Miasis cutánea. A propósito de un caso

The term myiasis refers to infestation of wounds of live vertebrate, animal and human, with dipterous larvae that, at least for a certain period, feed in the host. In this paper we will describe the case of a 75-year-old man, with a chronic elephantiasis. The patient lived in a rural area and he had low socioeconomic status. He had not traveled to any subtropical places. Analyzing the case and with all etiologic diagnosis, we concluded the patient had an infestation by Calliphora spp.Las miasis son un parasitismo producido por larvas de dípteros que, de forma obligatoria o accidental, necesitan alimentarse de tejidos vivos o muertos. Presentamos a un paciente de 75 años con elefantiasis crónica. El paciente vivía en un área rural y tenía bajo nivel socioeconómico. No había viajado recientemente a ningún país subtropical. Analizando el caso, y según el diagnóstico etiológico, concluimos que el paciente presentaba una infestación por Calliphora spp

Una ictericia de causa avergonzante

We present the case of a 63-year-old man who went to the Emergency Department complaining of jaundice, choluria, and generalised pruritus for several days. He was admitted to the General Surgery department with the initial diagnosis of obstructive jaundice and incipient cholecystitis. After being ruled out, the patient was referred to Internal Medicine for further investigation. Test results were consistent with acute cholestatic hepatitis of probable toxic origin. Although he had initially denied taking medication or other products, he eventually confessed to taking sildenafil purchased over the Internet.Presentamos el caso de un varón de 63 años que acudió a Urgencias por un cuadro de ictericia, coluria y prurito generalizado de varios días de evolución. Con el diagnóstico inicial de ictericia obstructiva y colecistitis incipiente ingresó en el servicio de Cirugía General. Tras descartarse, el paciente pasó a cargo de Medicina Interna para continuar el estudio. Los resultados de las pruebas fueron consistentes con una hepatitis colestásica aguda de probable origen tóxico. A pesar de que inicialmente había negado la ingesta de medicamentos u otros productos, finalmente reconoció la ingesta de sildenafilo comprado a través de Internet

Functional Decline Over 1-year Follow-up in a Multicenter Cohort of Polypathological Patients: A New Approach to Functional Prognostication

SummaryBackgroundLittle is known about the fitness of the available tools in predicting functional decline of polypathological patients (PPs). Our objective was to assess accuracy of the Triage Risk Screening Tool (TRST), the Variable Indicative of Placement risk (VIP) and to develop a specific functional prognostic index adjusted to this population in a multicenter cohort of hospital-based PP.MethodsProspective 12-month follow-up study of PPs from 36 hospitals. Functional decline was defined as loss of ≥20 points on Barthel’s index (BI). Accuracy of TRST/VIP was assessed by calibration/discrimination tests. Development of the new score was performed by dividing into a derivation cohort (constructing the index by logistic regression), and a validation cohort (in which calibration/discrimination of the index were tested).ResultsNine hundred and fifty-eight patients from the 1632 included survived during follow-up. Basal/12-month BI was 85/70, respectively. Mean fall in BI score was 11.7±24 points [353 (36.8%) fell by ≥20 points]. The activities for daily living that declined most frequently were toilet use, grooming, dressing and bathing. TRST/VIP fitted well but their discrimination power was poor (area under the curve=0.49 and 0.46, respectively). A simplified PROFUNCTION index was derived containing seven items (≥85 years, neurological condition, osteoarticular disease, III–IV functional class of dyspnea, ≥4 polypathology categories, basal BI<60, and social problems). Functional decline risk ranged from 21% to 24% in the lowest risk group (0 items) to 38–46% in the highest (4–7 items). Calibration as well as discrimination power (area under the curve=0.56–0.59) of this simplified index were good.ConclusionWe developed and validated a new functional prognostic index specifically focused on these patients with better discrimination power than other tools available

Gremlin regulates tubular epithelial to mesenchymal transition via VEGFR2: Potential role in renal fibrosis

