Molecular dynamics simulations in pre-polymerization mixtures for peptide recognition.

CONTEXT: Molecularly imprinted polymers (MIPs) have promising applications as synthetic antibodies for protein and peptide recognition. A critical aspect of MIP design is the selection of functional monomers and their adequate proportions to achieve materials with high recognition capacity toward their targets. To contribute to this goal, we calibrated a molecular dynamics protocol to reproduce the experimental trends in peptide recognition of 13 pre-polymerization mixtures reported in the literature for the peptide toxin melittin. METHODS: Three simulation conditions were tested for each mixture by changing the box size and the number of monomers and cross-linkers surrounding the template in a solvent-explicit environment. Fully atomistic MD simulations of 350 ns were conducted with the AMBER20 software, with ff19SB parameters for the peptide, gaff2 parameters for the monomers and cross-linkers, and the OPC water model. Template-monomer interaction energies under the LIE approach showed significant differences between high-affinity and low-affinity mixtures. Simulation systems containing 100 monomers plus cross-linkers in a cubic box of 90 Å3 successfully ranked the mixtures according to their experimental performance. Systems with higher monomer densities resulted in non-specific intermolecular contacts that could not account for the experimental trends in melittin recognition. The mixture with the best recognition capacity showed preferential binding to the 13-26-α-helix, suggesting a relevant role for this segment in melittin imprinting and recognition. Our findings provide insightful information to assist the computational design of molecularly imprinted materials with a validated protocol that can be easily extended to other templates.

Overnight stay in Spanish emergency departments and mortality in older patients.

To assess whether older adults who spend a night in emergency departments (ED) awaiting admission are at increased risk of mortality. This was a retrospective review of a multipurpose cohort that recruited all patients ≥ 75 years who visited ED and were admitted to hospital on April 1 to 7, 2019, at 52 EDs across Spain. Study groups were: patients staying in ED from midnight until 8:00 a.m. (ED group) and patients admitted to a ward before midnight (ward group). The primary endpoint was in-hospital mortality, truncated at 30 days, and secondary outcomes assessed length of stay for the index episode. The sample comprised 3,243 patients (median [IQR] age, 85 [81-90] years; 53% women), with 1,096 (34%) in the ED group and 2,147 (66%) in the ward group. In-hospital mortality for patients spending the night in the ED the ED group was 10.7% and 9.5% for patients transferred to a ward bed before midnight the ward group (adjusted OR: 1.12, 95%CI: 0.80-1.58). Sensitivity analyses rendered similar results (ORs ranged 1.06-1.13). Interaction was only detected for academic/non-academic hospitals (p < 0.001), with increased mortality risk for the latter (1.01, 0.33-3.09 vs 2.86, 1.30-6.28). There were no differences in prolonged hospitalization (> 7 days), with adjusted OR of 1.16 (0.94-1.43) and 1.15 (0.94-1.42) depending on whether time spent in the ED was or was not taken into consideration. No increased risk of in-hospital mortality or prolonged hospitalization was found in older patients waiting overnight in the ED for admission. Nonetheless, all estimations suggest a potential harmful effect of staying overnight, especially if a proper bedroom and hospitalist ward bed and hospitalized care are not provided.

Chlorin e6-Conjugated Mesoporous Titania Nanorods as Potential Nanoplatform for Photo-Chemotherapy.

