Significance of Markers of Monocyte Activation (CD163 and sCD14) and Inflammation (IL-6) in Patients Admitted for Alcohol Use Disorder Treatment.

BACKGROUND: Monocyte activation and inflammation are prominent features of alcohol-related liver disease; however, they have not been thoroughly assessed in patients with alcohol use disorder (AUD) without overt liver disease. This study aimed to analyze associations among clinical and laboratory variables and markers of monocyte activation (CD163 and sCD14), and inflammation (interleukin [IL]-6) among AUD patients. METHODS: We analyzed the aforementioned associations in the highest quartile in 289 patients (77.5% male; median age, 50 years) consecutively admitted for alcohol detoxification in 2 tertiary hospitals in the Barcelona metropolitan area, Spain. RESULTS: Median alcohol intake was 142 g/d; median glucose, albumin, creatinine, and bilirubin levels (mg/dl), 92, 40, 0.78, and 0.69, respectively; median AST, 41 U/l; median hemoglobin, median corpuscular volume, and platelet count, 14.1 g/dl, 94.8 fL, and 189 × 109 /l, respectively; median cholesterol, triglyceride, fibrinogen, and ferritin levels, 187 mg/dl, 109.3 mg/dl, 341 mg/dl, and 177 ng/ml, respectively. In addition, 36.7% patients had an erythrocyte sedimentation rate >20 mm, 32.5% had a C-reactive protein (CRP) level of >5 mg/l, and 10.9% were hepatitis C virus (HCV)-positive. Median CD163, sCD14, and IL-6 levels were 759, 1.68 × 106 , and 4.37 pg/ml, respectively. On logistic regression analyses, glucose, AST, bilirubin, hemoglobin levels, and HCV infection (adjusted odds ratio [aORs]: 1.01, 1.02, 3.04, and 9.73, respectively) were associated with CD163. Glucose, AST, triglyceride, and CRP >5 mg/l (aORs: 1.02, 1.01, 1.00, and 3.49, respectively) were associated with sCD14. Alcohol consumption upon admission, MCV, total cholesterol levels, and CRP >5 mg/l (aORs: 0.99, 1.05, 0.99, and 2.56, respectively) were associated with IL-6. CONCLUSIONS: Monocyte activation and systemic inflammation are associated with higher glucose, liver enzyme, and lipid levels, HCV infections, and CRP of >5 mg/l, thus potentially identifying patients with AUD at high risk of midterm poor outcomes.

DSM-5 in patients seeking their first treatment for alcohol use disorder. Sex differences in the multicenter CohRTA study. / DSM-5 en pacientes que solicitan el primer tratamiento del trastorno por uso de alcohol. Diferencias de sexo en el estudio multicéntrico CohRTA.

OBJECTIVE: We aimed to analyze sex differences in the DSM-5 criteria among patients admitted to  their first treatment of alcohol use disorder (AUD). METHODS: Assessment of AUD was carried out using DSM-5 diagnostic criteria in a multicenter study (CohRTA) within the Spanish Network on Addictive Disorders. Further, baseline questionnaires including socio-demographics, family history, lifetime alcohol consumption and other substance use, as well as clinical and laboratory parameters were obtained during admission. RESULTS: 313 patients (74.8%M) were eligible; mean age at first AUD treatment was 48.8 years (standard deviation (SD): 9.9 years). Age at onset of alcohol use was 15.9 years (SD: 3.3 years) and age at starting regular alcohol consumption was 25.6 years (SD: 9.6 years). Almost 69.3% of patients were tobacco smokers and 61% had family history of AUD. Regarding other substance use, 7.7% were current cocaine users and 18.2% were cannabis users. Women started regular alcohol consumption later than men (p<,001) and used benzodiazepines more frequently (p=.013). According to DSM-5, 89.5% of cases had severe AUD (≥6 criteria). In the adjusted analysis (logistic regression), men were more likely to neglect major rules (OR=1.92, 95%CI: 1.06-3.48) and to have hazardous alcohol use (OR=3.00, 95%CI: 1.65-5.46). DISCUSSION: DSM-5 detects sex differences in patients seeking their first AUD treatment. Social impairment and risky alcohol use are significantly more frequent in men.

