Search

Ibrutinib is a first-in-class Bruton's tyrosine kinase inhibitor approved for the treatment of various B-cell malignancies and chronic graft-versus-host disease. We evaluated the safety and efficacy of ibrutinib, alone or combined with standard-of-care regimens, in adults with advanced urothelial carcinoma (UC). Once-daily ibrutinib was administered orally at 840 mg (single-agent or with paclitaxel) or at 560 mg (with pembrolizumab). Phase 1b determined the recommended phase 2 dose (RP2D) of ibrutinib, and phase 2 assessed progression-free survival (PFS), overall response rate (ORR), and safety. Thirty-five, eighteen, and fifty-nine patients received ibrutinib, ibrutinib plus pembrolizumab, and ibrutinib plus paclitaxel at the RP2D, respectively. Safety profiles were consistent with those of the individual agents. The best-confirmed ORRs were 7% (two partial responses) with single-agent ibrutinib and 36% (five partial responses) with ibrutinib plus pembrolizumab. Median PFS was 4.1 months (range, 1.0-37.4+) with ibrutinib plus paclitaxel. The best-confirmed ORR was 26% (two complete responses). In previously treated patients with UC, ORR was higher with ibrutinib plus pembrolizumab than with either agent alone (historical data in the intent-to-treat population). ORR with ibrutinib plus paclitaxel was greater than historical values for single-agent paclitaxel or ibrutinib. These data warrant further evaluation of ibrutinib combinations in UC.

Reseña del libro: PANIAGUA LÓPEZ, Julián Antonio, El contrabando de armas en la guerra del Rif. Ceuta: Instituto de Estudios Ceutíes, 510 pp.

Background Fibrotic hypersensitivity pneumonitis (fHP) is an immune-mediated interstitial lung disease caused by sensitisation to chronic allergen inhalation. This study aimed to determine prognostic indicators of progression and mortality in fHP. Methods This was a retrospective, multicentre, observational, cross-sectional cohort study of consecutive patients diagnosed with fHP from 1 January 2012 to 31 December 2021. Multivariate Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals for predictors of progression and survival. Results A total of 403 patients were diagnosed with fHP: median (interquartile range) age 66.5 (14.0) years, 51.9% females and 55.1% never-smokers. The cause of fHP was mainly fungal (39.7%) or avian (41.4%). Lung biopsy was performed in 269 cases (66.7%). In the whole cohort the variables that were related to mortality or lung transplant were older age (HR 1.08; p

BackgroundLiver transplantation is the last therapeutic option for patients with end-stage liver disease. Postreperfusion syndrome (PRS), defined as a fall in mean arterial pressure of more than 30% within the first 5 minutes after reperfusion of at least 1 minute, can occur in liver transplantation as a deep hemodynamic instability with associated hyperfibrinolysis immediately after reperfusion of the new graft. Its incidence has remained unchanged since it was first described in 1987. PRS is related to ischemia-reperfusion (I/R) injury, whose pathophysiology involves the release of several mediators from both the donor and the recipient. The antioxidant effect of ascorbic acid has been studied in resuscitating patients with septic shock and burns. Even today, there are publications with conflicting results, and there is a need for further studies to confirm or rule out the usefulness of this drug in this group of patients. The addition of ascorbic acid to preservation solutions used in solid organ transplantation is under investigation to harness its antioxidant effect and mitigate I/R injury. Since PRS could be considered a manifestation of I/R injury, we believe that the possible beneficial effect of ascorbic acid on the occurrence of PRS should be investigated. ObjectiveThe aim of this randomized controlled trial is to assess the benefits of ascorbic acid over saline in the development of PRS in adult liver transplantation. MethodsWe plan to conduct a single-center randomized controlled trial at the Hospital Universitario Ramón y Cajal in Spain. A total of 70 participants aged 18 years or older undergoing liver transplantation will be randomized to receive either ascorbic acid or saline. The primary outcome will be the difference between groups in the incidence of PRS. The randomized controlled trial will be conducted under conditions of respect for fundamental human rights and ethical principles governing biomedical research involving human participants and in accordance with the international recommendations contained in the Declaration of Helsinki and its subsequent revisions. ResultsThe enrollment process began in 2020. A total of 35 patients have been recruited so far. Data cleaning and analysis are expected to occur in the first months of 2024. Results are expected around the middle of 2024. ConclusionsWe believe that this study could be particularly relevant because it will be the first to analyze the clinical effect of ascorbic acid in liver transplantation. Moreover, we believe that this study fills an important gap in the knowledge of the potential benefits of ascorbic acid in the field of liver transplantation, particularly in relation to PRS. Trial RegistrationEuropean Union Drug Regulating Authorities Clinical Trials Database 2020-000123-39; https://tinyurl.com/2cfzddw8; ClinicalTrials.gov NCT05754242; https://tinyurl.com/346vw7sm International Registered Report Identifier (IRRID)DERR1-10.2196/50091

