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 > 300mg/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 24h 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.

Alcoholic Liver Disease Among Patients with Wernicke Encephalopathy: A Multicenter Observational Study.

BACKGROUND: data regarding the association between Wernicke encephalopathy (WE) and alcoholic liver disease (ALD) are scarce in spite of alcohol consumption being the main risk factor for WE. AIMS: to describe the frequency of ALD in a cohort of patients diagnosed with WE and alcohol use disorders (AUDs) and to compare the characteristics of WE patients with and without ALD. METHODS: we conducted an observational study in 21 centers through a nationwide registry of the Spanish Society of Internal Medicine. WE Caine criteria were applied and demographic, clinical, and outcome variables were analyzed. RESULTS: 434 patients were included in the study, of which 372 were men (85.7%), and the mean age was 55 ± 11.8 years. ALD was present in 162 (37.3%) patients and we found a higher percentage of cases with tremor, flapping and hallucinations in the ALD group. A total of 22 patients (5.0%) died during admission (7.4% with ALD vs 3.7% without ALD; P = 0.087). Among the ALD patients, a relationship between mortality and the presence of anemia (Odds ratio [OR]=4.6 Confidence interval [CI]95% 1.1-18.8; P = 0.034), low level of consciousness (OR=4.9 CI95% 1.1-21.2; P = 0.031) and previous diagnosis of cancer (OR=10.3 CI95% 1.8-59.5; P = 0.009) was detected. Complete recovery was achieved by 27 patients with ALD (17.8%) and 71 (27.8%) without ALD (P = 0.030). CONCLUSION: the association of WE and ALD in patients with AUDs is frequent and potentially linked to differences in clinical presentation and to poorer prognosis, as compared to alcoholic patients with WE without ALD.

Handgrip strength and lean mass are independently related to brain atrophy among alcoholics.

BACKGROUND: In neurodegenerative disorders or in normal aging humans a relationship between muscle mass and/or performance and brain volume was observed, that is not dependent on age or other confounding factors. The aim of the present study is to analyse the relationship between lean mass and handgrip strength in alcoholics, who frequently show brain and muscle atrophy. METHODS: It was included 101 male patients aged 58.35 ± 11.59 years, and 44 controls, all of them workers of our hospital, drinkers of less than 20 g ethanol/day, of similar age. Patients and controls underwent dominant handgrip assessment with a Collins' dynamometer, whole body composition analysis by densitometry, and brain computed tomography (CT) examination, with further calculation of several indices indicative of brain atrophy. MAIN RESULTS: 1) Brain atrophy is a very common finding among alcoholics, both among cirrhotics and non-cirrhotics. 2) Alcoholics show a marked reduction in handgrip strength, and also in lean mass, especially at the arms and legs -but not in the trunk, even if patients with ascites were excluded.3) There is a relationship between reduced lean mass and brain atrophy, and a close correlation between handgrip strength and brain atrophy, that is independent of age and liver function. 4) Total fat amount is not different among alcoholics and controls, but there are marked differences in fat distribution: alcoholics show less fat in arms, but more fat in trunk, so that if we calculate the peripheral fat/trunk fat index, marked differences were observed among alcoholics and controls. Neither total fat nor fat distribution were related to brain atrophy. CONCLUSION: among alcoholics, as in other neurodegenerative conditions, there is a relationship between reduced lean mass and brain atrophy, and a close correlation between handgrip strength and brain atrophy, that is independent of age, duration of ethanol consumption and liver function.

Soluble Klotho and Brain Atrophy in Alcoholism.

