Liver Transplant From Controlled Cardiac Death Donors Using Normothermic Regional Perfusion: Comparison With Liver Transplants From Brain Dead Donors.

BACKGROUND: Liver transplantation from donors after either controlled or uncontrolled cardiac death (DCD) is associated with considerable rates of primary nonfunction (PNF) and ischemic cholangiopathy (IC). Normothermic regional perfusion (NRP) could significantly reduce such rates. METHODS: Retrospective study to analyze short-term (mortality, PNF, vascular complications) and long-term (IC, survival) complications in 11 liver transplants from controlled DCDs using NRP with extracorporeal membrane oxygenation (ECMO) (group 1). They were compared with 51 patients transplanted with grafts from donors after brain death (DBD) (group 2). Mean recipient age, sex, and Model for End-stage Liver Disease (MELD) score were not significantly different. RESULTS: In group 1, mean functional warm ischemia time was 15.8 (range, 7-40) minutes and 94.1 (range, 20-150) minutes on NRP. The ischemic damage was minimal, as shown by the slight alanine aminotransferase (ALT) and aspartate aminotransferase (AST) rises in the donor serum after 1 hour on NRP and similar rises 24 hours after transplantation in both groups. No patient had IC or acute renal failure. No significant difference was found between the groups for vascular or biliary complications. One group 1 patient had PNF (9.1%), resulting in death. Overall retransplantation and in-hospital death rates were 8.1% and 4.8%, respectively, with no significant difference between groups. Estimated mean survival was 24.6 (95% confidence interval [CI], 20.2-29.1) months in group 1 and 32.3 (95% CI, 30.4-34.2) months in group 2 (not a statistically significant difference). CONCLUSION: In our experience, liver transplants from controlled DCDs using NRP with ECMO is associated with a low risk of PNF and IC, with short- and long-term results comparable to those in DBD transplants.

Parkin loss of function contributes to RTP801 elevation and neurodegeneration in Parkinson's disease.

Mutations in the PARK2 gene are associated with an autosomal recessive form of juvenile parkinsonism (AR-JP). These mutations affect parkin solubility and impair its E3 ligase activity, leading to a toxic accumulation of proteins within susceptible neurons that results in a slow but progressive neuronal degeneration and cell death. Here, we report that RTP801/REDD1, a pro-apoptotic negative regulator of survival kinases mTOR and Akt, is one of such parkin substrates. We observed that parkin knockdown elevated RTP801 in sympathetic neurons and neuronal PC12 cells, whereas ectopic parkin enhanced RTP801 poly-ubiquitination and proteasomal degradation. In parkin knockout mouse brains and in human fibroblasts from AR-JP patients with parkin mutations, RTP801 levels were elevated. Moreover, in human postmortem PD brains with mutated parkin, nigral neurons were highly positive for RTP801. Further consistent with the idea that RTP801 is a substrate for parkin, the two endogenous proteins interacted in reciprocal co-immunoprecipitates of cell lysates. A potential physiological role for parkin-mediated RTP801 degradation is indicated by observations that parkin protects neuronal cells from death caused by RTP801 overexpression by mediating its degradation, whereas parkin knockdown exacerbates such death. Similarly, parkin knockdown enhanced RTP801 induction in neuronal cells exposed to the Parkinson's disease mimetic 6-hydroxydopamine and increased sensitivity to this toxin. This response to parkin loss of function appeared to be mediated by RTP801 as it was abolished by RTP801 knockdown. Taken together these results indicate that RTP801 is a novel parkin substrate that may contribute to neurodegeneration caused by loss of parkin expression or activity.

Fused in Sarcoma (FUS) gene mutations are not a frequent cause of essential tremor in Europeans.

