Advances and challenges in the diagnosis and management of left ventricular noncompaction in adults: A literature review.

In the realm of cardiovascular health, isolated left ventricular noncompaction (LVNC) stands out for its distinct morphological features and the clinical challenges it presents, particularly in adults. This literature review explores the intricacies of LVNC, aiming to unravel its epidemiological spread, diagnostic hurdles, and therapeutic strategies. Despite technological advancements in cardiac imaging that have improved the recognition of LVNC, a significant gap persists alongside a fragmented understanding of its pathogenesis. The studies scrutinized reveal a broad spectrum of prevalence rates influenced by diverse diagnostic tools and demographic variables. This variation underscores the complexity of accurately identifying LVNC and the resultant implications for clinical management. The review succinctly addresses the need for precise guidelines to navigate the diagnosis of LVNC and outlines the imperative for tailored clinical management approaches that cater to the wide array of patient presentations, from asymptomatic cases to those with severe cardiac dysfunction. By highlighting the critical gaps in current literature-namely the absence of standardized diagnostic criteria and a comprehensive pathogenic model-the review sets the stage for future research directions. These endeavors are essential for enhancing diagnostic accuracy, refining management protocols, and ultimately improving patient outcomes in this complex subset of cardiomyopathy, thus contributing significantly to the advancement of cardiovascular medicine.

Comprehensive detection of CRLF2 alterations in acute lymphoblastic leukemia: a rapid and accurate novel approach.

Introduction: Acute lymphoblastic leukemia (ALL) is a prevalent childhood cancer with high cure rate, but poses a significant medical challenge in adults and relapsed patients. Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype, with approximately half of cases characterized by CRLF2 overexpression and frequent concomitant IKZF1 deletions. Methods: To address the need for efficient, rapid, and cost-effective detection of CRLF2 alterations, we developed a novel RT-qPCR technique combining SYBR Green and highresolution melting analysis on a single plate. Results: The method successfully identified CRLF2 expression, P2RY8::CRLF2 fusions, and CRLF2 and JAK2 variants, achieving a 100% sensitivity and specificity. Application of this method across 61 samples revealed that 24.59% exhibited CRLF2 overexpression, predominantly driven by IGH::CRLF2 (73.33%). High Resolution Melting analysis unveiled concurrent CRLF2 or JAK2 variants in 8.19% of samples, as well as a dynamic nature of CRLF2 alterations during disease progression. Discussion: Overall, this approach provides an accurate identification of CRLF2 alterations, enabling improved diagnostic and facilitating therapeutic decision-making.

Impact of Bempedoic acid on LDL-C reduction and cardiovascular outcomes: A comprehensive meta-analysis of randomized controlled trials.

BACKGROUND: The management of LDL-C levels is pivotal in the prevention of cardiovascular morbidity, particularly among patients at high risk or those intolerant to statins. Bempedoic acid emerges as a novel agent in this therapeutic arena. OBJECTIVES: This systematic review and meta-analysis endeavor to quantify the effectiveness of Bempedoic acid in attenuating LDL-C levels and explore its impact on cardiovascular morbidity, emphasizing its role as an adjunctive or alternative therapy in statin-intolerant or high-risk patients. METHODS: A comprehensive search spanning PubMed, Google Scholar, and Cochrane Library databases furnished studies for this review. The inclusion was critiqued based on predefined PICOS parameters, ensuring a robust analytical framework. RESULTS: Bempedoic acid showcased a significant plunge in LDL-C levels (MD -20.69 %, 95 % CI [-23.20, -18.19]), outperforming placebo and ezetimibe monotherapy. The cardioprotective effect was further echoed with a reduced risk of major adverse cardiac events (MACE) in the Bempedoic acid cohort (RR 0.86, 95 % CI [0.80, 0.94]). However, a dive into the safety profile revealed no substantial augmentation in adverse events, affirming its tolerance and efficacy. CONCLUSIONS: Bempedoic acid represents a potent therapeutic ally, affirming its capacity to significantly pare down LDL-C levels and curtail cardiovascular events. Its favorable safety profile underscores its suitability, especially among those with statin intolerance or individuals categorized within the high-risk vascular bracket, necessitating a paradigm shift in current lipid management strategies.

