m6a methylation orchestrates IMP1 regulation of microtubules during human neuronal differentiation.

Neuronal differentiation requires building a complex intracellular architecture, and therefore the coordinated regulation of defined sets of genes. RNA-binding proteins (RBPs) play a key role in this regulation. However, while their action on individual mRNAs has been explored in depth, the mechanisms used to coordinate gene expression programs shaping neuronal morphology are poorly understood. To address this, we studied how the paradigmatic RBP IMP1 (IGF2BP1), an essential developmental factor, selects and regulates its RNA targets during the human neuronal differentiation. We perform a combination of system-wide and molecular analyses, revealing that IMP1 developmentally transitions to and directly regulates the expression of mRNAs encoding essential regulators of the microtubule network, a key component of neuronal morphology. Furthermore, we show that m6A methylation drives the selection of specific IMP1 mRNA targets and their protein expression during the developmental transition from neural precursors to neurons, providing a molecular principle for the onset of target selectivity.

From the Operating Room to the Laboratory: Role of the Neuroscience Tissue Biorepository in the Clinical, Translational, and Basic Science Research Pipeline.

OBJECTIVE: To establish a neurologic disorder-driven biospecimen repository to bridge the operating room with the basic science laboratory and to generate a feedback cycle of increased institutional and national collaborations, federal funding, and human clinical trials. METHODS: Patients were prospectively enrolled from April 2017 to July 2022. Tissue, blood, cerebrospinal fluid, bone marrow aspirate, and adipose tissue were collected whenever surgically safe. Detailed clinical, imaging, and surgical information was collected. Neoplastic and nonneoplastic samples were categorized and diagnosed in accordance with current World Health Organization classifications and current standard practices for surgical pathology at the time of surgery. RESULTS: A total of 11,700 different specimens from 813 unique patients have been collected, with 14.2% and 8.5% of patients representing ethnic and racial minorities, respectively. These include samples from a total of 463 unique patients with a primary central nervous system tumor, 88 with metastasis to the central nervous system, and 262 with nonneoplastic diagnoses. Cerebrospinal fluid and adipose tissue dedicated banks with samples from 130 and 16 unique patients, respectively, have also been established. Translational efforts have led to 42 new active basic research projects; 4 completed and 6 active National Institutes of Health-funded projects; and 2 investigational new drug and 5 potential Food and Drug Administration-approved phase 0/1 human clinical trials, including 2 investigator initiated and 3 industry sponsored. CONCLUSION: We established a comprehensive biobank with detailed notation with broad potential that has helped us to transform our practice of research and patient care and allowed us to grow in research and clinical trials in addition to providing a source of tissue for new discoveries.

Development of a specific and potent IGF2BP1 inhibitor: A promising therapeutic agent for IGF2BP1-expressing cancers.

IGF2BP1 is a protein that controls the stability, localization, and translation of various mRNA targets. Poor clinical outcomes in numerous cancer types have been associated with its overexpression. As it has been demonstrated to impede tumor growth and metastasis in animal models, inhibiting IGF2BP1 function is a promising strategy for combating cancer. A lead chemical, 7773, which specifically decreased IGF2BP1 RNA binding and cellular activities, was previously identified in a high-throughput screen for effective IGF2BP1 inhibitors. Additional optimization of 7773 described in this manuscript led to the discovery of six compounds that performed equally well or better than 7773. In cell lines with high levels of endogenous IGF2BP1, one of 7773 derivatives, AVJ16, was found to be most efficient at preventing cell migration. Further, AVJ16 was found to be IGF2BP1-specific because it had no effect on cell lines that expressed little or no IGF2BP1 protein. The direct binding of AVJ16 to IGF2BP1 was validated by binding tests, with a 12-fold increase in binding efficiency over the lead compound. AVJ16 was shown to bind to a hydrophobic region at the protein's KH34 di-domain interface between the KH3 and KH4 domains. Overall, the findings imply that AVJ16 is a potent and specific inhibitor of IGF2BP1 activity.

