Adenosine receptors are the on-and-off switch of astrocytic cannabinoid type 1 (CB1) receptor effect upon synaptic plasticity in the medial prefrontal cortex.

The medial prefrontal cortex (mPFC) is involved in cognitive functions such as working memory. Astrocytic cannabinoid type 1 receptor (CB1R) induces cytosolic calcium (Ca2+) concentration changes with an impact on neuronal function. mPFC astrocytes also express adenosine A1 and A2A receptors (A1R, A2AR), being unknown the crosstalk between CB1R and adenosine receptors in these cells. We show here that a further level of regulation of astrocyte Ca2+ signaling occurs through CB1R-A2AR or CB1R-A1R heteromers that ultimately impact mPFC synaptic plasticity. CB1R-mediated Ca2+ transients increased and decreased when A1R and A2AR were activated, respectively, unveiling adenosine receptors as modulators of astrocytic CB1R. CB1R activation leads to an enhancement of long-term potentiation (LTP) in the mPFC, under the control of A1R but not of A2AR. Notably, in IP3R2KO mice, that do not show astrocytic Ca2+ level elevations, CB1R activation decreases LTP, which is not modified by A1R or A2AR. The present work suggests that CB1R has a homeostatic role on mPFC LTP, under the control of A1R, probably due to physical crosstalk between these receptors in astrocytes that ultimately alters CB1R Ca2+ signaling.

Plant cell size: Links to cell cycle, differentiation and ploidy.

Cell size affects many processes, including exchange of nutrients and external signals, cell division and tissue mechanics. Across eukaryotes, cells have evolved mechanisms that assess their own size to inform processes such as cell cycle progression or gene expression. Here, we review recent progress in understanding plant cell size regulation and its implications, relating these findings to work in other eukaryotes. Highlights include use of DNA contents as reference point to control the cell cycle in shoot meristems, a size-dependent cell fate decision during stomatal development and insights into the interconnection between ploidy, cell size and cell wall mechanics.

Communication defects with astroglia contribute to early impairments in the motor cortex plasticity of SOD1G93A mice.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, involving the selective degeneration of cortical upper synapses in the primary motor cortex (M1). Excitotoxicity in ALS occurs due to an imbalance between excitation and inhibition, closely linked to the loss/gain of astrocytic function. Using the ALS SOD1G93A mice, we investigated the astrocytic contribution for the electrophysiological alterations observed in the M1 of SOD1G93A mice, throughout disease progression. Results showed that astrocytes are involved in synaptic dysfunction observed in presymptomatic SOD1G93A mice, since astrocytic glutamate transport currents are diminished and pharmacological inhibition of astrocytes only impaired long-term potentiation and basal transmission in wild-type mice. Proteomic analysis revealed major differences in neuronal transmission, metabolism, and immune system in upper synapses, confirming early communication deficits between neurons and astroglia. These results provide valuable insights into the early impact of upper synapses in ALS and the lack of supportive functions of cortical astrocytes, highlighting the possibility of manipulating astrocytes to improve synaptic function.

Patient and Family Preferences About Place of End-of-Life Care and Death: An Umbrella Review.

CONTEXT: The place where people are cared towards the end of their life and die is a complex phenomenon, requiring a deeper understanding. Honoring preferences is critical for the delivery of high-quality care. OBJECTIVES: In this umbrella review we examine and synthesize the evidence regarding preferences about place of end-of-life care and death of patients with life-threatening illnesses and their families. METHODS: Following the Joanna Briggs Institute methodology, we conducted a comprehensive search for systematic reviews in PsycINFO, MEDLINE, EMBASE, CINAHL, Epistemonikos, and PROSPERO without language restrictions. RESULTS: The search identified 15 reviews (10 high-quality, three with meta-analysis), covering 229 nonoverlapping primary studies. Home is the most preferred place of end-of-life care for both patients (11%-89%) and family members (23%-84%). It is also the most preferred place of death (patient estimates from two meta-analyses: 51%-55%). Hospitals and hospice/palliative care facilities are preferred by substantial minorities. Reasons and factors affecting preferences include illness-related, individual, and environmental. Differences between preferred places of care and death are underexplored and the evidence remains inconclusive about changes over time. Congruence between preferred and actual place of death ranges 21%-100%, is higher in studies since 2004 and a meta-analysis shows noncancer patients are at higher risk of incongruence than cancer patients (OR 1.23, 95% CI: 1.01-1.49, I2 = 62%). CONCLUSION: These findings are a crucial starting point to address gaps and enhance strategies to align care with patient and family preferences. To accurately identify patient and family preferences is an important opportunity to change their lives positively.