Temporal lobe epilepsy causes severe cognitive deficits, but the circuit mechanisms remain unknown. Interneuron death and reorganization during epileptogenesis may disrupt the synchrony of hippocampal inhibition. To test this, we simultaneously recorded from the CA1 and dentate gyrus in pilocarpine-treated epileptic mice with silicon probes during head-fixed virtual navigation. We found desynchronized interneuron firing between the CA1 and dentate gyrus in epileptic mice. Since hippocampal interneurons control information processing, we tested whether CA1 spatial coding was altered in this desynchronized circuit, using a novel wire-free miniscope. We found that CA1 place cells in epileptic mice were unstable and completely remapped across a week. This spatial instability emerged around 6 weeks after status epilepticus, well after the onset of chronic seizures and interneuron death. Finally, CA1 network modeling showed that desynchronized inputs can impair the precision and stability of CA1 place cells. Together, these results demonstrate that temporally precise intrahippocampal communication is critical for spatial processing.

Introduction: Seizures are a frequent reason for admission to emergency departments and require early, precise diagnosis and treatment. The objective of this study was to describe the clinical and prognostic characteristics of a series of patients with seizures attended at our hospital’s emergency department. Methods: We performed a retrospective, observational study of all patients with seizures who were admitted to our hospital’s emergency department and attended by the on-call neurology service between February and August 2017. Results: We included 153 patients, representing 9.9% of all neurological emergency department admissions. The median age was 58 years, 52.3% of patients were women, and 51% had history of epilepsy. Onset was focal in 82.4% of cases, and the most frequent aetiology was cerebrovascular disease (24.2%). Twelve patients (7.8%) developed status epilepticus, which was associated with higher scores on the ADAN scale (P

Background: Up to 30% of differentiated thyroid cancer (DTC) will develop advanced-stage disease (aDTC) with reduced overall survival (OS). Objective: The aim of this study is to characterize initial diagnosis of aDTC, its therapeutic management, and prognosis in Spain and Portugal. Methods: A multicentre, longitudinal, retrospective study of adult patients diagnosed with aDTC in the Iberian Peninsula was conducted between January 2007 and December 2012. Analyses of baseline characteristics and results of initial treatments, relapse- or progression-free survival ((RP)FS) from first DTC diagnosis, OS, and prognostic factors impacting the evolution of advanced disease were evaluated. Results: Two hundred and thirteen patients (median age: 63 years; 57% female) were eligible from 23 hospitals. Advanced disease presented at first diagnosis (de novo aDTC) included 54% of patients, while 46% had relapsed from early disease (recurrent/progressive eDTC). At initial stage, most patients received surgery (98%) and/or radioiodine (RAI) (89%), with no differences seen between median OS (95% CI) (10.4 (7.3–15.3) years) and median disease-specific-survival (95% CI) (11.1 (8.7–16.2) years; log-rank test P = 0.4737). Age at diagnosis being

El concepto de belleza está relacionado con el de estética desde los orígenes del pensamiento del ser humano. Este artículo analiza el concepto de belleza aplicado al cine, a modo de ensayo exploratorio, con la intención futura de aplicar dos conceptos contrapuestos: en primer lugar, el matemático, siguiendo las teorías de la sección áurea de los griegos y la ley de Fibonacci del Renacimiento; y, en segundo lugar, las dimensiones ontológica y ético moral, en donde se pueden contraponer los contrarios belleza estética y fealdad narrativa. El objetivo general será valorar si la belleza en sus dos campos de representación puede ser aplicada al cine. La metodología es cualitativa, recogiendo, por una parte, las principales teorías de la composición formal; y por otra, los planteamientos de Aristóteles (Ética a Nicómaco) y de Karl Rosenkranz (Estética de lo feo) -belleza y fealdad ontológica-.

COVID-19 is characterized by a wide range of symptoms where the genetic background plays a key role in SARS-CoV-2 infection. In this study, the relative expression of IRF9, CCL5, IFI6, TGFB1, IL1B, OAS1, and TFRC genes (related to immunity and antiviral activity) was analyzed in upper airway samples from 127 individuals (97 COVID-19 positive and 30 controls) by using a two-step RT-PCR. All genes excepting IL1B (p=0.878) showed a significantly higher expression (p

Este trabajo pretende poner de manifiesto la relevancia de África y de la población colonizada marroquí en la gestación de la identidad y del imaginario de los africanistas. Para procurar este objetivo, los autores exploran la imagen que los africanistas tuvieron del enemigo; una imagen siempre contradictoria, que conjugaba el esperable odio con algunas dosis de admiración. El artículo plantea, por último, la posibilidad de que la oficialidad colonial experimentara un fenómeno de asimilación discursiva de la africanidad como resultado, en parte, de su prolongado contacto con los magrebís y, en parte, de su lectura darviniana y decadente de la realidad nacional. Gracias al estudio de múltiples testimonios de los protagonistas de las contiendas y desde las premisas de la historiografía militar más volcada en la dimensión cultural de la guerra, se admite, en primer término, la tesis historiográfica de que la población colonizada sufrió un proceso de aculturación. En segundo lugar y, sobre todo, se ahonda en las particularidades del imaginario africanista y, también, en el sentimiento de admiración que estos oficiales experimentaron hacia sus enemigos.

