Biomarkers of Glycocalyx Injury and Endothelial Activation are Associated with Clinical Outcomes in Patients with Sepsis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Sepsis is one of the main causes of morbidity and mortality worldwide. Microcirculatory impairment, especially damage to the endothelium and glycocalyx, is often not assessed. The objective of this systematic review and meta-analysis was to summarize the available evidence of the risk of unsatisfactory outcomes in patients with sepsis and elevated glycocalyx injury and endothelial activation biomarkers. DESIGN: A systematic search was carried out on PubMed/MEDLINE, Embase, Cochrane and Google Scholar up to December 31, 2021, including studies in adults and children with sepsis which measured glycocalyx injury and endothelial activation biomarkers within 48 hours of hospital admission. The primary outcome was the risk of mortality from all causes and the secondary outcomes were the risk of developing respiratory failure (RF) and multiple organ dysfunction syndrome (MODS) in patients with elevations of these biomarkers. MEASUREMENTS AND MAIN RESULTS: A total of 17 studies (3,529 patients) were included: 11 evaluated syndecan-1 (n=2,397) and 6 endocan (n=1,132). Syndecan-1 was higher in the group of patients who died than in those who survived [255 ng/mL (IQR: 139-305) vs. 83 ng/mL (IQR:40-111); p=0.014]. Patients with elevated syndecan-1 had a greater risk of death (OR 2.32; 95% CI 1.89, 3.10: p<0.001), MODS (OR 3.3; 95% CI 1.51, 7.25: p=0.003;), or RF (OR 7.53; 95% CI 1.86-30.45: p=0.005). Endocan was higher in patients who died [3.1 ng/mL (IQR 2.3, 3.7) vs. 1.62 ng/mL (IQR 1.2, 5.7); OR 9.53; 95% CI 3.34, 27.3; p<0.001], who had MODS (OR 8.33; 95% CI 2.07, 33.58; p=0.003) and who had RF (OR 9.66; 95% CI 2.26, 43.95; p=0.002). CONCLUSION: Patients with sepsis and abnormal glycocalyx injury and endothelial activation biomarkers have a greater risk of developing respiratory failure, multiple organ failure, and death. Microcirculatory impairment should be routinely evaluated in patients with sepsis, using biomarkers to stratify risk groups.

Endothelial and Glycocalyx Biomarkers in Children With Sepsis After One Bolus of Unbalanced or Balanced Crystalloids.

OBJECTIVES: To assess the disruption of endothelial glycocalyx integrity in children with sepsis receiving fluid resuscitation with either balanced or unbalanced crystalloids. The primary outcome was endothelial glycocalyx disruption (using perfused boundary region >2 µm on sublingual video microscopy and syndecan-1 greater than 80 mg/dL) according to the type of crystalloid. The secondary outcomes were increased vascular permeability (using angiopoietin-2 level), apoptosis (using annexin A5 level), and associated clinical changes. DESIGN: A single-center prospective cohort study from January to December 2021. SETTING: Twelve medical-surgical PICU beds at a university hospital. PATIENTS: Children with sepsis/septic shock before and after receiving fluid resuscitation with crystalloids for hemodynamic instability. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 106 patients (3.9 yr [interquartile range, 0.60-13.10 yr]); 58 of 106 (55%) received boluses of unbalanced crystalloid. This group had greater odds of endothelial glycocalyx degradation (84.5% vs 60.4%; adjusted odds ratio, 3.78; 95% CI, 1.49-9.58; p < 0.01) 6 hours after fluid administration, which correlated with increased angiopoietin-2 (rho = 0.4; p < 0.05) and elevated annexin A5 ( p = 0.04). This group also had greater odds of metabolic acidosis associated with elevated syndecan-1 (odds ratio [OR], 4.88; 95% CI, 1.23-28.08) and acute kidney injury (OR, 1.7; 95% CI, 1.12-3.18) associated with endothelial glycocalyx damage. The perfused boundary region returned to baseline 24 hours after receiving the crystalloid boluses. CONCLUSIONS: Children with sepsis, particularly those who receive unbalanced crystalloid solutions during resuscitation, show loss and worsening of endothelial glycocalyx. The abnormality peaks at around 6 hours after fluid administration and is associated with greater odds of metabolic acidosis and acute kidney injury.

Paediatric cardiomyopathies: echocardiographic diagnosis, clinical profile, and demographic characteristics: the experience of a tertiary referral centre for Latin American paediatric cardiology.

BACKGROUND: Although multiple studies have been conducted in the adult population, there is a vast knowledge gap regarding the epidemiologic characteristics of cardiomyopathies in the paediatric population. This issue is even more crucial when the precarious situation of medical research in Latin America is considered. Given the potential impact that these disorders could have on Latin American health systems, a comprehensive epidemiologic study regarding the clinical profile and sociodemographic characteristics of these patients will influence the way we approach paediatric cardiomyopathies. METHODS: An observational retrospective study was conducted at a tertiary referral centre for Colombian and Latin American paediatric cardiology. We analysed all cases of primary cardiomyopathies in children younger than 18 years of age who presented at our institution between 2010 and 2016. Cases of cardiomyopathies were classified according to World Health Organization guidelines. RESULTS: From a total of 29,533 children who attended our institution during the study period, 89 new cases of primary cardiomyopathies were identified. The median age at diagnosis was 11 years (interquartile range 4-9). Dilated cardiomyopathy accounted for 57.3% (n = 51) of cases; hypertrophic cardiomyopathy, 12.3% (n = 11); restrictive cardiomyopathy, 8.9% (n = 8); non-compacted cardiomyopathy, 7.8% (n = 7); arrhythmogenic ventricular cardiomyopathy, 6.7% (n = 6); and unspecified cardiomyopathy, 6.7% (n = 6). Heart failure was observed in 53.93% of the patients. The overall mortality was 12.36% (n = 11), which included two of eight patients who underwent cardiac transplantation.