Direct m6A recognition by IMP1 underlays an alternative model of target selection for non-canonical methyl-readers.

m6A methylation provides an essential layer of regulation in organismal development, and is aberrant in a range of cancers and neuro-pathologies. The information encoded by m6A methylation is integrated into existing RNA regulatory networks by RNA binding proteins that recognise methylated sites, the m6A readers. m6A readers include a well-characterised class of dedicated proteins, the YTH proteins, as well as a broader group of multi-functional regulators where recognition of m6A is only partially understood. Molecular insight in this recognition is essential to build a mechanistic understanding of global m6A regulation. In this study, we show that the reader IMP1 recognises the m6A using a dedicated hydrophobic platform that assembles on the methyl moiety, creating a stable high-affinity interaction. This recognition is conserved across evolution and independent from the underlying sequence context but is layered upon the strong sequence specificity of IMP1 for GGAC RNA. This leads us to propose a concept for m6A regulation where methylation plays a context-dependent role in the recognition of selected IMP1 targets that is dependent on the cellular concentration of available IMP1, differing from that observed for the YTH proteins.

Tratamiento farmacológico del paciente que vive con diabetes mellitus tipo 2 / Pharmacological treatment of the patient living with type 2 diabetes mellitus

Resumen Introducción: el abordaje del paciente con diabetes mellitus tipo 2 ha cambiado a lo largo del tiempo. Años anteriores el enfoque terapéutico giraba en torno al nivel de hemoglobina glicada (HbA1c); ahora, con el advenimiento de nuevas moléculas, y luego de entender que la meta terapéutica no es sólo un punto de corte de HbA1c, se ha modificado el objetivo, para estar centrado en el paciente, en sus comorbilidades macro y microvasculares, riesgo cardiovascular y falla cardíaca. En esta revisión de la literatura se exponen las preguntas que se deben resolver al momento de definir una estrategia terapéutica en el paciente con diabetes mellitus tipo 2. Métodos: valoración de guías locales e internacionales de tratamiento de diabetes mellitus tipo 2. Resultados: se valoraron las guías del tratamiento de la diabetes mellitus tipo 2 realizadas por la Asociación Colombiana de Endocrinología, Asociación Colombiana de Medicina Interna, Asociación Colombiana de Nefrología, Sociedad Colombiana de Cardiología y Cirugía Cardiovascular, American Diabetes Association, American Association of Clinical Endocrinology, European Association for the Study of Diabetes y European Society of Cardiology. Además, se revisaron los ensayos clínicos que respaldan el uso de los diferentes grupos farmacológicos disponibles para el tratamiento de los pacientes con diabetes mellitus tipo 2. Conclusión: es menester del clínico realizar el abordaje terapéutico de los pacientes con diabetes mellitus tipo 2 de forma individualizada, centrado en el riesgo cardiovascular, comorbilidades asociadas, riesgo de hipoglucemia y costos de la intervención brindada.

Abstract Introduction: the approach to the patient with diabetes has changed over the past decade. Some years ago, the primary goal of treatment was to achieve a certain level of A1c as a marker of glucose control. Now, with new molecules in the market that can modify the disease and its complications the treatment is focused on the individual patient, his micro and macrovascular complications and the risk of cardiovascular, heart failure and renal complications. In this review of the literature, we expose some questions that need to be solved when approaching the treatment of a patient with type 2 diabetes. Methods: we reviewed local and international guidelines on the treatment of type 2 diabetes. Results: we reviewed guidelines in the treatment of diabetes, local guidelines; Asociación Colombiana de Endocrinología, Asociación Colombiana de Medicina Interna, Asociación Colombiana de Nefrología, Sociedad Colombiana de Cardiología y Cirugía Cardiovascular. International guidelines; American Diabetes Association, American Association of Clinical Endocrinology, European Association for the Study of Diabetes y European Society of Cardiology Additionally, we revised clinical trial that support the use of the different drugs that are recommended by the guidelines as first, second- or third-line treatment. Conclusion: as clinicians we are expected to give the patient an individualized approach, based on their own comorbidities, risk of cardiovascular and renal disease and risk of hypoglycemia guided by national and international guidelines and latest clinical trial that support our approach.

Small molecule inhibitor of Igf2bp1 represses Kras and a pro-oncogenic phenotype in cancer cells.