Introduction The Food and Drug Administration (FDA) recently issued new warnings about the possible effects of the repeated or prolonged use of general anaesthesia and sedatives on the brain development of children under 4 years old during surgeries or paediatric procedures. Objectives To evaluate the possible long-term neurotoxic impact the exposure to general anaesthesia has on the paediatric population from 0 to 4 years, which is the period during which the brain develops. Methods Initially, a search for observational studies that described the risk of neurotoxicity and alterations in the long-term cognitive development of children exposed to general anaesthesia before 4 years of age, was performed in PubMed between 2016 and 2020. Results Finally, 5 retrospective cohort studies comparing children exposed and not exposed to general anaesthesia were included in this study. None of these showed significant differences in their main study variables. However, three of this studies found significant differences in some of the secondary variables such as speed of processing, motor skills, internalization of behaviour and learning, and attention deficit hyperactivity disorder (ADHD). Conclusions In vitro and in vivo studies of anesthetics have shown serious neurotoxic effects in the developing brain. However, the clinical relevance of these findings for children undergoing anesthesia remains unclear. Most of these studies suggest a strong relationship between exposure to anesthesia in children aged 0 to 4 years, this being greater after multiple exposures. Despite these results, many of these articles conclude that further research is needed on this topic. Disclosure of Interest None Declared

Introduction The Autonomous Sensory Meridian (ASMR) is a static or tingling sensation on the skin that usually starts on the scalp and runs through the back of the neck and upper spine. It has been compared to tactile auditory synesthesia and may overlap with shivering. It is a subjective experience of “low-grade euphoria”, characterized by “a combination of positive feelings and a static tingling sensation on the skin”. It is most commonly triggered by auditory or visual stimuli, and less commonly by intentional attentional control. Objectives To determine the effects produced by the perception of ASMR in the population with mental disorders. Methods A literature review was carried out in Pubmed using the descriptors: “ASMR” AND “mental”. 7 results are obtained. The results of a time limit of 10 years were filtered, obtaining 6 results and selecting all of them for their relevance to the PICO question. Subsequently, the search was repeated using the same descriptors and time limit in the Cochrane Library and NICE, in which no results were found. Results The first result, an RCT of 475 people between the ages of 18 and 54, showed that 80% of the participants answered positively when asked if ASMR has an effect on their mood, while 14% were not sure and 6 % felt ASMR did not alter their mood. When subjected to a mixed ANOVA with factors for time (before, during, immediately after, and 3 h after ASMR) and for depression status (high, medium, or low as defined by the BDI), we found a significant main effect. of time in mood. [p

IntroductionState of the art artificial intelligence (AI) models have the potential to become a “one-stop shop” to improve diagnosis and prognosis in several oncological settings. The external validation of AI models on independent cohorts is essential to evaluate their generalization ability, hence their potential utility in clinical practice. In this study we tested on a large, separate cohort a recently proposed state-of-the-art convolutional neural network for the automatic segmentation of intraprostatic cancer lesions on PSMA PET images.MethodsEighty-five biopsy proven prostate cancer patients who underwent 68Ga PSMA PET for staging purposes were enrolled in this study. Images were acquired with either fully hybrid PET/MRI (N = 46) or PET/CT (N = 39); all participants showed at least one intraprostatic pathological finding on PET images that was independently segmented by two Nuclear Medicine physicians. The trained model was available at https://gitlab.com/dejankostyszyn/prostate-gtv-segmentation and data processing has been done in agreement with the reference work.ResultsWhen compared to the manual contouring, the AI model yielded a median dice score = 0.74, therefore showing a moderately good performance. Results were robust to the modality used to acquire images (PET/CT or PET/MRI) and to the ground truth labels (no significant difference between the model’s performance when compared to reader 1 or reader 2 manual contouring).DiscussionIn conclusion, this AI model could be used to automatically segment intraprostatic cancer lesions for research purposes, as instance to define the volume of interest for radiomics or deep learning analysis. However, more robust performance is needed for the generation of AI-based decision support technologies to be proposed in clinical practice.

Rearrangements involving the neurotrophin kinase (NTRK) genes NTRK1, NTRK2 and NTRK3 with different fusion partners have been observed in both adult and pediatric solid tumors. Larotrectinib and entrectinib have been the first tumor-agnostic compounds approved for the treatment of NTRK fusion-positive tumors. Here, we report the first case of a female patient with a diagnosis of stage IV lung adenocarcinoma harboring the EML4::NTRK3 gene fusion, and successfully treated with entrectinib.