The Prognosis of Glutamic Acid Decarboxylase Antibodies in Women With Hyperglycemia in Pregnancy.

CONTEXT: We recently reported that the presence of glutamic acid decarboxylase antibodies (GADA) was not associated with large-for-gestational-age infants in women with hyperglycemia in pregnancy (HIP). OBJECTIVE: We explored the association between the presence of GADA and other HIP-related adverse pregnancy outcomes. METHODS: This observational prospective study, conducted at a university hospital in a suburb of Paris, France, included 1182 consecutive women with HIP measured for GADA at HIP care initiation between 2012 and 2017. Post hoc analyses for outcomes included gestational weight gain, insulin therapy, cesarean delivery, hypertensive disorders, small-for-gestational-age infant, prematurity, and neonatal hypoglycemia. RESULTS: Of the 1182 women studied, 87 (7.4%) had positive (≥ 1 IU/mL) GADA. Although socioeconomic, clinical, and biological characteristics were similar across women in the positive and negative GADA groups, higher fasting plasma glucose values during early HIP screening were observed in the former (5.5 ± 1.5 vs 5.2 ± 0.7 mmol/L respectively, P < .001). At HIP care initiation, fructosamine levels were higher in women with positive GADA (208 ± 23 vs 200 ± 18 µmol/L; P < .05). In the homeostatic model assessment, insulin resistance (HOMA-IR) and beta secretion (HOMA-B) rates were similar in both groups. Gestational weight gain and the rates of all adverse outcomes were similar in both groups except for cesarean delivery (18.4 and 27.3% for positive and negative GADA, respectively; adjusted odds ratio 0.49 [95% CI, 0.26-0.92], P = .026). CONCLUSION: Universal measurement of GADA in women with HIP highlighted that 7.4% had positive GADA. No association was observed between GADA and HIP-related adverse pregnancy outcomes, except a lower risk of cesarean delivery.

Interaction between a water-soluble anionic porphyrin and human serum albumin unexpectedly stimulates the aggregation of the photosensitizer at the surface of the albumin.

The 5,10,15,20-tetrakis(2,6-difluoro-3-sulfophenyl)porphyrin (TDFPPS4) was reported as a potential photosensitizer for photodynamic therapy. The capacity of the photosensitizers to be carried in the human bloodstream is predominantly determined by its extension of binding, binding location, and binding mechanism to human serum albumin (HSA), influencing its biodistribution and ultimately its photodynamic therapy efficacy in vivo. Thus, the present work reports a biophysical characterization on the interaction between the anionic porphyrin TDFPPS4 and HSA by UV-visible absorption, circular dichroism, steady-state, time-resolved, and synchronous fluorescence techniques under physiological conditions, combined with molecular docking calculations and molecular dynamics simulations. The interaction HSA:TDFPPS4 is spontaneous (ΔG° < 0), strong, and enthalpically driven (ΔH° = -70.1 ± 3.3 kJ mol-1) into subdomain IIA (site I). Curiously, despite the porphyrin binding into an internal pocket, about 50 % of TDFPPS4 structure is still accessible to the solvent, making aggregation in the bloodstream possible. In silico calculations were reinforced by spectroscopic data indicating porphyrin aggregation between bound and unbound porphyrins. This results in an adverse scenario for anionic porphyrins to achieve their therapeutical potential as photosensitizers and control of effective dosages. Finally, a trend of anionic porphyrins to have a combination of quenching mechanisms (static and dynamic) was noticed.

Cross-cultural adaptation and content validity of the Adverse Events Associated with Nursing Practices instrument.

