Value of inflammatory response and oxidative damage in the diagnosis of infections in severe alcoholic hepatitis.

Severe alcoholic hepatitis is the most lethal complication in alcohol dependent patients. The concurrence of infections in these patients is very frequent. Both produce a systemic inflammatory response syndrome (SIRS), secondary to intense release of inflammatory cytokines, which can complicate the diagnosis. In our study, Interleukin (IL)-6 and IL-10 levels are higher in patients with SIRS (p<0.001 and p = 0.033, respectively). IL-4, IL-6, Interferon-gamma (IFNγ), Tumor necrosis factor alpha (TNFα) and IL-17 levels correlate with liver function, as estimated by MELD-Na (p = 0.018, p = 0.008, p = 0.009, p = 0.016 and p = 0.006, respectively). Malondialdehyde (MDA), a product of lipid peroxidation and marker of cell damage, also correlates with liver function (p = 0.002), but not with SIRS or infections. Only elevated IL-6 correlates independently with the presence of infections (RR=1.023 IC 95% 1.000-1.047), so it may be useful for the correct diagnosis in these patients. Values greater than 30 pg/mL have a sensitivity: 86.7% and specificity: 94.7% for the diagnosis of infections.

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.

Sarcopenic Obesity in People with Alcoholic Use Disorder: Relation with Inflammation, Vascular Risk Factors and Serum Vitamin D Levels.

In recent years, the terms sarcopenia, sarcopenic obesity, and osteosarcopenic obesity (OSO) were coined to define a situation in elderly people strongly associated with frailty and increased mortality. Possibly, a complex interplay of several hormones and cytokines are involved in its development. Ongoing research detected that OSO may occur at any age and in several conditions. The prevalence of OSO in alcoholism was poorly analyzed. The aim of this study was to analyze the prevalence of OSO in alcoholism and its relationship with proinflammatory cytokines and/or common complications of alcoholism, such as cirrhosis, cancer, or vascular disease. We included 115 patients with alcoholic use disorder. Body composition analysis was performed by double X-ray absorptiometry. Handgrip strength was recorded using a dynamometer. We assessed liver function according to Child's classification, and determined serum levels of proinflammatory cytokines (TNF-α, IL-6, IL-8), routine laboratory variables, and vitamin D. People with alcoholic use disorder showed a high prevalence of OSO, especially regarding OSO obesity (60%), OSO osteopenia (55.65%), and OSO lean mass (60.17%). OSO handgrip was closely, independently, related to the presence of vascular calcification (χ2 = 17.00; p < 0.001). OSO handgrip was related to several proinflammatory cytokines and vitamin D. Vitamin D deficiency kept a close correlation with OSO handgrip (rho = -0.54, p < 0.001). Therefore, among people with alcohol use disorder, OSO prevalence was high. OSO handgrip is related to serum proinflammatory cytokine levels supporting the possible pathogenetic role of these cytokines on OSO development. Vitamin D deficiency is related to OSO handgrip suggesting its pathogenetic involvement in sarcopenia in patients with alcohol use disorder. The close association between OSO handgrip and vascular calcification is clinically relevant and suggests that OSO handgrip may constitute a prognostic tool in these patients.

Mean platelet volume and mortality in patients with alcohol use disorder.

Several recent studies have pointed out the relationship of platelet size with increased mortality or adverse clinical course. Most studies show that increased mean platelet volume (MPV) may be associated with a deleterious outcome in different settings such as sepsis or neoplasia, whereas other researchers have found the opposite. In inflammatory conditions there is an altered secretion of several cytokines, some of them exerting a marked influence on platelet biogenesis and/or on platelet activation and aggregation. Alcohol use disorder is a chronic situation characterized by a protracted low-grade inflammation. In this study we analyze the relationship between proinflammatory cytokines and MPV and their relationships with mortality in patients with alcohol abuse. We determined serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 and routine laboratory variables among 184 patients with alcohol use disorder admitted to our hospital and followed-up for a median of 42 months. We found that MPV was inversely related to TNF-α (ρ=-0.34), and directly to IL-8 (ρ=0.32, p<0.001 in both cases) and to IL-6 (ρ=0.15; p = 0.046). Reduced MPV was related both with short-term (<6 months) and long-term mortality. Conclusion: These results suggest that inflammatory cytokines are strongly related to MPV. A low MPV is associated with a poor prognosis among patients with alcohol use disorder.