AIM: Fibroblast growth factor (FGF-23) and α-Klotho (Klotho) levels may be altered in inflammatory conditions, possibly as compensatory mechanisms. Klotho exerts a protective effect on neurodegeneration and improves learning and cognition. No data exist about the association of Klotho and FGF-23 levels with brain atrophy observed in alcoholics. The aim of this study is to explore these relationships. SHORT SUMMARY: FGF-23 and Klotho levels are altered in inflammation, possibly as compensatory mechanisms. Klotho enhances learning, but its role in ethanol-mediated brain atrophy is unknown. We found higher FGF-23 and lower Klotho levels in 131 alcoholics compared with 41 controls. Among cirrhotics, Klotho was higher and inversely related to brain atrophy. METHODS: The study was performed on 131 alcoholic patients (54 cirrhotics) and 41 age- and sex-matched controls, in whom a brain computed tomography (CT) was performed and several indices were calculated. RESULTS: Marked brain atrophy was observed among patients when compared with controls. Patients also showed higher FGF-23 and lower Klotho values. However, among cirrhotics, Klotho values were higher. Klotho was inversely related to brain atrophy (for instance, ventricular index (ρ = -0.23, P = 0.008)), especially in cirrhotics. Klotho was also directly related to tumor necrosis factor (TNF) alpha (ρ = 0.22; P = 0.026) and inversely to transforming growth factor (TGF)-ß (ρ = -0.34; P = 0.002), but not to C-reactive protein (CRP) or malondialdehyde levels. FGF-23 was also higher among cirrhotics but showed no association with CT indices. CONCLUSIONS: Klotho showed higher values among cirrhotics, and was inversely related to brain atrophy. FGF-23, although high among patients, especially cirrhotics, did not show any association with brain atrophy. Some inflammatory markers or cytokines, such as CRP or TGF-ß were related to brain atrophy.

Differences Between Alcoholic and Nonalcoholic Patients With Wernicke Encephalopathy: A Multicenter Observational Study.

OBJECTIVE: To analyze the differences in characteristics and prognosis between alcoholic and nonalcoholic patients with Wernicke encephalopathy (WE). PATIENTS AND METHODS: A retrospective observational cohort of 468 patients diagnosed with WE with at least 2 Caine criteria was selected from all patients discharged with a diagnosis of WE from 21 medical centers in Spain from January 1, 2000, through December 31, 2012. Demographic, clinical, and outcome variables were described. RESULTS: Among the 468 patients, the most common risk factor was alcoholism (n=434 [92.7%]). More than one-third of patients (n=181 [38.7%]) had the classic WE triad of symptoms (ocular signs, cerebellar dysfunction, and confusion). Among 252 patients for whom magnetic resonance imaging data were available, 135 (53.6%) had WE-related lesions and 42 (16.7%) had cerebellar lesions. Of the 468 patients, 25 (5.3%) died during hospitalization. Alcoholic patients presented more frequently than nonalcoholic patients with cerebellar signs (P=.01) but less frequently with ocular signs (P=.02). Alcoholic patients had a significantly higher frequency of hyponatremia (P=.04) and decreased platelet count (P=.005) compared with nonalcoholics. Alcoholic patients were diagnosed earlier than nonalcoholics (median time to diagnosis, 1 vs 4 days; P=.001) and had shorter hospitalizations (13 vs 23 days; P=.002). CONCLUSION: Compared with nonalcoholic patients, alcoholic patients with WE are more likely to present with cerebellar signs and less likely to have ocular signs. Diagnosis may be delayed in nonalcoholic patients. Mortality in the present series was lower than described previously.

Metabolic syndrome and cardiovascular risk in diabetic population of El Hierro, Canary Islands / Síndrome metabólico y riesgo cardiovascular en la población diabética de El Hierro, Islas Canarias

Introduction: In the Canary Islands there is a high prevalence of vascular risk factors. Objective: To analyze the clinical characteristics of 300 patients with type 2 diabetes in El Hierro, in the Canary Islands. Methods: Patients were assessed at the Internal Medicine Unit of the hospital from 1982 to 2010, and followed up until December 2014 or until death. The sample is composed of 154 women and 156 men (52%). Results: mean age was 66.40 ± 11.60 years, with an average follow-up time of 11.04 ± 4.93 years, and 80.3% were diagnosed of metabolic syndrome, signifi cantly more frequent among women (86.43% vs74.67%, χ2 = 5.62, p = 0.018). During the follow-up period, 51 patients died and a signifi cant proportion developed new cardiovascular complications, such as heart failure (6.7%), ischemic heart disease (17.3%), atrial fi brillation (14.3%), stroke 7%), or peripheral arterial disease (6.9%). Cox regression analysis showed that, although advanced age was the major factor involved in the development of all these complications and in mortality, low cholesterol levels were related to the development of ischemic heart disease and mortality, results that were not dependent on the consumption of statins (as in other examples of inverse epidemiology). Ethanol consumption was related to the incidence of peripheral arterial disease. Conclusions: Old age was the main factor involved in the development of complications and mortality. In addition, low cholesterol levels were related to the development of ischemic heart disease and mortality.