Objetivo: Analizar las diferencias de sexo en los criterios diagnósticos del DSM-5 de los pacientes que solicitan un tratamiento para el trastorno por uso de alcohol (TUA) por primera vez. Métodos: Pacientes incluidos entre enero 2014 y marzo 2016 en el estudio multicéntrico CohRTA de la Red de Trastornos Adictivos. El diagnóstico del TUA se realizó mediante el DSM-5. Además, se recogieron datos sociodemográficos, sobre el consumo de alcohol y otras sustancias, variables clínicas y una analítica general. Resultados: se incluyeron 313 pacientes (74,8% hombres); la edad al inicio del primer tratamiento fue de 48,8 años (desviación estándar (DE): 9,9 años), la edad al inicio del consumo de alcohol de 15,9 años (DE: 3,3 años) y la de inicio del consumo regular de 25,6 años (DE: 9,6 años). Un 69,3% de los pacientes eran fumadores y un 61% tenían antecedentes familiares de TUA. Un 7,7% eran consumidores de cocaína y un 18,2% de cannabis. Las mujeres iniciaron el consumo regular de alcohol más tarde que los hombres (p<,001) y usaban benzodiacepinas con mayor frecuencia (p=,013). Según el DSM-5, el 89,5% de los pacientes presentaban un TUA grave (≥6 criterios). En el análisis ajustado (regresión logística), los hombres tenían mayor probabilidad de presentar el criterio diagnóstico relacionado con el incumplimiento de los deberes fundamentales en el trabajo o en el hogar (OR=1,92, IC95%: 1,06-3,48) y el criterio diagnóstico de consumir alcohol en situaciones de riesgo físico (OR=3,00, IC95%: 1,65-5,46). Discusión: El DSM-5 detecta diferencias de sexo en pacientes que solicitan el primer tratamiento del TUA. El deterioro social y el consumo de alcohol de riesgo son significativamente más frecuentes en hombres.

Five-Year Incidence of Hospital-Based Emergencies Related to Acute Recreational Intoxication in Minors.

BACKGROUND: Alcohol or other drug (AOD) intoxication in minors is a public health challenge. We characterized underage patients admitted to an emergency department (ED) with acute, recreational AOD intoxication. METHODS: We conducted a 5-year (2012 to 2016) analysis of minors admitted to the only hospital-based pediatric ED in an urban area. Episodes of AOD intoxication were selected using ICD-9-CM diagnostic codes. Sociodemographics, substance use and clinical characteristics, laboratory parameters, and discharge dispositions were collected through the revision of clinical charts. RESULTS: A total of 266 admissions related to recreational AOD intoxication in 258 patients occurred during the study period. Among the 258 patients, 127 (49.2%) were men, median age 16 years [IQR: 15 to 17 years], and 234 (90.7%) of episodes were alcohol-related. At admission, 202/256 (78.9%) patients had a Glasgow Coma Scale ≥ 13 points, the median systolic and diastolic blood pressure was 109 mmHg (IQR: 101 to 118 mmHg) and 67 mmHg (IQR: 60 to 73 mmHg), respectively, and the median blood glucose level was 112 mg/dl (IQR: 99 to 127 mg/dl). Only 72/258 (27.9%) patients underwent urine screening (22/72 (30.5%) were positive for cannabis), and only 30/258 (11.6%) were tested for blood ethanol (median: 185 mg/dl, IQR: 163 to 240 mg/dl). There was a trend in admissions occurring early in the morning of weekend days, and 249 (96.5%) patients were discharged home the day of admission. CONCLUSIONS: Though the severity of AOD intoxication seems to be mild to moderate, assessment of substance exposure is low and may underestimate polydrug use in underage populations.

Patients with alcohol use disorder: initial results from a prospective multicenter registry in the Spanish Network on Addiction Disorders. CohRTA Study. / Pacientes con trastorno por uso de alcohol: resultados iniciales de un registro multicéntrico en la Red de Trastornos Adictivos-RTA. Estudio CohRTA.

The Alcohol Program of the Spanish Network on Addictive Disorders-RTA requires a longitudinal study to address different research questions related to alcoholism. The cohort study (CohRTA) focuses on patients seeking treatment for alcohol use disorder, as a multicentre, collaborative research project aimed to improve secondary prevention and early diagnosis of pathological processes associated with the disorder. Methods: multicentre cohort study in adults (>18 years) seeking their first treatment of the disorder. Patients sign an informed consent and data is collected in an online platform specifically designed for the study; patients are also requested to provide biological samples that are stored in a biobank. Baseline and prospective, socio-demographic, epidemiological, clinical and treatment data are collected. Currently there are 10 participating centres that expect to recruit more than 1,000 patients. Results: As of December 2015, 344 patients (77% men) were included. Median age at admission was 50 years (IQR: 43-55 years). Median age at the start of alcohol consumption was 15 years (IQR: 14-18 years) and 61% of cases reported antecedents of alcohol use disorder in the family. During the 30 days prior to admission, alcohol consumption amounted to 12.5 SDU/day (IQR: 7.1-20 SDU/day), 72% of the patients were tobacco smokers and 30% currently used cocaine. Organising an open cohort of patients with alcohol use disorder may be crucial to better understand the clinical consequences of alcoholism in Spain. This cohort may potentiate quantitative and qualitative research within the Spanish Network on Addictive Disorders-RTA/RETICS. Having a well-established, representative cohort of patients will increase translational research on consequences of alcoholism in our country.