Sclerostin, vascular risk factors, and brain atrophy in excessive drinkers.

Objective: Heavy alcohol consumption causes several organic complications, including vessel wall calcification. Vascular damage may be involved in the development of brain atrophy and cognitive impairment. Recently, sclerostin (whose levels may be altered in alcoholics) has emerged as a major vascular risk factor. The objective of the present study is to analyze the prevalence of vascular calcifications in alcoholics, and the relationships of these lesions with brain atrophy, as well as the role of sclerostin on these alterations. Patients and methods: A total of 299 heavy drinkers and 32 controls were included. Patients underwent cranial computed tomography, and several indices related to brain atrophy were calculated. In addition, patients and controls underwent plain radiography and were evaluated for the presence or absence of vascular calcium deposits, cardiovascular risk factors, liver function, alcohol intake, serum sclerostin, and routine laboratory variables. Results: A total of 145 (48.47%) patients showed vascular calcium deposits, a proportion significantly higher than that observed in controls (χ2 = 16.31; p < 0.001). Vascular calcium deposits were associated with age (t = 6.57; p < 0.001), hypertension (t = 5.49; p < 0.001), daily ethanol ingestion (Z = 2.18; p = 0.029), duration of alcohol consumption (Z = 3.03; p = 0.002), obesity (χ2 = 4.65; p = 0.031), total cholesterol (Z = 2.04; p = 0.041), triglycerides (Z = 2.05; p = 0.04), and sclerostin levels (Z = 2.64; p = 0.008). Calcium deposits were significantly related to Bifrontal index (Z = 2.20; p = 0.028) and Evans index (Z = 2.25; p = 0.025). Serum sclerostin levels were related to subcortical brain atrophy, assessed by cella media index (Z = 2.43; p = 0.015) and Huckmann index (ρ = 0.204; p = 0.024). Logistic regression analyses disclosed that sclerostin was the only variable independently related to brain atrophy assessed by altered cella media index. Sclerostin was also related to the presence of vascular calcifications, although this relationship was displaced by age if this variable was also included. Conclusion: Prevalence of vascular calcification in alcoholics is very high. Vascular calcium deposits are related to brain atrophy. Serum sclerostin is strongly related to brain shrinkage and also shows a significant relationship with vascular calcifications, only displaced by advanced age.

Serum Myostatin among Excessive Drinkers.

Myostatin acts as a negative regulator of muscle growth. Its effect on fat mass is subject to debate. Among alcoholics, there is a high prevalence of muscle atrophy, and increased fat deposition has been also described in these patients. Myostatin could be involved in these alterations, but its relationships with body composition have been scarcely studied in alcoholic patients. To analyze the behavior of myostatin among alcoholics and its relationship with alcohol intake, liver function, and body composition. We investigated serum myostatin in 59 male patients and 18 controls. Patients were all heavy drinkers admitted with organic complications related to excessive ethanol ingestion. Densitometry analysis was used to assess body composition in 46 patients. Handgrip was assessed in 51 patients. Patients showed lower myostatin values than controls (Z = 3.80; p < 0.001). There was a significant relationship between myostatin and fat at the right leg (ρ = 0.32; p = 0.028), left leg (ρ = 0.32; p = 0.028), trunk (ρ = 0.31, p = 0.038), total fat proport ion (ρ = 0.33, p = 0.026), and gynecoid fat distribution (ρ = 0.40, p = 0.006) but not with lean mass (total lean ρ = 0.07; p = 0.63; trunk lean ρ = 0.03; p = 0.85; lower limbs ρ = 0.08; p = 0.58; upper limbs ρ = 0.04 p = 0.82; android ρ = 0.02; p = 0.88, or gynoid lean mass ρ = 0.20; p = 0.19). In total, 80.43% of patients showed at least one criterion of osteosarcopenic adiposity (OSA). Myostatin was related to OSA obesity. We also observed higher myostatin values among patients with body mass index > 30 kg/m2. Serum myostatin was lower among excessive drinkers, and it was related to increased fat deposition among these patients but not to lean mass, handgrip, or bone mineral density.