Introducción: en Canarias existe una elevada prevalencia de factores de riesgo vascular, superior a la del resto de España.Objetivo: analizar las características clínicas de 300 adultos diabéticos tipo II de El Hierro, en el Archipiélago Canario. Métodos: los pacientes fueron valorados en la Unidad de Medicina Interna del hospital entre 1982 a 2010, y seguidos hasta diciembre de 2014 o hasta su fallecimiento. La muestra se compone de 154 mujeres y 156 hombres (52%). Resultados: la edad media fue de 66.40 ± 11,60 años, con un tiempo medio de seguimiento de 11,04 ± 4,93 años, y el 80,3% fue diagnosticados de síndrome metabólico, significativamente más frecuente entre las mujeres (86,43% vs.74,67%; χ2 = 5,62, p = 0,018). Durante el periodo de seguimiento 51 pacientes murieron, y una proporción significativa desarrolló nuevas complicaciones cardiovasculares, como insuficiencia cardiaca (6,7%), cardiopatía isquémica (17,3%), fibrilación auricular (14,3%), ictus (4,7%), o enfermedad arterial periférica (6,9%). Mediante análisis de regresión de Cox observamos que, aunque la edad avanzada fue el factor principal implicado en el desarrollo de todas estas complicaciones y en la mortalidad, los niveles bajos de colesterol se relacionaron con el desarrollo de cardiopatía isquémica y de mortalidad, resultados que no eran dependientes del consumo de estatinas (como en otros ejemplos de epidemiología inversa). El consumo de etanol se relacionó con la incidencia de la enfermedad arterial periférica. Conclusiones: la edad avanzada fue el factor principal implicado en el desarrollo de complicaciones y mortalidad. Además, los niveles bajos de colesterol se relacionaron con el desarrollo de cardiopatía isquémica y mortalidad.

Vitamina D, riesgo vascular y mortalidad en pacientes alcohólicos / Vitamin D, vascular risk, and mortality in alcoholic patients

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Vitamin D, vascular calcification and mortality among alcoholics.

AIMS: To analyze the relationship between low vitamin D levels and mortality among alcoholics. METHODS: One hundred twenty-eight alcoholic patients admitted to our hospital were followed up as outpatients. Nutritional status was evaluated measuring percentages of fat and lean mass in different body compartments. RESULTS: Lower vitamin D levels were observed in patients with worse liver function. Vitamin D was lower in patients with lower total lean mass (Z = 2.8, P = 0.005), but it was not related to fat mass. There was a significant trend to higher long-term mortality among non-cirrhotics with vitamin D levels below 30 ng/ml, although Cox's regression model revealed that only Child score and age were independently related to mortality. CONCLUSION: Vitamin D deficiency is common among alcoholic patients and is associated with low lean mass and liver dysfunction. Among non-cirrhotics, serum vitamin D levels below 30 ng/ml are associated with a greater long-term mortality.

Prognosis of osteopenia in chronic alcoholics.