OBJECTIVE: To conduct the cross-cultural adaptation and evaluate the evidence of content validity of the Adverse Events Associated with Nursing Practices instrument in the Brazilian context. METHOD: Psychometric study, conducted between June 2021 and February 2023, following the stages of the Patient-Reported Outcomes Measurement Information System protocol. Semantic, idiomatic, experimental and conceptual equivalences were evaluated, along with content validity evidence, considering Content Validity Ratio (CVR) parameters, with the participation of 25 experts. RESULTS: A Brazilian version with 55 items was obtained, demonstrating good linguistic equivalence to the original version (agreement rate=99.2%), and adjustments in the items writing. CVR values remained above 0.60. Cognitive testing indicated good understanding, confirmed by the 31 participants in this stage, with a short application time (average = 17 minutes). CONCLUSION: The final version of the instrument showed good linguistic equivalence, strong evidence of content validity and a good response process in the Brazilian context.

Analysis of a telephone hotline for palliative care patients at home and their families.

BACKGROUND: To describe the use of a telephone consultation (TC) hotline for palliative care (PC) patients and their families at home provided by a PC service, during the COVID-19 lockdown. METHODS: Observational and cross-sectional study of a TC hotline performed by a PC service from 1 January to 31 December 2020. Data was collected through a record sheet completed during the call. Descriptive analyses were performed using the SPSS software (V.21 for Windows). RESULTS: A total of 494 calls were retrieved (n=187 patients; 6500 minutes recorded). Compared to 2019, incoming calls increased 33.8%. Most callers were a family member (n=419) or a community health worker (n= 60). The peak of calls was registered in April (13.5%), May (13.2%) and October (15.0%). Main problems included uncontrolled symptoms (81.9%), need for medication (8.6%), information (4.8%) and consultation rescheduling (2.6%). In 81.9% of the cases, the call occurred during a crisis. The PC team solved 92.9% of the problems. Only 20 patients were admitted in the emergency department (this was 30.5% less compared to 2019). CONCLUSIONS: The TC is a feasible alternative to traditional in-person follow-ups. Callers considered it very useful, especially during the COVID-19 lockdown. Communication was improved and admissions to emergency services were reduced.

Models of spiritual intelligence interventions: A scoping review.

OBJECTIVE: To summarize the effects of spiritual intelligence (SI) training in several contexts and to identify the most consensual patterns in SI intervention design. INTRODUCTION: The "adaptive application" of spirituality in life is called SI, the ability to use spirituality in everyday problem-solving and it is proven to relate to better clinical and spiritual care (SC) competency in healthcare professionals. Interventions aiming to increase SI have been tested in different settings with benefits that can have a significant impact on the way healthcare professionals approach SC. INCLUSION CRITERIA: It included any quantitative studies that used reproducible methodology and reported on the implementation of interventions aiming to increase SI. Text, proceedings, conference or opinion papers, abstracts, reviews, mixed methods and qualitative studies were excluded from this scoping review. METHODS: Scoping review of quantitative studies on "spiritual intelligence" (query term) that include SI intervention programs (inclusion criteria) conducted on PubMed Central, Scopus, Web Of Science and PsycInfo databases, using the Joanna Briggs Institute methodology. Studies published until the 1st january 2022 were included. The studies' selection, extraction and synthesis of data was carried out by two independent reviewers. RESULTS: From the 10 articles/studies included, six were quasi-experimental and three experimental. Most (n=9) were conducted in Iran. The most common target samples of the studies were nurses (4 studies) and students (4 studies). SI training protocols, although based in group sessions, varied in their content between the different studies. SI interventions reported significant increase of SI levels, improvement of communications skills and reduction of anxiety, stress and depression levels. CONCLUSIONS: Despite the consensus among studies regarding the benefits of spiritual intelligence programs, more studies are needed to gauge long-term outcomes. There is also a need to standardize training protocols in spiritual intelligence.

Impact of experiencing multiple vulnerabilities on fetal growth and complications in women with hyperglycemia in pregnancy.

