A landscape of liver cirrhosis and transplantation in Mexico: Changing leading causes and transplant as response.

Liver cirrhosis causes include alcoholism, viral infections (hepatitis B virus (HBV) and hepatitis C virus (HCV)), alcohol-associated liver disease (ALD), and metabolic dysfunction associated with steatotic liver disease (MASLD), among others. Cirrhosis frequency has increased in recent years, with a prevalence of 1395 cases per 100,000 and a mortality rate of 18 per 100,000, which corresponded to 1,472,000 deaths during 2017. In Mexico, liver disease is a public health problem since it was associated to 41,890 deaths in 2022, including liver cirrhosis (>25,000) and ALD (14,927). This represents 114 daily deaths due to these causes, and corresponds to the 4th or 5th place of all causes. The global prevalence of MASLD is estimated to affect 25% of the world's population, while in the pediatric population it could be higher. In Mexican population it is more prevalent since estimations were around 41.3% in 2023. Alcohol consumption, a global health issue due to its high prevalence and associated morbidities, is associated to ALD in 32.9%, with a mortality rate of 23.9%, primarily due to liver-related causes. In Mexico, ALD is present in 23% of all cirrhosis cases, already surpassed by hepatitis B cases in 2009. HCV and HBV frequencies changed due to programs implementing screening detection, vaccines and direct-acting antivirals during the last years. A switch of causes has occurred, increasing MASLD and diminishing viral causes. Efficient performed liver transplantation has grown as a response to increasing cirrhosis cases, including recent authorized centers. These efforts are necessary, whereas preventive strategies should be implemented according to leading causes.

Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis.

FAM20C (family with sequence similarity 20, member C) is a serine/threonine-specific protein kinase that is ubiquitously expressed and mainly associated with biomineralization and phosphatemia regulation. It is mostly known due to pathogenic variants causing its deficiency, which results in Raine syndrome (RNS), a sclerosing bone dysplasia with hypophosphatemia. The phenotype is recognized by the skeletal features, which are related to hypophosphorylation of different FAM20C bone-target proteins. However, FAM20C has many targets, including brain proteins and the cerebrospinal fluid phosphoproteome. Individuals with RNS can have developmental delay, intellectual disability, seizures, and structural brain defects, but little is known about FAM20C brain-target-protein dysregulation or about a potential pathogenesis associated with neurologic features. In order to identify the potential FAM20C actions on the brain, an in silico analysis was conducted. Structural and functional defects reported in RNS were described; FAM20C targets and interactors were identified, including their brain expression. Gene ontology of molecular processes, function, and components was completed for these targets, as well as for potential involved signaling pathways and diseases. The BioGRID and Human Protein Atlas databases, the Gorilla tool, and the PANTHER and DisGeNET databases were used. Results show that genes with high expression in the brain are involved in cholesterol and lipoprotein processes, plus axo-dendritic transport and the neuron part. These results could highlight some proteins involved in the neurologic pathogenesis of RNS.

Body mass index in offspring of mothers with diabetes mellitus: follow-up at 2, 4, 6, and 8 years of age / Índice de masa corporal en hijos de madres con diabetes mellitus: seguimiento a los 2, 4, 6 y 8 años de edad

Abstract Background: Offspring of mothers with diabetes mellitus (DM) during pregnancy may be at high risk for developmental alterations. This study aimed to identify the effects of maternal pre- and gestational diabetes on the body mass index of infants and children at two, four, six, and eight years of age. Methods: We studied children of mothers with type 1, type 2, and gestational diabetes and a control group. Maternal and neonatal variables were analyzed for associations with children overweight/obesity. Results: Mothers with DM were older than controls (32 ± 6 vs. 22 ± 6 years, p < 0.001). The frequency of preeclampsia in mothers with DM was 28%. Gestational age and weight at birth were lower in infants from the groups of mothers with DM in comparison with controls (32.8 ± 3.1 vs. 36.4 ± 2.2 weeks, p < 0.001, and 1,637 ± 600 vs. 2,208 ± 518 g, p < 0.001, respectively). At 8 years of age, 47% of the offspring of mothers with DM type 2 had overweight/obesity (odds ratio (OR 8.25) 95% confidence interval (CI) 1.3-51, p = 0.01), while 27% of offspring of mothers with type 1 DM had overweight/obesity, and 10% of offspring of mothers with gestational diabetes presented overweight/obesity. Conclusions: Offspring of pre-gestational DM mothers have a higher risk to develop overweight/obesity, as was observed with follow-up until school age, for which they require continuous vigilance.

