Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology.

Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments.

Prevalence of Glucose-6-Phosphate Dehydrogenase Deficiency in Newborns in Northeast Mexico.

OBJECTIVE: Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is the most common enzymatic disease worldwide and the prevalence is not well established because of the lack of screening. This study aimed to estimate the prevalence of G6PDd in a Hispanic population from Northeast Mexico. STUDY DESIGN: In this retrospective study, a database was used to analyze the G6PDd in neonates included in the expanded newborn metabolic screening of inherited metabolic disorders during a period of 4 years through the GSP Neonatal G6 kit (PerkinElmer). RESULTS: Among 96,152 (48,462 male) neonates screened for G6PD enzyme activity, a total of 566 (0.58%) cases were deficient for G6PD. Of those 566 patients, 469 (82.8%) attended the second test and the other 97 (17.2%) patients were lost. Of those 469 who did attend, 384 (81.9%) neonates were deficient in the second test and 85 (18.1%) were normal. With the data collected, 384 neonates were confirmed with G6PDd, 348 (88.6%) were male and 36 (11.4%) patients were female. The calculated prevalence for this population was 0.72 cases per 100 male newborns. CONCLUSION: The prevalence of G6PDd in the Northeastern Mexican population is high. Since migration is increasing in the United States, pediatricians should be aware of the need to search for G6PDd in newborns and the wide clinical manifestations they can present. KEY POINTS: · The calculated prevalence of glucose-6-phosphate dehydrogenase deficiency in Northeast Mexico is 3.99 cases per 1,000 newborns.. · Glucose-6-phosphate dehydrogenase deficiency screenings should be included in all newborn metabolic screenings.. · Glucose-6-phosphate dehydrogenase deficiency is a common erythroenzymopathy that must be addressed as a public health concern. To anticipate clinical complications, target population monitoring is required..

Serum biomarkers and Doppler pulsatile index increases likelihood ratio for prediction of preeclampsia in the second trimester of pregnancy.

This study aims to compare the accuracy of risk prediction for preeclampsia (PE) of three calculators during the second trimester of gestation: American College of Obstetricians and Gynaecologists (ACOG), National Institute for Health and Care Excellence (NICE), and Foetal Medicine Foundation (FMF). Complete medical history, mean uterine artery Doppler pulsatile index were performed (PI) and venous blood samples for placental growth factor (PIGF), soluble fms-like tyrosine kinase-1 (sFLT-1), and Endoglin measurements were obtained from 214 women between 20-24 weeks gestation. PE frequency was 8.4% (18/214). Sensitivity and specificity were 94.4% and 37.2% and 44.4% and 74.5% for ACOG and NICE respectively. Sensitivity for FMF was 66.7% and 44.4% at <32 weeks and <36 weeks respectively and specificity was 97.2% and 98.1%. The highest positive likelihood ratio, 22, was obtained for FMF as compared to 1.49 and 1.76 for ACOG and NICE. These findings suggest that the addition of US and serum biomarkers in the FMF calculator increases accuracy for prediction of PE.Impact StatementWhat is already known on this subject? Several strategies have been implemented to evaluate risk for PE. The ACOG and NICE calculators, based on medical and anthropomorphic data, and the FMF calculator, which includes ultrasound and serum biomarkers, have been used for the prediction of PE risk in the first trimester of gestation.What do the results of this study add? Although the identification of markers for the prediction of PE during the first trimester of pregnancy has been of major clinical interest, in many countries women attend their first prenatal visit up until the second trimester of pregnancy. This is the first multicentre study in Latin American population to compare the three risk prediction systems including serum biomarkers during the second trimester of pregnancy.What are the implications of these findings for clinical practice and/or further research? We propose the FMF calculator (including PI and serum biomarkers) as a useful tool for PE risk detection during the second trimester of pregnancy. However, as this study is limited by its small sample size, larger multicenter studies are needed to confirm our findings and assert the usefulness of the FMF calculator.

The molecular adsorbent recirculating system as a liver support system: summary of Mexican experience.