El Programa Alcohol de la Red de Trastornos Adictivos (RTA) requiere de un estudio clínico longitudinal para dar respuesta a preguntas de investigación en el trastorno por uso de alcohol. El proyecto CohRTA es un estudio multicéntrico de investigación cooperativa que se pone en marcha para mejorar la prevención secundaria y el diagnóstico precoz de los procesos patológicos asociados al trastorno por uso de alcohol. Método: estudio observacional en cohorte multicéntrica de pacientes mayores de 18 años que solicitan tratamiento del trastorno por primera vez y autorizan su participación. La información clínica se recoge en una plataforma online diseñada para el estudio y puede ir acompañada de una muestra biológica que se deposita en un biobanco. Se recogen datos basales y prospectivos, sociodemográficos, epidemiológicos, clínicos y de tratamiento. A diciembre de 2015 son 10 los centros proveedores de pacientes y se espera reclutar más de 1.000 pacientes en los próximos años. Resultados: se dispone de 344 pacientes (77% hombres) que cumplen los criterios de inclusión en el estudio y con una edad de 50 años (RIQ: 43-55 años). La edad de inicio de consumo de alcohol fue de 15 años (RIQ: 14-18 años) y un 61% tenían antecedente familiar de trastorno por uso de alcohol. Durante los 30 días previos al inicio del tratamiento los pacientes bebían 12.5 UBE/día (RIQ: 7.1-20 UBE/día), el 72% fumaba tabaco y el 30% consumía cocaína. Conclusiones: Disponer de una cohorte abierta y multicéntrica de pacientes con trastorno por uso de alcohol será útil para analizar las consecuencias del abuso de alcohol, potenciar la investigación traslacional y añadir valor a la investigación clínica y básica del Programa Alcohol dentro de RTA/RETICS. Con una cohorte bien establecida y representativa se espera aumentar la cantidad y calidad científica en relación a las complicaciones del trastorno por uso de alcohol y sus consecuencias clínicas y sociales en España.

Long-Term Mortality of Patients with an Alcohol-Related Wernicke-Korsakoff Syndrome.

AIMS: To characterize a series of contemporary patients with alcohol-related Wernicke's encephalopathy (WE) or Korsakoff's syndrome (KS) and to update the current prognosis of disease. METHODS: Retrospective and prospective study of patients diagnosed with an alcohol-related WE or KS between 2002 and 2011 in a tertiary hospital. Socio-demographic, alcohol use characteristics, signs and symptoms, co-morbidity and blood parameters were obtained at admission. Patients were followed up until 2013 and causes of death were ascertained through the review of charts. RESULTS: Sixty-one patients were included (51 with WE and 10 with KS). Among patients with WE, 78% were men and age at diagnosis was 57 years (interquartile range (IQR): 49-66). Twenty-three percent fulfilled the classic WE triad. Regarding Caine's criteria for WE, 70.6% presented with at least two out of four signs or symptoms. Median follow-up of patients with WE syndrome was 5.3 years (IQR: 2.6-8.8), the cumulated mortality was 45% and death rate of 7.4 × 100 person-years (95% confidence interval (CI): 4.8-10.9). Overall, 50% of patients would be expected to die within 8 years of WE episode and main causes of death included serious bacterial infections (44.5%) and cancer (33.3%). CONCLUSIONS: Survival of patients with an alcohol-related Wernicke-Korsakoff syndrome is poor; pursuing treatment of alcohol use disorder and early diagnosis of thiamine deficiency is a priority for improving clinical outcomes.

Alcohol Consumption during Pregnancy: Analysis of Two Direct Metabolites of Ethanol in Meconium.

Alcohol consumption in young women is a widespread habit that may continue during pregnancy and induce alterations in the fetus. We aimed to characterize prevalence of alcohol consumption in parturient women and to assess fetal ethanol exposure in their newborns by analyzing two direct metabolites of ethanol in meconium. This is a cross-sectional study performed in September 2011 and March 2012 in a series of women admitted to an obstetric unit following childbirth. During admission, socio-demographic and substance use (alcohol, tobacco, cannabis, cocaine, and opiates) during pregnancy were assessed using a structured questionnaire and clinical charts. We also recorded the characteristics of pregnancy, childbirth, and neonates. The meconium analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect the presence of ethyl glucuronide (EtG) and ethyl sulfate (EtS). Fifty-one parturient and 52 neonates were included and 48 meconium samples were suitable for EtG and EtS detection. The median age of women was 30 years (interquartile range (IQR): 26-34 years); EtG was present in all meconium samples and median concentration of EtG was 67.9 ng/g (IQR: 36.0-110.6 ng/g). With respect to EtS, it was undetectable (<0.01 ng/g) in the majority of samples (79.1%). Only three (6%) women reported alcohol consumption during pregnancy in face-to-face interviews. However, prevalence of fetal exposure to alcohol through the detection of EtG and EtS was 4.2% and 16.7%, respectively. Prevention of alcohol consumption during pregnancy and the detection of substance use with markers of fetal exposure are essential components of maternal and child health.