BACKGROUND: In women with hyperglycemia in pregnancy living in France, psychosocial deprivation is associated with both earlier and greater exposure to the condition, as well as poorer maternofetal prognosis. We explored the impact of this and two other socioeconomic vulnerability indicators-food insecurity and poor language proficiency-on adherence to prenatal care and maternal and fetal outcomes. METHODS: In a socially deprived suburb of Paris, we selected women who delivered between 01/01/2012 and 31/12/2018 and received care (nurse, dietician, diabetologist evaluation, advice, regular follow-up to adjust insulin doses if requested) for hyperglycemia in pregnancy. We analyzed the associations between individual psychosocial deprivation, food insecurity, French language proficiency (variables assessed by individual questionnaires) and fetal growth (main outcome), as well as other core maternal and fetal outcomes. RESULTS: Among the 1,168 women included (multiethnic cohort, 19.3% of whom were Europeans), 56%, 17.9%, and 27.5% had psychosocial deprivation, food insecurity, and poor French language proficiency, respectively. Forty-three percent were prescribed insulin therapy. Women with more than one vulnerability had more consultations for diabetes. The rates for small (SGA), appropriate (AGA), and large-for-gestational-age (LGA) infant were 11.4%, 76.5% and 12.2%, respectively. These rates were similar in women with and without psychosocial deprivation, and in those with and without food insecurity. Interestingly, women with poor French language proficiency had a higher odds ratio of delivering a small- or large-for-gestational age infant than those with good proficiency. CONCLUSION: We found similar pregnancy outcomes for women with hyperglycemia in pregnancy living in France, irrespective of whether or not they had psychosocial deprivation or food insecurity. Optimized single-center care with specialized follow-up could contribute to reduce inequalities in maternal and fetal outcomes in women with hyperglycemia in pregnancy.

Selective, broad-spectrum antiviral photodynamic disinfection with dicationic imidazolyl chlorin photosensitizers.

The COVID-19 pandemic exposes our vulnerability to viruses that acquire the ability to infect our cells. Classical disinfection methods are limited by toxicity. Existing medicines performed poorly against SARS-CoV-2 because of their specificity to targets in different organisms. We address the challenge of mitigating known and prospective viral infections with a new photosensitizer for antimicrobial photodynamic therapy (aPDT). Photodynamic inactivation is based on local oxidative stress, which is particularly damaging to enveloped viruses. We synthesized a cationic imidazolyl chlorin that reduced by > 99.999% of the percentage inhibition of amplification of SARS-CoV-2 collected from patients at 0.2 µM concentration and 4 J cm-2. Similar results were obtained in the prevention of infection of human ACE2-expressing HEK293T cells by a pseudotyped lentiviral vector exhibiting the S protein of SARS-CoV-2 at its surface. No toxicity to human epidermal keratinocytes (HaCaT) cells was found under similar conditions. aPDT with this chlorin offers fast and safe broad-spectrum photodisinfection and can be repeated with low risk of resistance.

Combining inflammatory miRNA molecules as diagnostic biomarkers for depression: a clinical study.

Background: Inflammation has been implicated in core features of depression pathophysiology and treatment resistance. Therefore, new challenges in the discovery of inflammatory mediators implicated in depression have emerged. MicroRNAs (miRNAs) have been found aberrantly expressed in several pathologies, increasing their potential as biomarkers and therapeutical targets. In this study, the aim was to assess the changes and biomarker potential of inflammation-related miRNAs in depression patients. Methods: Depression diagnosis was performed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). 40 healthy controls and 32 depression patients were included in the study. The levels of inflammatory cytokines were measured in plasma, and expression levels of cytokines and inflammation-related miRNAs were evaluated in peripheral blood mononuclear cells (PBMCs). Results: Depression patients were found to have a pro-inflammatory profile in plasma, with significantly higher levels of TNF-α and CCL2 compared with controls. In PBMCs of depression patients, TNF-α and IL-6 expression levels were significantly up and downregulated, respectively. Moreover, miR-342 levels were found upregulated, while miR-146a and miR-155 were significantly downregulated. miR-342 expression levels were positively correlated with TNF-α. Importantly, when analyzed as a diagnostic panel, receiver operating characteristics (ROC) analysis of miR-342, miR-146a, miR-155 in combination, showed to be highly specific and sensitive in distinguishing between depression patients and healthy controls. Conclusion: In summary, these findings suggest that inflammation-related miRNAs are aberrantly expressed in depression patients. Moreover, we show evidences on the potential of the combination of dysregulated miRNAs as a powerful diagnostic tool for depression.

Glycemic status during pregnancy according to fasting and post-load glucose values: The association with adverse pregnancy outcomes. An observational study.

