and malodorous urine incontinence. Simple abdominal radiography showed a ball of retained cable in the bladder coming out through the meatus. He was operated on by performing a cystotomy. He was discharged 24 hours later. CONCLUSIONS: Urethral and bladder foreign bodies by electric wire are a rare pathology. They can be due to different motivations. The treatment consists of the extraction of the cable, which can be carried out by endoscopic or open surgery depending on the size and morphology of the cable. It is advisable to study the mental state of these patients.

INTRODUCCIÓN Y OBJETIVOS: Los cuerpos extraños uretro-vesicales y vesicales por cables eléctricos son los más infrecuentes. Los objetivos de este artículo son presentar el primer caso mundial de cuerpo extraño uretro-vesical por el cable de un videojuego y revisar las 5 publicaciones españolas.CASO CLÍNICO: Varón de 14 años que acudió a urgencias por cable retenido en uretra, uretralgia, dolor hipogástrico e incontinencia de orina maloliente. La radiografía simple de abdomen mostró un ovillo de cable retenido en vejiga que salía por meato. Fue intervenido practicándose cistotomía. Fue dado de alta 24 horas después. CONCLUSIONES: Los cuerpos extraños uretrales y vesicales por cable eléctrico son una patología poco frecuente. Pueden obedecer a diversas motivaciones. El tratamiento consiste en la extracción del cable, pudiendo ser llevado a cabo mediante cirugía endoscópica o abierta según el tamaño y morfología del cable. Es aconsejable estudiar el estado mental de estos pacientes.

Nutrition Label Use Is Related to Chronic Conditions among Mexicans: Data from the Mexican National Health and Nutrition Survey 2016.

BACKGROUND: Non-communicable diseases, such as obesity, diabetes, and hypertension, can be prevented and treated through a balanced nutrient-rich diet. Nutrition labels have been recognized as crucial to preventing obesity and non-communicable diseases through a healthier diet. OBJECTIVE: Our aim was to examine the association between nutrition label use and chronic conditions (overweight, obesity, previously diagnosed diabetes, and hypertension) among an adult Mexican population. DESIGN: This was a cross-sectional study that used data from the Mexican National Health and Nutrition Survey of 2016 (ENSANUT MC 2016). PARTICIPANTS/SETTING: The participants were 5,013 adults aged 20 to 70 years old. Older adults (>70 years), illiterate participants, pregnant women, and participants with implausible blood pressure data were excluded from the sample. The survey was conducted from May to August 2016 in the participants' households. MAIN OUTCOME MEASURES: We measured chronic conditions (overweight, obesity, previously diagnosed diabetes, and hypertension). STATISTICAL ANALYSES PERFORMED: Pearson χ2 test was used to examine the associations among the use of nutrition labels and sociodemographic characteristics and chronic conditions. Multiple logistic regression was used to determine the association between nutrition label use and chronic conditions adjusting for the effect of confounding variables like sex, age, body mass index, education level, marital status, ethnicity, residence area, region, and socioeconomic status. RESULTS: From the total sample, 40.9% (95% CI 38.4% to 43.8%) reported using nutrition labeling. Respondents with overweight or obesity were less likely to use nutrition labels (odds ratio 0.74; P<0.05). Participants who self-reported diabetes had significantly lower odds of nutrition label use than participants who did not report to have diabetes (odds ratio 0.66; P<0.05). Participants having 3 chronic conditions had lower odds of nutrition label use (odds ratio 0.34; P<0.01) relative to having zero chronic conditions. CONCLUSIONS: This study suggests an association between nutrition label use and chronic conditions (obesity and diabetes). These findings demonstrate that people with obesity, diabetes, and a combination of chronic conditions were less likely to use nutrition labels than people without these conditions.