Igf2bp1 is an oncofetal RNA binding protein whose expression in numerous types of cancers is associated with upregulation of key pro-oncogenic RNAs, poor prognosis, and reduced survival. Importantly, Igf2bp1 synergizes with mutations in Kras to enhance signalling and oncogenic activity, suggesting that molecules inhibiting Igf2bp1 could have therapeutic potential. Here, we isolate a small molecule that interacts with a hydrophobic surface at the boundary of Igf2bp1 KH3 and KH4 domains, and inhibits binding to Kras RNA. In cells, the compound reduces the level of Kras and other Igf2bp1 mRNA targets, lowers Kras protein, and inhibits downstream signalling, wound healing, and growth in soft agar, all in the absence of any toxicity. This work presents an avenue for improving the prognosis of Igf2bp1-expressing tumours in lung, and potentially other, cancer(s).

The distinct RNA-interaction modes of a small ZnF domain underlay TUT4(7) diverse action in miRNA regulation.

TUT4 and the closely related TUT7 are non-templated poly(U) polymerases required at different stages of development, and their mis-regulation or mutation has been linked to important cancer pathologies. While TUT4(7) interaction with its pre-miRNA targets has been characterized in detail, the molecular bases of the broader target recognition process are unclear. Here, we examine RNA binding by the ZnF domains of the protein. We show that TUT4(7) ZnF2 contains two distinct RNA binding surfaces that are used in the interaction with different RNA nucleobases in different targets, i.e that this small domain encodes diversity in TUT4(7) selectivity and molecular function. Interestingly and unlike other well-characterized CCHC ZnFs, ZnF2 is not physically coupled to the flanking ZnF3 and acts independently in miRNA recognition, while the remaining CCHC ZnF of TUT4(7), ZnF1, has lost its intrinsic RNA binding capability. Together, our data suggest that the ZnFs of TUT4(7) are independent units for RNA and, possibly, protein-protein interactions that underlay the protein's functional flexibility and are likely to play an important role in building its interaction network.

Equity policies in health plans: accessibility and something more? / Políticas de equidad en los planes de salud: accesibilidad ¿y algo más?

ABSTRACT OBJECTIVE: To examine the approach adopted by the health plans of the autonomous communities of Spain, verifying the weight given to the concept of equity; to detect referenced communities or situations, as well as to distinguish the perspective of approaching it, from access, equity or equalization. METHODS: Qualitative study, of content analysis using Nvivo12, carried out in 2020 on health plans in force since 2019 in the different regions (autonomous communities) of Spain. Sixteen current regional health plans were compiled to establish base categories (equity, accessibility and equality) and determine associated terms using Nvivo12, from which a content analysis was performed. RESULTS: The concept of equity is not emphasized in the regional health plans and its relevance is surpassed by the concepts of accessibility and equality. The use of these three concepts is associated with various categories indicating circumstances, conditions or groups to which the plans give greater attention. CONCLUSIONS: The results obtained coincide with previous studies on the contents and orientation of health plans, revealing a discrete presence of the concept of equity in the approaches adopted, although this does not undermine the alignment of health policies with the visions emanating from transnational organizations. It is detected the existence of a group to which special attention is given from the accessibility approach, the population with functional diversity.

RESUMEN OBJETIVO: Examinar el enfoque adoptado por los planes de salud de las comunidades autónomas de España verificando el peso otorgado al concepto de equidad; detectar a qué colectivos o situaciones se hace referencia; así como distinguir la perspectiva de abordaje del mismo, desde el acceso, la igualación o la equiparación. MÉTODOS: Estudio cualitativo, de análisis de contenido mediante Nvivo12, realizado en 2020 sobre planes de salud en vigencia a fecha de 2019 en las diferentes regiones (comunidades autónomas) de España. Se han recopilado 16 planes de salud regionales vigentes para establecer categorías base (equidad, accesibilidad e igualdad) y determinar términos asociados a través de Nvivo12, a partir de los que se realizó un análisis de contenido. RESULTADOS: El concepto de equidad no resulta destacado por los planes de salud autonómicos y su relevancia es superada por los conceptos de accesibilidad e igualdad. El empleo de estos tres conceptos está asociado a diversas categorías que connotan circunstancias, condiciones o colectivos a los que los planes prestan mayor atención. CONCLUSIONES: Los resultados obtenidos coinciden con estudios previos sobre los contenidos y orientación de los planes de salud, revelando una presencia discreta del concepto de equidad en los enfoques adoptados, sin que ello menoscabe el alineamiento de las políticas de salud respecto de las visiones emanadas de organizaciones transnacionales. Se detecta la existencia de un colectivo al que se presta especial atención desde el enfoque de accesibilidad, la población con diversidad funcional.