Case Report: Endothelial Glycocalyx Damage in Critically ill Patients With SARS-CoV-2-Related Multisystem Inflammatory Syndrome (MIS-C).

Endothelial insult and damage is one of the reported consequences of SARS-CoV-2 infection. It has been associated with severe inflammation, thrombotic phenomena and profound hypoxemia in critically ill patients. Endothelial activation leads to a loss of the endothelium's antithrombotic properties which, under normal conditions, are maintained by the endothelial glycocalyx, a carbohydrate-rich layer that covers the luminal surface of endothelial cells. In children, one of the serious forms of SARS-CoV-2 virus disease (COVID-19) is multisystem inflammatory syndrome (MIS-C). This new disease is characterized by a large inflammatory response and frequent cardiovascular, cutaneous and gastrointestinal disorders. We describe the first two cases of critically ill children with MIS-C who evidenced a large inflammatory response associated with elevated plasma and imaging biomarkers of endothelial activation and endothelial glycocalyx degradation. This microcirculation involvement in MIS-C could, at least partially, explain some of the clinical manifestations and laboratory and imaging alterations found in these patients. These findings contribute to a better understanding of this disease and suggest that medications to modulate the inflammatory response and protect or restore the endothelial glycocalyx should be considered in future studies.

Fármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafío! / Pharmaco-therapy of sepsis: a frustrating process and a great challenge!

La sepsis ocupa el primer lugar entre las causas de mortalidad en las unidades de cuidado intensivo, razón por la cual su comprensión ha sido objetivo de múltiples estudios. Esta patología representa un reto para el médico ya que sus criterios diagnósticos nunca han podido llegar a un consenso, dificultando así su enfoque terapéutico. El panorama de su fisiopatología tampoco ha sido diferente, hasta hace pocos años logró comprenderse que la sepsis se trata de una estrecha relación entre el agente infeccioso y la participación del sistema inmune, particular en cada hospedero, lo cual impulsó el uso de diferentes fármacos dirigidos a contrarrestar esta respuesta, obteniendo resultados algunas veces contradictorios. Todo lo anterior confluye en un gran rompecabezas de conocimientos que poco a poco ha ido descifrándose, en espera de futuras investigaciones que continúen con más avances en la fármaco-terapéutica de la sepsis. [Torres-Dueñas D, Espinosa AE, Alarcón LC, Niño ME, Cárdenas ME. Fármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafío! MedUNAB 2010; 13:13-16].

Sepsis ranks first among causes of death in intensive care units, which is why their understanding has been the subject of several studies. This condition is a medical challenge because its diagnostic criteria have never been able to reach a consensus, thus hidering their therapeutic approach. The overview of its pathophysiology has not been different, until recent years was understood that sepsis is a close relationship between the infectious agent and inmune system involvement, particularly in each host, which prompted the use of different drugs that target to counteract this response, sometimes contradictory results obtained. All this comes together in one big puzzle of knowledge that has gradually been deciphered, awaiting further research to continue with furter progress in the drug-treatment of sepsis. [Torres-Dueñas D, Espinosa Peña AE, Alarcón LC, Niño ME, Cárdenas ME. Drug-treatment of sepsis: a frustrating process and a great challenge! MedUNAB 2010; 13:13-36].

Maltrato infantil y sus consecuencias a largo plazo / Child abuse and long-term consequences

La violencia intrafamiliar constituye una de las formas más frecuentes de violencia encontradas tanto a nivel nacional como internacional y dentro de estas el maltrato infantil presenta cifras alarmantes, y es el objeto de nuestra revisión. Los efectos de este problema repercuten notablemente en aquellos que sobreviven, ya que las consecuencias a largo plazo del maltrato infantil son más perjudiciales para las víctimas y sus familias, y más costoso para la sociedad, que las lesiones agudas inmediatas que puedan producir. Las consecuencias a largo plazo para estos niños varían desde efectos nocivos en su desarrollo hasta trastornos psicológicos, psiquiátricos y orgánicos. Es importante resaltar que aún con muy buenas intervenciones no todas tienen el éxito esperado si no se hacen de manera correcta. Es indispensable contar con estrategias de prevención que incluyan personal bien entrenado, una supervisión adecuada, los recursos necesarios, y un tiempo mínimo óptimo para enfrentar el problema y obtener los mejores resultados. [Alarcón LC, Araujo AP, Godoy AP, Vera ME. Maltrato infantil y sus consecuencias a largo plazo. MedUNAB 2010; 13:103-115]

Domestic violence is one of the most common forms of violence found both domestically and internationally. Within these, child abuse has alarming figures. This is the subject of this review. The effects of this problem significantly impact on those who survive; their long-term consequences are most severe and expensive for victimized child and his/her family than associated primary physical injuries. The long-term consequences for these children range from adverse effects on its psycholigical development to psychological, psychiatric organic disoders. It is important to note that good speeches are not enough to achieve success if any intervention are not done correctly. All prevention strategies include well-trained staff, appropriate supervision, resources, and a optimal time for addressing this problem to get the best results. [Alarcón LC, Araujo AP, Godoy AP, Vera ME. Child abuse and its long-term consequences. MedUNAB 2010, 13:103-115].