Autophagy in inflammation, infection, neurodegeneration and cancer

In its classical form, autophagy is an essential, homeostatic process by which cytoplasmic components are degraded in a double-membrane-bound autophagosome in response to starvation. Paradoxically, although autophagy is primarily a protective process for the cell, it can also play a role in cell death. The roles of autophagy bridge both the innate and adaptive immune systems and autophagic dysfunction is associated with inflammation, infection, neurodegeneration and cancer. In this review, we discuss the contribution of autophagy to inflammatory, infectious and neurodegenerative diseases, as well as cancer.Fil: Arroyo, Daniela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Gaviglio, Emilia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Peralta Ramos, Javier María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Bussi, Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Rodriguez Galan, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Iribarren, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin

Increased expression of autophagy protein LC3 in two patients with progressing chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in the western hemisphere. It is characterized by a clonal proliferation of a population of CD5+ B lymphocytes that accumulate in the secondary lymphoid tissues, bone marrow, and blood. Some CLL patients remain free of symptoms for decades, whereas others rapidly become symptomatic or develop high-risk disease. Studying autophagy, which may modulate key protein expression and cell survival, may be important to the search for novel prognostic factors and molecules. Here, we applied flow cytometry technology to simultaneously detect autophagy protein LC3B with classical phenotypical markers used for the identification of tumoral CLL B cell clones. We found that two patients with progressing CLL showed increased expression of the autophagy protein LC3B, in addition to positive expression of CD38 and ZAP70 and unmutated status of IGHV. Our data suggest that activation of autophagy flux may correlate with CLL progression even before Ibrutinib treatment.Fil: Arroyo, Daniela Soledad. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodríguez, Cecilia Inés. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; ArgentinaFil: Bussi, Claudio. The Francis Crick Institute; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Manzone Rodriguez, Clarisa. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Sastre, Darío. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Heller, Viviana. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Stanganelli, Carmen Graciela. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Iribarren, Pablo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Uso de Dieta Cetogénica en Epilepsia Resistente a Farmacoterapia

La epilepsia es una enfermedad multifactorial ampliamente estudiada. Existen subgrupos de pacientes en quienes la clásica terapia farmacológica anticrisis no proporciona un adecuado control, aproximadamente un 30% de los portadores de la enfermedad. Algunos de estos pacientes se podrían beneficiar de una intervención quirúrgica como tratamiento curativo para su enfermedad. Cuando se encuentra con una persona resistente al control con anticrisis, se puede iniciar la dieta cetogénica como alternativa terapéutica paliativa. Esta opción consiste en una alimentación rica en grasas y en menor proporción proteínas y carbohidratos. Existen diferentes subtipos de dietas cetogénicas, con diferente nivel de restrictividad y se puede seleccionar una u otra dependiendo de los objetivos plantados y del trinomio paciente-sistema de salud-personal médico. Hasta un 50% de los sujetos afectados han experimentado una reducción significativa en las crisis. La mayoría de los efectos adversos se presentan a corto plazo y son previsibles por lo cual estos no tienen un peso significativo en abandono al tratamiento, respecto a los efectos a largo plazo, se necesita una ampliación en los estudios al respecto ya que no hay una posición completamente establecida al respecto

Epilepsia de ausencias en la niñez y adolescencia, diagnóstico, tratamiento y pronóstico

Typical absence seizures are part of a group of idiopathic generalized epileptic syndromes, including childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE). Typical absences are the main clinical feature of these syndromes whose characteristics include transient loss of consciousness of sudden onset and termination without loss of muscle tone with a variable degree of automatisms whose frequency and severity may vary according to each case. Pathophysiologically, crises are associated with overactivation of the thalamic-cortical circuit. CAE is usually associated with a good prognosis with a high percentage of remission, while JAE is usually a disorder that persists for life. Pharmacological treatment is based on the use of anticonvulsants such as ethosuximide, valproic acid and lamotrigine. Absences can also manifest atypically, which usually occur in Lennox Gastaut Syndrome, Epilepsy with myoclonic-atonic seizures, epileptic encephalopathy with spike and continuous wave during sleep (CSWS), among others. Generally, this type of crisis associates an unfavorable prognosis in which therapeutic goals are often focused on achieving a reduction in the incidence of crises and not complete remission.Las crisis de ausencias típicas forman parte de una gama de síndromes epilépticos generalizados idiopáticos dentro de los cuales se incluye la epilepsia de ausencia infantil (EAI) y la epilepsia de ausencia juvenil (EAJ). Las ausencias típicas son el signo pivote de dichos síndromes cuyas características incluyen la pérdida transitoria de consciencia, de inicio y terminación súbita, sin pérdida de tono muscular con grado variable de automatismos cuya frecuencia y severidad puede variar según cada caso. Fisiopatológicamente las crisis se asocian a una sobreactivación del circuito tálamo cortical. La EAI suele asociar buen pronóstico con alto porcentaje de remisión mientras que la EAJ suele ser un trastorno que persiste de por vida. El tratamiento se fundamenta en el uso de fármacos anticrisis tal como la etosuximida, ácido valproico y lamotrigina. Las ausencias también se pueden manifestar de manera atípica las cuales suelen presentarse en el Síndrome de Lennox Gastaut, epilepsia con crisis mioclónicas-atónicas, encefalopatía epiléptica con punta y onda continua durante el sueño (CSWS), entre otras. Generalmente dicho tipo de crisis asocia un pronóstico poco favorable en donde con frecuencia la meta terapéutica se enfoca en lograr una reducción en la incidencia de las crisis y no la remisión completa