Chronic kidney disease (CKD) is emerging as an important health problem due to the increase number of CKD patients and the absence of an effective curative treatment. Gremlin has been proposed as a novel therapeutic target for renal inflammatory diseases, acting via Vascular Endothelial Growth Factor Receptor-2 (VEGFR2). Although many evidences suggest that Gremlin could regulate renal fibrosis, the receptor involved has not been yet clarified. Gremlin, as other TGF-β superfamily members, regulates tubular epithelial to mesenchymal transition (EMT) and, therefore, could contribute to renal fibrosis. In cultured tubular epithelial cells Gremlin binding to VEGFR2 is linked to proinflammatory responses. Now, we have found out that in these cells VEGFR2 is also involved in the profibrotic actions of Gremlin. VEGFR2 blockade by a pharmacological kinase inhibitor or gene silencing diminished Gremlin-mediated gene upregulation of profibrotic factors and restored changes in EMT-related genes. Moreover, VEGFR2 inhibition blocked EMT phenotypic changes and dampened the rate of wound healing in response to Gremlin. The role of VEGFR2 in experimental fibrosis was evaluated in experimental unilateral ureteral obstruction. VEFGR2 inhibition diminished the upregulation of profibrotic genes and EMT changes, as well as the accumulation of extracellular matrix proteins, such as fibronectin and collagens in the obstructed kidneys. Notch pathway activation participates in renal damage progression by regulating cell growth/proliferation, regeneration and inflammation. In cultured tubular epithelial cells, Notch inhibition markedly downregulated Gremlin-induced EMT changes and wound healing speed. These results show that Gremlin regulates the EMT process via VEGFR2 and Notch pathway activation, suggesting that the Gremlin/VEGFR2 axis could be a potential therapeutic target for CKD.This work was supported by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI16/02057, PI17/00119, PI17/01495, and Red de Investigación Renal REDINREN: RD16/0009), Sociedad Española de Nefrologia, “NOVELREN-CM: Enfermedad renal crónica: nuevas Estrategias para la prevención, Diagnóstico y tratamiento”; B2017/BMD-3751, B2017/BMD-3686 CIFRA2-CM, PAI 82140017, and FONDECYT 1160465 (Chile) and Bayer HealthCare AG (Grants4Targets initiative, Berlin, Germany)

Mujer joven asmática con disnea de etiología muy inusual

We present the case of a 36-year-old woman with a history of bronchial asthma who presented progressive dyspnea without improvement, despite intensive steroid and bronchodilator treatment. In view of the multiple consultations in the Emergency Room, admission to Internal Medicine was decided for study. After the initial approach, and always focused on his asthmatic background, it was a surprise to find the true cause of dyspnea: an infiltrating malignant cardiac tumor of the left atrium of sarcomatous lineage, which despite being operated on, led the patient to death.Presentamos el caso de una mujer de 36 años con antecedentes de asma bronquial que presentó un cuadro de disnea progresiva sin mejoría, a pesar de tratamiento esteroideo y broncodilatador intensivo. Ante las múltiples consultas en Urgencias, se decidió ingreso en Medicina Interna para estudio. Tras el estudio inicial, y siempre enfocado por su antecedente asmático, fue una sorpresa encontrar la verdadera causa de la disnea: un tumor cardíaco maligno infiltrante de aurícula izquierda de estirpe sarcomatosa que, a pesar de ser intervenido, condujo a la paciente a la muerte

The Spanish version of the reflective functioning questionnaire: Validity data in the general population and individuals with personality disorders.

Introduction Mentalization or reflective functioning (RF) is the capacity to interpret oneself or the others in terms of internal mental states. Its failures have been linked to several mental disorders and interventions improving RF have a therapeutic effect. Mentalizing capacity of the parents influences the children’s attachment. The Reflective Functioning Questionnaire (RFQ-8) is a widely used tool for the assessment of RF. No instrument is available to assess general RF in Spanish-speaking samples. The aim of this study is to develop a Spanish version of the RFQ-8 and to evaluate its reliability and validity in the general population and in individuals with personality disorders. Methods 602 non-clinical and 41 personality disordered participants completed a Spanish translation of the RFQ and a battery of self-reported questionnaires assessing several RF related constructs (alexithymia, perspective taking, identity diffusion and mindfulness), psychopathology (general and specific) and interpersonal problems. Temporal stability was tested in a non-clinical sub-sample of 113 participants. Results Exploratory and confirmatory factor analyses suggested a one-factor structure in the Spanish version of the RFQ-8. RFQ-8 understood as a single scale was tested, with low scorings reflecting genuine mentalizing, and high scorings uncertainty. The questionnaire showed good internal consistence in both samples and moderate temporal stability in non-clinical sample. RFQ correlated significantly with identity diffusion, alexithymia, and general psychopathology in both samples; and with mindfulness, perspective taking, and interpersonal problems in clinical sample. Mean values of the scale were significantly higher in the clinical group. Discussion This study provides evidence that the Spanish version of the RFQ-8, understood as a single scale, has an adequate reliability and validity assessing failures in reflective functioning (i.e., hypomentalization) in general population and personality disorders.The study received a Health Strategic Action fund from the Carlos III Health Institute of the Spanish Ministry of Science and Innovation. ID PI16/02058. https://www.isciii.es/QueHacemos/Financiacion/solicitudes/Paginas/default.aspx No researcher have received money from the fund. This kind of public funds are managed by public institutes (in this case BIOEF) that ensure this money is only used for some of the material resources necessary to carry out the investigation. https://www.bioef.org/es/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Gremlin Regulates Tubular Epithelial to Mesenchymal Transition via VEGFR2: Potential Role in Renal Fibrosis