Osteoporosis is frequent among alcoholics all by a direct effect of ethanol, malnutrition, and liver failure. Therefore, it may be related to survival. The aim of this study was to assess bone mineral density (BMD), bone mineral content, hormonal status, and to determine prognostic value of these parameters in a total of 124 alcoholics followed up for a median period of 57 months. Several bone homeostasis-related hormones were measured in patients and age- and sex-matched controls. Whole-body densitometry was performed by a Hologic QDR-2000 (Waltham, MA) densitometer; nutritional status and liver function were assessed. Sixty patients underwent a second evaluation 6 months later. Patients showed lower serum insulin-like growth factor-1 (median=58, interquartile range [IQR]=33-135 vs. 135ng/mL, IQR=116-243ng/mL, P<.001), vitamin D (25.5, IQR=18.3-36.8 vs. 79.9pg/mL, IQR=59.2-107.8pg/mL, P<.001), and osteocalcin (2.1, IQR=1.1-4.5 vs. 6.5ng/mL, IQR=4.7-8.7ng/mL, P<.001) than controls, and lower BMD values, and lower Z- and T-scores at right and left legs and arms, thoracic and lumbar spine, pelvis, and right and left ribs. By multiple regression analysis, BMD mainly depends on nutritional parameters and liver function. Kaplan-Meier curves show that subtotal BMD and BMD at both arms and pelvis were significantly related with survival. Patients who had lost total hip BMD after 6 months showed a shorter survival than those who had not, but using Cox's regression, encephalopathy, ascites, and nutritional parameters displaced BMD as prognostic factor. Therefore, osteopenia ensues in chronic alcoholic patients. It mainly depends on poor nutrition and is related to survival, although surpassed in this sense by encephalopathy, ascites, and nutritional parameters.

Relative and combined effects of chronic alcohol consumption and HCV infection on serum zinc, copper, and selenium.

In alcoholic hepatitis, Kupffer cells are activated by intestinal gram-bacteria, leading to cytokine production and free radicals release, which, enhancing cytokine secretion, create a positive feedback loop which contributes to liver inflammation. Free radicals also damage the liver in chronic hepatitis C virus (HCV) infection, a condition frequently associated to alcohol consumption. In both situations, activity of antioxidant enzymes and of its cofactors zinc (Zn), selenium (Se), and copper (Cu) is important. This study was performed to assess the relative and combined effects of chronic alcoholism and HCV infection on serum Se, Zn, and Cu, and its relation with serum malondialdehyde (MDA) and tumor necrosis factor-α, interferon-γ, and interleukins (IL) 4, 6, and 8, in 19 HCV- alcoholic patients, 12 HCV+ alcoholic patients, nine HCV+ non-alcoholic patients, and 20 controls. Serum Zn and Se were lower in both HCV+ and HCV- alcoholic patients, whereas serum Cu was lower in HCV+ individuals. Serum Zn and Se were related to liver function derangement. MDA levels were higher in alcoholics, but no relation was observed between trace elements and MDA or cytokines, so that our results do not support a relevant role of the analyzed trace elements in the pathogenesis of chronic liver disease.

Prognostic value of serum selenium levels in alcoholics.

In alcoholics, exposure of Kupffer cells to intestinal-borne Gram-negative bacteria increases free radical release, which may, in turn, enhance cytokine secretion, creating a positive feedback loop, which contributes to liver inflammation. Impaired antioxidant mechanisms further aggravates this scenario. Some trace elements, such as selenium, are main cofactors of antioxidant enzymes. Some authors have found low Se levels in alcoholics in relation either with undernutrition, liver dysfunction, or intensity of alcoholism, but in general, Se supplementation has no effect on survival. In this study we measured serum Se in 16 controls and 76 alcoholics, 34 of them cirrhotics, 68 of whom were followed up for a median period of 38 months; 17 died during this period. Se levels were lower in patients than in controls and were related to prothrombin activity and nutritional status, more closely to this last parameter (stepwise logistic regression analysis). Patients who died showed lower Se values than those who survived. Se values over the median were associated with better survival, assessed by Kaplan-Meier curves and log-rank test. However, in multivariate analysis (Cox regression model), prothrombin activity displaced serum Se as a prognostic factor. We conclude that serum Se levels are low in alcoholics; these low values depend more heavily on impaired nutrition but also on liver dysfunction; although low Se levels were associated with a higher mortality, prothrombin activity displaced serum Se when survival was assessed using Cox's regression model.