AIM: The aim of this study was to assess the effects of the molecular absorbent recirculating system (MARS) on patients with acute liver failure (ALF) and liver failure with cirrhosis (AoCLF) as well as in cholestatic patients with intractable pruritus in a Mexican population. MATERIAL AND METHODS: From August 2003 to December 2011, MARS was used in 38 patients with ALF, 15 patients with AoCLF, and 17 cholestatic patients with intractable pruritus. The patients were examined using a standard liver function test and for vital signs, presence of ascites and encephalopathy before and after each treatment. The therapeutic response, patient status, follow-up status, and need for liver transplantation were determined. RESULTS: Seventy-nine MARS procedures were performed. MARS was used for ALF in 54.3% of patients, AoCLF in 24.2%, and cholestatic disease in 21.5%. There were significant improvements in serum bilirubin (p = 0.000), aspartate aminotransferase (p = 0.000), alanine aminotransferase (p = 0.030), gamma-glytamyl transpeptidase (p = 0.044), alkaline phosphatase (p = 0.006), and encephalopathy grade (p = 0.000). Thirty-eight ALF patients were listed for emergency liver transplantation and treated with MARS; 20 of these patients died on a waiting list, 18 survived. only four underwent liver transplantation and 14 (37%) recovered without transplantation after the MARS procedure. CONCLUSION: MARS is a safe and effective procedure, especially for ALF patients. Our results suggest that MARS therapy can contribute to native liver recovery in ALF patients.

COVID-19 associated transverse myelitis: case report.

BACKGROUND: Transverse myelitis (TM) is a demyelinating inflammatory disease that presents with motor, sensory, and autonomic dysfunction, which may be acute or subacute. COVID-19-associated TM has been described in a scarce number of patients. CLINICAL CASE: A 15-year-old previously healthy male patient with respiratory disease before his neurological deterioration presented to the emergency room after developing a complete medullary syndrome located at the cervical-dorsal level, with ascending and symmetric paraparesis that rapidly progressed to paraplegia, with sensory dysfunction from the T3 level, sphincter dysfunction and sudden ventilatory deterioration that required mechanical ventilation. Magnetic resonance imaging was compatible with acute TM. Inflammatory and non-inflammatory etiologies were discarded. In addition, a positive severe acute respiratory syndrome coronavirus 2 test was obtained. Treatment included steroid pulses and plasmapheresis, with an insidious evolution. CONCLUSION: COVID-19 is an infrequent cause of TM and should be suspected when other etiologies have been ruled out.

INTRODUCCIÓN: La mielitis transversa (MT) es una enfermedad inflamatoria desmielinizante que se presenta con disfunción motora, sensitiva y autonómica, de forma aguda o subaguda. La MT asociada al COVID-19 se ha escrito en un escaso número de pacientes. CASO CLÍNICO: Se presenta el caso de un masculino de 15 años previamente sano, quien cursaba con un cuadro respiratorio y que desarrollo un deterioro neurológico súbito que involucro un síndrome medular completo localizado en el nivel cérvico dorsal, con paraparesia simétrica que progreso a la paraplejia, con disfunción sensitiva desde el nivel medular de T3, disfunción de esfínteres y deterioro ventilatorio que requirió manejo avanzado de la vía aérea. Su resonancia magnética fue compatible con mielitis transversa aguda. Se descartaron causas inflamatorias y no inflamatorias de la patología. Además, se obtuvo un resultado positivo de SARS-COV-2. Se inició tratamiento con pulsos de metilprednisolona y plasmaféresis, con una evolución insidiosa. CONCLUSIÓN: El COVID-19 es una causa infrecuente de MT y debe sospecharse cuando otras causas han sido descartadas.

Limb-body wall complex: Literature review and case report.