Photodynamic therapy (PDT) has developed as an efficient strategy for cancer treatment. PDT involves the production of reactive oxygen species (ROS) by light irradiation after activating a photosensitizer (PS) in the presence of O2. PS-coupled nanomaterials offer additional advantages, as they can merge the effects of PDT with conventional enabling-combined photo-chemotherapeutics effects. In this work, mesoporous titania nanorods were surface-immobilized with Chlorin e6 (Ce6) conjugated through 3-(aminopropyl)-trimethoxysilane as a coupling agent. The mesoporous nanorods act as nano vehicles for doxorubicin delivery, and the Ce6 provides a visible light-responsive production of ROS to induce PDT. The nanomaterials were characterized by XRD, DRS, FTIR, TGA, N2 adsorption-desorption isotherms at 77 K, and TEM. The obtained materials were tested for their singlet oxygen and hydroxyl radical generation capacity using fluorescence assays. In vitro cell viability experiments with HeLa cells showed that the prepared materials are not cytotoxic in the dark, and that they exhibit photodynamic activity when irradiated with LED light (150 W m-2). Drug-loading experiments with doxorubicin (DOX) as a model chemotherapeutic drug showed that the nanostructures efficiently encapsulated DOX. The DOX-nanomaterial formulations show chemo-cytotoxic effects on Hela cells. Combined photo-chemotoxicity experiments show enhanced effects on HeLa cell viability, indicating that the conjugated nanorods are promising for use in combined therapy driven by LED light irradiation.

Weak neuronal glycolysis sustains cognition and organismal fitness.

The energy cost of neuronal activity is mainly sustained by glucose1,2. However, in an apparent paradox, neurons modestly metabolize glucose through glycolysis3-6, a circumstance that can be accounted for by the constant degradation of 6-phosphofructo-2-kinase-fructose-2,6-bisphosphatase-3 (PFKFB3)3,7,8, a key glycolysis-promoting enzyme. To evaluate the in vivo physiological importance of this hypoglycolytic metabolism, here we genetically engineered mice with their neurons transformed into active glycolytic cells through Pfkfb3 expression. In vivo molecular, biochemical and metabolic flux analyses of these neurons revealed an accumulation of anomalous mitochondria, complex I disassembly, bioenergetic deficiency and mitochondrial redox stress. Notably, glycolysis-mediated nicotinamide adenine dinucleotide (NAD+) reduction impaired sirtuin-dependent autophagy. Furthermore, these mice displayed cognitive decline and a metabolic syndrome that was mimicked by confining Pfkfb3 expression to hypothalamic neurons. Neuron-specific genetic ablation of mitochondrial redox stress or brain NAD+ restoration corrected these behavioural alterations. Thus, the weak glycolytic nature of neurons is required to sustain higher-order organismal functions.

Unexpected diagnosis: large hemangioma in the interatrial septum.

BACKGROUND: Cardiac hemangiomas are very uncommon benign primary tumors. They are usually located preferentially in the right atrium and their location in the interatrial septum is extremely rare. CASE PRESENTATION: We report the case of a 41-year-old patient who was admitted due to a stroke. The transthoracic echocardiogram revealed a large mass in the right atrium adhered to the interatrial septum. Suspecting an atrial myxoma, surgical intervention was performed confirming that the mass extended within the thickness of the interatrial septum, protruding into the right atrial cavity. The histologic report confirmed a hemangioma. CONCLUSIONS: Cardiac hemangiomas are rare primary tumors and are usually misdiagnosed as other cardiac tumors. Histopathological examination is essential for a definitive diagnosis.

Type 1 diabetes in pediatrics during the COVID-19 pandemic: Time from symptom onset and forms of presentation at a referral hospital. / Diabetes tipo 1 en pediatría durante la pandemia por COVID-19: tiempo de evolución de síntomas y formas de presentación en un centro de referencia.

Introduction. The COVID-19 pandemic impacted on the health care of patients with type 1 diabetes mellitus (DM1). An increase in diabetic ketoacidosis (DKA) as a form of diagnosis was reported. Objectives. To assess whether there were changes in the time from symptom onset, the causes of hospitalization due to DM1, and the proportion of severe forms, and to describe SARS-CoV-2 infection in these patients. Population and methods. Cross-sectional study in patients younger than 19 years hospitalized due to DM1 from March 2018 to August 2019 (pre-pandemic) and from March 2020 to August 2021 (pandemic). Results. The assessment included 135 hospitalizations in the pre-pandemic period and 96 during the pandemic. The time from symptom onset during the pandemic in those with debut of diabetes was shorter than in the pre-pandemic period (18.8 ± 10.2 versus 52.1 ± 12.1 days, respectively; p < 0.001). Hospitalizations due to all forms of diabetes debut and debut with DKA were more common during the pandemic than before it (59.4% versus 39.3%; odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.3-3.8; p = 0.003 and 40.6% versus 20.7%; OR: 2.6; 95% CI: 1.4-5.2; p = 0.006, respectively). Severe forms of DKA did not change between both periods (48.1% versus 59.9%; p = 0.3). Only 6 patients developed SARS-CoV-2 infection; 3 were severe. Conclusion. During the pandemic, the time from symptom onset decreased and the frequency of hospitalizations due to debut of DM1 increased. The proportion of severe forms of DKA did not change.