FUS/TLS (denoting fused in sarcoma/translocated in liposarcoma [MIM 137070]) codifies an RNA binding protein. Mutations in this gene cause amyotrophic lateral sclerosis (ALS; MIM 608030). Essential tremor (ET [MIM 190300]) is the most frequent movement disorder. Despite its strong familiar aggregation, recently a whole exome sequencing study has identified FUS mutations as a cause of familial ET. To determine whether mutations in FUS are also common in other populations, we sequenced FUS gene in 178 unrelated Spanish subjects with ET. We detected only an intronic single-pair nucleotide deletion (c.1293-37delC), which was predicted to affect mRNA splicing. However, leukocyte mRNA analysis showed no changes in FUS expression. In conclusion, coding or splicing FUS mutations are not a frequent cause of ET in the Spanish population.

Meta-analysis of vascular endothelial growth factor variations in amyotrophic lateral sclerosis: increased susceptibility in male carriers of the -2578AA genotype.

BACKGROUND: Targeted delivery of the angiogenic factor, vascular endothelial growth factor (VEGF), to motor neurons prolongs survival in rodent models of amyotrophic lateral sclerosis (ALS), while mice expressing reduced VEGF concentrations develop motor neuron degeneration reminiscent of ALS, raising the question whether VEGF contributes to the pathogenesis of ALS. An initial association study reported that VEGF haplotypes conferred increased susceptibility to ALS in humans, but later studies challenged this initial finding. METHODS AND FINDINGS: A meta-analysis was undertaken to critically reappraise whether any of the three common VEGF gene variations (-2578C/A, -1154G/A and -634G/C) increase the risk of ALS. Over 7000 subjects from eight European and three American populations were included in the analysis. Pooled odds ratios were calculated using fixed-effects and random-effects models, and four potential sources of heterogeneity (location of disease onset, gender, age at disease onset and disease duration) were assessed. After correction, none of the genotypes or haplotypes was significantly associated with ALS. Subgroup analysis by gender revealed, however, that the -2578AA genotype, which lowers VEGF expression, increased the risk of ALS in males (OR = 1.46 males vs females; 95% CI = 1.19 to 1.80; p = 7.8 10E-5), even after correction for publication bias and multiple testing. CONCLUSIONS: This meta-analysis does not support the original conclusion that VEGF haplotypes increase the risk of ALS in humans, but the significant association of the low-VEGF -2578AA genotype with increased susceptibility to ALS in males reappraises the link between reduced VEGF concentrations and ALS, as originally revealed by the fortuitous mouse genetic studies.

Lumbociática como síntoma de presentación de un tumor del nervio ciático / No disponible

El dolor lumbar es una consulta frecuente en Atención Primaria por su elevada prevalencia e incidencia. Es preciso para su abordaje realizar una buena historia clínica y exploración física que nos permita poner de manifiesto la presencia de factores de riesgo que hagan sospechar una etiología grave. Presentamos el caso de una paciente afecta de un tumor maligno de la vaina del nervio ciático que comenzó con síntomas compatibles con una lumbociática

Low back pain is a reason for frequent consultation in Primary Health Care due to its high prevalence and incidence. It is importance to study it by means of a good clinical history and physical examination that allows us to observe the presence of risk factors that may lead to suspicion of a serious etiology. We present the case of a female patient affected by a malignant tumor in the sciatic nerve that began with symptoms consists with low back painyy

Neutropenia y fármacos / Neutropenia and drugs

La incidencia de la neutropenia por fármacos es baja, sin embargo tiene una mortalidad importante. Presentamos el caso de una paciente con una neutropenia severa secundaria a la toma de un antiepiléptico (levetiracetam). Cualquier fármaco puede ser el causante de esta patología, aunque la mayor parte de los casos son secundarios a un grupo reducido de medicamentos. Su evolución y pronóstico dependen de la rapidez del diagnóstico y de la cifra inicial de neutrófilos, ya que se pueden producir complicaciones infecciosas severas

Drug induced neutropenia is a disease having low incidence, however, it has high mortality. We present the case of a woman with severe neutropenia caused by an antiepileptic drug (levetiracetam). Any drug can be the cause of this disease, although most of them are secondary to a reduced group of medicines. Its course and prognosis depend on the speed of the diagnosis and initial neutrophil values since severe infectious complications may appear