Hepatitis C associated to substance abuse: ever closer to a treatment without Interferon.

With 3-4 million of new infections occurring annually, hepatitis C virus (HCV) infection is a global Public Health problem. In fact, hepatitis C virus infection is one of the leading causes of liver disease in the world; in Western countries, two thirds of the new HCV infections are associated with injection drug use. The treatment of hepatitis C will change in the coming years with the irruption of new anti-HCV drugs, the so called Direct Antiviral Agents (DAA) that attack key proteins of the HCV life cycle. The new antiviral drugs are effective, safer and better tolerated. The 2014 WHO HCV treatment guidelines include some of them. The new DAA are used in combination and it is expected that Interferon will be not necessary in future treatment regimens against HCV infection. The irruption of new and potent antivirals mandate the review of the current standards of care in the HCV infected population. More inclusive and proactive treatment policies will be necessary in those individuals with substance use disorders.

La infección por el virus de la hepatitis C (VHC) es un problema de Salud Pública de primera magnitud; cada año ocurren entre 3 y 4 millones de nuevas infecciones y de hecho, la hepatitis crónica C es una de las principales causas de enfermedad hepática en el mundo. Usar drogas por vía parenteral está en el origen de dos de cada tres nuevas infecciones por VHC en el mundo occidental.El tratamiento de la hepatitis C va a cambiar en los próximos años. El cambio es debido a la aparición de los llamados Antivirales de Acción Directa (AAD), unos fármacos que actúan contra proteínas clave del ciclo vital del VHC y que serán más eficaces, mejor tolerados y se administrarán durante menos tiempo. En este sentido, la nueva guía de tratamiento de la OMS en 2014 ya incluye alguno de ellos en sus recomendaciones; los nuevos fármacos se utilizarán en combinación y probablemente se podrá prescindir del Interferón.Con la aparición de más y mejores antivirales contra el VHC es probable que debamos revisar el modelo asistencial vigente y orientarlo hacia uno más ágil e integrador, que trate al mayor número posible de pacientes, incluyendo a aquellos con abuso de sustancias.

Sex-specific disease outcomes of HIV-positive and HIV-negative drug users admitted to an opioid substitution therapy program in Spain: a cohort study.

BACKGROUND: Opioid substitution therapy has improved the survival of heroin users with and without HIV infection. We aimed to analyze sex differences in mortality rates and predictors of death among those admitted to a methadone treatment program (MTP). METHODS: Longitudinal study of patients enrolled in a MTP from 1992 to 2010. Socio-demographic and drug use characteristics, and markers of viral infections were assessed at entry. Vital status was ascertained by clinical charts and the mortality register. Four calendar periods were defined according to the introduction of preventive and treatment interventions in Spain. Predictors of death were analyzed by Cox regression models. RESULTS: 1,678 patients (82.8% men) were included; age at first heroin use was 18.6 years (IQR: 16-23 years), and age at first entry into a MTP was 30.7 years (IQR: 26-36 years). A total of 441 (26.3%) deaths occurred during 15,124 person-years (p-y) of follow-up (median: 9.2 years, IQR: 4-13 years). HIV infection was the main predictor of death in men (HR = 3.5, 95% CI: 2.1-5.7) and women (HR = 3.2, 95% CI: 1.2-8.7 ) and main cause of death was HIV/AIDS. Overall mortality rate was 2.9 per 100 p-y (95% CI: 2.7-3.2 per 100 p-y) and death rates decreased over time: 7.4 per 100 p-y (95% CI: 6.3-8.8 per 100 p-y) for the 1992-1996 period to 1.9 per 100 p-y (95% CI: 1.6-2.4 per 100 p-y) for the 2007-2010 period. In women, a slightly increase in mortality was observed in recent periods specifically among HIV-positive women (3.7 per 100 p-y in period 2002-2006 and 4.5 per 100 p-y in 2007-2010). CONCLUSIONS: Significant reductions in mortality of patients in MTP are observed after nineteen years of observation. However, HIV infection shows a great impact on survival, particularly among HIV-infected women.

Impact of the 2009 influenza A H1N1 pandemic on invasive pneumococcal disease in adults.