This study proposed a new workflow for co-registering prostate PET images from a dual-tracer PET/MRI study with histopathological images of resected prostate specimens. The method aims to establish an accurate correspondence between PET/MRI findings and histology, facilitating a deeper understanding of PET tracer distribution and enabling advanced analyses like radiomics. To achieve this, images derived by three patients who underwent both [68Ga]Ga-PSMA and [68Ga]Ga-RM2 PET/MRI before radical prostatectomy were selected. After surgery, in the resected fresh specimens, fiducial markers visible on both histology and MR images were inserted. An ex vivo MRI of the prostate served as an intermediate step for co-registration between histological specimens and in vivo MRI examinations. The co-registration workflow involved five steps, ensuring alignment between histopathological images and PET/MRI data. The target registration error (TRE) was calculated to assess the precision of the co-registration. Furthermore, the DICE score was computed between the dominant intraprostatic tumor lesions delineated by the pathologist and the nuclear medicine physician. The TRE for the co-registration of histopathology and in vivo images was 1.59 mm, while the DICE score related to the site of increased intraprostatic uptake on [68Ga]Ga-PSMA and [68Ga]Ga-RM2 PET images was 0.54 and 0.75, respectively. This work shows an accurate co-registration method for histopathological and in vivo PET/MRI prostate examinations that allows the quantitative assessment of dual-tracer PET/MRI diagnostic accuracy at a millimetric scale. This approach may unveil radiotracer uptake mechanisms and identify new PET/MRI biomarkers, thus establishing the basis for precision medicine and future analyses, such as radiomics.

Abstract Human neutrophils constitutively express high amounts of arginase-1, which depletes arginine from the surrounding medium and downregulates T-cell activation. Here, we have found that neutrophil arginase-1, released from activated human neutrophils or dead cells, induced apoptosis in cancer cells through an endoplasmic reticulum (ER) stress pathway. Silencing of PERK in cancer cells prevented the induction of ER stress and apoptosis. Arginase inhibitor Nω-hydroxy-nor-arginine inhibited apoptosis and ER stress response induced by conditioned medium from activated neutrophils. A number of tumor cell lines, derived from different tissues, were sensitive to neutrophil arginase-1, with pancreatic, breast, ovarian and lung cancer cells showing the highest sensitivity. Neutrophil-released arginase-1 and arginine deprivation potentiated the antitumor action against pancreatic cancer cells of the ER-targeted antitumor alkylphospholipid analog edelfosine. Our study demonstrates the involvement of neutrophil arginase-1 in cancer cell killing and highlights the importance and complex role of neutrophils in tumor surveillance and biology.

Introduction Anti-NMDA receptor encephalitis is a disease occurring when antibodies produced by the body’s own immune system attack NMDA receptors in the brain. Their functions are critical for judgement, perception of reality, human interaction, the formation and retrieval of memory, and the control of autonomic functions. The objective of treatment is to reduce the levels of antibodies in the blood and spinal fluid. Treatments include corticosteroids, intravenous immunoglobulin and plasmapheresis in addition to other immunomodulators, such as cyclophosphamide or rituximab. Objectives To present a case of a 64 year-old patient who came to the emergency service of our hospital with long-standing anxiety, irritability, recurrent amnestic failures, visual hallucinations and recent-onset episodes of aggressiveness with his family. He required admission to the psychiatry department and was finally diagnosed with autoimmune anti-NMDA encephalitis by detecting antibodies in blood and CSF. Methods Clinical case presentation and literature review of cases, focusing on psychotic symptoms. Results A 65-year-old patient who was being studied by neurology and psychiatry departments for cognitive impairment and psychotic symptoms was admitted to Neurology after a positive lumbar puncture result for NMDA antibodies.During admission, the patient continued with a significant behavioral alteration that gradually remitted with the use of Quetiapine, corticosteroids and rituximab. Conclusions NMDA-encephalitis has a highly variable clinical presentation, which can lead to confusion with infectious etiology or psychiatric disorders, making the diagnosis difficult, which is only possible by detecting anti-NMDA antibodies in CSF. Recognition of the disease and coordination between services is essential for early diagnosis and treatment. Disclosure No significant relationships.

Introduction Nowdays there are different strategies for the treatment of smoking cessation. The treatment include drugs such as varenicline, which acts as a high-affinity partial agonist for the alpha-4 beta-2 nicotinic acetylcholine receptor subtype (nACh). We report a case of a suicidal behaviour in a 39 year-old woman with no previous history of mental illness, who was brought to the emergency department after intentional intoxication with benzodiazepines. The patient was on 10th day of treatment with varenicline. Objectives To present a case of sucidal behavior that developed in a 39 year-old woman after starting varenicline. Review of literature and total number of cases reported in the european database of suspected adverse drug reactions (EudraVigilance). Methods We carried out a literature review in Pubmed electing those articles focused on mental disorders in those patients that have been taking varenicline. Review number of cases suicidal behavior reported by the European database of suspected adverse drug reactions. Results A 39-year-old female was brought to the emergency department after voluntary ingestion of Lorazepam 1mg (40 tablets) in a sucide attempt. The family reported the starting of thoughts of suicide after 1 week of treatment. No previous history of mental disorders. The patient reported low mood and drowsiness in the last 5 days not linked to any cause. After 5 days of discontinuation these mood symptoms and sucidal behavior remited. Conclusions Varenicline is associated with different neuropsychiatric sypmtoms. In patients with or without history of mental disorders we should warn about the symptoms for discontinuation of the treatment. Disclosure No significant relationships.