Klotho Levels and Their Relationship with Inflammation and Survival among Alcoholic Patients.

α-Klotho (Klotho) is an antiaging hormone with anti-inflammatory and antioxidative properties. Some studies suggest that Klotho increases in response to enhanced oxidative damage and inflammation. Alcoholism is a proinflammatory condition. The aim of this study was to analyze the relationship between Klotho and the serum levels of the inflammatory markers in alcoholic liver disease and to assess its prognostic value. We included 184 alcoholics and 35 age- and sex-matched controls. We determined the serum levels of Klotho, the tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and malondialdehyde (MDA), and routine laboratory variables. Patients were followed-up with during 16 ± 18 months; 67 patients died. Klotho levels were higher among cirrhotics (with KW = 37.00 and p < 0.001) and were related to the Child−Pugh score (with KW = 15.96 and p < 0.001) and to the TNF-α (ρ = 0.28; p < 0.001) and MDA (ρ = 0.21; p = 0.006). The child's groups were associated with mortality, both in the univariate (with the log-rank = 13.56, p = 0.001, Breslow = 12.33, and p = 0.002) and multivariate (with ß = 0.43, p = 0.02, and OR = 1.53 (1.07−2.15)) analyses, also introducing Klotho and the TNF-α as dichotomic variables. However, the independent prognostic value of the Child's groups was displaced by Klotho when only cirrhotics were considered; Klotho, over the median (574.4 pg/mL), was associated with higher mortality (with p = 0.04 and OR = 2.68 (1.06−6.84)). We conclude that Klotho is increased in liver cirrhosis. It is directly related to TNF-α, MDA, and to mortality in cirrhotics.

Sclerostin in Excessive Drinkers: Relationships with Liver Function and Body Composition.

BACKGROUND: Sclerostin was initially described as an inhibitor of the Wnt-ß catenin bone-forming pathway, but it also exerts important effects on intermediate metabolism and body composition. Osteosarcopenia and altered body fat distribution are common findings in excessive drinkers. The role of sclerostin in these patients is uncertain. We aim to analyze the behavior of sclerostin in excessive drinkers and its relationships with body composition (fat mass, lean mass, bone mass), handgrip strength, body mass index (BMI), liver function and ethanol intake. METHODS: 107 male active heavy drinkers and 26 age-matched controls were included. Serum sclerostin was determined by ELISA. Body composition analysis was performed by double X-ray absorptiometry. Handgrip strength was recorded using a dynamometer. Liver function was assessed according to Child's classification. RESULTS: Sclerostin was higher among Child's C patients, keeping a relationship with deranged liver function. Obesity, defined according to BMI, and body fat were strongly related to sclerostin, being independent of serum creatinine and of liver function. The relationship of sclerostin with total hip bone mineral density was displaced by BMI. CONCLUSION: Deranged liver function is associated with higher sclerostin levels in alcoholics. Raised sclerostin levels are related to fat deposition and increased BMI.

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.

Brain-derived neurotrophic factor among patients with alcoholism.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is involved in neurogenesis and in the protection against oxidative damage and neuronal apoptosis. After exercise, there is an increased expression of this myokine, especially in skeletal muscle and brain. Low BDNF levels have been described in neurodegenerative diseases. Alcoholics show both muscle atrophy and brain atrophy. Thus, this study was performed in order to analyze serum BDNF levels among alcoholics and their associations with brain atrophy and muscle strength. METHODS: Serum BDNF values were determined to 82 male alcoholics and 27 age-matched controls, and compared with handgrip strength, with the presence of brain atrophy, assessed by computed tomography, and with the intensity of alcoholism and liver function derangement. RESULTS: BDNF levels and handgrip strength were significantly lower among patients. Handgrip strength was correlated with BDNF values, both in the whole population and in alcoholics, especially in patients over 59 years of age. BDNF was poorly related to liver dysfunction but showed no relationship with brain atrophy or age. CONCLUSION: Chronic alcoholics show decreased BDNF serum levels that are related to muscle function impairment rather than to age, brain atrophy, liver dysfunction, or the amount of ethanol consumed.