Introducción. La pandemia por COVID-19 afectó la atención de pacientes con diabetes mellitus tipo 1 (DM1). Además, se reportó un aumento de cetoacidosis diabética (CAD) como forma de diagnóstico. Objetivos. Evaluar si durante la pandemia por COVID-19 se modificaron el tiempo de evolución de síntomas, las causas de hospitalización por DM1 y la proporción de formas graves, y describir la infección por SARS-CoV-2 en estos pacientes. Población y métodos. Estudio transversal que incluyó pacientes menores de 19 años hospitalizados por DM1 en un centro pediátrico de referencia de marzo de 2018 a agosto de 2019 (prepandemia) y de marzo de 2020 a agosto de 2021 (pandemia). Resultados. Se analizaron 231 internaciones, 135 prepandemia y 96 en pandemia. Los pacientes con debut diabético presentaron menor tiempo de evolución de síntomas en pandemia que en prepandemia (18,8 ± 10,2 vs. 52,1 ±12,1 días, respectivamente; p <0,001). Las hospitalizaciones por todas las formas de debut diabético y el debut con CAD fueron más frecuentes en pandemia que en prepandemia (59,4 % vs. 39,3 %; OR 2,3; IC95% 1,3-3,8; p = 0,003); y (40,6 % vs. 20,7 %; OR 2,6; IC95% 1,4-5,2; p = 0,006) respectivamente. La proporción de formas graves de CAD no se modificó entre ambos períodos (48,1 % vs. 59,9 %; p = 0,3). Solo 6 pacientes presentaron infección por SARS-CoV-2; 3 fueron formas graves. Conclusión. Durante la pandemia, disminuyó el tiempo de evolución de síntomas y aumentó la frecuencia de hospitalizaciones por debut de DM1, con mayor proporción de CAD. No se modificó la proporción de formas graves de CAD.

Predicting Kidney Transplantation Outcomes from Donor and Recipient Characteristics at Time Zero: Development of a Mobile Application for Nephrologists.

(1) Background: We report on the development of a predictive tool that can estimate kidney transplant survival at time zero. (2) Methods: This was an observational, retrospective study including 5078 transplants. Death-censored graft and patient survivals were calculated. (3) Results: Graft loss was associated with donor age (hazard ratio [HR], 1.021, 95% confidence interval [CI] 1.018-1.024, p < 0.001), uncontrolled donation after circulatory death (DCD) (HR 1.576, 95% CI 1.241-2.047, p < 0.001) and controlled DCD (HR 1.567, 95% CI 1.372-1.812, p < 0.001), panel reactive antibody percentage (HR 1.009, 95% CI 1.007-1.011, p < 0.001), and previous transplants (HR 1.494, 95% CI 1.367-1.634, p < 0.001). Patient survival was associated with recipient age (> 60 years, HR 5.507, 95% CI 4.524-6.704, p < 0.001 vs. < 40 years), donor age (HR 1.019, 95% CI 1.016-1.023, p < 0.001), dialysis vintage (HR 1.0000263, 95% CI 1.000225-1.000301, p < 0.01), and male sex (HR 1.229, 95% CI 1.135-1.332, p < 0.001). The C-statistics for graft and patient survival were 0.666 (95% CI: 0.646, 0.686) and 0.726 (95% CI: 0.710-0.742), respectively. (4) Conclusions: We developed a mobile app to estimate survival at time zero, which can guide decisions for organ allocation.

Metabolomics approach for phenolic compounds profiling of soursop (Annona muricata L.) fruit during postharvest storage.