Introduction Alcohol-based hand sanitizers containing ethanol or isopropanol are being used in order to prevent person-to-person transmission during the COVID-19. Early signs and symptoms of this ingestion include nausea, vomiting, headache, abdominal pain, blurred vision, loss of coordination, and decreased level of consciousness. After hand sanitizer ingestion we have to suspect about methanol poisoning, monitoring the start of anion-gap metabolic acidosis, seizures, and blindness is essential. Treatment includes supportive care, acidosis correction, and the administration of an alcohol dehydrogenase inhibitor. In servere cases hemodialysis may be required. Objectives To present a case of an 29-year-old woman who was taken to the emergency department after voluntary ingestion of alcohol-based hand sanitizer in a suicide attempt. To describe the most common side effects of hand sanitizer ingestion and the literature review. Methods Clinical case presentation and literature review of similar cases. Results A 29-year-old woman, with diagnosis of borderline personality disorder and previous suicide attempts was taken to the emergency department after 3 hours of voluntary ingestion of an unknown quantity of alcohol-based hand sanitizer. Initial laboratory findings showed laboratory a blood methanol concentration of 66 mg/dL, with an anion gap of 30 mEq/L, arterial blood pH of 7.2, serum bicarbonate concentration of 12 mEq/L. Patient complained of abdominal pain and nervoussness. Conclusions Most common signs and symptoms of alcohol-based hand sanitizer ingestion include nausea, vomiting, headache, abdominal pain, blurred vision, loss of coordination, and decreased level of consciousness. Treatment includes supportive care, acidosis correction, the administration of an alcohol dehydrogenase inhibitor and sometimes may be required. Disclosure No significant relationships.

Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy.

According to the current pathological classification, lung adenocarcinoma includes histological subtypes with significantly different prognoses, which may require specific surgical approaches. The aim of the study was to assess the role of CT and PET parameters in stratifying patients with stage I adenocarcinoma according to prognosis.

Immune checkpoint inhibitors have entailed a change of paradigm in the management of multiple malignant diseases and are acquiring a key role in an increasing number of clinical sceneries. However, since their mechanism of action is not limited to the tumor microenvironment, their systemic activity may lead to a wide spectrum of immune-related side effects. Although neurological adverse events are much less frequent than gastrointestinal, hepatic, or lung toxicity, with an incidence of

En este trabajo se pretende ofrecer una visión panorámica y crítica del progreso académico logrado en el análisis de la repercusión pública de las campañas hispano-marroquíes. Se aspira, además, a que estas páginas sirvan de base para investigaciones futuras y que permitan anticipar algunas novedosas líneas de estudio. A propósito de la tan compleja implantación del Protectorado hispano-francés en Marruecos (1912) y de las traumáticas campañas bélicas que lo acompañaron, se conocía con bastante rigor la opinión del sector militar, sobre todo a raíz de las célebres derrotas ocurridas en el Barranco del Lobo (1909) y en Annual (1921). En las últimas décadas, no obstante, se va avanzando en la comprensión del posicionamiento civil ante los mismos sucesos. Con una perspectiva más amplia, por último, se confirma que el estudio de la opinión pública —de su gestación, sus cambios y divisiones— constituye un terreno de análisis historiográfico cada vez mejor abonado, más fecundo, con enfoques y metodologías de lo más variopintas.

La guerra asimétrica se ha convertido en una expresión con buena acogida y gran popularidad para referirse a las “nuevas” guerras del siglo XXI. Sin embargo, su definición plantea algunas controversias. Por un lado, no es fácil caracterizarla, pues en la guerra asimétrica se conjugan medios irregulares de lucha y también, con limitaciones, algunos instrumentos convencionales. Por otro lado, tampoco es sencillo detallar su presunto carácter novedoso, desde un enfoque histórico. El presente artículo aborda ambas cuestiones con el objetivo de revisar las principales aportaciones hasta la fecha e intentar delinear algunos rasgos distintivos de esta modalidad de conflicto. Abstract Asymmetric war has turned into an expression with good reception and great popularity to refer to the "new" wars of the 21st century. However, its definition presents some controversy. On one hand, its characterization is not easy because asymmetric war combines irregular tolls of fight and also, with restrictions, conventional ones. On the other hand, from a historical approach it is also difficult to detail what its alleged original character consists of. This article will address both subjects in order to review the main contributions made until now and to feature some distinctive characters of this kind of conflict.

Reseña del libro: DE LUIS MARTÍN, Francisco, Pablo Iglesias. Muerte y memoria de un mito. Córdoba, Almuzara, 2021, 271 pp.