BACKGROUND: The incidence of invasive pneumococcal disease (IPD) appears to be associated with influenza. The objectives of this study were to evaluate the changes in IPD incidence and clinical data as well as the trends in Streptococcus pneumoniae serotype distribution in adults during the peak period of the 2009 influenza A H1N1 pandemic (IAP). METHODS: We performed a prospective multicentre study on IPD from week 42 to 48, 2009 in an area of Barcelona (Catalonia, Spain) covering 1,483,781 adult inhabitants. Serotyping was done by Quellung reaction. The data from 2009 were compared to those from the same periods in 2008 and 2010. RESULTS: Two hundred and three cases of IPD were detected during 2009, compared with 182 in 2008 and 139 in 2010. The incidence of IPD during the 7-week study period in 2009 (2.89) was statistically higher than that observed in 2008 (1.96) and 2010 (1.46). IAP was confirmed in 3/30 patients during the 2009 study period. Patients with IPD in 2009 were significantly healthier and younger than those in the other years, although the mortality was higher than in 2008 (p = 0.05) and 2010 (p > 0.05). Eleven (10 non-PCV-7) serotypes not present in 2008 appeared in 2009. CONCLUSIONS: During weeks 42 to 48, in which the 2009 IAP peaked in Catalonia, the incidence of IPD was statistically higher than that observed in the same time period in 2008 and 2010, with some differences in the epidemiological data, showing a close relationship between S. pneumoniae and influenza.

[Substance use disorder: Epidemiology, medical consequences and treatment]. / Trastorno por uso de sustancias: epidemiología, complicaciones médicas y tratamiento.

Substance use is a common health problem, and substance use disorder, which is its most severe presentation, is associated with multiple medical consequences and a negative impact on individual and on population health. Substance use disorder needs to be addressed as any chronic medical condition; therefore, it has to be detected at the early stages and has to be properly treated to prevent drug-related harm. Internists should be able to recognize and treat intoxication and abstinence. Internists should also be able to refer the patient to state of the art long term treatment, aimed to detoxification and treatment induction to promote abstinence and prevent relapse. In this narrative review we will discuss substance use epidemiology, its main medical consequences and its treatment, with a focus on alcohol, opiates, cocaine and other stimulants, cannabis and benzodiazepines.

Treatment of alcohol use disorder in patients with alcohol-associated liver disease: Innovative approaches and a call to action.

Alcohol-associated liver disease is currently the leading cause of liver transplantation and liver deaths both in Europe and the United States. Efficacious treatments exist for alcohol use disorder, but they are seldomly prescribed for patients who need them. Besides, the presence of liver cirrhosis can complicate pharmacological treatment choices. In this review, we discuss established and innovative treatment strategies to treat unhealthy alcohol use in patients with alcohol-associated liver disease. We also describe the experience of our own institutions, Hospital Universitari Germans Trias i Pujol in Badalona (Spain) and Yale-New Haven Health and Yale Medicine (Connecticut. United States of America).

Vitamin D Deficiency Is Associated with Advanced Liver Fibrosis and Impaired Fasting Glucose in Alcohol Use Disorder.

BACKGROUND: Vitamin D deficiency is a risk factor for liver disease, insulin resistance, and beta cell dysfunction. Individuals with alcohol use disorder (AUD) have many comorbidities, with a heavy burden of liver disease and metabolic complications, including type 2 diabetes mellitus (T2DM). OBJECTIVE: We aimed to analyze the prevalence and associations of vitamin D deficiency in patients admitted for in-hospital treatment of AUD. METHODS: A cross-sectional study was conducted in patients consecutively admitted for the treatment of AUD between January 2017 and October 2023. Sociodemographic data, substance use characteristics, and blood parameters were available at admission. Vitamin D status was assessed through the serum concentrations of 25-hydroxyvitamin D [25(OH)D] levels using a direct competitive chemiluminescent immunoassay method. Deficiency of vitamin D was defined as a concentration less than 20 ng/mL; impaired fasting glucose (IFG) was defined by fasting blood glucose >100 mg/dL (5.6 mmol/L), and advanced liver fibrosis by an FIB-4 index >3.25. RESULTS: Two hundred and forty-three patients were included (75% male) with a mean age of 49 ± 10 years, mean BMI of 26.4 ± 7.3, mean alcohol consumption of 163 ± 81 g/day, and a mean duration of AUD of 18.1 ± 11.2 years. Mean 25(OH)D, fasting blood glucose, AST, ALT, and platelets were 14.4 ± 10.2 ng/mL, 103.4 ± 40.9 mg/dL, 55.1 ± 75.8 U/L, 44.8 ± 76.6 U/L, and 206.3 ± 84.8 × 109/L, respectively. The prevalence of vitamin D deficiency was 80.6%, and 41.1% of patients had levels less than 10 ng/mL. IFG was present in 32.3% of patients, and 20.5% had FIB-4 values >3.25. In the multivariable analysis, IFG (OR, 2.51; 95% CI: 1.02-6.17, p = 0.04) and advanced liver fibrosis (OR, 4.27; 95% CI: 1.21-15.0, p = 0.02) were the only factors associated with vitamin D deficiency. CONCLUSIONS: Vitamin D deficiency was very prevalent in this series of patients with AUD and was associated with impaired fasting glucose and advanced liver fibrosis.