Efficacy and Complication Profiles of Left Ventricular Assist Devices in Adult Heart Failure Management: A Systematic Review and Meta-Analysis.

Left ventricular assist devices (LVADs) have marked a milestone in the evolution of treatment for patients with end-stage heart failure. Their popularity and use are steadily rising. This systematic review and meta-analysis aimed to evaluate the effectiveness of LVADs in improving the survival rate of patients with end-stage heart failure and to identify the complications or adverse events associated with LVAD use. Articles for this systematic review and meta-analysis were sourced from PubMed, Google Scholar, and the Cochrane Library databases. Only studies that met the predefined PICOS eligibility criteria were analyzed. LVADs significantly improved the 6, 12, 18, and 24-month survival rates in patients with end-stage heart failure compared to no LVAD or other therapies: OR 1.87 (95%CI [1.27-2.76]), OR 2.29 (95%CI [1.61-3.26]), OR 2.07 (95%CI [0.61-6.61]), and OR 1.73 (95%CI [0.88-3.41]) for 6, 12, 18, and 24 months, respectively. The incidence of adverse events was significantly higher in the LVAD group than in the non-LVAD treatments: bleeding OR 12.53 (95%CI [2.60-60.41]), infections OR 4.15 (95%CI [1.19-14.45]), stroke OR 2.58 (95%CI [1.38-4.82]), and arrhythmia OR 2.81 (95%CI [1.64-4.80]). Overall, complications were higher in the LVAD group compared to those without LVAD treatment. Hospital readmissions due to adverse events were significantly more frequent in the LVAD group, OR 2.98 (95%CI [1.38-6.43]). Despite the elevated risk of adverse events associated with LVADs, these devices have demonstrated a notable enhancement in the survival outcomes for patients with end-stage heart failure.

Treosulfan-Based Conditioning Regimen In Pediatric Hematopoietic Stem Cell Transplantation: A Retrospective Analysis on Behalf of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC).

Increasing data on treosulfan-based conditioning regimens before hematopoietic stem cell transplantation (HSCT) demonstrate the consistent benefits of this approach, particularly regarding acute toxicity. This study aimed to describe the results of treosulfan-based conditioning regimens in children, focusing on toxicity and outcomes when used to treat both malignant and nonmalignant diseases. This retrospective observational study of pediatric patients treated in Spain with treosulfan-based conditioning regimens before HSCT was based on data collection from electronic clinical records. We studied a total of 160 treosulfan-based conditioning HSCTs to treat nonmalignant diseases (n = 117) or malignant diseases (n = 43) in 158 children and adolescents. The median patient age at HSCT was 5.1 years (interquartile range, 2 to 10 years). The most frequent diagnoses were primary immunodeficiency (n = 42; 36%) and sickle cell disease (n = 42; 36%) in the nonmalignant disease cohort and acute lymphoblastic leukemia (n = 15; 35%) in the malignant disease cohort. Engraftment occurred in 97% of the patients. The median times to neutrophil engraftment (17 days versus 14 days; P = .008) and platelet engraftment (20 days versus 15 days; P = .002) were linger in the nonmalignant cohort. The 1-year cumulative incidence of veno-occlusive disease was 7.98% (95% confidence interval [CI], 4.6% to 13.6%), with no significant differences between cohorts. The 1-year cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was higher in the malignant disease cohort (18% versus 3.2%; P = .011). Overall, the malignant cohort had both a higher total incidence (9% versus 3%; P < .001) and a higher 2-year cumulative incidence (16% versus 1.9%; P < .001) of total chronic GVHD. The 2-year cumulative transplantation-related mortality was 15%, with no difference between the 2 cohorts. The 5-year overall survival was 80% (95% CI, 72% to 86%) and was higher in the nonmalignant cohort (87% versus 61%; P = .01). The 2-year cumulative incidence of relapse was 25% in the malignant cohort. The 5-year cumulative GVHD-free, relapse-free survival rate was 60% (95% CI, 51% to 70%) and was higher in the nonmalignant cohort (72% versus 22%; P < .001). A treosulfan-based radiation-free conditioning regimen is feasible, achieving a high engraftment rate and 5-year overall survival, and is an emerging option for the first HSCT in nonmalignant diseases.