Introduction Skin and subcutaneus tissue disorders are common type of adverse drug reactions reported with a wide variety of both typical and atypical antipsychotics. Aripiprazole is a quinolinone antipsychotic that is a partial agonist at the D2 and 5-HT1A receptors and antagonist at the 5-HT2A receptors. We report a case of rosacea that developed after starting aripiprazole in a patient with schizophrenia and which remitted after the drug was stopped. Objectives To present a case of rosacea that developed in a schizophrenic patient after starting aripiprazole. Review of literature and search for the total number of cases reported in the european database of suspected adverse drug reactions (EudraVigilance). Methods We carried out a literature review in Pubmed electing those articles focused on skin ad subcutaneous skin disorders in those patients that have been taking aripiprazole. Review number of cases of skin reactions reported by the European database of suspected adverse drug reactions. Results A 43-year-old man previously diagnosed with schizophrenia with low adherence to different treatments. He came to our service seeking for help in order to decrease delusions with a treatment with minimun adverse reactions. We started aripirazole 10 mg every day and, after 7 days appeared signs of rosacea in his face. After discontinuation of aripiprazol, after 5 days, rosacea remitted. Conclusions Rosacea in our case posibly point aripiprazole as the agent that produced the skin reaction. After stopping the treatment the signs disapeared. Awareness of skins manifestations produced by aripiprazole is essential to prevents worse skin reactions.

Peptide receptor radionuclide therapy (PRRT) is an established treatment in advanced neuroendocrine tumors (NETs), which overexpressed somatostatin receptors. However, after progression there are a limited number of available treatments. We want to share a case report about a patient with a NET re-treated with 177Lu-DOTATATE and a literature review about salvage treatment with PRRT. We present a 26-year-old man who started with pelvic pain and after a biopsy of a retro-rectal mass observed in a magnetic resonance was diagnosed with an advanced neuroendocrine tumour. After progression to lanreotide, everolimus and sunitinib, treatment with 177Lu-DOTATATE was initiated, achieving an excellent response with a progression free survival (PFS) of 38 months. At the time of progression, re-treatment with 177Lu-DOTATATE was decided, showing a new partial response, which is currently stable after 15 months. The patient had not presented significant treatment-related toxicity. Although there are no randomized phase III trials or a consensus about the number or dose of cycles, there is evidence about the efficacy and low toxicity of salvage treatment with 177Lu-DOTATATE in NETs. Median progression-free survival ranges from 6 to 22 months. Toxicity is mostly hematologic (anemia and neutropenia), 4-7% grade 3/4.

Objectives:. This study aims to determine similarities and differences in clinical characteristics between the patients from two waves of severe acute respiratory syndrome coronavirus-2 infection at the time of hospital admission, as well as to identify risk biomarkers of coronavirus disease 2019 severity. Design:. Retrospective observational study. Setting:. A single tertiary-care center in Madrid. Patients:. Coronavirus disease 2019 adult patients admitted to hospital from March 4, 2020, to March 25, 2020 (first infection wave), and during July 18, 2020, and August 20, 2020 (second infection wave). Interventions:. Treatment with a hospital-approved drug cocktail during hospitalization. Measurements and Main Results:. Demographic, clinical, and laboratory data were compared between the patients with moderate and critical/fatal illness across both infection waves. The median age of patients with critical/fatal coronavirus disease 2019 was 67.5 years (interquartile range, 56.75–78.25 yr; 64.5% male) in the first wave and 59.0 years (interquartile range, 48.25–80.50 yr; 70.8% male) in the second wave. Hypertension and dyslipidemia were major comorbidities in both waves. Body mass index over 25 and presence of bilateral pneumonia were common findings. Univariate logistic regression analyses revealed an association of a number of blood parameters with the subsequent illness progression and severity in both waves. However, some remarkable differences were detected between both waves that prevented an accurate extrapolation of prediction models from the first wave into the second wave. Interleukin-6 and d-dimer concentrations at the time of hospital admission were remarkably higher in patients who developed a critical/fatal condition only during the first wave (p < 0.001), although both parameters significantly increased with disease worsening in follow-up studies from both waves. Multivariate analyses from wave 1 rendered a predictive signature for critical/fatal illness upon hospital admission that comprised six blood biomarkers: neutrophil-to-lymphocyte ratio (≥ 5; odds ratio, 2.684 [95% CI, 1.143–6.308]), C-reactive protein (≥ 15.2 mg/dL; odds ratio, 2.412 [95% CI, 1.006–5.786]), lactate dehydrogenase (≥ 411.96 U/L; odds ratio, 2.875 [95% CI, 1.229–6.726]), interleukin-6 (≥ 78.8 pg/mL; odds ratio, 5.737 [95% CI, 2.432–13.535]), urea (≥ 40 mg/dL; odds ratio, 1.701 [95% CI, 0.737–3.928]), and d-dimer (≥ 713 ng/mL; odds ratio, 1.903 [95% CI, 0.832–4.356]). The predictive accuracy of the signature was 84% and the area under the receiver operating characteristic curve was 0.886. When the signature was validated with data from wave 2, the accuracy was 81% and the area under the receiver operating characteristic curve value was 0.874, albeit most biomarkers lost their independent significance. Follow-up studies reassured the importance of monitoring the biomarkers included in the signature, since dramatic increases in the levels of such biomarkers occurred in critical/fatal patients over disease progression. Conclusions:. Most parameters analyzed behaved similarly in the two waves of coronavirus disease 2019. However, univariate logistic regression conducted in both waves revealed differences in some parameters associated with poor prognosis in wave 1 that were not found in wave 2, which may reflect a different disease stage of patients on arrival to hospital. The six-biomarker predictive signature reported here constitutes a helpful tool to classify patient’s prognosis on arrival to hospital.