Clinical features of individuals with laboratory values suggestive of advanced liver fibrosis when first treated for alcohol use disorder.

BACKGROUND: Effective screening for alcohol-associated liver disease is relevant in the context of chronic, excessive alcohol consumption. Patients with alcohol-associated liver disease are often not diagnosed until their liver disease is decompensated. We analyzed the prevalence and associations of Fibrosis-4 index (FIB-4) values suggestive of advanced liver fibrosis in patients referred for their first treatment of alcohol use disorder (AUD). METHODS: We conducted a cross-sectional, multicenter study of noncirrhotic individuals referred for their first AUD treatment between March 2013 and April 2021. We obtained sociodemographic data, substance use characteristics, and blood samples at admission. We considered a FIB-4 value ≥2.67 suggestive of advanced liver fibrosis and used logistic regression analyses to identify features associated with this value. RESULTS: We included 604 patients (67% male), with a median age at admission of 48 years [IQR: 41-56 years]. The median duration of regular alcohol consumption was 21 years [IQR: 18-30 years] and the median alcohol consumption was 105 standard drink units (SDU)/week [IQR: 63-160 SDU/week]. A FIB-4 value ≥ 2.67 was present in 19.3% of cases. These patients reported more frequent binge drinking (75.4% vs. 66%, p = 0.05) than those with FIB-4 values below 2.67. In multivariate analysis, a history of binge drinking (OR 1.9, 95% CI, 1.05-3.47), anemia (OR 2.95, 95% CI, 1.42-6.11), leukopenia (OR 7.46, 95% CI, 2.07-26.8), and total serum bilirubin >1 mg/dL (OR 6.46, 95% CI, 3.57-11.7) were independently associated with FIB-4 values ≥2.67. CONCLUSIONS: One in five patients admitted to treatment for AUD without evidence of decompensated liver disease have FIB-4 values suggestive of advanced liver fibrosis. The presence of a binge drinking history, anemia, leukopenia, and elevated bilirubin levels is associated with high FIB-4 values.

Multiplatform web app (My Way Up) plus motivational interviewing for improving treatment retention in patients with onset of alcohol-related liver disease and alcohol use disorder - an example of participatory research.

Background: With the aim of improving treatment retention in patients with the onset of alcohol-related liver disease (ArLD), we designed a blended intervention (brief motivational intervention + 'serious game' (SG)). We present the participatory design methodology and outcomes and the usability assessment of the intervention. Methods: (1) The design of the SG was based on the outcomes of two 3-h co-creation sessions with 37 participants (healthcare and technology professionals, patients, and patients' relatives). The brief face-to-face motivational intervention was based on the 5 As Model and adapted to the ArLD population. (2) Usability pilot study: 20 participants (10 ArLD patients + 10 healthcare professionals) received the intervention. System Usability Scale (SUS) and Post-Study System Usability Questionnaire (PSSUQ) were applied to assess the SG usability and patients' satisfaction with it. Weekly semi-structured interviews on the phone were conducted to identify the preferred elements in the SG and those aspects that should be improved. Results: (1) Design: an SG in the form of a gamified web app, consisting of a daily activity for six weeks and adapted brief motivational interviewing. (2) Usability pilot study: usability results were excellent for both patients and healthcare professionals (SUS median score = 85). The general usability, the quality of the information provided by the SG and the quality of the interface were very positively rated in the PSSUQ (overall median score = 2, IQR = 1-2). The best-rated aspects were the provision of feedback, the use of metaphors and the application of audiovisual material. Changes in the design, response mechanics and content were applied after the study. Conclusions: The usability and acceptability of an intervention for increasing retention to treatment in patients with recent onset of ArLD and AUD were excellent for patients and healthcare professionals. A randomized-controlled trial is required to test the efficacy of this approach.

Pneumocystis jirovecii pneumonia in HIV-1-infected patients in the late-HAART era in developed countries.