Advances in the Physiology of Transvascular Exchange and A New Look At Rational Fluid Prescription.

The Starling principle is a model that explains the transvascular distribution of fluids essentially governed by hydrostatic and oncotic forces, which dynamically allow vascular refilling according to the characteristics of the blood vessel. However, careful analysis of fluid physiology has shown that the principle, while correct, is not complete. The revised Starling principle (Michel-Weinbaum model) provides relevant information on fluid kinetics. Special emphasis has been placed on the endothelial glycocalyx, whose subendothelial area allows a restricted oncotic pressure that limits the reabsorption of fluid from the interstitial space, so that transvascular refilling occurs mainly from the lymphatic vessels. The close correlation between pathological states of the endothelium (eg: sepsis, acute inflammation, or chronic kidney disease) and the prescription of fluids forces the physician to understand the dynamics of fluids in the organism; this will allow rational fluid prescriptions. A theory that integrates the physiology of exchange and transvascular refilling is the "microconstant model", whose variables include dynamic mechanisms that can explain edematous states, management of acute resuscitation, and type of fluids for common clinical conditions. The clinical-physiological integration of the concepts will be the hinges that allow a rational and dynamic prescription of fluids.

Haploidentical vs. HLA-matched donor hematopoietic stem-cell transplantation for pediatric patients with acute lymphoblastic leukemia in second remission: A collaborative retrospective study of the Spanish Group for Bone Marrow Transplantation in Children (GETMON/GETH) and the Spanish Childhood Relapsed ALL Board (ReALLNet).

Introduction: Studies addressing the role of haploidentical as alternative to HLA-matched donors for stem cell transplantation (SCT) often include patients with diverse hematological malignancies in different remission statuses. Methods: We compared outcomes of children with acute lymphoblastic leukemia (ALL) undergoing SCT in second complete remission (CR2) from haploidentical (n = 25) versus HLA-matched donor (n = 51). Results: Patients were equally distributed across both groups according to age, immunophenotype, time to and site of relapse, relapse risk-group allocation, and minimal residual disease (MRD) before SCT. Incidence of graft failure, acute graft versus host disease (GVHD), and other early complications did not differ between both groups. We found no differences in overall survival (58.7% versus 59.5%; p = .8), leukemia free survival (LFS) (48% versus 36.4%; p = .5), event free survival (40% versus 34.4%; p = .69), cumulative incidence (CI) of subsequent relapse (28% versus 40.9%; p = .69), treatment related mortality (24% versus 23.6%; p = .83), CI of cGVHD (4.5% versus 18.7%; p = .2), and chronic GVHD-free and leukemia-free survival (44% versus 26.3%; p = .3) after haploidentical donor SCT. Chronic GVHD (HR = 0.09; p=.02) had protective impact, and MRD ≥ 0.01% before SCT (HR = 2.59; p=.01) had unfavorable impact on LFS. Discussion: These results support the role of haploidentical donor SCT in children with ALL in CR2.

Design and Validation of a Custom Next-Generation Sequencing Panel in Pediatric Acute Lymphoblastic Leukemia.

The molecular landscape of acute lymphoblastic leukemia (ALL) is highly heterogeneous, and genetic lesions are clinically relevant for diagnosis, risk stratification, and treatment guidance. Next-generation sequencing (NGS) has become an essential tool for clinical laboratories, where disease-targeted panels are able to capture the most relevant alterations in a cost-effective and fast way. However, comprehensive ALL panels assessing all relevant alterations are scarce. Here, we design and validate an NGS panel including single-nucleotide variants (SNVs), insertion-deletions (indels), copy number variations (CNVs), fusions, and gene expression (ALLseq). ALLseq sequencing metrics were acceptable for clinical use and showed 100% sensitivity and specificity for virtually all types of alterations. The limit of detection was established at a 2% variant allele frequency for SNVs and indels, and at a 0.5 copy number ratio for CNVs. Overall, ALLseq is able to provide clinically relevant information to more than 83% of pediatric patients, making it an attractive tool for the molecular characterization of ALL in clinical settings.