The arrival of subsequent generations of tyrosine-kinase inhibitors (TKIs) has significantly broaden the EGFR-mutated lung cancer therapeutic landscape. Results from the FLAURA clinical trial have pushed osimertinib to the first-line treatment for patients with advanced-stage disease, showing outstanding control rates of intracranial metastases, considerably higher than those of the first and second-generation EGFR TKIs. A progressively better knowledge of short and long-term neurocognitive side effects of radiotherapy, as well as the lack of evidence about the benefit of its combination with TKIs, has opened a debate about its indication at diagnosis of intracranial disease, at least before the response to targeted therapy has been evaluated. However, there is a small percentage of primarily resistant cases to osimertinib, mainly due to histologic transformation, acquired EGFR mutations and off-target genetic resistances that lead to a scenery of poor clinical prognosis in which radiotherapy may have a higher relevance for the management of brain metastases. We offer a review of the current recommendations for the management of intracranial metastases in EGFR-mutated NSCLC and the resistance mechanisms to third-generation TKIs, following the report of an unusual clinical case with a rapid progression to osimertinib.

Introduction: Since the beginning of the Covid-19 epidemic produced by SARS2-Cov virus, olfactory alterations have been observed at a greater frequency than in other coronavirus epidemics. While olfactory alterations may be observed in patients with rhinovirus, influenza virus, or parainfluenza virus infection, they are typically explained by nasal obstruction with mucus or direct epithelial damage; in the case of SARS-CoV-2, olfactory alterations may present without nasal congestion with mucus. We performed a study of patients presenting olfactory/gustatory alterations in the context of SARS-CoV-2 infection in order to contribute to the understanding of this phenomenon.Material and Methods: We performed a descriptive, cross-sectional, observational study of the clinical characteristics of olfactory/gustatory alterations using a self-administered, anonymous online questionnaire.Results: A total of 909 patients with SARS-CoV-2 infection and olfactory/gustatory alterations responded to the questionnaire in the 4-day data collection period; 824 cases (90.65%) reported simultaneous olfactory and gustatory involvement. Patients' responses to the questionnaire revealed ageusia (581, 64.1% of respondents), hypogeusia (256, 28.2%), dysgeusia (22, 2.4%), anosmia (752 82.8%), hyposmia (142, 15.6%), and dysosmia (8, 0.9%). Fifty-four percent (489) did not report concomitant nasal congestion or mucus.Conclusion: Olfactory alterations are frequent in patients with SARS-CoV-2 infection and is only associated with nasal congestion in half of the cases.

The advent of immunotherapy has revolutionized cancer treatment. Unfortunately, this has not been the case for metastatic castration-resistant prostate cancer (mCRPC), likely due to the heterogeneous and immune-suppressive microenvironment present in prostate cancer. The identification of molecular biomarkers that could predict response to immunotherapy represents one of the current challenges in this clinical scenario. The management of advanced castration-resistant prostate cancer is rapidly evolving and immunotherapy treatments, mostly consisting of immune checkpoint inhibitors combinations, BiTE® (bispecific T-cell engager) immune therapies, and chimeric antigen receptors (CAR) are in development with promising results. This review analyses the current evidence of immunotherapy treatments for mCRPC, evaluating past failures and promising approaches and discussing the directions for future research.

Adnan Tufail,1 Sue Lightman,1 Ahmed Kamal,2 Uwe Pleyer,3 Nuria María Gajate Paniagua,4 Corrine Dot,5,6 Xiao-Yan Li,7 Jenny Jiao,7 Jean Lou,7 Yehia Hashad7 For the CONSTANCE Study Group 1Moorfields Eye Hospital, London, UK; 2Aintree University Hospital, Liverpool, UK; 3University Eye Hospital, Uveitis Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt University Berlin, and Berlin Institute of Health, Berlin, Germany; 4University Hospital of Burgos, Burgos, Spain; 5Department of Ophthalmology, Desgenettes Military Hospital, Lyon, France; 6French Military Health Service Academy, Val de Grâce, Paris, France; 7Allergan Plc, Irvine, CA, USA Purpose: To evaluate the long-term safety of dexamethasone intravitreal implant (DEX) in patients treated for macular edema associated with retinal vein occlusion (RVO) or noninfectious posterior segment uveitis (NIPSU) in clinical practice.Patients and methods: Multicenter (102 sites in France, Germany, Spain, UK), prospective, observational, post-authorization safety study in adult patients treated with DEX. Data collected up to 2 years after enrollment included serious adverse events (SAEs) and adverse events of special interest (AESIs; adverse drug reactions that are considered important risks associated with DEX and listed in the European Union Ozurdex Risk Management Plan).Results: Overall, 803 patients (652 RVO, 151 NIPSU) received on-study DEX treatment, and 73.1% completed 24 months of follow-up; 72.6% were DEX-naïve. Median number of on-study injections per treated eye was 2 (range, 1–7); median reinjection interval was 27.1 weeks. Nonocular SAEs affected 9.5% of patients; none were considered DEX-related. Ocular SAEs (most common: cataract progression) occurred in 3.2% of treated eyes. SAEs were similar in eyes stratified by previous DEX use and number of on-study DEX injections (≤2 or >2), in both RVO and NIPSU. The most common AESIs were cataract formation and progression (20.0% and 19.2% of treated phakic eyes, n=551), increased intraocular pressure (19.0% of treated eyes), and vitreous hemorrhage (3.3% of treated eyes). Cataract progression was more frequent in baseline phakic eyes that were previously treated with DEX or received >2 on-study DEX injections.Conclusion: The long-term safety profile of DEX was acceptable. No new safety concerns were identified. Keywords: corticosteroid, dexamethasone, drug delivery device, retinal vein occlusion, safety profile, uveitis