BACKGROUND: In developed countries with free access to health care, primary chemoprophylaxis with co-trimoxazole, and antiretroviral treatment, Pneumocystis pneumonia (PCP) in HIV-infected subjects should be restricted to undiagnosed late presenters. METHODS: We retrospectively identified confirmed PCP hospital admissions in HIV-1 patients (period 1986-2010) and examined their characteristics and factors associated with mortality. RESULTS: Three hundred and twelve episodes (median CD4 27 cells/µl) were identified during 3 periods: pre-HAART (1986-1995), 49%; early-HAART (1996-1999), 17.3%; and late-HAART (2000-2010), 33.7%. PCP was the initial AIDS-defining diagnosis in only 86 (27.6%). Thirty-four (10.9%) patients died during their hospital stay, without a significant reduction in mortality in recent periods (p = 0.311). However, the 12-month mortality decreased through the periods (33.3% to 16.2%; p = 0.003). Drug users (p = 0.001) and those naïve to HAART (p < 0.001) decreased in the late-HAART era, while heterosexuals (p = 0.001), immigrants (p < 0.001), and HAART initiation before hospital discharge (p < 0.001) increased. A partial pressure of oxygen (PaO2) ≤ 55 (p = 0.04), intensive care admission (p < 0.001), and the absence of HAART initiation before discharge (p = 0.02) were correlated with mortality. CONCLUSIONS: The epidemiology and 12-month mortality of HIV-1-infected subjects with PCP have changed significantly in the late-HAART era, while mortality during hospital stay has remained unchanged. HIV diagnosed individuals lost to follow-up in care have emerged as the main driver of PCP in developed countries. Like HIV late presenters, they are more likely to have AIDS-defining illnesses, to be hospitalized, and to die. This finding has important implications for the design of better strategies to retain HIV-1-infected individuals in care.

Complete genome sequence of Pediococcus acidilactici A40, a bacterium with biocontrol and plant growth-promoting properties.

We report the complete genome assembly of Pediococcus acidilactici A40, a bacterium with biocontrol and plant growth-promoting properties, obtained from Colombia.

Cytotoxic NK cells phenotype and activated lymphocytes are the main characteristics of patients with alcohol-associated liver disease.

T cells, natural killer (NK) and NKT cells have opposing actions in the development of alcohol-associated liver fibrosis. We aimed to evaluate the phenotype of NK cells, NKT cells and activated T cells in patients with alcohol use disorder (AUD) according to the presence of advanced liver fibrosis (ALF). Totally, 79 patients (51-years, 71% males) were admitted to treatment of AUD. ALF was defined as FIB4-score > 2.67. Immunophenotyping of NK cells (CD3-CD56+CD16+, CD3-CD56+CD16-, CD3-CD56-CD16+), NKT-like (CD3+CD56+), and the activation status of CD4+, CD8+ and regulatory T cells (Tregs) were evaluated according to the HLA-DR expression. Patients had an AUD duration of 18 ± 11 years with a daily alcohol consumption of 155 ± 77 gr/day prior to hospital admission. The values of absolute cells were 2 ± 0.9 cells/L for total lymphocytes, 1054 ± 501 cells/µL for CD4+, 540 ± 335 cells/µL for CD8+, 49.3 ± 24.8 cells/µL for Tregs, 150.3 ± 97.5 cells/µL for NK cells and 69.8 ± 78.3 cells/µL for NKT-like. The percentage of total NK cells (11.3 ± 5.5% vs. 7 ± 4.3%, p < 0.01), CD3-CD56+CD16+ regarding total lymphocytes (9.7 ± 5.1% vs. 5.8 ± 3.9%, p < 0.01), activated CD4+ cells (5.2 ± 3.2% vs. 3.9 ± 3%, p = 0.04) and activated CD8+ cells (15.7 ± 9.1% vs. 12.2 ± 9%, p = 0.05) were significantly higher in patients with ALF. The percentage of CD3-CD56+CD16- regarding NK cells (5.1 ± 3.4% vs. 7.6 ± 6.2%, p = 0.03) was significantly lower in patients with ALF. Activated Tregs (39.9 ± 11.5 vs. 32.4 ± 9.2, p = 0.06) showed a tendency to be higher in patients with ALF. The proportion of activated CD4+ cells (r = 0.40, p < 0.01) and activated CD8+ cells (r = 0.51, p < 0.01) was correlated with the proportion of NKT-like in patients without ALF. Patients with ALF presented an increased NK cytotoxic phenotype and activated T cells concomitant with a decreased NK cytokine-secreting phenotype.

Fungal plasma biomarkers in patients admitted for inpatient treatment of alcohol use disorder.