Incidence of cancer and mortality among heavy alcoholics.

BACKGROUND AND AIMS: Cancer risk is increased in alcoholics. Heavy ethanol consumption is also associated with other potentially lethal conditions such as cirrhosis, diabetes, hypertension, dyslipidemia or malnutrition, that increase mortality. The aim of the present study is to analyze the impact on mortality of new cancer development in a cohort of heavy alcoholics. METHODS: Three hundred and thirty nine heavy alcoholics (about 200 g ethanol/daily during more than 15 years), initially admitted for organic problems to our service (reference hospital) were prospectively followed up for a maximum period of 120 months (median = 26, interquartile range = 12-60 months), either as outpatients or during successive admissions. Clinical and laboratory evaluation including incidence of new cancer and drinking habits were recorded at each appointment, as well as mortality. RESULTS: During the study period 57 patients developed cancer and 151 died. Only 75 did not relapse in alcohol drinking. Mortality was related to deranged liver function, relapse of alcohol drinking, and malnutrition, whereas age, the development of new cancer, or the presence of diabetes, dyslipidemia or hypertension did not influence on mortality, especially in cirrhotics and among those who did not quit drinking. Cancer was related to mortality only among non-cirrhotics, together with ethanol abstention and age. CONCLUSIONS: Heavy drinking is associated with high mortality among alcoholic patients admitted to the hospital. If a patient is already cirrhotic or if there is drinking relapse, the development of a new cancer, the concurrent presence of diabetes, hypertension, dyslipidemia, or advanced age have no impact on survival. Mortality is only related to deranged liver function, relapse of alcohol drinking, and malnutrition.

Ferritin and liver fibrosis among patients with chronic hepatitis C virus infection.

INTRODUCTION: In chronic hepatitis C virus (HCV) infection there is increased iron absorption leading to iron overload, a fact that may promote ferritin synthesis. Theoretically, increased ferritin should promote ongoing liver fibrosis but disparate results have been described. OBJECTIVE: We analyze the behavior of iron metabolism- related variables, comparing them with fibrosis and inflammatory activity in liver biopsy in HCV infected patients. PATIENTS AND METHODS: We analyzed among 90 HCV patients subjected to liver biopsy prior to antiviral treatment the relationships of serum levels of iron, ferritin, transferrin, transferrin saturation index (TSI) and total iron binding capacity (TIBC) with liver fibrosis and histological severity, assessed by Metavir-f, Metavir-a and Knodell indices, as well as with liver function, and also compared the aforementioned iron metabolism- related variables with 34 controls. RESULTS: Patients showed higher values of sideremia (T = 2.04; p = 0.044) and transferrin (T = 2.29; p = 0.004) compared with controls; but not ferritin, that was significantly higher among the 33 patients who also consumed alcohol (Z = 2.05; p = 0.041). Most patients showed a well preserved liver function (86 cases, Child A). Patients with Child B or C showed higher ferritin levels (Z = 2.68; p = 0.007) and TSI (Z = 2.41; p = 0.016), but lower transferrin and TIBC (Z = 3.25; p = 0.001) than Child A patients. Transferrin and TIBC were directly related to albumin (ρ = 0.24; p = 0.026), whereas bilirubin showed direct relationships with iron (ρ = 0.25; p = 0.016), TSI (ρ = 0.39; p < 0.001) and ferritin (ρ = 0.36; p < 0.001). Both ferritin (ρ = -0.22; p = 0.04) and TSI (ρ = -0.25; p = 0.016) were related to platelet count. No relationships were observed between iron variables and Knodell index, but serum iron, serum transferrin, and TSI were directly related to Metavir-f score (ρ = 0.28; p = 0.009, ρ = 0.22; p = 0.044, and ρ = 0.22; p = 0.044, in this order). CONCLUSION: Alterations of iron related variables are relatively subtle in our series of 90 well compensated HCV patients. Serum ferritin was not related to liver fibrosis and increases only when alcoholism co-exists with HCV infection.