Deficient birth outcomes entail greater mortality risks, and higher probabilities of poor future health. This study is the first statistical examination of the effect of the World Health Organization’s recommended number of prenatal care visits for developing countries on birth outcomes. This study accounts for the endogenous nature of prenatal care decisions by using an instrumental variables approach based on the accessibility of prenatal services. Using the CLHN Survey I construct a measure of prenatal care which involves both timing and intensity and that shows positive impacts for the combination of both. The results are highly robust to changes in measures of birth outcome but are only significant for urban areas. The lack of impact on rural areas could be due to the inferior quality of prenatal care services received there. This theory is corroborated when controlling directly for care quality.

The aim of the present study is to investigate the synergic role of 68Ga-PSMA PET/MRI and 68Ga-DOTA-RM2 PET/MRI in prostate cancer (PCa) staging. We present pilot data on twenty-two patients with biopsy-proven PCa that underwent 68Ga-PSMA PET/MRI for staging purposes, with 19/22 also undergoing 68Gaa-DOTA-RM2 PET/MRI. TNM classification based on image findings was performed and quantitative imaging parameters were collected for each scan. Furthermore, twelve patients underwent radical prostatectomy with the availability of histological data that were used as the gold standard to validate intraprostatic findings. A DICE score between regions of interest manually segmented on the primary tumour on 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and on T2 MRI was computed. All imaging modalities detected the primary PCa in 18/19 patients, with 68Ga-DOTA-RM2 PET not detecting any lesion in 1/19 patients. In the remaining patients, 68Ga-PSMA and MRI were concordant. Seven patients presented seminal vesicles involvement on MRI, with two of these being also detected by 68Ga-PSMA, and 68Ga-DOTA-RM2 PET being negative. Regarding extraprostatic disease, 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI resulted positive in seven, four and five patients at lymph-nodal level, respectively, and at a bone level in three, zero and one patients, respectively. These preliminary results suggest the potential complementary role of 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI in PCa characterization during the staging phase.

A raíz del desplome de la Comandancia General de Melilla (julio de 1921), el Ejército de África, encabezado por la Legión, asumió la tarea de recuperar el territorio perdido. Las guerras coloniales entre España y Marruecos durante las primeras décadas del siglo XX acapararon la atención de muchos reporteros, especialmente, el episodio conocido como Desastre de Annual. Tal fue el caso de Teresa de Escoriaza (1891-1968), una profesional polifacética, capaz de hacerse un hueco en el panorama periodístico de aquel entonces. Teresa llegaría al Protectorado hispano-francés como enviada del rotativo izquierdista La Libertad. Mostrando su plena identificación con el patriotismo castrense, envío un total de dieciocho crónicas a su periódico, que se publicaron entre los días 3 y 27 de septiembre de ese mismo año. El objetivo del presente trabajo consiste en analizar minuciosamente estas crónicas y reflexionar sobre la relación de Teresa con la oficialidad africanista y su sintonía con el público en general y su sintonía con el público en general.

The main objective of this study is to review the ways in which adolescents relate to traditional radio and television, and the influence of Internet, such a meta-medium, may have on these modes of consumption. Attention was focused on Internet access via mobile phone. The study was carried out on the total population of a secondary education center, applying questionnaires with closed Likert-type questions, reliability scales and open-ended questions. The data were analyzed with the SPSS program to obtain descriptive statistics and perform multivariable analysis. The analysis of the data leads us to affirm that there are remarkable differences in the modes of radio consumption and the modes of television consumption by the adolescents subject of the study. In the same way, a homogenization of the consumption by sex is observed, giving small differences in some tastes on contents. Finally, it can be affirmed that the possibility of accessing the Internet in the mobile phone has not exerted any influence on the modes of consumption of radio and television in the subjects analyzed. Rather, the Internet facilitates and opens access to endless new formats of leisure, non-radio and television. Leisure time is distributed, and consumers are redirected out of the traditional media.