INTRODUCTION: Soursop (Annona muricata L.) is a crop with medicinal properties and numerous bioactive compounds. Ripening is a complex process that regulates fruit quality and changes in metabolite content, such as flavonoids, polyphenols, and organic acids. OBJECTIVES: This study aimed to analyze the phenolic profiling of soursop fruit ripening. METHODS: The metabolic changes in different days of storage of soursop fruits were investigated using a semi-metabolomic approach based on ultra-performance liquid chromatography coupled to electrospray ionization quadrupole-time of flight mass spectrometry (UPLC-ESI-QTOF-MS). Further, multivariate analysis such as supervised partial least squares discriminant analysis (PLS-DA) was conducted to identify differential metabolites. RESULTS: A total of 68 metabolites were identified in soursop fruit during postharvest storage. A higher number of metabolites were identified in the Day zero (D0) compared to the Day one (D1), Day three (D3), and Day five (D5), belonging to flavonoids, other polyphenols, phenolic acids, and organic acids. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the pathways of flavone and flavonol biosynthesis, flavonoid biosynthesis, and biosynthesis of secondary metabolites were mostly enriched. Additionally, we included all the compounds and their postharvest storage in the public Phenolics profile database. CONCLUSIONS: Here, we show that the stage of ripening has a significant effect on the phenolic content, highlighting the point of cut (D0) and the onset of senescence (D5). The findings of this study provide new insights into the soursop fruit quality and may contribute to the identification of metabolic markers for its storage.

Treatment of infantile-onset Pompe disease in a rat model with muscle-directed AAV gene therapy.

OBJECTIVE: Pompe disease (PD) is caused by deficiency of the lysosomal enzyme acid α-glucosidase (GAA), leading to progressive glycogen accumulation and severe myopathy with progressive muscle weakness. In the Infantile-Onset PD (IOPD), death generally occurs <1 year of age. There is no cure for IOPD. Mouse models of PD do not completely reproduce human IOPD severity. Our main objective was to generate the first IOPD rat model to assess an innovative muscle-directed adeno-associated viral (AAV) vector-mediated gene therapy. METHODS: PD rats were generated by CRISPR/Cas9 technology. The novel highly myotropic bioengineered capsid AAVMYO3 and an optimized muscle-specific promoter in conjunction with a transcriptional cis-regulatory element were used to achieve robust Gaa expression in the entire muscular system. Several metabolic, molecular, histopathological, and functional parameters were measured. RESULTS: PD rats showed early-onset widespread glycogen accumulation, hepato- and cardiomegaly, decreased body and tissue weight, severe impaired muscle function and decreased survival, closely resembling human IOPD. Treatment with AAVMYO3-Gaa vectors resulted in widespread expression of Gaa in muscle throughout the body, normalizing glycogen storage pathology, restoring muscle mass and strength, counteracting cardiomegaly and normalizing survival rate. CONCLUSIONS: This gene therapy holds great potential to treat glycogen metabolism alterations in IOPD. Moreover, the AAV-mediated approach may be exploited for other inherited muscle diseases, which also are limited by the inefficient widespread delivery of therapeutic transgenes throughout the muscular system.

The Gap in Sustainable Food Services in Public Institutions: The Perceptions of Young Consumers from Public Universities in the Madrid Region (Spain).

The agri-food system needs to transition into a more balanced system that takes into account economic, social, and environmental factors. Young people are a key demographic group to consider as they are open to new trends of consumption, including sustainable buying practices. Public universities can play a significant role in promoting sustainable and healthy eating habits among students. In this paper, we focus on the perceptions of young people regarding sustainable food in the Madrid Region. We conducted a survey using a questionnaire-based approach among 1940 students in 2022. The results highlight that young consumers are highly concerned about food sustainability. They perceive sustainability as local and non-processed foods. However, this perception varies among young consumers, and we identified five different consumer profiles. Principal component analysis and cluster analysis provide insights into potential actions that universities can take to promote sustainable and healthy eating habits among students.

Arginine reprograms metabolism in liver cancer via RBM39.