Resumen Introducción: Los hijos de madres con diabetes mellitus durante el embarazo pueden tener un alto riesgo de alteraciones del desarrollo. El objetivo de este estudio fue buscar los efectos de la diabetes pregestacional y gestacional en el índice de masa corporal de niños a los 2, 4, 6 y 8 años de edad. Métodos: Se estudiaron los hijos de madres con diabetes tipo 1, 2 y gestacional, así como un grupo control. Se analizaron las variables maternas y neonatales en búsqueda de una asociación con sobrepeso u obesidad en los niños. Resultados: La edad de las madres con diabetes mellitus fue mayor que la del grupo control (32 ± 6 vs. 22 ± 6 años, p < 0.001). La frecuencia de preeclampsia en las madres con diabetes mellitus fue del 28%. La edad gestacional y el peso al nacer fueron menores en los hijos de las madres con diabetes en comparación con los controles (32.8 ± 3.1 vs 36.4 ± 2.2 semanas, p < 0.001, y 1,637 ± 600 vs. 2,208 ± 518 g, p < 0.001, respectivamente). A los 8 años, el 47% de los hijos de madres con diabetes tipo 2 tuvieron sobrepeso u obesidad (RM: 8.25; intervalo de confianza del 95%: 1.3-51; p = 0.01), frente al 27% de los hijos de madres con diabetes tipo 1 y el 10% de los hijos de madres con diabetes gestacional. Conclusiones: Los hijos de madres con diabetes pregestacional presentan un mayor riesgo de desarrollar sobrepeso u obesidad, como se observó en el seguimiento hasta la edad escolar, por lo que requieren una vigilancia continua.

FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes.

FAM20C is a gene coding for a protein kinase that targets S-X-E/pS motifs on different phosphoproteins belonging to diverse tissues. Pathogenic variants of FAM20C are responsible for Raine syndrome (RS), initially described as a lethal and congenital osteosclerotic dysplasia characterized by generalized atherosclerosis with periosteal bone formation, characteristic facial dysmorphisms and intracerebral calcifications. The aim of this review is to give an overview of targets and variants of FAM20C as well as RS aspects. We performed a wide phenotypic review focusing on clinical aspects and differences between all lethal (LRS) and non-lethal (NLRS) reported cases, besides the FAM20C pathogenic variant description for each. As new targets of FAM20C kinase have been identified, we reviewed FAM20C targets and their functions in bone and other tissues, with emphasis on novel targets not previously considered. We found the classic lethal and milder non-lethal phenotypes. The milder phenotype is defined by a large spectrum ranging from osteonecrosis to osteosclerosis with additional congenital defects or intellectual disability in some cases. We discuss our current understanding of FAM20C deficiency, its mechanism in RS through classic FAM20C targets in bone tissue and its potential biological relevance through novel targets in non-bone tissues.

Cochleopalpebral reflex: sensitivity and specificity in the auditory screening of newborns discharged from the neonatal intensive care unit / Reflejo cocleopalpebral: sensibilidad y especificidad en el tamiz auditivo de recién nacidos egresados de una unidad de cuidados intensivos neonatales

