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Aim Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is an autosomal recessive inherited neurodegenerative lysosomal storage disorder caused by deficient tripeptidyl peptidase 1 (TPP1) enzyme, leading to progressive deterioration of neurological functions commonly occurring in children aged 2–4 years and culminating in early death. Atypical cases associated with earlier or later symptom onset, or even protracted course, have already been reported. Such variable manifestations may constitute an additional challenge to early diagnosis and initiation of appropriate treatment. The present work aimed to analyse clinical data from a cohort of Latin American CLN2 patients with atypical phenotypes. Methods Experts in inborn errors of metabolism from Latin America selected patients from their centres who were deemed by the clinicians to have atypical forms of CLN2, according to the current literature on this topic and their practical experience. Clinical and genetic data from the medical records were retrospectively revised. All cases were presented and analysed by these experts at an Advisory Board Meeting in São Paulo, Brazil, in October 2018. Results Seizures, language abnormalities and behavioural disorders were found as the first manifestations, appearing at the median age of 6 years, an older age than classically described for the late infantile form. Three novel mutations were also identified. Conclusion Our findings reinforce the inclusion of CLN2 in the differential diagnosis of children presenting with seizures, behavioural disorders and language abnormalities. Early diagnosis will allow early initiation of specific therapy.

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resumen introducción: el objetivo de esta revisión fue determinar el riesgo de hemorragia postoperatoria en pacientes con tratamiento anticoagulante oral (TACO) sometidos a cirugía oral que no suspenden su tratamiento comparado con quienes lo modifican o suspenden. materiales y métodos: se realizó una búsqueda en CENTRAL, Medline y EMBASE, junto con una revisión manual de revistas especializadas y resúmenes de la IADR. Dos revisores realizaron la selección de estudios, evaluación de riesgo de sesgo y extracción de datos de forma independiente. Se seleccionaron los ensayos clínicos aleatorizados que miden la aparición de hemorragias en pacientes sometidos a procedimientos quirúrgicos orales con TACO en comparación con un grupo que interrumpió o modificó su terapia. resultados: Solo 5 estudios cumplieron los criterios de inclusión (549 pacientes). El metanálisis mostró que el mantenimiento de la TACO no aumenta el riesgo de hemorragia postoperatoria (riesgo relativo: 1,41 [0,93-2,16], IC del 95% p = 0,11) en comparación con la interrupción del tratamiento. conclusión: Aunque se encontró una mayor cantidad de hemorragia postoperatoria en pacientes con TACO comparado con quienes lo interrumpieron o modificaron, esta diferencia no fue estadística ni clínicamente significativa. Por lo tanto, TACO no debe suspenderse en pacientes sometidos a cirugía oral. Palabras clave Cirugía oral, Hemorragia, Anticoagulantes orales. rev. clin. Periodoncia implantol. rehabil. Oral vol. 11(2); 121-127, 2018. abstract introduction: This systematic review aims to determine the postoperative bleeding risk in patients on oral anticoagulant therapy (OAT) undergoing oral surgical procedures when continuing with the treatment, compared with those modifying or discontinuing the treatment. materials and methods: A search was performed using CENTRAL,Medline and EMBASE, in conjunction with a manual review of indexes of specialized journals and abstracts of the IADR. Study selection, assessments of risk of bias and data extraction were performed independently by 2 reviewers. Randomized clinical trials measuring the occurrence of bleeding in patients on OAT undergoing oral surgical procedures compared with a group discontinuing or modifying their therapy were selected. results: A total of 5 studies were included based on inclusion criteria (549 patients). The metaanalysis showed that the maintenance of OAT does not increasethe risk of postoperative bleeding (relative risk [RR] 1.41 [0.93-2.16]; 95% CI p= 0,11)compared with the discontinuation of therapy. conclusion: Although a larger quantityof oral postoperative bleeding episodes were found in patients continuing with OATcompared with patients discontinuing or modifying their therapy, this difference was neither statistically nor clinically significant. Therefore, OAT should not be discontinued in patients undergoing oral surgery.