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.

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

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 (AU)

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, significantly more frequent among women (86.43% vs 74.67%, χ2 = 5.62, p = 0.018). During the follow-up period, 51 patients died and a significant proportion developed new cardiovascular complications, such as heart failure (6.7%), ischemic heart disease (17.3%), atrial fibrillation (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 (AU)

Homocysteine, Liver Function Derangement and Brain Atrophy in Alcoholics.

AIMS: Hyperhomocysteinemia may be involved in the development of brain atrophy in alcoholics. Its pathogenesis is multifactorial. In the present study, we analyse the relationship between homocysteine levels and brain atrophy, and the relative weight of co-existing factors such as liver function impairment, the amount of ethanol consumed, serum vitamin B12, B6, and folic acid levels on homocysteine levels and brain alterations in alcoholic patients. METHODS: We included 59 patients admitted to this hospital for major withdrawal symptoms and 24 controls. The mini-mental state examination test and a brain computed tomography (CT) scan were performed and several indices were calculated. Serum levels of homocysteine, folic acid, vitamin B6 and vitamin B12 were determined. Liver function was assessed by Child-Pugh score. The daily consumption of ethanol in grams per day and years of addiction were recorded. RESULTS: A total of 83.6% and 80% of the patients showed cerebellar or frontal atrophy, respectively. Patients showed altered values of brain indices, higher levels of homocysteine and vitamin B12, but lower levels of folic acid, compared with controls. Homocysteine, B12 and liver function variables showed significant correlations with brain CT indices. Multivariate analyses disclosed that Pugh's score, albumin and bilirubin were independently related to cerebellar atrophy, frontal atrophy, cella index or ventricular index. Serum vitamin B12 was the only factor independently related to Evans index. It was also related to cella index, but after bilirubin. Homocysteine levels were independently related to ventricular index, but after bilirubin. CONCLUSION: Vitamin B12 and homocysteine levels are higher among alcoholics. Liver function derangement, vitamin B12 and homocysteine are all independently related to brain atrophy, although not to cognitive alterations. SHORT SUMMARY: Hyperhomocysteinemia has been described in alcoholics and may be related to brain atrophy, a reversible condition with an obscure pathogenesis. We studied 59 patients and found that liver function derangement, vitamin B12 and homocysteine levels are all independently related to brain atrophy assessed by computed tomography, although we found no association between these parameters and cognitive alterations.

Alcoholism: a systemic proinflammatory condition.

Excessive ethanol consumption affects virtually any organ, both by indirect and direct mechanisms. Considerable research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of alcoholism. These cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria, which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut permeability. Reactive oxygen species (ROS) that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of ethanol. The effects of this increased cytokine secretion and ROS generation lie far beyond liver damage. In addition to the classic consequences of endotoxemia associated with liver cirrhosis that were described several decades ago, important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain, bone, muscle, heart, lung, gonads, peripheral nerve, and pancreas. These effects are even seen in alcoholics without significant liver disease. Therefore, alcoholism can be viewed as an inflammatory condition, a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent disease. In this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver.

Antioxidant vitamins and brain dysfunction in alcoholics.

AIMS: Alcohol induces cytokine secretion by Kupffer cells, which may exert also deleterious effects on distant organs, mediated in part by cytokine-derived increased production of reactive oxygen species (ROS). It is therefore important to assess antioxidant levels. The objective of this study is to analyse the relation of antioxidant vitamins with brain atrophy and cognitive dysfunction. METHODS: In 77 alcoholic patients admitted for withdrawal syndrome, subjected to brain computed tomography (CT), and 19 controls, we determined antioxidant vitamin levels and analysed their relationships with data of brain atrophy and dysfunction. Searching for causes of altered vitamin levels, we also assessed liver function, nutritional status, eating habits, alcohol intake, proinflammatory cytokine (TNF-α, IL-6, IL-8) levels and malondialdehyde (MDA) levels. RESULTS: Both retinol (vitamin A) and tocopherol (vitamin E) levels were decreased in alcoholics, the former in relation with liver failure, and the latter in relation with triglyceride levels and fat mass. Both were related to data of brain atrophy and cerebellar shrinkage (to which also IL-6 was significantly related). CONCLUSION: Among alcoholics, liver function impairment leads to altered serum vitamin A levels, which are related to brain alterations. Vitamin E levels are also decreased, but although in relation with liver function impairment, its decrease seems to be more dependent on nutritional status and irregular eating habits. Both vitamins are lower in patients with cerebellar atrophy and other features related to brain atrophy.