INTRODUCTION: Body wall anomalies comprise a wide range of malformations. Limb-Body wall complex (LBWC) represents the most severe presentation of this group, with life threatening malformations in practically all the cases, including craniofacial, body wall defects, and limb anomalies. There is no consensus about its etiology and folding and gastrulation defects have been involved. Also, impaired angiogenesis has been proposed as a causative process. CASE REPORT: We present the case of a masculine stillborn, product of the first pregnancy in a 15-year-old, apparently healthy mother. He was delivered at 31 weeks of gestation due to an early rupture of membranes. He presented with multiple malformations including a wide body wall defect with multiple organ herniation and meromelia of the lower right limb. DISCUSSION AND CONCLUSIONS: LBWC represents a severe and invariably fatal pathology. There are no described risk factors, nevertheless, this case presented in a teenage mother, a well-described risk factor for other body wall anomalies. Its diagnosis allows us to discriminate between other pathologies that require prenatal or postnatal specialized treatment.

Hepatocellular Carcinoma in Mexico.

Content available: Author Interview and Audio Recording.

Correlation Between CD133+ Stem Cells and Clinical Improvement in Patients with Autism Spectrum Disorders Treated with Intrathecal Bone Marrow-derived Mononuclear Cells.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental pathologies characterized by social and communication deficits, for which treatments are limited. Cell therapies, including intrathecal (IT) administration of bone marrow (BM) mononuclear cells (BM-MNC), improves symptoms in patients with ASD. Twenty-four patients diagnosed with ASD, according to the Diagnostic and Statistical Manual of Mental Disorders Text Revision Fourth Edition (DSM-IV-TR) criteria, were autologously treated with IT BM-MNC, and the clinical effect was evaluated using the Childhood Autism Rating Scale (CARS) on Days 30 (n=24) and 180 (n=14) post-treatment. IT BM-MNC improved clinical outcomes by Day 30 (p=0.0039), and those benefits remained and were further accentuated by Day 180 post-treatment (n=14; p=<0.0001). Clinical benefit at Days 30 (p=0.001; r= -0.51) and 180 (p=0.01; r= -0.60) posttreatment positively correlated with the enrichment of a putative BM stem cell population expressing the cluster of differentiation 133+ (CD133+) surface marker.

[Current advances in hepatitis C treatment]. / Nuevos avances en el manejo de la hepatitis C.

Infection by hepatitis C virus constitutes an important health problem in Mexico. Diagnosis of high-risk population is essential given the probability of developing chronic disease, cirrhosis and cirrhosis decompensation, likely leading to the need of a liver transplant and/or the development of hepatocellular carcinoma. Currently, the standard of care (SOC) treatment includes pegylated interferon and ribavirin, which have shown an approximately 57% rate response in genotype 1, the most prevalent in Mexico. It is known that between 30 and 60% of the infected population does not show a sustained virological response or cure. Therefore, in this article, we review existing therapeutic strategies in order to optimize the treatment. Future treatment strategies are also described. Eventually, it will be possible to add one or two molecules of the new directly acting antiviral drugs, to the SOC treatment. Each of them has a different action mechanism, and we are envisioning the possibility of an interferon-free therapy after 2015.

[Liver transplant at the UMAE 25 IMSS Monterrey]. / Trasplante hepático en la Unidad Médica de Alta Especialidad Núm. 25, IMSS Monterrey.

BACKGROUND: Liver transplantation is the best treatment for end stage liver diseases. In April 2003, our institution started a Liver Transplantation Program for both pediatric and adults population. OBJECTIVE: Shown the results of the Liver Transplantation Program in the UMAE 25 Monterrey N.L. MATERIALS AND METHODS: This is a retrospective cohort study of patients with liver transplantation. RESULTS: A total of 51 liver transplantations have been done in 49 patients with two retrasplantation, 15 in children and 36 in adults. The principal indication for liver transplantation in children was biliary atresia and hepatitis C cirrhosis in adults. The acute renal failure was the main early complication, the acute cellular rejection in the mediate period, and the cardiovascular diseases as late complication related to obesity, metabolic syndrome, diabetes mellitus and hypertension. Overall survival at 1 and 5 years was 57.1 and 54.2%, respectively. During the first three years post-transplantation, the quality of life was good or very good. CONCLUSIONS: Although still a young and perfectible program, the effort of a multidisciplinary team has made possible to perform liver transplantation in two patient populations, pediatric and adults.