BACKGROUND: Fungal plasma biomarkers have not been studied in patients with unhealthy alcohol use and no apparent end-stage liver disease. METHODS: We examined the prevalence of fungal plasma biomarkers, assessed by the presence of anti-Saccharomyces cerevisiae antibodies (ASCA; IgA and IgM), and its disease correlates in patients with alcohol use disorder (AUD). We performed logistic regression analyses to detect the association between clinical and laboratory characteristics and the presence of fungal plasma biomarkers. RESULTS: We included 395 patients (75.9% male, median age of 49 years, and median body mass index of 25.6) who drank a median of 150 g of alcohol daily and had a median duration of AUD of 20 years. ASCA IgA and IgG were present in 34.4% and 14.9%, respectively, and 9.9% had both ASCA IgA and ASCA IgG. The presence of ASCA IgA was associated with male sex (p < 0.01); values of serum aspartate transferase (AST) (p = 0.02), gamma-glutamyl transferase (GGT) (p < 0.01), alkaline phosphatase (ALP) (p < 0.01), and bilirubin in the highest quartile (p < 0.01); Fibrosis-4 Index (FIB-4) values suggestive of advanced liver fibrosis (p < 0.01); and values of the macrophage activation factors sCD163 (p < 0.01) and sCD14 (p < 0.01), the cytokine IL-6 (p = 0.01), and lipopolysaccharide-binding protein in the highest quartile (p < 0.01). The presence of ASCA IgG was associated with omeprazole use (p = 0.04); values of AST (p = 0.04) and GGT (p = 0.04) in the highest quartile; FIB-4 values suggestive of advanced liver fibrosis (p < 0.01); and values of sCD163 (p < 0.01) in the highest quartile. The variables associated with the presence of both ASCA IgA and IgG were male sex (p = 0.04) and values of GGT (p = 0.04) and sCD163 in the highest quartile (p < 0.01). CONCLUSIONS: In AUD patients, the presence of fungal biomarkers in plasma was common and associated with FIB-4 values suggestive of advanced liver fibrosis and with markers of liver damage, monocyte activation, and microbial translocation, male gender, and omeprazole use. These findings suggest that the presence of plasma anti-Saccharomyces cerevisiae antibodies could be used as a biomarker for an elevated risk of progressive liver disease in patients with AUD.

Associations of hypomagnesemia in patients seeking a first treatment of alcohol use disorder.

INTRODUCTION: Hypomagnesemia (hypoMg) has not yet been extensively studied in alcohol use disorder (AUD) . We hypothesize that chronic, excessive alcohol consumption favors oxidative stress and pro-inflammatory alterations that may be exacerbated by hypoMg. The objective of this study was to analyze the prevalence and associations of hypoMg in AUD. PATIENTS AND METHODS: Cross-sectional study in patients admitted for a first treatment of AUD in six tertiary centers between 2013 and 2020. Socio-demographic, alcohol use characteristics, and blood parameters were ascertained at admission. RESULTS: 753 patients (71% men) were eligible; age at admission was 48 years [IQR, 41-56 years]. Prevalence of hypoMg was 11.2%, higher than that observed for hypocalcemia (9.3%), hyponatremia (5.6%), and hypokalemia (2.8%). HypoMg was associated with older age, longer duration of AUD, anemia, higher erythrocyte sedimentation rate, gamma-glutamyl transpeptidase, glucose levels, advanced liver fibrosis (FIB-4 ≥3.25) and estimated glomerular filtration rate (eGFR) < 60 mL/min. In multivariate analysis, advanced liver fibrosis (OR, 8.91; 95% CI, 3.3-23.9) and eGFR < 60 mL (OR, 5.2; 95% CI, 1.0-26.2) were the only factors associated with hypoMg. CONCLUSIONS: Mg deficiency in AUD is associated with liver damage and glomerular dysfunction suggesting that both comorbidities should be assessed in the course of serum hypoMg.

Increased Natural Killer Cells Are Associated with Alcohol Liver Fibrosis and with T Cell and Cytotoxic Subpopulations Change.

Natural killer (NK) cells play a therapeutic role in liver fibrosis (LF). We aimed to analyze NK cells in heavy drinkers without cirrhosis or decompensated liver disease and establish correlations with other related subpopulations. Data on sociodemographic characteristics, alcohol consumption, laboratory parameters, and immunophenotyping of NK (CD16+/CD56+), T (CD3+), B (CD19+), NKT (CD16+/CD56+/CD3+), and cytotoxic (CD3-CD8+) cells were collected. Fibrosis-4 (FIB-4) scores were used to compare patients without (FIB-4 < 1.45) and with (FIB-4 > 3.25) advanced LF (ALF). We included 136 patients (76% male) with a mean age of 49 years who had a 15-year alcohol use disorder (AUD) and alcohol consumption of 164 g/day. Patients with ALF (n = 25) presented significantly lower absolute total lymphocyte, T cell, B cell, and NKT cell numbers than patients without LF (n = 50; p < 0.01). However, the NK cells count was similar (208 ± 109 cells/µL vs. 170 ± 105 cells/µL) in both groups. The T cells percentage was lower (80.3 ± 5.6% vs. 77 ± 7%; p = 0.03) and the NK cells percentage was higher (9.7 ± 5% vs. 13 ± 6%; p = 0.02) in patients with ALF than in those without LF. The percentages of NK cells and T cells were inversely correlated in patients without (r = -0.65, p < 0.01) and with ALF (r = -0.64; p < 0.01). Additionally, the NK cells and CD3-CD8+ cell percentages were positively correlated in patients without (r = 0.87, p < 0.01) and with (r = 0.92; p < 0.01) ALF. Conclusions: Heavy drinkers without decompensated liver disease showed an increase in NK cells related to T cells lymphopenia and an increase in cytotoxic populations. The interaction of NK cells with other subpopulations may modify alcohol-related liver disease progression.