AIM: Prognosis of treated hyperglycemia in pregnancy (HIP) may differ according to whether diagnosis following an oral glucose tolerance test (OGTT) is based on high fasting and/or high post-load glucose values. METHODS: From a multiethnic prospective study, we included 8,339 women screened for HIP after 22 weeks of gestation. We evaluated the risk of large-for-gestational-age (LGA) infant (primary endpoint) and other adverse pregnancy outcomes according to HIP status in four groups defined as follows: no HIP (n = 6,832, reference); isolated fasting HIP (n = 465), isolated post-load HIP (n = 646), and fasting and post-load HIP (n = 396). RESULTS: After adjusting for age, body mass index, ethnicity, smoking during pregnancy and parity, compared with no HIP, the adjusted odds ratios [95% confidence interval] for LGA infant were higher in the isolated fasting HIP (1.47 [1.11-1.96]) and fasting and post-load HIP (1.65 [1.23-2.21]) groups, but not in the isolated post-load HIP (1.13 [0.86-1.48]) group. The adjusted odds ratios for preterm delivery and neonatal intensive care unit were higher in the post-load HIP group (1.44 [1.03-2.03] and 1.28 [1.04-1.57], respectively), the fasting and post-load HIP group (1.81 [1.23-2.68] and 1.42 [1.10-1.81], respectively) but not in the isolated fasting HIP group (1.34 [0.90-2.00] and 1.20 [0.94-1.52], respectively). CONCLUSION: Despite glucose-lowering care and adjustment for confounders, compared with no HIP, fasting HIP was associated with a higher rate of LGA infant, whereas post-load HIP was associated with higher preterm delivery and neonatal intensive care unit admission rates.

Fluorinated Mn(III)/(II)-Porphyrin with Redox-Responsive 1 H and 19 F Relaxation Properties.

A new fluorinated manganese porphyrin, (Mn-TPP-p-CF3 ) is reported capable of providing, based on the Mn(III)/Mn(II) equilibrium, dual 1 H relaxivity and 19 F NMR response to redox changes. The physical-chemical characterization of both redox states in DMSO-d6 /H2 O evidenced that the 1 H relaxometric and 19 F NMR properties are appropriate for differential redox MRI detection. The Mn(III)-F distance (dMn-F =9.7-10 Å), as assessed by DFT calculations, is well tailored to allow for adequate paramagnetic effect of Mn(III) on 19 F T1 and T2 relaxation times. Mn-TPP-p-CF3 has a reversible Mn(II)/Mn(III) redox potential of 0.574 V vs. NHE in deoxygenated aqueous HEPES/ THF solution. The reduction of Mn(III)-TPP-p-CF3 in the presence of ascorbic acid is slowly, but fully reversed in the presence of air oxygen, as monitored by UV-Vis spectrometry and 19 F NMR. The broad 1 H and 19 F NMR signals of Mn(III)-TPP-p-CF3 disappear in the presence of 1 equivalent ascorbate replaced by a shifted and broadened 19 F NMR signal from Mn(II)-TPP-p-CF3 . Phantom 19 F MR images in DMSO show a MRI signal intensity decrease upon reduction of Mn(III)-TPP-p-CF3 , retrieved upon complete reoxidation in air within ~24 h. 1 H NMRD curves of the Mn(III)/(II)-TPP-p-CF3 chelates in mixed DMSO/water solvent have the typical shape of Mn(II)/Mn(III) porphyrins.

Genetic and Phenotypic Analysis of Ovule Development in Arabidopsis.

The plant seed is a remarkable structure that represents the single most important energy source in global diets. The stages of reproductive growth preceding seed formation are particularly important since they influence the number, size, and quality of seed produced. The progenitor of the seed is the ovule, a multicellular organ that produces a female gametophyte while maintaining a range of somatic ovule cells to protect the seed and ensure it receives maternal nourishment. Ovule development has been well characterized in Arabidopsis using a range of molecular, genetic, and cytological assays. These can provide insight into the mechanistic basis for ovule development, and opportunities to explore its evolutionary conservation. In this chapter, we describe some of these methods and tools that can be used to investigate early ovule development and cell differentiation.

Ultrathin materials for wide bandwidth laser ultrasound generation: titanium dioxide nanoparticle films with adsorbed dye.