Abstract Background: The sensitivity and specificity of the clinical audiological evaluation in newborns are debatable compared to neurophysiological methods of a hearing evaluation. This study aimed to determine the sensitivity and specificity of the cochleopalpebral reflex as a clinical test for hearing screening in newborns. Methods: A case-control study was designed. Newborns discharged from a neonatal intensive care unit (NICU) were included. Brainstem evoked auditory potentials were recorded. A wooden rattle was used to explore the cochleopalpebral reflex. The sensitivity and specificity of the cochleopalpebral reflex were calculated. Continuous data were analyzed with Student's t-test, with statistically significant p-values < 0.05. Results: We selected 450 newborns who were divided into two groups: group A, with bilateral sensory neural hearing loss (n = 150), and group B, with normal hearing (n = 300). Group A showed a significantly lower gestation age at birth (p = 0.005) compared to group B (32.5 ± 2.6 vs. 34.4 ± 3.5 weeks). In group A, the cochleopalpebral reflex's sensitivity was 80% using the wooden rattle. In group B, the specificity was 98%. Conclusions: The NICU discharged newborns' clinical hearing evaluation is not enough to exclude hearing loss. Although it may be the only diagnostic tool for hearing loss in some settings, its limitations should be considered.

Resumen Introducción: La sensibilidad y la especificidad de la evaluación audiológica clínica en recién nacidos son cuestionables en comparación con los métodos neurofisiológicos de evaluación auditiva. El objetivo de este estudio fue determinar la sensibilidad y la especificidad del reflejo cocleopalpebral como prueba clínica de tamizaje auditivo en recién nacidos. Métodos: Se diseñó un estudio de casos y controles en el que se incluyeron recién nacidos egresados de una unidad de cuidados intensivos neonatales (UCIN). Se les efectuaron potenciales auditivos evocados de tallo cerebral. Para la exploración del reflejo cocleopalpebral se utilizó una matraca de madera. Se calcularon la sensibilidad y la especificidad del reflejo cocleopalpebral. Los datos continuos se analizaron con la prueba t de Student y se consideraron estadísticamente significativos los valores de p < 0.05. Resultados: Se seleccionaron 450 recién nacidos y se dividieron en dos grupos: el grupo A (n = 150) con hipoacusia sensorineural y el grupo B (n = 300) con audición normal. El grupo A mostró una diferencia significativa (p = 0.005) en cuanto a la edad de gestación al nacer en comparación con el grupo B (32.5 ± 2.6 vs. 34.4 ± 3.5 semanas). En el grupo A, la sensibilidad del reflejo cocleopalpebral fue del 80% utilizando la matraca de madera. En el grupo B se encontró una especificidad del 98%. Conclusiones: La evaluación del reflejo cocleopalpebral como prueba clínica de tamizaje auditivo en una población de recién nacidos egresados de una UCIN no es suficiente para descartar la pérdida de la audición. Aunque puede ser la única herramienta de diagnóstico para evaluar la pérdida de la audición en algunos casos, es importante considerar sus limitaciones.

Cochleopalpebral reflex: sensitivity and specificity in the auditory screening of newborns discharged from the neonatal intensive care unit.

BACKGROUND: The sensitivity and specificity of the clinical audiological evaluation in newborns are debatable compared to neurophysiological methods of a hearing evaluation. This study aimed to determine the sensitivity and specificity of the cochleopalpebral reflex as a clinical test for hearing screening in newborns. METHODS: A case-control study was designed. Newborns discharged from a neonatal intensive care unit (NICU) were included. Brainstem evoked auditory potentials were recorded. A wooden rattle was used to explore the cochleopalpebral reflex. The sensitivity and specificity of the cochleopalpebral reflex were calculated. Continuous data were analyzed with Student's t-test, with statistically significant p-values < 0.05. RESULTS: We selected 450 newborns who were divided into two groups: group A, with bilateral sensory neural hearing loss (n = 150), and group B, with normal hearing (n = 300). Group A showed a significantly lower gestation age at birth (p = 0.005) compared to group B (32.5 ± 2.6 vs. 34.4 ± 3.5 weeks). In group A, the cochleopalpebral reflex's sensitivity was 80% using the wooden rattle. In group B, the specificity was 98%. CONCLUSIONS: The NICU discharged newborns' clinical hearing evaluation is not enough to exclude hearing loss. Although it may be the only diagnostic tool for hearing loss in some settings, its limitations should be considered.