Chronic kidney disease (CKD) is emerging as an important health problem due to the increase number of CKD patients and the absence of an effective curative treatment. Gremlin has been proposed as a novel therapeutic target for renal inflammatory diseases, acting via Vascular Endothelial Growth Factor Receptor-2 (VEGFR2). Although many evidences suggest that Gremlin could regulate renal fibrosis, the receptor involved has not been yet clarified. Gremlin, as other TGF-β superfamily members, regulates tubular epithelial to mesenchymal transition (EMT) and, therefore, could contribute to renal fibrosis. In cultured tubular epithelial cells Gremlin binding to VEGFR2 is linked to proinflammatory responses. Now, we have found out that in these cells VEGFR2 is also involved in the profibrotic actions of Gremlin. VEGFR2 blockade by a pharmacological kinase inhibitor or gene silencing diminished Gremlin-mediated gene upregulation of profibrotic factors and restored changes in EMT-related genes. Moreover, VEGFR2 inhibition blocked EMT phenotypic changes and dampened the rate of wound healing in response to Gremlin. The role of VEGFR2 in experimental fibrosis was evaluated in experimental unilateral ureteral obstruction. VEFGR2 inhibition diminished the upregulation of profibrotic genes and EMT changes, as well as the accumulation of extracellular matrix proteins, such as fibronectin and collagens in the obstructed kidneys. Notch pathway activation participates in renal damage progression by regulating cell growth/proliferation, regeneration and inflammation. In cultured tubular epithelial cells, Notch inhibition markedly downregulated Gremlin-induced EMT changes and wound healing speed. These results show that Gremlin regulates the EMT process via VEGFR2 and Notch pathway activation, suggesting that the Gremlin/VEGFR2 axis could be a potential therapeutic target for CKD

The Spanish version of the reflective functioning questionnaire: Validity data in the general population and individuals with personality disorders

INTRODUCTION: Mentalization or reflective functioning (RF) is the capacity to interpret oneself or the others in terms of internal mental states. Its failures have been linked to several mental disorders and interventions improving RF have a therapeutic effect. Mentalizing capacity of the parents influences the children's attachment. The Reflective Functioning Questionnaire (RFQ-8) is a widely used tool for the assessment of RF. No instrument is available to assess general RF in Spanish-speaking samples. The aim of this study is to develop a Spanish version of the RFQ-8 and to evaluate its reliability and validity in the general population and in individuals with personality disorders. METHODS: 602 non-clinical and 41 personality disordered participants completed a Spanish translation of the RFQ and a battery of self-reported questionnaires assessing several RF related constructs (alexithymia, perspective taking, identity diffusion and mindfulness), psychopathology (general and specific) and interpersonal problems. Temporal stability was tested in a non-clinical sub-sample of 113 participants. RESULTS: Exploratory and confirmatory factor analyses suggested a one-factor structure in the Spanish version of the RFQ-8. RFQ-8 understood as a single scale was tested, with low scorings reflecting genuine mentalizing, and high scorings uncertainty. The questionnaire showed good internal consistence in both samples and moderate temporal stability in non-clinical sample. RFQ correlated significantly with identity diffusion, alexithymia, and general psychopathology in both samples; and with mindfulness, perspective taking, and interpersonal problems in clinical sample. Mean values of the scale were significantly higher in the clinical group. DISCUSSION: This study provides evidence that the Spanish version of the RFQ-8, understood as a single scale, has an adequate reliability and validity assessing failures in reflective functioning (i.e., hypomentalization) in general population and personality disorders