Interleukin-15 and other myokines in chronic alcoholics.

AIMS: Interleukin (IL)-15 is highly expressed in skeletal muscle, where it exerts anabolic effects, increasing protein content in muscle fibres and promoting muscle growth. Alcoholics frequently suffer myopathy. Therefore, we analyse the behaviour of IL-15 (and other myokines, such as IL-6, IL-8 and tumour necrosis factor α (TNF-α)) in alcoholics. METHODS: These myokines and also malondialdehyde (MDA)--a lipid peroxidation product--were determined by radioimmunoanalytic techniques in blood samples of 35 chronic alcoholics and 13 age- and sex-matched controls, and compared with body composition, nutritional status, liver function, amount of ethanol and routine biochemical variables. RESULTS: IL-15, IL-6, TNF-α, IL-8 and MDA were all higher in alcoholics than in controls; MDA and IL-6 were clearly related with liver function impairment and short-term prognosis, whereas IL-15 was higher among those who died and was related to serum bilirubin. No relation was found between IL-15 and lean mass. CONCLUSION: IL-15 levels were higher in alcoholics than in controls, especially among those who died within 18 months after admission. They are not related with muscle mass, intensity of alcoholism or nutritional status, but only with serum bilirubin. IL-6 showed inverse correlations with liver function, intensity of alcoholism, nutritional status, left arm muscle mass and short-term mortality.

Vitamin D and nutritional status are related to bone fractures in alcoholics.

BACKGROUND: Bone fractures are common in alcoholics. AIMS: To analyse which factors (ethanol consumption; liver function impairment; bone densitometry; hormone changes; nutritional status, and disrupted social links and altered eating habits) are related to bone fractures in 90 alcoholic men admitted to our hospitalization unit because of organic problems. METHODS: Bone homoeostasis-related hormones were measured in patients and age- and sex-matched controls. Whole-body densitometry was performed by a Hologic QDR-2000 (Waltham, MA, USA) densitometer, recording bone mineral density (BMD) and fat and lean mass; nutritional status and liver function were assessed. The presence of prevalent fractures was assessed by anamnesis and chest X-ray film. RESULTS: Forty-nine patients presented at least one fracture. We failed to find differences between patients with and without fractures regarding BMD parameters. Differences regarding fat mass were absent, but lean mass was lower among patients with bone fracture. The presence of fracture was significantly associated with impaired subjective nutritional evaluation (χ² = 5.79, P = 0.016), lower vitamin D levels (Z = 2.98, P = 0.003) and irregular eating habits (χ² = 5.32, P = 0.02). Reduced lean mass and fat mass, and altered eating habits were more prevalent among patients with only rib fractures (n = 36) than in patients with multiple fractures and/or fractures affecting other bones (n = 13). These last were more closely related to decompensated liver disease. Serum vitamin D levels showed a significant relationship with handgrip strength (ρ = 0.26, P = 0.023) and lean mass at different parts of the body, but not with fat mass. By logistic regression analysis, only vitamin D and subjective nutritional evaluation were significantly, independently related with fractures. CONCLUSION: Prevalent fractures are common among heavy alcoholics. Their presence is related more closely to nutritional status, lean mass and vitamin D levels than to BMD. Lean mass is more reduced, nutritional status is more impaired and there is a trend to more altered eating habits among patients with rib fractures, whereas multiple fractures depend more heavily on advanced liver disease.