Molecular Characterization of Associated Pathogens in Febrile Patients during Inter-Epidemic Periods of Urban Arboviral Diseases in Tapachula Southern Mexico.

Emerging and re-emerging vector-borne infections are a global public health threat. In endemic regions, fever is the main reason for medical attention, and the etiological agent of such fever is not usually identified. In this study, non-specific febrile pathogens were molecularly characterized in serum samples from 253 patients suspected of arbovirus infection. The samples were collected in the southern border region of Mexico from April to June 2015, and February to March 2016. ZIKV, CHIKV, DENV, leptospirosis, and rickettsiosis were detected by qPCR and nested PCR to identify flavivirus and alphavirus genera. The results indicated that 71.93% of the samples were positive for CHIKV, 0.79% for ZIKV, and 0.39% for DENV, with the number positive for CHIKV increasing to 76.67% and those positive for ZIKV increasing to 15.41% under the nested PCR technique. Leptospira Kmetyi was identified for the first time in Mexico, with a prevalence of 3.16%. This is the first report of ZIKV in Mexico, as well the first detection of the virus in early 2015. In conclusion, the etiological agent of fever was determined in 94% of the analyzed samples.

Distribution of HCV genotypes and HCV RNA viral load in different regions of Mexico.

BACKGROUND AND AIM: To identify the geographic distribution of hepatitis C virus (HCV) genotypes and HCV RNA viral load in a large number of HCV-infected carriers in Mexico. METHODS: Patients with chronic hepatitis C (n = 8,802) were studied to identify HCV genotype using an immune line probe assay in samples shown previously to be positive for viral RNA by an RT-PCR test. Baseline HCV RNA was also evaluated. RESULTS: Genotype 1 accounted for 70.3%, genotype 2 for 21.8%, genotype 3 for 7.2%, genotype 4 for 0.3%, and genotype 5 for 0.1% of all cases; coinfection was present in 0.3%. Overall, Genotype 1 was the most prevalent Genotype. Regionally, genotype 1 occurred more frequently in the North-East, North, and Center- East regions of Mexico; genotype 2 was more prevalent in the South, East, and Peninsula regions; and genotype 3 was more prevalent in the North and North-West regions. Only 22.4% of patients with genotype 1 were classified in the low HCV RNA viral load category, and the distribution of this genotype did not differ significantly between regions. CONCLUSION: The prevalence of HCV genotypes and viral load in Mexico was 70.3% for genotype 1, but only 22.4% of these patients had a low HCV viral load. Distribution was not uniform in Mexico, with greater frequency of genotype 2 in South, East and Peninsula Regions and Genotype 3 in North and North-West Regions.

Immuno-castration of female and male pigs with anti-gonadotrophin releasing hormone vaccine: Morphometric, histopathological and functional studies of the reproductive system.

Immuno-castration is increasingly recommended in pigs due to welfare reasons; however, there are few studies in females compared to males. This aim of this study was to investigate the effects of immuno-castration in female and male pigs. The weight, the morphometric and microscopic characteristics of the reproductive organs, and the hormone concentrations were studied in 12 immunocastrated females (IF) and 12 immunocastrated males (IM) and compared with control animals (C). At slaughter, IF tended to have greater body weights than CF (P =  0.051), whereas in IM and CM pigs there were not body weight differences (P =  0.140). The weight of the reproductive tract and size of all individual organs were less in IF compared with CF. Results from histological assessments indicated IF had more atretic follicles and a thinner endometrial mucosa than control females. Hormone concentrations were not different between CF and IF (P >  0.050). As a result of immuno-castration, there was impaired spermatogenesis in most males. Results from microscopic evaluations indicated there was a marked decrease of spermatogonial cells and size of Leydig cells in the testicles. Accessory gland structures were affected in CM and IM with there being differences in gross and microscopic characteristics. Testosterone concentrations, unlike estradiol, were different in IM compared to CM (P <  0.001). These results provide evidence that immuno-castration with the anti-gonadotrophin releasing hormone vaccine is effective in female and male pigs and induces morphological and endocrine changes incompatible with fertility.