La eSalud en España: evolución, estado actual y perspectivas de futuro / eHealth in Spain: evolution, current status and future prospects

Resumen Ofrecer un análisis pormenorizado de la evolución e implantación de las Tecnologías de la Información y la Comunicación (TIC) en el ámbito sanitario -eSalud- en España, atendiendo a los principales servicios implementados, su situación actual y sus perspectivas de futuro, así como a su posible impacto en el sistema sanitario y particularmente en sus usuarios. Se ha revisado la literatura científica sobre eSalud para identificar los servicios implementados más extendidos y sus características. En función de esa información se ha diseñado y administrado una encuesta a nivel estatal a usuarios del sistema nacional de salud de España (SNS) para conocer su percepción sobre los servicios recibidos y los obstáculos existentes para su pleno desarrollo. Los resultados fueron contrastados con otras fuentes secundarias. Existen servicios plenamente implementados y con un elevado nivel de uso; otros todavía permanecen en una fase más inicial. Se confirma una asimetría en los servicios ofertados por las administraciones de salud de las Comunidades Autónomas. Se confirma que el sistema sanitario español ha experimentado un importante avance tecnológico, orientando la eSalud hacia la oferta de servicios centrados en la equidad, la calidad y la eficiencia, aunque todavía subsisten obstáculos a superar.

Abstract This article aims to offer a detailed analysis of the evolution and implementation of Information and Communications Technology (ICT) in the health sector -eHealth- in Spain. Considering the main services implemented, their current situation and future prospects, as well as their possible impact on the health system and particularly on their users. The scientific literature on eHealth has been reviewed to identify the most widely implemented services and their characteristics. Based on this information, a statewide survey has been designed and administered to users of the Spanish National Health System (SNS) to learn about their perception of the services received and the existing obstacles to their full development. The results were contrasted with other secondary sources. Some services are fully implemented and have a high level of use; others are still at an early stage. It is also confirmed an asymmetric evolution of services delivered by Spanish regional health organizations. It is confirmed that the Spanish health system has experienced an important technological improvement, focusing eHealth towards the delivery of services which highlight equity, quality and efficiency, although there are still obstacles to overcome.

Structural basis for Fullerene geometry in a human endogenous retrovirus capsid.

The HML2 (HERV-K) group constitutes the most recently acquired family of human endogenous retroviruses, with many proviruses less than one million years old. Many maintain intact open reading frames and provirus expression together with HML2 particle formation are observed in early stage human embryo development and are associated with pluripotency as well as inflammatory disease, cancers and HIV-1 infection. Here, we reconstruct the core structural protein (CA) of an HML2 retrovirus, assemble particles in vitro and employ single particle cryogenic electron microscopy (cryo-EM) to determine structures of four classes of CA Fullerene shell assemblies. These icosahedral and capsular assemblies reveal at high-resolution the molecular interactions that allow CA to form both pentamers and hexamers and show how invariant pentamers and structurally plastic hexamers associate to form the unique polyhedral structures found in retroviral cores.

Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery.

Cyclic AMP (cAMP) is an important signalling molecule across evolution, but its role in malaria parasites is poorly understood. We have investigated the role of cAMP in asexual blood stage development of Plasmodium falciparum through conditional disruption of adenylyl cyclase beta (ACß) and its downstream effector, cAMP-dependent protein kinase (PKA). We show that both production of cAMP and activity of PKA are critical for erythrocyte invasion, whilst key developmental steps that precede invasion still take place in the absence of cAMP-dependent signalling. We also show that another parasite protein with putative cyclic nucleotide binding sites, Plasmodium falciparum EPAC (PfEpac), does not play an essential role in blood stages. We identify and quantify numerous sites, phosphorylation of which is dependent on cAMP signalling, and we provide mechanistic insight as to how cAMP-dependent phosphorylation of the cytoplasmic domain of the essential invasion adhesin apical membrane antigen 1 (AMA1) regulates erythrocyte invasion.

IMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties.

