Role of microRNAs in alcohol-induced liver disorders and non-alcoholic fatty liver disease

[EN]MicroRNAs (miRNAs) are small non-coding RNAs that regulate multiple physiological and pathological functions through the modulation of gene expression at the post-transcriptional level. Accumulating evidence has established a role for miRNAs in the development and pathogenesis of liver disease. Specifically, a large number of studies have assessed the role of miRNAs in alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD), two diseases that share common underlying mechanisms and pathological characteristics. The purpose of the current review is to summarize and update the body of literature investigating the role of miRNAs in liver disease. In addition, the potential use of miRNAs as biomarkers and/or therapeutic targets is discussed. Among all miRNAs analyzed, miR-34a, miR-122 and miR-155 are most involved in the pathogenesis of NAFLD. Of note, these three miRNAs have also been implicated in ALD, reinforcing a common disease mechanism between these two entities and the pleiotropic effects of specific miRNAs. Currently, no single miRNA or panel of miRNAs has been identified for the detection of, or staging of ALD or NAFLD. While promising results have been shown in murine models, no therapeutic based-miRNA agents have been developed for use in humans with liver disease

Paciente con síndrome de intestino corto y progresión atípica de adenocarcinoma de endometrio

The most common location of distant metastasis of endometrial adenocarcinoma is the lung, although sometimes it could appear soft tissue involvement. Short bowel syndrome can potentially cause serious electrolite changes that require a global management. Patient admitted for severe electrolyte changes secondary to a short bowel syndrome after an intestinal resection. Octreotide LAR was successfully used to control intestinal losses. During the outpatient follow up was detected two soft tissue masses in gluteal region compatible with tumour progression of an endometrial adenocarcinoma diagnosed 10 years before. The usefulness of octreotide to control chronic diarrhoea in short bowel syndrome and other diseases should be taken into account as an option for the management of these diseases. The presence of soft tissue masses in a patient with a history of endometrial adenocarcinoma should alert on the possibility of tumour progression at that level.La afectación metastásica del adenocarcinoma de endometrio más frecuente es la pulmonar, ocasionalmente puede progresar a nivel de partes blandas. El síndrome de intestino corto puede provocar alteraciones iónicas potencialmente graves. Paciente que ingresa por alteraciones iónicas graves secundarias a un síndrome de intestino corto tras una resección por bridas. Para lograr un óptimo control de las pérdidas intestinales se utilizó con éxito octreótido LAR. Durante su seguimiento ambulatorio se detectaron dos masas de partes blandas en región glútea compatibles con progresión tumoral del adenocarcinoma de endometrio que había sido diagnosticado más de 10 años antes. La utilidad del octreótido para el control de la diarrea crónica en casos de síndrome de intestino corto y otras patologías, debe ser tenida en cuenta como una opción más a valorar de forma individualizada en cada enfermo. La presencia de masas de partes blandas en un paciente con antecedentes de adenocarcinoma de endometrio debe alertar sobre la posibilidad de una progresión tumoral a dicho nivel

Sphingobacterium multivorum: An Atypical Bacterium in an Atypical Place

We present the case of a 75-year-old woman admitted to hospital because of an infected pressure ulcer. Cultures revealed that the responsible bacterium was Sphingobacterium multivorum, which was successfully eradicated with ciprofloxacin. Over the last few years, there have been reports of new cases of infection caused by bacteria previously not thought to be harmful to humans, like S. multivorum. Previous cases were reported mostly in immunosuppressed patients and the present report is, to our knowledge, the first describing a pressure ulcer infected by this bacterium

A Single Nucleotide Polymorphism in the RASGRF2 Gene Is Associated with Alcoholic Liver Cirrhosis in Men

Background Genetic polymorphisms in the RAS gene family are associated with different diseases, which may include alcohol-related disorders. Previous studies showed an association of the allelic variant rs26907 in RASGRF2 gene with higher alcohol intake. Additionally, the rs61764370 polymorphism in the KRAS gene is located in a binding site for the let-7 micro-RNA family, which is potentially involved in alcohol-induced inflammation. Therefore, this study was designed to explore the association between these two polymorphisms and susceptibility to alcoholism or alcoholic liver disease (ALD). Methods We enrolled 301 male alcoholic patients and 156 healthy male volunteers in this study. Polymorphisms were genotyped by using TaqMan® PCR assays for allelic discrimination. Allelic and genotypic frequencies were compared between the two groups. Logistic regression analysis was performed to analyze the inheritance model. Results The A allele of the RASGRF2 polymorphism (rs26907) was significantly more prevalent among alcoholic patients with cirrhosis (23.2%) compared to alcoholic patients without ALD (14.2%). This difference remained significant in the group of patients with alcohol dependence (28.8% vs. 14.3%) but not in those with alcohol abuse (15.1% vs. 14.4%). Multivariable logistic regression analysis showed that the A allele of this polymorphism (AA or GA genotype) was associated with alcoholic cirrhosis both in the total group of alcoholics (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.32–4.11; P = 0.002) and in the group of patients with alcohol dependence (OR: 3.1, 95% CI: 1.50–6.20; P = 0.001). Allelic distributions of the KRAS polymorphism (rs61764370) did not differ between the groups. Conclusions To our knowledge, this genetic association study represents the first to show an association of the RASGRF2 G>A (rs26907) polymorphism with ALD in men, particularly in the subgroup of patients with AD. The findings suggest the potential relevance of the RAS gene family in alcoholism and ALD