Association study in Mexican patients with thyrotoxic hypokalemic periodic paralysis.

Hypokalemic periodic paralysis type 1 (OMIM; HOKPP1) and type 2 (OMIM; HOKPP2) are diseases of the muscle characterized by episodes of painless muscle weakness, and is associated with low potassium blood levels. Hyperthyroidism has been associated with thyrotoxic periodic paralysis (TTPP) (OMIM; TTPP1 and TTPP2), and genetic susceptibility has been implicated. In the present study, the clinical and epidemiological characteristics of patients with TTPP are described, together with their association with genetic variants reported previously in other populations. A prospective and a retrospective search of the medical records of patients who attended the emergency department at the Hospital Universitario 'Dr. Jose E. Gonzalez' in Monterrey, Nuevo León, Mexico, and were diagnosed with TTPP was performed. A total of 16 gene variants in the genes MUC1, CACNA1S, KCNE3 and SCN4A, and nine ancestry informative markers (AIMs), were analysed by Multiplex TaqMan™ Open Array assay, and a genetic association study was performed. A total of 11 patients were recruited, comprising nine males and two females (age range, 19-52 years) and 64 control subjects. Only two cases (18%) had a previous diagnosis of hyperthyroidism; the rest were diagnosed subsequently with Graves' disease. Based on the analysis, two DNA variants were found to potentially confer an increased risk for TTPP: S1PR1 rs3737576 [odds ratio (OR), 4.38; 95% confidence interval (CI), 1.08-17.76] and AIM rs2330442 (OR, 4.50; 95% CI, 1.21-16.69), and one variant was suggested to be possibly associated with TTPP, namely MUC1 rs4072037 (OR, 3.08; 95% CI, 0.841-1.38). However, there were no statistically significant associations between any of the 24 DNA variants and TTPP in a population from northeast Mexico.

Genetic Variants at the rs4720169 Locus of TBX20 and the rs12921862 Locus of AXIN1 May Increase the Risk of Congenital Heart Defects in the Mexican Population: A Pilot Study.

Background: Congenital heart defects (CHDs) are the most common type of birth defects and a major cause of infant mortality. Although knowledge of genetic risk variants for CHDs is scarce, most cases of CHDs are considered to be due to multifactorial inheritance. Objective: To analyze the association of 14 single nucleotide polymorphic variants previously associated with a risk of CHDs in a Mexican population with isolated CHDs. Materials and Methods: DNA samples obtained from healthy subjects and from subjects with isolated atrial, ventricular, or atrioventricular septal defects living in Northeastern Mexico were analyzed by real time-polymerase chain reaction for allelic discrimination of genetic variants of the genes TBX1, TBX20, ASTX-18-AS1, AXIN1, MTHFR, NKX2.5, BMP4, and NFATc1. The odds ratios (ORs) for allele and genotype frequencies and inheritance models were obtained. Results: Forty-two patients and 138 controls were included. Two variants were found to confer a risk of CHDs: variant rs4720169 of TBX20 in which the OR for the heterozygous state was 1.88 (95% confidence interval [CI]: 1.12-3.14, p = 0.010), whereas the OR for the homozygous state was 3.82 (95% CI: 1.18-12.3, p = 0.010); and variant rs12921862 of AXIN1 in which the OR for the heterozygous state was 4.15 (95% CI: 2.42-7.10; p ≤ 0.001), whereas the OR for the homozygous state was 9.2 (95% CI: 1.31-64.7, p = 0.008) for allele A. Conclusion: Genetic variants of the TBX20 and AXIN1 genes confer a significantly increased risk of congenital septal heart defects in a population from Northeastern Mexico.

mRTVP-1, a novel p53 target gene with proapoptotic activities.