Programa vaso de leche en el asentamiento humano Torres de San Borja, municipalidad de moche, Trujillo, Perú

RESUMEN En el Perú, actualmente existen muchas organizaciones sin fines de lucro que buscan apoyar a los sectores menos favorecidos con el fin de cambiar y reducir esa realidad tan adversa que tienen estas comunidades, estas organizaciones necesitan ser aprobadas por los municipios para trabajar junto con estos órganos del estado, para poder así financiar sus actividades y ser administrados de la manera más eficaz. Sin embargo muchas veces se presentan casos de insatisfacción por parte de las comunidades que reciben este apoyo, lo que genera bastante incertidumbre en el sector, cómo es el funcionamiento de estas Organizaciones No Gubernamentales (ONG). Anteriormente el objetivo del informe era poder plasmar las acciones realizadas en la gestión de un proyecto de Responsabilidad Social dentro del A.A.H.H Las Torres de San Borja, en Moche-La Libertad. No obstante, la investigación tomó otro camino al percibir que uno de los problemas con la comunidad era la constante queja e insatisfacción con uno de los programas que brinda apoyo a este Asentamiento Humano; como es el “ Programa Vaso de Leche” a partir de esto, se decidió investigar el porqué de toda esta problemática existente

Dynamics of soluble immune mediators in COVID-19 patients from an Argentinean cohort with moderate and severe symptoms

The cytokine storm, a form of systemic inflammatory response syndrome, is one of the most dreadful complications that can occur during COVID-19. The severity of infection is associated at different levels of these immune mediators and many molecules are considered marker of COVID mortality. Because of its central role in the pathogenesis of SARS-CoV-2 infection, the cytokine storm have become a therapeutic target in the treatment of COVID-19 patients.In this work, we aimed at studying the concentration of different pro- and anti-inflammatory cytokines in a cohort of COVID-19 patients from Córdoba (Argentine). The immunological reaction triggered by infection with SARS-CoV-2 mobilizes numerous cytokines, mainly of proinflammatory character. Changes in their levels are associated with the presence of the disease and with a more severe prognosis. Although our data have similarities with those in international reports, the complete profiling of different parameters (cytokine/chemokines, risk factors, epidemiological and clinical characteristics) in the local cases add value by identifying particularities that may be relevant for the management and prognosis during SARS-CoV2 infection in Argentine.Fil: Almada, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Angiolin, Sofia C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Dho, Nicolás. Universidad Nacional de Córdoba; ArgentinaFil: Dutto, Jeremias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Gazzon, Yamila. Universidad Nacional de Córdoba; ArgentinaFil: Manzone, Clarisa. Universidad Nacional de Córdoba; ArgentinaFil: Marin, Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Ponce, Nicolás Eric. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Iribarren, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Cerban, Fabio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Morón, Gabriel. Universidad Nacional de Córdoba; ArgentinaFil: Amezcua Vesely, Carolina. Universidad Nacional de Córdoba; ArgentinaFil: Ana, Yamile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Cervi, Laura Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Chiapello, Laura Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Fozzatt, Laura. Universidad Nacional de Córdoba; ArgentinaFil: Icely, Paula Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Maccioni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Mena, Cristian Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Motrán, Cristina. Universidad Nacional de Córdoba; ArgentinaFil: Rodríguez Galán, Cecilia. Universidad Nacional de Córdoba; ArgentinaFil: Stempin, Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Viano, María Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Bertone, M.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Abiega, Claudio Daniel. Hospital Privado Universitario de Córdoba; ArgentinaFil: Escudero, Daiana Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Privado Universitario de Córdoba; ArgentinaFil: Kahn, Adrian Mario. Hospital Privado Universitario de Córdoba; ArgentinaFil: Caeiro, Juan Pablo. Hospital Privado Universitario de Córdoba; ArgentinaFil: Arroyo, Daniela Soledad. Hospital Privado Universitario de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maletto, Belkys Angélica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Gruppi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Sotomayor, Claudia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaLXVI reunión anual de la sociedad argentina de investigación clínica (saic), LXIX reunión anual de la sociedad argentina de inmunología (sai), LIII reunión anual de la asociación argentina de farmacología experimental (aafe), XI reunión anual de la asociación argentina de nanomedicinas (nanomed-ar)Buenos AiresArgentinaSociedad Argentina de Inmunologí

PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (ADNo ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. Methods: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. Results: Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. Conclusions: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis. Lay summary: Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF. A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded. Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC). Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. ClinicalTrials.gov number: NCT03056612. Lay summary: Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life