Endometriosis de pared abdominal / Endometriosis of the abdominal wall

La endometriosis es una enfermedad caracterizada por la presencia de tejido endometrial fuera de la cavidad uterina. La localización en la pared abdominal de una endometriosis (endometrioma) es una patología muy poco frecuente y puede simular otro tipo de tumoraciones. Presentamos el caso de una paciente que consulta por nódulo doloroso en pared abdominal cercano a la cicatriz de cesárea

Endometriosis is a disease characterized by the presence of endometrial tissue outside of the uterine cavity. Abdominal wall localization of an endometriosis (endometrioma) is an unusual disease that may simulate other types of nodules. We report the case of a female patient who consults due to a painful abdominal wall mass near a cesarean scar

Possible gender-dependent association of vascular endothelial growth factor (VEGF) gene and ALS.

Individuals homozygous for haplotypes -2578-A/-1154-A/-634-G or -2578-A/-1154-G/-634-G in the promoter/5'UTR of the VEGF gene have a 1.8-fold increased risk of ALS in several European populations. We did not observe any significant association with single markers, or haplotype pairs, in a German sample of 580 sporadic ALS patients and 628 controls. However, the promoter SNP-1154 (rs1570360) was associated with affection status in women (p = 0.036), suggesting that the VEGF effect may be dependent on the sex ratio of the sample.

Fasting plasma ghrelin levels increase progressively after biliopancreatic diversion: one-year follow-up.

BACKGROUND: The role of ghrelin in weight control after surgery is not clear. We examined plasma ghrelin and leptin levels in patients with morbid obesity undergoing biliopancreatic diversion (BPD) of Scopinaro. METHODS: 30 adult patients (27 females, 3 males), undergoing elective BPD were recruited from the Hospital Surgery Service. Fasting blood samples for biochemical determinations were drawn before surgery and 1, 3 and 12 months after BPD. Human plasma ghrelin was measured by RIA. RESULTS: During the study period, weight, BMI and serum leptin levels decreased significantly at all sample points compared to preoperative values. Ghrelin plasma levels increased during the study, with statistical significance at 3 months and 1 year after surgery compared with preoperative levels. While leptin changes correlated with changes in BMI, no correlation was found between ghrelin and leptin or BMI changes. CONCLUSION: Plasma ghrelin levels could be decreased in obese patients as a compensatory mechanism to their nutritional state, but our results do not support the postulated beneficial role of ghrelin in the 1-year weight loss after BPD. They rather suggest that weight loss somehow stimulates ghrelin secretion, even in the absence of part of the stomach.

Nódulo tiroideo en el niño: a propósito de un caso / Thyroid node in the child: based on one case

Los nódulos tiroideos son una patología poco frecuente en la edad pediátrica, sin embargo presentan un elevado índice de malignización con respecto al adulto, que se sitúa entre el 2 y el 50 por ciento según los autores, lo que hace que en la mayoría de los casos el tratamiento definitivo sea la extirpación quirúrgica. Se presenta el caso clínico de un niño de 10 años de edad diagnosticados de un nódulo tiroideo de características benignas, funcionalmente eutiroideo y con una citología por punción-aspiración con aguja fina (PAAF) de proliferación folicular moderada. Se le realizó una hemitiroidectomía derecha y el análisis anatomopatológico demostró un adenoma folicular con hiperplasia papilar. Asimismo, se realiza una breve revisión de la epidemiología, clínica, diagnóstico y tratamiento del nódulo tiroideo en el niño. Aun siendo una patología poco frecuente, requiere unos conocimientos básicos para su manejo. Entre ellos cabe destacar la importancia de la PAAF en los últimos tiempos en relación a otros métodos diagnósticos, como la ecografía y la gammagrafía, así como la certeza de que la extirpación quirúrgica y posterior estudio anatomopatológico es el mejor método diagnóstico y terapéutico, tanto en patología benigna como maligna (AU)