Clustered variants in the 5' coding region of TRA2B cause a distinctive neurodevelopmental syndrome.

PURPOSE: Transformer2 proteins (Tra2α and Tra2ß) control splicing patterns in human cells, and no human phenotypes have been associated with germline variants in these genes. The aim of this work was to associate germline variants in the TRA2B gene to a novel neurodevelopmental disorder. METHODS: A total of 12 individuals from 11 unrelated families who harbored predicted loss-of-function monoallelic variants, mostly de novo, were recruited. RNA sequencing and western blot analyses of Tra2ß-1 and Tra2ß-3 isoforms from patient-derived cells were performed. Tra2ß1-GFP, Tra2ß3-GFP and CHEK1 exon 3 plasmids were transfected into HEK-293 cells. RESULTS: All variants clustered in the 5' part of TRA2B, upstream of an alternative translation start site responsible for the expression of the noncanonical Tra2ß-3 isoform. All affected individuals presented intellectual disability and/or developmental delay, frequently associated with infantile spasms, microcephaly, brain anomalies, autism spectrum disorder, feeding difficulties, and short stature. Experimental studies showed that these variants decreased the expression of the canonical Tra2ß-1 isoform, whereas they increased the expression of the Tra2ß-3 isoform, which is shorter and lacks the N-terminal RS1 domain. Increased expression of Tra2ß-3-GFP were shown to interfere with the incorporation of CHEK1 exon 3 into its mature transcript, normally incorporated by Tra2ß-1. CONCLUSION: Predicted loss-of-function variants clustered in the 5' portion of TRA2B cause a new neurodevelopmental syndrome through an apparently dominant negative disease mechanism involving the use of an alternative translation start site and the overexpression of a shorter, repressive Tra2ß protein.

Angiotensin-(1-9) in hypertension.

Angiotensin-(1-9) [Ang-(1-9)] is a peptide of the non-canonical renin-angiotensin system (RAS) synthesized from angiotensin I by the monopeptidase angiotensin-converting enzyme type 2 (ACE2). Using osmotic minipumps, infusion of Ang-(1-9) consistently reduces blood pressure in several rat hypertension models. In these animals, hypertension-induced end-organ damage is also decreased. Several pieces of evidence suggest that Ang-(1-9) is the endogenous ligand that binds and activates the type-2 angiotensin II receptor (AT2R). Activation of AT2R triggers different tissue-specific signaling pathways. This phenomenon could be explained by the ability of AT2R to form different heterodimers with other G protein-coupled receptors. Because of the antihypertensive and protective effects of AT2R activation by Ang-(1-9), associated with a short half-life of RAS peptides, several synthetic AT2R agonists have been synthesized and assayed. Some of them, particularly CGP42112, C21 and novokinin, have demonstrated antihypertensive properties. Only two synthetic AT2R agonists, C21 and LP2-3, have been tested in clinical trials, but none of them like an antihypertensive. Therefore, Ang-(1-9) is a promising antihypertensive drug that reduces hypertension-induced end-organ damage. However, further research is required to translate this finding successfully to the clinic.

Radiological Findings Increased the Successful of COVID-19 Diagnosis in Hospitalized Patients Suspected of Respiratory Viral Infection but with a Negative First SARS-CoV-2 RT-PCR Result.