IGF2 mRNA-binding protein 1 (IMP1) is a key regulator of messenger RNA (mRNA) metabolism and transport in organismal development and, in cancer, its mis-regulation is an important component of tumour metastasis. IMP1 function relies on the recognition of a diverse set of mRNA targets that is mediated by the combinatorial action of multiple RNA-binding domains. Here, we dissect the structure and RNA-binding properties of two key RNA-binding domains of IMP1, KH1 and KH2, and we build a kinetic model for the recognition of RNA targets. Our data and model explain how the two domains are organized as an intermolecular pseudo-dimer and that the important role they play in mRNA target recognition is underpinned by the high RNA-binding affinity and fast kinetics of this KH1KH2-RNA recognition unit. Importantly, the high-affinity RNA-binding by KH1KH2 is achieved by an inter-domain coupling 50-fold stronger than that existing in a second pseudo-dimer in the protein, KH3KH4. The presence of this strong coupling supports a role of RNA re-modelling in IMP1 recognition of known cancer targets.

[Prescription frequency of physical therapy and analgesics before total hip and knee arthroplasy : An epidemiological analysis of routine health care data from Germany]. / Verordnungshäufigkeit physikalischer Therapien und Analgetika vor dem Einsatz einer Hüft- bzw. Kniegelenks-Endoprothese : Eine versorgungsepidemiologische Analyse basierend auf GKV-Routinedaten aus Deutschland.

BACKGROUND: Osteoarthritis of the hip or knee joint is a widespread disease with a strong influence on the quality of life. At present, the extent of conservative treatment with physical therapies and analgesics before the use of a total joint arthroplasty (TJA) of the hip or knee is largely unclear in Germany. OBJECTIVES: The aim was to analyze the prescription frequency according to regional and socio-demographic factors. MATERIALS AND METHODS: Based on routine health care data from BARMER insurance, patients who received a TJA of the hip or knee from 2011 to 2013 were analyzed. Included were consistently insured patients with the main discharge diagnosis of osteoarthritis who did not receive any further TJA for eight quarters before and after replacement. The prescription frequency of physical therapies and analgesics, stratified according to age groups, gender, number of comorbidities and federal state was analyzed. RESULTS: 40,242 persons with hip TJA and 35,652 persons with knee TJA were included. In the year prior to surgery, 49.4% of patients (hip TJA: 49.9%; knee TJA: 48.9%) received at least one physical therapy and 81.0% were prescribed analgesics. Regionally, the prescription frequency of physical therapies for hip TJA varied between 35.7% (Bremen) and 70.6% (Saxony) and for knee TJA between 37.6% (Saarland) and 66.9% (Saxony). CONCLUSION: The prescription frequency of physical therapy does not fully correspond to current treatment recommendations. The prescription of physical therapies in the year before the TEP shows regional differences, with fundamentally lower prescription frequencies in the former states of West Germany.

A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets.

Exosomal miRNA transfer is a mechanism for cell-cell communication that is important in the immune response, in the functioning of the nervous system and in cancer. Syncrip/hnRNPQ is a highly conserved RNA-binding protein that mediates the exosomal partition of a set of miRNAs. Here, we report that Syncrip's amino-terminal domain, which was previously thought to mediate protein-protein interactions, is a cryptic, conserved and sequence-specific RNA-binding domain, designated NURR (N-terminal unit for RNA recognition). The NURR domain mediates the specific recognition of a short hEXO sequence defining Syncrip exosomal miRNA targets, and is coupled by a non-canonical structural element to Syncrip's RRM domains to achieve high-affinity miRNA binding. As a consequence, Syncrip-mediated selection of the target miRNAs implies both recognition of the hEXO sequence by the NURR domain and binding of the RRM domains 5' to this sequence. This structural arrangement enables Syncrip-mediated selection of miRNAs with different seed sequences.

An RRM-ZnF RNA recognition module targets RBM10 to exonic sequences to promote exon exclusion.

