Genotypic spectrum underlying tetrahydrobiopterin metabolism defects: Experience in a single Mexican reference center.

Background: Pterin profiles or molecular analyses of hyperphenylalaninemia (HPA) caused by phenylalanine hydroxylase (PAH) deficiency or tetrahydrobiopterin deficiency (BH4D) are not always available in low- or middle-income countries, including Mexico, limiting information regarding the phenotypic and genotypic characteristics of patients exhibiting BH4D. Objective: To report the genotypes underlying BH4D and the clinical presentation in unrelated Mexican HPA pediatric patients with normal PAH genotypes who attended a single metabolic reference center in Mexico. Methods: Automated Sanger sequencing of the PTS, QDPR, and PCBD1 genes of 14 HPA patients was performed. Predicted effects on protein structure caused by missense variants were assessed by in silico protein modeling. Results and discussion: A high prevalence of BH4D was noted in our HPA cohort (9.8%, N = 14/142). Clinically relevant biallelic genotypes were identified in the PTS (N = 7/14 patients), QDPR (N = 6/14 patients), and PCBD1 (N = 1/14 patients) genes. Four novel QDPR variants [c.714dup or p.(Leu239Thrfs*44), c.106-1G>T or p.(?), c.214G>T or p.(Gly72*), and c.187_189dup or p.(Gln63dup)] were identified. In silico protein modeling of six missense variants of PTS [p.(Thr67Met), p.(Glu81Ala), and p.(Tyr113Cys)], QDPR [p.(Cys161Phe) and p.(Pro172Leu)], and PCBD1 [p.(Glu97Lys)] supports their pathogenicity. Progressive neurological symptoms (mainly intellectual and motor impairment and even death in three patients) were noted in all patients with biallelic QDPR genotypes and in 5/7 patients bearing biallelic PTS genotypes. The single homozygous PCBD1 p.(Glu97Lys) patient remains asymptomatic. Conclusion: A higher proportion of BH4D (9.8 vs. 1%-2% worldwide), attributable to a heterogeneous mutational spectrum and wide clinical presentation, was noted in our Mexican HPA cohort, with the PTS-related HPA disorder being the most frequent. Sequencing-based assays could be a reliable approach for diagnosing BH4D in our population.

Fractura patológica del húmero con diagnóstico posterior de displasia fibrosa poliostótica / Pathological fracture of the humerus and subsequent diagnosis of polyostotic fibrous dysplasia

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Intervención multidimensional que mejora el pronóstico a corto plazo entre los ancianos frágiles dados de alta desde una unidad de corta estancia: estudio cuasiexperimental / Multidimensional intervention to improve the short-term prognosis of frail elderly patients discharged from a short-stay unit: A quasiexperimental study

Objetivo. Estudiar el efecto de una intervención multidimensional en el pronóstico a 30 días en los ancianos frágiles dados de alta desde una unidad de corta estancia. Material y método. Estudio cuasiexperimental con una cohorte de control histórica. Se incluyeron pacientes frágiles (Identification of Senior at Risk≥2), de≥75 años, dados de alta desde la unidad de corta estancia durante 2 meses en 2013 (grupo control) y un año (2016; grupo de intervención). Se realizó una intervención basada en la activación de recursos, en función de los déficits detectados tras una valoración geriátrica abreviada, más la coordinación con Atención Primaria. La variable de resultado principal fue la presencia de algún resultado adverso (muerte o reingreso por cualquier causa o deterioro funcional grave) a los 30 días del alta. Resultados. Se incluyeron 137 (62,8%) pacientes en el grupo de intervención y 81 (37,2%) en el control. Dieciocho (13,1%) pacientes en el grupo de intervención y 29 (35,8%) en el control presentaron algún evento adverso a los 30 días. Tras un análisis multivariable, se demostró que la realización de una intervención multidimensional fue un factor de protección para la presentación de algún evento adverso a los 30 días tras el alta (RR ajustado 0,40; IC 95% 0,23-0,68; p=0,001). Conclusiones. La realización de un plan de atención individualizado, basado en la activación de recursos, en función de los déficits detectados tras una valoración geriátrica abreviada, y la coordinación con Atención Primaria, entre los pacientes ancianos frágiles podría mejorar los resultados a los 30 días tras el alta desde una UCE