Materials that convert the energy of a laser pulse into heat can generate a photoacoustic wave through thermoelastic expansion with characteristics suitable for improved sensing, imaging, or biological membrane permeation. The present work involves the production and characterization of materials composed of an ultrathin layer of titanium dioxide (<5 µm), where a strong absorber molecule capable of very efficiently converting light into heat (5,10,15,20-tetrakis(4-sulfonylphenyl)porphyrin manganese(iii) acetate) is adsorbed. The influence of the thickness of the TiO2 layer and the duration of the laser pulse on the generation of photoacoustic waves was studied. Strong absorption in a thin layer enables bandwidths of ∼130 MHz at -6 dB with nanosecond pulse laser excitation. Bandwidths of ∼150 MHz at -6 dB were measured with picosecond pulse laser excitation. Absolute pressures reaching 0.9 MPa under very low energy fluences of 10 mJ cm-2 enabled steep stress gradients of 0.19 MPa ns-1. A wide bandwidth is achieved and upper high-frequency limits of ∼170 MHz (at -6 dB) are reached by combining short laser pulses and ultrathin absorbing layers.

Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.

Trombosis venosa cerebral: una etiología rara / Cerebral Venous Thrombosis – A Rare Etiology

Idiopathic thrombocytopenic purpura is an immune-mediated disease that courses with thrombocytopenia. Eltrombopag is a thrombopoietin receptor agonist used as a second-line treatment for this disease to increase platelet count. The association of this drug with thrombotic events is known, however, with few cases of venous sinus thrombosis described in the literature. We present a 26-year-old female with idiopathic thrombocytopenic purpura diagnosed at the of age 14, splenectomized and previously treated with immunoglobulins, corticosteroids, and rituximab, with no response, who was started on oral estroprogestative and eltrombopag, with multiple dose increases, for 3 months. She was admitted to the emergency room with a 3-day history of severe frontal headache, with phono and photophobia, nausea, vomiting, and confusion. Physical examination was remarkable only for mild paraphasias, anomalous pauses, and difficulty in reading. Routine labs showed mild thrombocytopenia, leukocytosis, and elevated C-reactive Protein. She performed a brain computerized tomography and magnetic resonance that demonstrated extensive venous sinus thrombosis. She was admitted to the ward with eltrombopag suspension and enoxaparin 1mg/kg bid. Increasing thrombocytosis was observed for nine days, with a subsequent decrease to normal levels. Sequenced cerebral tomography showed hemorrhage reabsorption. At discharge, there was no improvement of neurological deficits and dabigatran 150mg bid was started for secondary prophylaxis. (AU)

La púrpura trombocitopénica idiopática es una enfermedad inmunomediada que cursa con trombocitopenia. Eltrombopag es un agonista del receptor de trombopoyetina que se utiliza como tratamiento de segunda línea de esta enfermedad para aumentar el recuento de plaquetas. Sin embargo, se conoce la asociación de este fármaco con acontecimientos trombóticos, con pocos casos de trombosis del seno venoso descritos en la literatura. Presentamos el caso de una mujer de 26 años con púrpura trombocitopénica idiopática diagnosticada a los 14 años, esplenectomizada y tratada previamente con inmunoglobulinas, corticoides y rituximab, sin respuesta, a la que se inició tratamiento con estroprogestativos orales y eltrombopag, con múltiples incrementos de dosis, durante 3 meses. Ingresó en urgencias con un cuadro de 3 días de evolución de cefalea frontal intensa, con fono y fotofobia, náuseas, vómitos y confusión. En la exploración física sólo destacaban parafasias leves,pausas anómalas y dificultad para leer. Los análisis de rutina mostraron trombocitopenia leve, leucocitosis y proteína C reactiva elevada. Se le realizó una tomografía computarizada cerebral y una resonancia magnética que demostraron una extensa trombosis del seno venoso. Fue ingresada en planta con eltrombopag en suspensión y enoxaparina 1mg/kg bid. Se observó un aumento de la trombocitosis durante nueve días, con una disminución posterior a niveles normales. La tomografía cerebral secuenciada mostró reabsorción de la hemorragia. Al alta, no hubo mejoría de los déficits neurológicos y se inició dabigatrán 150mg bid para profilaxis secundaria. (AU)