Acute Kidney Injury is Aggravated in Aged Mice by the Exacerbation of Proinflammatory Processes

Acute kidney injury (AKI) is more frequent in elderly patients. Mechanisms contributing to AKI (tubular cell death, inflammatory cell infiltration, impaired mitochondrial function, and prolonged cell-cycle arrest) have been linked to cellular senescence, a process implicated in regeneration failure and progression to fibrosis. However, the molecular and pathological basis of the age-related increase in AKI incidence is not completely understood. To explore these mechanisms, experimental AKI was induced by folic acid (FA) administration in young (3-months-old) and old (1-year-old) mice, and kidneys were evaluated in the early phase of AKI, at 48 h. Tubular damage score, KIM-1 expression, the recruitment of infiltrating immune cells (mainly neutrophils and macrophages) and proinflammatory gene expression were higher in AKI kidneys of old than of young mice. Tubular cell death in FA-AKI involves several pathways, such as regulated necrosis and apoptosis. Ferroptosis and necroptosis cell-death pathways were upregulated in old AKI kidneys. In contrast, caspase-3 activation was only found in young but not in old mice. Moreover, the antiapoptotic factor BCL-xL was significantly overexpressed in old, injured kidneys, suggesting an age-related apoptosis suppression. AKI kidneys displayed evidence of cellular senescence, such as increased levels of cyclin dependent kinase inhibitors p16ink4a and p21cip1, and of the DNA damage response marker γH2AX. Furthermore, p21cip1 mRNA expression and nuclear staining for p21cip1 and γH2AX were higher in old than in young FA-AKI mice, as well as the expression of senescence-associated secretory phenotype (SASP) components (Il-6, Tgfb1, Ctgf, and Serpine1). Interestingly, some infiltrating immune cells were p21 or γH2AX positive, suggesting that molecular senescence in the immune cells (“immunosenescence”) are involved in the increased severity of AKI in old mice. In contrast, expression of renal protective factors was dramatically downregulated in old AKI mice, including the antiaging factor Klotho and the mitochondrial biogenesis driver PGC-1α. In conclusion, aging resulted in more severe AKI after the exposure to toxic compounds. This increased toxicity may be related to magnification of proinflammatory-related pathways in older mice, including a switch to a proinflammatory cell death (necroptosis) instead of apoptosis, and overactivation of cellular senescence of resident renal cells and infiltrating inflammatory cells

Ferric carboxymaltose with or without erythropoietin for the prevention of red-cell transfusions in the perioperative period of osteoporotic hip fractures: a randomized contolled trial. The PAHFRAC-01 project

Background: Around one third to one half of patients with hip fractures require red-cell pack transfusion. The increasing incidence of hip fracture has also raised the need for this scarce resource. Additionally, red-cell pack transfusions are not without complications which may involve excessive morbidity and mortality. This makes it necessary to develop blood-saving strategies. Our objective was to assess safety, efficacy, and cost-effictveness of combined treatment of i.v. ferric carboxymaltose and erythropoietin (EPOFE arm) versus i.v. ferric carboxymaltose (FE arm) versus a placebo (PLACEBO arm) in reducing the percentage of patients who receive blood transfusions, as well as mortality in the perioperative period of hip fracture intervention. Methods/Design: Multicentric, phase III, randomized, controlled, double blinded, parallel groups clinical trial. Patients > 65 years admitted to hospital with a hip fracture will be eligible to participate. Patients will be treated with either a single dosage of i.v. ferric carboxymaltose of 1 g and subcutaneous erythropoietin (40.000 IU), or i.v. ferric carboxymaltose and subcutaneous placebo, or i.v. placebo and subcutaneous placebo. Follow-up will be performed until 60 days after discharge, assessing transfusion needs, morbidity, mortality, safety, costs, and health-related quality of life. Intention to treat, as well as per protocol, and incremental cost-effectiveness analysis will be performed. The number of recruited patients per arm is set at 102, a total of 306 patients. Discussion: We think that this trial will contribute to the knowledge about the safety and efficacy of ferric carboxymaltose with/without erythropoietin in preventing red-cell pack transfusions in patients with hip fracture. ClinicalTrials.gov identifier: NCT01154491