Objective. To study the effect of a multidimensional intervention on the prognosis at 30 days for frail elderly patients discharged from a short-stay unit. Material and method. A quasiexperimental study was conducted with a historical control cohort. We included frail patients (Identification of Seniors at Risk score≥2) 75 years of age or older, discharged from an short-stay unit over 2 months in 2013 (control group) and in 2016 (intervention group). An intervention was conducted based on the activation of resources, based on the deficiencies detected after an abbreviated geriatric assessment, in conjunction with Primary Care. The main endpoint was the presence of an adverse result (death or readmission for any cause or severe functional impairment) at 30 days of discharge. Results. We included 137 (62.8%) patients in the intervention group and 81 (37.2%) in the control group. Eighteen (13.1%) patients in the intervention group and 29 (35.8%) in the control group presented an adverse event at 30 days. A multivariate analysis showed that the implementation of a multidimensional intervention was a protective factor for presenting an adverse event at 30 days of discharge (adjusted RR 0.40; 95% CI 0.23-0.68; P=.001). Conclusions. The implementation of an individual care plan for frail elderly patients, based on the activation of resources according to the deficiencies detected after an abbreviated geriatric assessment and in conjunction with Primary Care, could improve the results at 30 days of discharge from an short-stay unit

Multidimensional intervention to improve the short-term prognosis of frail elderly patients discharged from a short-stay unit: A quasiexperimental study. / Intervención multidimensional que mejora el pronóstico a corto plazo entre los ancianos frágiles dados de alta desde una unidad de corta estancia: estudio cuasiexperimental.

OBJECTIVE: To study the effect of a multidimensional intervention on the prognosis at 30 days for frail elderly patients discharged from a short-stay unit. MATERIAL AND METHOD: A quasiexperimental study was conducted with a historical control cohort. We included frail patients (Identification of Seniors at Risk score≥2) 75 years of age or older, discharged from an short-stay unit over 2 months in 2013 (control group) and in 2016 (intervention group). An intervention was conducted based on the activation of resources, based on the deficiencies detected after an abbreviated geriatric assessment, in conjunction with Primary Care. The main endpoint was the presence of an adverse result (death or readmission for any cause or severe functional impairment) at 30 days of discharge. RESULTS: We included 137 (62.8%) patients in the intervention group and 81 (37.2%) in the control group. Eighteen (13.1%) patients in the intervention group and 29 (35.8%) in the control group presented an adverse event at 30 days. A multivariate analysis showed that the implementation of a multidimensional intervention was a protective factor for presenting an adverse event at 30 days of discharge (adjusted RR 0.40; 95% CI 0.23-0.68; P=.001). CONCLUSIONS: The implementation of an individual care plan for frail elderly patients, based on the activation of resources according to the deficiencies detected after an abbreviated geriatric assessment and in conjunction with Primary Care, could improve the results at 30 days of discharge from an short-stay unit.

Wide allelic heterogeneity with predominance of large IDS gene complex rearrangements in a sample of Mexican patients with Hunter syndrome.

Hunter syndrome or mucopolysaccharidosis type II (MPSII) is caused by pathogenic variants in the IDS gene. This is the first study that examines the mutational spectrum in 25 unrelated Mexican MPSII families. The responsible genotype was identified in 96% of the families (24/25) with 10 novel pathogenic variants: c.133G>C, c.1003C>T, c.1025A>C, c.463_464delinsCCGTATAGCTGG, c.754_767del, c.1132_1133del, c.1463del, c.508-1G>C, c.1006+1G>T and c.(-217_103del). Extensive IDS gene deletions were identified in four patients; using DNA microarray analysis two patients showed the loss of the entire AFF2 gene, and epilepsy developed in only one of them. Wide allelic heterogeneity was noted, with large gene alterations (e.g. IDS/IDSP1 gene inversions, partial to extensive IDS deletions, and one chimeric IDS-IDSP1 allele) that occurred at higher frequencies than previously reported (36% vs 18.9-29%). The frequency of carrier mothers (80%) is consistent with previous descriptions (>70%). Carrier assignment allowed molecular prenatal diagnoses. Notably, somatic and germline mosaicism was identified in one family, and two patients presented thrombocytopenic purpura and pancytopenia after idursulfase enzyme replacement treatment. Our findings suggest a wide allelic heterogeneity in Mexican MPSII patients; DNA microarray analysis contributes to further delineation of the resulting phenotype for IDS and neighboring loci deletions.