RBM10 is an RNA-binding protein that plays an essential role in development and is frequently mutated in the context of human disease. RBM10 recognizes a diverse set of RNA motifs in introns and exons and regulates alternative splicing. However, the molecular mechanisms underlying this seemingly relaxed sequence specificity are not understood and functional studies have focused on 3΄ intronic sites only. Here, we dissect the RNA code recognized by RBM10 and relate it to the splicing regulatory function of this protein. We show that a two-domain RRM1-ZnF unit recognizes a GGA-centered motif enriched in RBM10 exonic sites with high affinity and specificity and test that the interaction with these exonic sequences promotes exon skipping. Importantly, a second RRM domain (RRM2) of RBM10 recognizes a C-rich sequence, which explains its known interaction with the intronic 3΄ site of NUMB exon 9 contributing to regulation of the Notch pathway in cancer. Together, these findings explain RBM10's broad RNA specificity and suggest that RBM10 functions as a splicing regulator using two RNA-binding units with different specificities to promote exon skipping.

Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels positively and negatively.

Lin28a inhibits the biogenesis of let-7 miRNAs by triggering the polyuridylation and degradation of their precursors by terminal uridylyltransferases TUT4/7 and 3'-5' exoribonuclease Dis3l2, respectively. Previously, we showed that Lin28a also controls the production of neuro-specific miRNA-9 via a polyuridylation-independent mechanism. Here we reveal that the sequences and structural characteristics of pre-let-7 and pre-miRNA-9 are eliciting two distinct modes of binding to Lin28a. We present evidence that Dis3l2 controls miRNA-9 production. Finally, we show that the constitutive expression of untagged Lin28a during neuronal differentiation in vitro positively and negatively affects numerous other miRNAs. Our findings shed light on the role of Lin28a in differentiating cells and on the ways in which one RNA-binding protein can perform multiple roles in the regulation of RNA processing.

Structure of a Spumaretrovirus Gag Central Domain Reveals an Ancient Retroviral Capsid.

The Spumaretrovirinae, or foamy viruses (FVs) are complex retroviruses that infect many species of monkey and ape. Despite little sequence homology, FV and orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking and membrane targeting. However, there is a paucity of structural information for FVs and it is unclear how disparate FV and orthoretroviral Gag molecules share the same function. To probe the functional overlap of FV and orthoretroviral Gag we have determined the structure of a central region of Gag from the Prototype FV (PFV). The structure comprises two all α-helical domains NtDCEN and CtDCEN that although they have no sequence similarity, we show they share the same core fold as the N- (NtDCA) and C-terminal domains (CtDCA) of archetypal orthoretroviral capsid protein (CA). Moreover, structural comparisons with orthoretroviral CA align PFV NtDCEN and CtDCEN with NtDCA and CtDCA respectively. Further in vitro and functional virological assays reveal that residues making inter-domain NtDCEN-CtDCEN interactions are required for PFV capsid assembly and that intact capsid is required for PFV reverse transcription. These data provide the first information that relates the Gag proteins of Spuma and Orthoretrovirinae and suggests a common ancestor for both lineages containing an ancient CA fold.

PolyQ-mediated regulation of mRNA granules assembly.

RNA granules have been observed in different organisms, cell types and under different conditions, and their formation is crucial for the mRNA life cycle. However, very little is known about the molecular mechanisms governing their assembly and disassembly. The aggregation-prone LSCRs (low-sequence-complexity regions), and in particular, the polyQ/N-rich regions, have been extensively studied under pathological conditions due to their role in neurodegenerative diseases. In the present review, we discuss recent in vitro, in vivo and computational data that, globally, suggest a role for polyQ/N regions in RNA granule assembly.

KSRP controls pleiotropic cellular functions.

The single-strand-RNA binding protein KSRP is able to negatively regulate gene expression operating with at least two distinct and integrated postranscriptional mechanisms: (i) by promoting decay of unstable mRNAs and (ii) by favoring maturation from precursors of select microRNAs (miRNAs) including the prototypical tumor suppressor let-7. Studies performed in primary and cultured cells as well as in mice proved that the ability of KSRP to integrate different levels of gene expression is required for proper immune response, lipid metabolism, cell-fate decisions, tissue regeneration, and DNA damage response.

Reversible right-sided heart failure secondary to carcinoid crisis.

Carcinoid crisis is an infrequent and little-described complication of neuroendocrine tumors that can be life threatening. It may develop during induction of anesthesia, intraoperatively, during tumor manipulation and arterial embolization, or even spontaneously. The massive release of neuroendocrine substances can lead to potentially fatal complications. Somatostatin analogs inhibit the release of these substances and are the mainstay of treatment. The following case report describes a patient with reversible acute right-sided heart failure posterior to hepatic artery embolization.