Metabolic reprogramming is a hallmark of cancer. However, mechanisms underlying metabolic reprogramming and how altered metabolism in turn enhances tumorigenicity are poorly understood. Here, we report that arginine levels are elevated in murine and patient hepatocellular carcinoma (HCC), despite reduced expression of arginine synthesis genes. Tumor cells accumulate high levels of arginine due to increased uptake and reduced arginine-to-polyamine conversion. Importantly, the high levels of arginine promote tumor formation via further metabolic reprogramming, including changes in glucose, amino acid, nucleotide, and fatty acid metabolism. Mechanistically, arginine binds RNA-binding motif protein 39 (RBM39) to control expression of metabolic genes. RBM39-mediated upregulation of asparagine synthesis leads to enhanced arginine uptake, creating a positive feedback loop to sustain high arginine levels and oncogenic metabolism. Thus, arginine is a second messenger-like molecule that reprograms metabolism to promote tumor growth.

Cell internalization kinetics and surface charge accessibility of surface-modified PAMAM dendrimers.

Surface-modified PAMAM dendrimers have important applications in drug delivery, yet a gap remains about the role that surface functionalization plays on their cell internalization capacity. We examined the cell internalization kinetics of PAMAM dendrimers that were surface-modified with acetyl, folate and poly(ethylene glycol), as model functional groups differing in size, charge, and chemical functionality. Dendrimers with 25% functionalization were internalized by HEK cells, but with slower rates and lower maximum uptakes than the native dendrimer between 1-6 h of incubation. Dendrimers with 50% functionalization exhibited negligible internalization capacities at all incubation times. Molecular dynamics simulations revealed that the solvent accessibility of the cationic surface charges is a key factor affecting cell internalization, unlike the total charge, functionality or size of surface-modified PAMAM dendrimers. These findings provide valuable insights to assist the design of PAMAM-based systems for drug delivery applications.

DPP9 Comes of Age: Highly Selective Inhibitors Promise New Therapeutic Opportunities.

Dipeptidyl peptidase-like protein 9 (DPP9) is emerging as a promising drug target for the treatment of hematological diseases. Two novel DPP9 inhibitors with nanomolar affinity and unprecedented selectivity to DPP9 over DPP8 have been discovered, paving the way for future progress in DPP9-mediated treatments.

Inhibition of Enzymatic Acetylation-Mediated Resistance to Plazomicin by Silver Ions.

Plazomicin is a recent U.S. Food and Drug Administration (FDA)-approved semisynthetic aminoglycoside. Its structure consists of a sisomicin scaffold modified by adding a 2(S)-hydroxy aminobutyryl group at the N1 position and a hydroxyethyl substituent at the 6' position. These substitutions produced a molecule refractory to most aminoglycoside-modifying enzymes. The main enzyme within this group that recognizes plazomicin as substrate is the aminoglycoside 2'-N-acetyltransferase type Ia [AAC(2')-Ia], which reduces the antibiotic's potency. Designing formulations that combine an antimicrobial with an inhibitor of resistance is a recognized strategy to extend the useful life of existing antibiotics. We have recently found that several metal ions inhibit the enzymatic inactivation of numerous aminoglycosides mediated by the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib]. In particular, Ag+, which also enhances the effect of aminoglycosides by other mechanisms, is very effective in interfering with AAC(6')-Ib-mediated resistance to amikacin. Here we report that silver acetate is a potent inhibitor of AAC(2')-Ia-mediated acetylation of plazomicin in vitro, and it reduces resistance levels of Escherichia coli carrying aac(2')-Ia. The resistance reversion assays produced equivalent results when the structural gene was expressed under the control of the natural or the blaTEM-1 promoters. The antibiotic effect of plazomicin in combination with silver was bactericidal, and the mix did not show significant toxicity to human embryonic kidney 293 (HEK293) cells.

Integrated gene expression profiles reveal a transcriptomic network underlying the thermogenic response in adipose tissue.