<b><i>Introduction:</i></b> Morquio syndrome or mucopolysaccharidosis type IV-A (MPS IV-A) is an autosomal recessive disease caused by biallelic variants in the <i>GALNS</i> gene, encoding the lysosomal enzyme GalN6S, responsible for glycosaminoglycan keratan sulfate and chondroitin-6-sulfate degradation. Studies have shown that the degree of evolutionary and chemical divergence of missense variants in GalN6S when compared to ancestral amino acids is associated with the severity of the syndrome, suggesting a genotype-phenotype correlation. There is little information on Latin American patients with MPS IV-A that replicate these findings. This study aimed to characterize the phenotype and genotype from patients with MPS IV-A, who are under Enzyme Replacement Therapy at the Children’s Neuropsychiatry Service of the Hospital Clínico San Borja Arriarán, Santiago, Chile, and to determine if there is any association between genotype and phenotype with those findings. <b><i>Methods:</i></b> Information was collected from medical charts, all patients went through a GalN6S enzymatic activity measurement in leukocytes from peripheral blood, and the <i>GALNS</i> gene was sequenced for all cases. <b><i>Results:</i></b> 12 patients with MPS IV-A were recruited, all patients presented multisystem involvement, mostly skeletal, and 75% of cases underwent surgical interventions, and cervical arthrodesis was the most frequent procedure. In regards of the genotype, the two most frequent variants were c.319+2T&gt;C (<i>n</i> = 10, 41.66%) and p.(Arg386Cys) (<i>n</i> = 8, 33.33%), the first one was previously described in 2018 in a patient from Chile [Bochernitsan et al., 2018]. <b><i>Conclusion:</i></b> This is the first time that a genotype-phenotype correlation has been studied by analyzing the variants effect on the molecular structure of human GalN6S and the evolutionary conservation degree of affected residues in a cohort of patients in Chile. Albeit our work could not find statistically significant associations, we may infer that the evolutionary conservations of affected amino acids and the effect of variants on enzyme structure may play a main role. Further analyzes should consider a meta-analysis of published cases with genotype data and larger samples and include other variables that could provide more information. Finally, our data strongly suggest that variant c.319+2T&gt;C could have a founder effect in Chilean patients with MPS IV-A.

Heart failure with preserved ejection fraction (HFpEF) is a growing public health problem in nearly 50% of patients with heart failure. Therefore, research on new strategies for its diagnosis and management has become imperative in recent years. Few drugs have successfully improved clinical outcomes in this population. Therefore, numerous attempts are being made to find new pharmacological interventions that target the main mechanisms responsible for this disease. In recent years, pathological mechanisms such as cardiac fibrosis and inflammation, alterations in calcium handling, NO pathway disturbance, and neurohumoral or mechanic impairment have been evaluated as new pharmacological targets showing promising results in preliminary studies. This review aims to analyze the new strategies and mechanical devices, along with their initial results in pre-clinical and different phases of ongoing clinical trials for HFpEF patients. Understanding new mechanisms to generate interventions will allow us to create methods to prevent the adverse outcomes of this silent pandemic.

Introduction: Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), is a neurodegenerative autosomal recessive disease caused by TPP1 gene variants, with a spectrum of classic and atypical phenotypes. The aim of treatment is to slow functional decline as early as possible, improving quality of life and survival. This study describes the clinical characteristics as well as response to treatment with cerliponase alfa. Materials and Methods: A retrospective study was conducted in five Latin-American countries, based on clinical records from patients with CLN2. Clinical follow-up and treatment variables are described. A descriptive and bivariate statistical analysis was performed. Results: A total of 36 patients are reported with a mean age of symptom onset and time to first specialized consultation of 4.7±2.3 and 6±3.1 years, respectively. Seizures were the predominant symptom (80.6%). In a subgroup analysis, most patients with the classic phenotype exhibited regression in language (90%), while the patients with the atypical phenotype had seizures as the predominant symptom (87%). The mean age of symptom onset and time to first specialized consultation was 3.5±2.0 and 4.9±3.2 years, respectively, in patients with the classic phenotype and 6.2±1.8 and 7.5±2.4 in patients with the atypical phenotype. The mean time interval between onset of symptoms and treatment initiation was 3.8 years in patients with classic phenotype and 7.4 in patients with atypical phenotype. All patients were treated with cerliponase alfa, maintaining overall functional stability as compared to pretreatment values. Discussion and conclusion: This study reports at this time the largest number of patients with CLN2 in treatment with cerliponase alfa in the world. Data show a higher frequency of patients with atypical phenotype and a high allelic proportion of intron variants in our region. There was evidence of long intervals until first specialized consultation, diagnosis, and enzyme replacement therapy. Follow-up after the initiation of cerliponase alfa showed slower-to-no-progression of the disease, associated with adequate clinical outcomes and stable functional scores. These improvements were consistent in both clinical phenotypes.