SARS-CoV-2 is the etiological agent of COVID-19 and may evolve from asymptomatic disease to fatal outcomes. Real-time reverse-transcription polymerase chain reaction (RT-PCR) screening is the gold standard to diagnose severe accurate respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but this test is not 100% accurate, as false negatives can occur. We aimed to evaluate the potential false-negative results in hospitalized patients suspected of viral respiratory disease but with a negative previous SARS-CoV-2 RT-PCR and analyze variables that may increase the success of COVID-19 diagnosis in this group of patients. A total of 55 hospitalized patients suspected of viral respiratory disease but with a previous negative RT-PCR result for SARS-CoV-2 were included. All the participants had clinical findings related to COVID-19 and underwent a second SARS-CoV-2 RT-PCR. Chest-computed axial tomography (CT) was used as an auxiliary tool for COVID-19 diagnosis. After the second test, 36 patients (65.5%) were positive for SARS-CoV-2 (COVID-19 group), and 19 patients (34.5%) were negative (controls). There were differences between the groups in the platelet count and the levels of D-dimer, procalcitonin, and glucose (p < 0.05). Chest CT scans categorized as COVID-19 Reporting and Data System 5 (CO-RADS 5) were more frequent in the COVID-19 group than in the control group (91.7% vs. 52.6%; p = 0.003). CO-RADS 5 remained an independent predictor of COVID-19 diagnosis in a second SARS-CoV-2 screening (p = 0.013; odds ratio = 7.0, 95% confidence interval 1.5−32.7). In conclusion, chest CT classified as CO-RADS 5 was an independent predictor of a positive second SARS-CoV-2 RT-PCR, increasing the odds of COVID-19 diagnosis by seven times. Based on our results, in hospitalized patients with a chest CT classified as CO-RADS 5, a second SARS-CoV-2 RT-PCR test should be mandatory when the first one is negative. This approach could increase SARS-CoV-2 detection up to 65% and could allow for isolation and treatment, thus improving the patient outcome and avoiding further contagion.

Social+Me: a persuasive application to increase communication between students and their support networks in Southern Chile.

Technology can improve university students' communication, helping them maintain relationships. Although there are many available technological tools, students face challenges-e.g., living far from home, failing grades, depression-that may isolate them from their networks. Most research into these topics has been conducted in countries in which students leave their parents' home while at university, which is not the case for most students in southern Chile. In this context that has been seldom studied, this paper presents two studies, focusing on two research questions: (1) How do university students in southern Chile communicate? (2) Can a mobile application persuade university students to increase their communication patterns? To answer these questions, we conducted a survey with 90 students in southern Chile, and then developed a persuasive application called Social+Me, aimed at monitoring communication with students' support networks and persuading them to keep in touch. We conducted a preliminary evaluation of Social+Me, and the application was well received by participants, who felt that it improved their communication with their social network. The main impact of our study lies in applying persuasive technologies to the communicative practice of university students to prevent students from feeling isolated or unsupported.

Subcutaneous nanotherapy repurposes the immunosuppressive mechanism of rapamycin to enhance allogeneic islet graft viability.

Standard oral rapamycin (that is, Rapamune) administration is plagued by poor bioavailability and broad biodistribution. Thus, this pleotropic mammalian target of rapamycin (mTOR) inhibitor has a narrow therapeutic window and numerous side effects and provides inadequate protection to transplanted cells and tissues. Furthermore, the hydrophobicity of rapamycin limits its use in parenteral formulations. Here, we demonstrate that subcutaneous delivery via poly(ethylene glycol)-b-poly(propylene sulfide) polymersome nanocarriers significantly alters rapamycin's cellular biodistribution to repurpose its mechanism of action for tolerance, instead of immunosuppression, and minimize side effects. While oral rapamycin inhibits T cell proliferation directly, subcutaneously administered rapamycin-loaded polymersomes modulate antigen presenting cells in lieu of T cells, significantly improving maintenance of normoglycemia in a clinically relevant, major histocompatibility complex-mismatched, allogeneic, intraportal (liver) islet transplantation model. These results demonstrate the ability of a rationally designed nanocarrier to re-engineer the immunosuppressive mechanism of a drug by controlling cellular biodistribution.

Germline Predisposition to Pediatric Cancer, from Next Generation Sequencing to Medical Care.