Obesity and type 2 diabetes are two closely related diseases representing a serious threat worldwide. An increase in metabolic rate through enhancement of non-shivering thermogenesis in adipose tissue may represent a potential therapeutic strategy. Nevertheless, a better understanding of thermogenesis transcriptional regulation is needed to allow the development of new effective treatments. Here, we aimed to characterize the specific transcriptomic response of white and brown adipose tissues after thermogenic induction. Using cold exposure to induce thermogenesis in mice, we identified mRNAs and miRNAs that were differentially expressed in several adipose depots. In addition, integration of transcriptomic data in regulatory networks of miRNAs and transcription factors allowed the identification of key nodes likely controlling metabolism and immune response. Moreover, we identified the putative role of the transcription factor PU.1 in the regulation of PPARγ-mediated thermogenic response of subcutaneous white adipose tissue. Therefore, the present study provides new insights into the molecular mechanisms that regulate non-shivering thermogenesis.

Beyond the classroom: The development of collective structural competency in pro-migrant activism.

Structural competency proposals have been developed as part of an effort to infuse clinical training with a structural focus. Framed in the context of medical education, the discussion on structural competency naturally emphasises the development of such competency in healthcare workers. In this article, we shift the focus to reflect on how the work of migrant community leaders may involve the development of structural competencies and what can be learned from this complementary perspective. We analysed the development of structural competency in an immigrant rights organisation in northern Chile. We conducted focus groups with migrant leaders and volunteers and used the tools proposed by the Structural Competency Working Group to facilitate dialogue. This allowed us to verify the development of structural competency and other collective competencies, including the capacity to create a protected space for circulating experiences and knowledge; coordinate a heterogeneous group of agents; have a socio-legal impact; and maintain autonomy concerning ideological production. This article introduces the concept of collective structural competency and reflects on the importance of expanding beyond the common medical-centred approach when considering structural competency.

Best practices during COVID-19 pandemic in solid organ transplant programs in Spain.

Clinical management of transplant patients abruptly changed during the first months of COVID-19 pandemic (March to May 2020). The new situation led to very significant challenges, such as new forms of relationship between healthcare providers and patients and other professionals, design of protocols to prevent disease transmission and treatment of infected patients, management of waiting lists and of transplant programs during state/city lockdown, relevant reduction of medical training and educational activities, halt or delays of ongoing research, etc. The two main objectives of the current report are: 1) to promote a project of best practices in transplantation taking advantage of the knowledge and experience acquired by professionals during the evolving situation of the COVID-19 pandemic, both in performing their usual care activity, as well as in the adjustments taken to adapt to the clinical context, and 2) to create a document that collects these best practices, thus allowing the creation of a useful compendium for the exchange of knowledge between different Transplant Units. The scientific committee and expert panel finally standardized 30 best practices, including for the pretransplant period (n = 9), peritransplant period (n = 7), postransplant period (n = 8) and training and communication (n = 6). Many aspects of hospitals and units networking, telematic approaches, patient care, value-based medicine, hospitalization, and outpatient visit strategies, training for novelties and communication skills were covered. Massive vaccination has greatly improved the outcomes of the pandemic, with a decrease in severe cases requiring intensive care and a reduction in mortality. However, suboptimal responses to vaccines have been observed in transplant recipients, and health care strategic plans are necessary in these vulnerable populations. The best practices contained in this expert panel report may aid to their broader implementation.

Insight into the Role of Active Site Protonation States and Water Molecules in the Catalytic Inhibition of DPP4 by Vildagliptin.