We identified a novel mouse gene, mRTVP-1, as a p53 target gene using differential display PCR and extensive promoter analysis. The mRTVP-1 protein has 255 amino acids and differs from the human RTVP-1 (hRTVP-1) protein by two short in-frame deletions of two and nine amino acids. RTVP-1 mRNA was induced in multiple cancer cell lines by adenovirus-mediated delivery of p53 and by gamma irradiation or doxorubicin both in the presence and in the absence of endogenous p53. Analysis of RTVP-1 expression in nontransformed and transformed cells further supported p53-independent gene regulation. Using luciferase reporter and electrophoretic mobility shift assays we identified a p53 binding site within intron 1 of the mRTVP-1 gene. Overexpression of mRTVP-1 or hRTVP-1 induced apoptosis in multiple cancer cell lines including prostate cancer cell lines 148-1PA, 178-2BMA, PC-3, TSU-Pr1, and LNCaP, a human lung cancer cell line, H1299, and two isogenic human colon cancer cell lines, HCT116 p53(+/+) and HCT116 p53(-/-), as demonstrated by annexin V positivity, phase-contrast microscopy, and in selected cases 4',6'-diamidino-2-phenylindole staining and DNA fragmentation. Deletion of the signal peptide from the N terminus of RTVP-1 reduced its apoptotic activities, suggesting that a secreted and soluble form of RTVP-1 may mediate, in part, its proapoptotic activities.

Phenotypic Variation in Patients with Homozygous c.1678G>T Mutation in EVC Gene: Report of Two Mexican Families with Ellis-van Creveld Syndrome.

BACKGROUND Ellis-van Creveld syndrome is an autosomal recessive chondro-ectodermal dysplasia characterized by disproportionate short stature, limb shortening, narrow chest, postaxial polydactyly and dysplastic nails and teeth. In addition, 60% of cases present congenital heart defects. Ellis-van Creveld syndrome is predominantly caused by mutations in the EVC or EVC2 (4p16) genes, with only a few cases caused by mutations in WDR35.  CASE REPORT Here, we report on two Mexican families with patients diagnosed with Ellis-van Creveld syndrome. Family 1 includes four patients: three females of 15, 18, and 23 years of age and a 7-year old male. Family 2 has only one affected newborn male. All patients exhibited multiple features including hypodontia, dysplastic teeth, extra frenula, mild short stature, distal limb shortening, postaxial polydactyly of hands and feet, nail dystrophy, and knee joint abnormalities. Only two patients had an atrial septal defect. In all cases, molecular analysis by Sanger sequencing identified the same homozygous mutation in exon 12 of EVC, c.1678G>T, which leads to a premature stop codon.  CONCLUSIONS The mutation c.1678G>T has been previously reported in another Mexican patient and it appears to be a recurrent mutation in Mexico which could represent a founder mutation. The large number of patients in this case allows the clinical variability and spectrum of manifestations present in individuals with Ellis-van Creveld syndrome even if they carry the same homozygous mutation in a same family.

Genetic variants in KCNJ11, TCF7L2 and HNF4A are associated with type 2 diabetes, BMI and dyslipidemia in families of Northeastern Mexico: A pilot study.

The aim of the present study was to investigate whether genetic markers considered risk factors for metabolic syndromes, including dyslipidemia, obesity and type 2 diabetes mellitus (T2DM), can be applied to a Northeastern Mexican population. A total of 37 families were analyzed for 63 single nucleotide polymorphisms (SNPs), and the age, body mass index (BMI), glucose tolerance values and blood lipid levels, including those of cholesterol, low-density lipoprotein (LDL), very LDL (VLDL), high-density lipoprotein (HDL) and triglycerides were evaluated. Three genetic markers previously associated with metabolic syndromes were identified in the sample population, including KCNJ11, TCF7L2 and HNF4A. The KCNJ11 SNP rs5210 was associated with T2DM, the TCF7L2 SNP rs11196175 was associated with BMI and cholesterol and LDL levels, the TCF7L2 SNP rs12255372 was associated with BMI and HDL, VLDL and triglyceride levels, and the HNF4A SNP rs1885088 was associated with LDL levels (P<0.05).