Relación entre la adquisición del gateo y la marcha independiente en el niño de alto riesgo en seguimiento / Relationship between gait acquisition and independent gait in the high-risk child in follow-up

Resumen Introducción: El gateo representa la primera forma de locomoción autónoma. Se han mencionado las implicaciones de la adquisición del gateo para lograr la marcha independiente y el control motor en el niño, pero son pocos los estudios relacionados con el gateo y sus efectos en el niño de alto riesgo biológico. Por eso se intentó conocer la relación entre la adquisición del gateo y la marcha independiente en una población de niños nacidos de alto riesgo en un programa de seguimiento pediátrico. Material y métodos: Estudio observacional, retrospectivo y descriptivo de una cohorte de niños de alto riesgo que acuden al seguimiento pediátrico, en el cual se revisó el periodo de adquisición del patrón de gateo y la marcha independiente. Resultados: Se integraron cuatro grupos: gateo normal, gateo limítrofe, gateo con retraso y gateo nulo. Se estudió a 558 lactantes; los grupos se integraron con gateo normal, 238 niños; gateo limítrofe, 96 lactantes; retraso en la adquisición del gateo, 207 niños; y gateo nulo, 17 niños. Por género, las niñas gatean mejor, con peso y edad gestacional mayores y predominio en los gateadores. La escala de Bayley señala mejores puntuaciones para los gateadores. En los niños con gateo normal, la marcha independiente se adquirió en el periodo normal a diferencia del grupo con retraso en el gateo en el cual la marcha independiente apareció con retraso. Conclusiones: En este estudio se identificó una relación entre la edad de inicio del gateo con la edad de adquisición de la marcha independiente, con mejor evolución en los niños gateadores.

Abstract Background: Crawling represents the first form of autonomous human locomotion. Much has been said about the implications that an adequate acquisition of crawling has on development in order to achieve independent gait in the short term and the child's motor control in the long term. There are few studies related to crawling and its implications in children who were high biologic risk newborns. Therefore, we wanted to know the relation between crawling acquisition and independent gait in a population of children who were high risk at birth in our Pediatric Follow up clinic. Material and Methods: An observational, retrospective, and analytical study of a cohort of children who were high risk at birth, and attended our pediatric follow-up clinic was done. The period between crawling acquisition and independent gait was reviewed. Results: 4 groups were integrated; normal crawling, borderline crawling, delayed crawling and null crawling. 558 infants were studied; the groups were integrated by: normal crawling 238 children; borderline crawling with 96 infants; delayed crawling with 207 children and null crawling with 17 children. By gender distribution, girls achieved better crawling. Weight and higher gestational age predominated in children with normal crawling. Crawlers had the best scores in the Bayley Scale. In children with normal crawling, independent gait was acquired within the normal period unlike the group with delay in crawling where independent gait was behind. Conclusions: In this study, we found a relation between the age of onset of crawling with the age of acquisition of the independent gait, with better skill in children who crawled.

Results of the Universal Neonatal Hearing Screening in a Tertiary Care Hospital in Mexico city.

INTRODUCTION: Universal Neonatal Hearing Screening (UNHS) includes as its main objective, that all Newborns (NB) receive an audiological evaluation during their first month of life. OBJECTIVE: To determine the prevalence of hearing loss in a population of healthy NB in a tertiary care hospital in Mexico City. MATERIAL AND METHODS: A prospective cross-sectional study was designed. The period was from October 1, 2011 to May 15, 2019. UNHS was performed with a flowchart in three phases using Transient Evoked Otoacoustic Emissions and Brainstem auditory evoked potentials. Data were analyzed using descriptive statistics. RESULTS: 14,000 NB were evaluated, 28,000 ears. Gender was distributed in n = 7038 (50.3%) males and n = 6962 (49.7%) females. The mean age at the time of the first UNHS study was 48.3 ± 22.2 days. Hearing loss was confirmed in n = 31 (0.22%) NB, in 20 (64%) of the cases with hearing loss there were no documented audiological risk factors. CONCLUSIONS: The prevalence of hearing loss was 2.2 per 1000 NB in a tertiary care hospital in Mexico City. Diagnosis and early habilitation of hearing loss in NB constitute quality indicators in health care and guarantee the best prognosis for NB with hearing loss.

Two Novel FAM20C Variants in A Family with Raine Syndrome.