Análisis de decisión: coste-efectividad en el tratamiento quirúrgico de la neuralgia del trigémino / No disponible

Introducción: La neuralgia trigeminal es un síndrome de dolor facial conocido y caracterizado por dolores severos, intermitentes, eléctricos y como de sacudidas en la cara, para el cual han sido aplicados diversos tratamientos quirúrgicos, hasta la fecha, no hay un tratamiento ideal que sea invasivo en grado mínimo y aceptable para el paciente, como consecuencia, los pacientes y los especialistas se enfrentan a una incertidumbre considerable al hacer decisiones sobre la conducta terapéutica. Objetivo: Identificar cuál de los tratamientos quirúrgicos para la NT brinda la mejor oportunidad en términos de coste-efectividad. Material y método: Se realizó un estudio con un diseño de Análisis de Decisión: coste-efectividad considerando cinco alternativas quirúrgicas en el tratamiento de la NT: termocoagulación por radiofrecuencia, microcompresión con glicerol, microcompresión con balón, radiocirugía, y microdescompresión vascular. Los datos se obtuvieron de la literatura. Se revisó la base de datos MEDLINE desde el año 2000 hasta el 2010, a través de PubMed Central. Se seleccionaron los estudios que abordaran la neuralgia trigeminal primaria y mostraran resultados relacionados con el alivio del dolor, la tasa de mortalidad o la presencia de complicaciones. Se identificaron 196 estudios pero solo 22 (11,22 %) fueron elegibles para el estudio. Se utilizo el programa DATA 3.5 for Health Care, versión 3.5.5 de TreeAge Software Inc. Resultados: La microdescompresión vascular y la termocoagulación son las técnicas que ofrecen mayores probabilidades de efectividad para el alivio del dolor con valores esperados de 0,8946 y 0,8863. Para la relación que se establece entre coste y resultado se consideró los días libres de dolor. La mejor elección costeefectividad es el tratamiento quirúrgico con termocoagulación con menos valor en la razón coste-efectividad marginal, $171.58 para una efectividad de la cirugía de 89 % por cada paciente tratado. Conclusión: Considerando que la termocoagulación por radiofrecuencia y la microdescompresión vascular constituyen las variantes quirúrgicas más utilizadas por la alta efectividad, concluimos que la termocoagulación por radiofrecuencia es más beneficiosa, ofrece escasas complicaciones y es menos costosa (AU)

Introduction: Trigeminal neuralgia is a facial pain syndrome known and characterized by severe, intermittent, electric shocklike, shooting pain in the face for which a number of surgical therapies have been used. To date no ideal, minimally invasive, patient-acceptable treatment is available, hence both patients and specialists face substantial uncertainty when making decisions regarding therapeutic action. Objective: To identify which surgical treatment for TN offers the best opportunity in terms of cost-effectiveness. Material and method: A study was performed using a decision analysis/cost-effectiveness analysis design considering five surgical alternatives in the management of TN: radiofrequency thermocoagulation, glycerol microcompression, balloon microcompression, radiosurgery, and microvascular decompression. Data were obtained from the literature. A review was carried out of the MEDLINE database from 2000 to 2010 via PubMed Central. Studies were selected that addressed primary trigeminal neuralgia and demonstrated pain relief and reduced mortality and complication rates. In all 196 studies were identified but only 22 (11.22 %) were eligible for the study. The software package used was the DATA 3.5 for Health Care, version 3.5.5, program by TreeAge Software Inc. Results: Microvascular decompression and thermocoagulation are the techniques more likely to provide effective pain relief, with expected values of 0.8946 and 0.8863, respectively. For the relationship between cost and outcome pain-free days were considered; the best choice in terms of cost-effectiveness is surgery and thermocoagulation, with a lower value in the marginal cost-effectiveness ratio: $171.58 for an effectiveness of 89 % per treated patient. Conclusion: Considering that both radiofrequency thermocoagulation and microvascular decompression are the most commonly used surgical procedures because of their high effectiveness, we conclude that radiofrequency thermocoagulation is more beneficial, has few complications, and is less costly (AU)

Serum levels of keratin-18 fragments [tissue polypeptide-specific antigen (TPS)] are correlated with hepatocyte apoptosis in alcoholic hepatitis.

Apoptosis is a major feature in alcoholic hepatitis. During apoptosis, the M30 neoepitope becomes exposed after keratin-18 cleavage. The tissue polypeptide-specific antigen (TPS) is a keratin-18 fragment that is routinely used as a tumor marker. Serum TPS levels are increased in patients with alcoholic hepatitis. The aim of this study was to investigate the possible relationship of TPS levels with hepatocyte apoptosis in alcoholic hepatitis. Thirty-one patients with alcoholic hepatitis and 22 with fatty liver were included. Hepatocyte apoptosis was evaluated by M30 immunostaining. Serum TPS levels were measured by a commercial immunoassay. The apoptotic score was higher in patients with alcoholic hepatitis than in patients with fatty liver. There was a significant correlation between the apoptotic score and TPS levels. The correlation of the apoptotic score with TPS levels was stronger than with standard liver tests. Serum TPS may be a marker of apoptosis in alcoholic hepatitis.

Neumonía por Mycoplasma pneumoniae y síndrome de distrés respiratorio del adulto / Mycoplasma pneumoniae pneumonia ad adult respiratory distress syndrome

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