Vildagliptin (VIL) is an antidiabetic drug that inhibits dipeptidyl peptidase-4 (DPP4) through a covalent mechanism. The molecular bases for this inhibitory process have been addressed experimentally and computationally. Nevertheless, relevant issues remain unknown such as the roles of active site protonation states and conserved water molecules nearby the catalytic center. In this work, molecular dynamics simulations were applied to examine the structures of 12 noncovalent VIL-DPP4 complexes encompassing all possible protonation states of three noncatalytic residues (His126, Asp663, Asp709) that were inconclusively predicted by different computational tools. A catalytically competent complex structure was only achieved in the system with His126 in its ε-form and nonconventional neutral states for Asp663/Asp709. This complex suggested the involvement of one water molecule in the catalytic process of His740/Ser630 activation, which was confirmed by QM/MM simulations. Our findings support the suitability of a novel water-mediated mechanism in which His740/Ser630 activation occurs concertedly with the nucleophilic attack on VIL and the imidate protonation by Tyr547. Then, the restoration of His740/ Tyr547 protonation states occurs via a two-water hydrogen bonding network in a low-barrier process, thus describing the final step of the catalytic cycle for the first time. Additionally, two hydrolytic mechanisms were proposed based on the hydrogen bonding networks formed by water molecules and the catalytic residues along the inhibitory mechanism. These findings are valuable to unveil the molecular features of the covalent inhibition of DPP4 by VIL and support the future development of novel derivatives with improved structural or mechanistic profiles.

Manejo conservador de pseudoaneurisma de vena cava iatrogénico / Conservative management of iatrogenic vena cava pseudoaneurysm

Introducción: los pseudoaneurismas de vena cava infrarrenal (VCI) son una patología infrecuente, sin tratamiento estandarizado; la mayoría, secundarios a traumatismos abdominales. Presentan una mortalidad del 20-57 %. Su manejo debe ser individualizado, con opciones como conservador, quirúrgico o endovascular. Caso clínico: varón de 23 años con cardiopatía congénita compleja que ingresa por síncope extrahospitalario con posterior aleteo auricular e inestabilidad hemodinámica. Durante el procedimiento de ablación presenta shock hemorrágico. Precisa drogas vasoactivas y transfusión masiva. Tras su estabilización, se realiza angio TAC abdominal en el que se visualiza hematoma retroperitoneal dependiente de VCI sin hemorragia activa. Dada la comorbilidad del paciente y la estabilidad hemodinámica, se decide tratamiento conservador y control radiológico. En el angio TAC a los 15 días se visualiza pseudoaneurisma de VCI. Decide mantenerse actitud conservadora, retirar la anticoagulación y realizar revisiones periódicas. Se mantiene estable y se decide el alta, con vigilancia estrecha. En el control a los dos meses se objetiva completa resolución del pseudoaneurisma. Discusión: dada la complejidad de la patología, la estabilidad hemodinámica y las comorbilidades del paciente, se optó por manejo conservador, sin descartar otras opciones terapéuticas si presentaba empeoramiento clínico o radiológico. El tratamiento del pseudoaneurisma de VCI debe individualizarse, priorizando la clínica y la estabilidad del paciente y vigilando la evolución de la lesión con control radiológico estrecho.(AU)

Background: infrarenal cava vein (ICV) pseudoaneurysms are an infrequent pathology, without standardized treatment. Most secondary to abdominal trauma and may associate arterial injuries. Presenting a mortality of 20-57 %, which has not been reduced, despite advances in treatment. Iatrogenic IVC injuries can develop retroperitoneal hematomas and pseudoaneurysms. Its management must be individualized, with options such as conservative, surgical or endovascular. Case report: a 23-year-old male with complex congenital heart disease was admitted due to out-of-hospital syncope with subsequent atrial flutter and hemodynamic instability. During the ablation procedure, he presented hemorrhagic shock requiring doses of vasoactive drugs and massive transfusion. After stabilizing the patient, an abdominal angio-CT was performed, visualizing an IVC-dependent retroperitoneal hematoma with no signs of active bleeding. Given the patient's comorbidity and hemodynamic stability, conservative treatment and radiological control were implemented. CT angiography at 15 days shows IVC pseudoaneurysm. It was decided to maintain a conservative attitude, withdraw anticoagulation and periodic check-ups. Remaining stable, discharge is decided, with close monitoring. At the two months check-up, complete resolution of the pseudoaneurysm is observed. Discussion: given the complexity of the pathology, the patient's hemodynamic stability and comorbidities, conservative management was chosen, without ruling out other therapeutic options if presented with clinical or radiological worsening. The treatment of IVC pseudoaneurysm must be individualized, prioritizing the patient's symptoms and stability and monitoring the evolution of the lesion with close radiological control.(AU)