Two siblings from a Mexican family who carried lethal Raine syndrome are presented. A newborn term male (case 1) and his 21 gestational week brother (case 2), with a similar osteosclerotic pattern: generalized osteosclerosis, which is more evident in facial bones and cranial base. Prenatal findings at 21 weeks and histopathological features for case 2 are described. A novel combination of biallelic FAM20C pathogenic variants were detected, a maternal cytosine duplication at position 456 and a paternal deletion of a cytosine in position 474 in exon 1, which change the reading frame with a premature termination at codon 207 and 185 respectively. These changes are in concordance with a negative detection of the protein in liver and kidney as shown in case 2. Necropsy showed absence of pancreatic Langerhans Islets, which are reported here for the first time. Corpus callosum absence is added to the few reported cases of brain defects in Raine syndrome. This report shows two new FAM20C variants not described previously, and negative protein detection in the liver and the kidney. We highlight that lethal Raine syndrome is well defined as early as 21 weeks, including mineralization defects and craniofacial features. Pancreas and brain defects found here in FAM20C deficiency extend the functional spectrum of this protein to previously unknown organs.

Hearing and neurological impairment in children with history of exchange transfusion for neonatal hyperbilirubinemia.

The objective was to determine frequency of sensorineural hearing loss (SNHL), identified by abnormal threshold in evoked potentials, absence of otoacoustic emissions and behavioral responses, auditory neuropathy (AN) (absence of evoked potentials, with preservation of otoacoustic emissions), and neurological comorbidity in infants with hyperbilirubinemia (HB) treated with exchange-transfusion (ET). From a total of 7,219 infants, ET was performed on 336 (4.6%). Inclusion criteria were fulfilled in 102; 234 children did not meet criteria (182 outside of the study period, 34 did not have complete audiological evaluation, and 18 rejected the followup). Thirty-five children (34%) were born at-term and 67 (66%) were preterm. Children had a mean age of 5.5 ± 3.9 years. Main causes of ET were Rh isoimmunization in 48 (47%), ABO incompatibility in 28 (27.5%), and multifactorial causes in 26 (25.5%). Fifteen (15%) children presented with SNHL. Preterm newborns presented more often with SNHL. Indirect bilirubin level was higher in children with SNHL (22.2 versus 18.7 mg/dL, P = 0.02). No cases of AN were documented. An increased risk of neurologic sequelae was observed in children with SNHL. In conclusion, we disclosed a high frequency of SNHL in children with neonatal HB and ET and neurological alterations. No cases of AN were observed.

Hearing loss, auditory neuropathy, and neurological co-morbidity in children with birthweight <750 g.

BACKGROUND AND AIMS: The current literature considers a birthweight <1,500 g as a risk factor for sensorineural hearing loss (SNHL, hearing threshold >25 decibels), auditory neuropathy (AN), and several neurological sequelae. The aim of the study was to determine the frequency and risk factors associated with SNHL, AN, and neurological morbidity in a group of children with birthweights of <750 g treated at a neonatal care unit and recruited into a long-term follow-up program. METHODS: A case-control study was carried out. Inclusion criteria were birthweight <750 g and born between the years 2000 and 2010. We performed brainstem auditory-evoked potentials (BAEP), evoked otoacoustic emissions (EOAE) and free-field audiometry (FFA) in this population. Neonatal variables and procedures were compared between children with SNHL and children with normal bilateral hearing (NBH). RESULTS: A total of 93 children with a mean age of 4 years were included in the follow-up. Six children (6.4%) had SNHL and 87 had NBH. We were unable to identify AN in the sample. Mean weight for this sample was 673 ± 68 g and gestational age 27.5 ± 2 weeks. Variables reflecting differences between groups included days under mechanical ventilation, furosemide treatment, and bronchopulmonary dysplasia. In the SNHL group, three patients had periventricular leukomalacia, two had hydrocephalus, and one patient had cerebral palsy. CONCLUSIONS: Frequency of SNHL in children with birthweights <750 g was higher than in other premature infants and was related with mechanical ventilation, furosemide application, and bronchopulmonary dysplasia. Association with other neurological morbidities was frequent. Early diagnosis and intervention are required.