Knowledge about genetic predisposition to pediatric cancer is constantly expanding. The categorization and clinical management of the best-known syndromes has been refined over the years. Meanwhile, new genes for pediatric cancer susceptibility are discovered every year. Our current work shares the results of genetically studying the germline of 170 pediatric patients diagnosed with cancer. Patients were prospectively recruited and studied using a custom panel, OncoNano V2. The well-categorized predisposing syndromes incidence was 9.4%. Likely pathogenic variants for predisposition to the patient's tumor were identified in an additional 5.9% of cases. Additionally, a high number of pathogenic variants associated with recessive diseases was detected, which required family genetic counseling as well. The clinical utility of the Jongmans MC tool was evaluated, showing a high sensitivity for detecting the best-known predisposing syndromes. Our study confirms that the Jongmans MC tool is appropriate for a rapid assessment of patients; however, the updated version of Ripperger T criteria would be more accurate. Meaningfully, based on our findings, up to 9.4% of patients would present genetic alterations predisposing to cancer. Notably, up to 20% of all patients carry germline pathogenic or likely pathogenic variants in genes related to cancer and, thereby, they also require expert genetic counseling. The most important consideration is that the detection rate of genetic causality outside Jongmans MC et al. criteria was very low.

Mitochondria and Mitochondrial DNA: Key Elements in the Pathogenesis and Exacerbation of the Inflammatory State Caused by COVID-19.

Background and Objectives. The importance of mitochondria in inflammatory pathologies, besides providing energy, is associated with the release of mitochondrial damage products, such as mitochondrial DNA (mt-DNA), which may perpetuate inflammation. In this review, we aimed to show the importance of mitochondria, as organelles that produce energy and intervene in multiple pathologies, focusing mainly in COVID-19 and using multiple molecular mechanisms that allow for the replication and maintenance of the viral genome, leading to the exacerbation and spread of the inflammatory response. The evidence suggests that mitochondria are implicated in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which forms double-membrane vesicles and evades detection by the cell defense system. These mitochondrion-hijacking vesicles damage the integrity of the mitochondrion's membrane, releasing mt-DNA into circulation and triggering the activation of innate immunity, which may contribute to an exacerbation of the pro-inflammatory state. Conclusions. While mitochondrial dysfunction in COVID-19 continues to be studied, the use of mt-DNA as an indicator of prognosis and severity is a potential area yet to be explored.

Novel Insights Into the Pathogenesis of Diabetic Cardiomyopathy and Pharmacological Strategies.

Diabetic cardiomyopathy (DCM) is a severe complication of diabetes developed mainly in poorly controlled patients. In DCM, several clinical manifestations as well as cellular and molecular mechanisms contribute to its phenotype. The production of reactive oxygen species (ROS), chronic low-grade inflammation, mitochondrial dysfunction, autophagic flux inhibition, altered metabolism, dysfunctional insulin signaling, cardiomyocyte hypertrophy, cardiac fibrosis, and increased myocardial cell death are described as the cardinal features involved in the genesis and development of DCM. However, many of these features can be associated with broader cellular processes such as inflammatory signaling, mitochondrial alterations, and autophagic flux inhibition. In this review, these mechanisms are critically discussed, highlighting the latest evidence and their contribution to the pathogenesis of DCM and their potential as pharmacological targets.

Peripheral Blood Mitochondrial DNA Levels Were Modulated by SARS-CoV-2 Infection Severity and Its Lessening Was Associated With Mortality Among Hospitalized Patients With COVID-19.

Introduction: During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the virus hijacks the mitochondria causing damage of its membrane and release of mt-DNA into the circulation which can trigger innate immunity and generate an inflammatory state. In this study, we explored the importance of peripheral blood mt-DNA as an early predictor of evolution in patients with COVID-19 and to evaluate the association between the concentration of mt-DNA and the severity of the disease and the patient's outcome. Methods: A total 102 patients (51 COVID-19 cases and 51 controls) were included in the study. mt-DNA obtained from peripheral blood was quantified by qRT-PCR using the NADH mitochondrial gene. Results: There were differences in peripheral blood mt-DNA between patients with COVID-19 (4.25 ng/µl ± 0.30) and controls (3.3 ng/µl ± 0.16) (p = 0.007). Lower mt-DNA concentrations were observed in patients with severe COVID-19 when compared with mild (p= 0.005) and moderate (p= 0.011) cases of COVID-19. In comparison with patients with severe COVID-19 who survived (3.74 ± 0.26 ng/µl) decreased levels of mt-DNA in patients with severe COVID-19 who died (2.4 ± 0.65 ng/µl) were also observed (p = 0.037). Conclusion: High levels of mt-DNA were associated with COVID-19 and its decrease could be used as a potential biomarker to establish a prognosis of severity and mortality of patients with COVID-19.