Atrial fibrillation as a new prognosis factor in chronic patients after hospitalization: the CHRONIBERIA index

A collaborative project in different areas of Spain and Portugal was designed to find out the variables that influence the mortality after discharge and develop a prognostic model adapted to the current healthcare needs of chronic patients in an internal medicine ward. Inclusion criteria were being admitted to an Internal Medicine department and at least one chronic disease. Patients’ physical dependence was measured through Barthel index (BI). Pfeiffer test (PT) was used to establish cognitive status. We conducted logistic regression and Cox proportional hazard models to analyze the influence of those variables on one-year mortality. We also developed an external validation once decided the variables included in the index. We enrolled 1406 patients. Mean age was 79.5 (SD = 11.5) and females were 56.5%. After the follow-up period, 514 patients (36.6%) died. Five variables were identified as significantly associated with 1 year mortality: age, being male, lower BI punctuation, neoplasia and atrial fibrillation. A model with such variables was created to estimate one-year mortality risk, leading to the CHRONIBERIA. A ROC curve was made to determine the reliability of this index when applied to the global sample. An AUC of 0.72 (0.7–0.75) was obtained. The external validation of the index was successful and showed an AUC of 0.73 (0.67–0.79). Atrial fibrillation along with an advanced age, being male, low BI score, or an active neoplasia in chronic patients could be critical to identify high risk multiple chronic conditions patients. Together, these variables constitute the new CHRONIBERIA index

De-novo non-convulsive status epilepticus in adult medical inpatients without known epilepsy: Analysis of mortality related factors and literature review

BACKGROUND: Non-convulsive status epilepticus (NCSE) often goes unnoticed and is not easily detected in patients with a decreased level of consciousness, especially in older patients. In this sense, lack of data in this population is available. AIMS: The aim of the present study was to examine daily clinical practice and evaluate factors that may influence the prognosis of NCSE in non-epileptic medical inpatients. METHODS: We conducted a retrospective analysis including patients admitted by any cause in an Internal Medicine ward. All patients with compatible symptoms, exclusion of other causes, clinical suspicion or diagnosis of NCSE, and compatible EEG were included. Patients with a previous diagnosis of epilepsy were excluded. We also conducted a literature review by searching the PubMed/Medline database with the terms: Nonconvulsive Status OR Non-Convulsive Status. RESULTS: We included 54 patients, mortality rate reached 37% and the main factors linked to it were hypernatremia (OR = 16.2; 95% CI, 1.6-165.6; P = 0.019) and atrial fibrillation (OR = 6.7; 95% CI, 1.7-26; P = 0.006). There were no differences regarding mortality when comparing different diagnosis approach or treatment regimens. Our literature review showed that the main etiology of NCSE were neurovascular causes (17.8%), followed by antibiotic treatment (17.2%) and metabolic causes (17%). Global mortality in the literature review, excluding our series, reached 20%. DISCUSSION: We present the largest series of NCSE cases in medical patients, which showed that this entity is probably misdiagnosed in older patients and is linked to a high mortality. CONCLUSION: The presence of atrial fibrillation and hypernatremia in patients diagnosed with NCSE should advise physicians of a high mortality risk

Genetic susceptibility to telomere shortening through the rs2293607 polymorphism is associated with a greater risk of alcohol use disorder

Telomere shortening is usually considered a biomarker of ageing. Harmful alcohol use promotes accelerated biological ageing and alcohol use disorders (AUDs) are associated with short telomere length (TL). This study was conducted to examine the relationship of TL to AUD and determine whether single nucleotide polymorphisms (SNPs) in TERC and TERT modulate this association. For this purpose, we genotyped TERC SNPs rs2293607, rs12696304, and rs16847897 and TERT SNPs rs2735940, rs2736100, and rs2736098 in 308 male patients with AUD and 255 sex-matched healthy controls and measured TL in a subset of 99 patients and 99 controls paired by age and smoking status. Our results showed that the mean TL was shorter in patients with AUD than in controls. The area under the ROC curve was 0.70 (P < 0.001). The GG genotype of TERC rs2293607 was more common among patients with AUD than among controls (9.8% vs. 5.1%; P = 0.038). No difference was found for the other SNPs. Carriers of the GG genotype of rs2293607 had shorter telomeres than did allele A carriers. In conclusion, patients with AUD had shorter telomeres. Genetic susceptibility to telomere shortening through the rs2293607 SNP is associated with a greater risk of AUD

Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: A multicenter retrospective study

Background: Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability.Aims: Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome.Methods: This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed.Results: We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300 mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24 h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality.Conclusions: Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE

The Lancet Psychiatry Commission : a blueprint for protecting physical health in people with mental illness

No abstract available