Vaccines against components of the renin-angiotensin system.

Even though effective drugs for treating hypertension are available, a great percentage of patients have inadequate control of their blood pressure. Unwanted side effects and inappropriate oral drug adherence are important factors that contribute to the global problem of uncontrolled hypertension. Vaccination could provide a revolutionary therapy with long-lasting effects, increasing patient compliance and therefore better control of high blood pressure. Nowadays, current immunization approaches against hypertension target renin, angiotensin I, angiotensin II, and angiotensin II type 1 receptor, key elements of the renin-angiotensin system. This article reviews the different vaccination attempts with proteins and peptides against the different molecules of the renin-angiotensin system in the last two decades, safety issues, and other novel prospects biomarkers in hypertension, and summarizes the potential of this immunomodulatory approach in clinical practice.

Sobrecarga, equivocación, falta de capacitación: factores contribuyentes en errores de medicación en hospital público chileno / Overload, mistake, lack of training: contributing factors in medication errors in a Chilean public hospital

OBJETIVO: Analizar errores de medicación notificados en 2018 en un hospital público de alta complejidad chileno. METODOLOGÍA: Estudio cuantitativo, retrospectivo, descriptivo y correlacional. Se analizaron las variables sexo y edad del paciente, mes del incidente, tipo de error, servicio, etapa del proceso de medicación y factores contribuyentes. RESULTADOS: Los incidentes fueron más frecuentes en meses estivales, en pacientes mayores de 60 años y de sexo femenino. Los errores más notificados fueron dosis, medicamento y paciente incorrecto. En farmacia se registraron el mayor número de notificaciones. Los errores ocurrieron con mayor frecuencia en las etapas de administración y dispensación. Entre los factores contribuyentes destacan chequeo ineficiente, desgaste o sobrecarga laboral, exceso de confianza, falta de capacitación y confusión del paciente. CONCLUSIÓN: Los periodos vacacionales concentran el mayor número de errores de medicación, asociados a la sobrecarga laboral y falta de capacitación de los profesionales de reemplazo, cuya formación debe ser reforzada

OBJECTIVE: To analyze medication errors reported in 2018 in a highly complex Chilean public hospital. METHODOLOGY: Quantitative, retrospective, descriptive and correlational study. The variables sex and age of the patient, month of the incident, type of error, service, stage of the medication process and contributing factors were analyzed. RESULTS: The incidents were more frequent in summer months, in female patients over 60 years of age. The most commonly reported errors were incorrect dose, medication and patient. The highest number of notifications were registered in the pharmacy. Errors occurred more frequently in the administration and dispensing stages. Among the contributing factors are inefficient check-up, attrition or work overload, overconfidence, lack of training, and patient confusion. CONCLUSION: Vacation periods concentrate the highest number of medication errors, associated with work overload and lack of training for replacement professionals, whose training must be reinforced

Blinatumomab and inotuzumab for B cell precursor acute lymphoblastic leukaemia in children: a retrospective study from the Leukemia Working Group of the Spanish Society of Pediatric Hematology and Oncology (SEHOP).

Blinatumomab and inotuzumab ozogamycin represent promising alternatives to conventional chemotherapy in acute lymphoblastic leukaemia (ALL). We analysed data from 29 children with ALL treated under compassionate use with blinatumomab, inotuzumab or both. The complete remission (CR) rate in a heavily pretreated population with overt relapse was 47·6%. At earlier stages (first/second CR), both antibodies represented a useful tool to reduce minimal residual disease, and/or avoid further toxic chemotherapy until stem cell transplantation. Six patients developed grade 3 reversible non-haematological toxicity. The 12-month overall survival and event-free survival rates were 50·8 ± 26·4% and 38·9 ± 25·3% with blinatumomab, 45·8 ± 26% and 27·5 ± 25% with inotuzumab.