The trinomial health, safety and happiness promote rural tourism.

BACKGROUND: Health and safety protocols have become a requirement to promote rural tourism (PRT). From this perspective, this paper empirically analyses how the health and safety dimensions influence the happiness of hotel managers and rural tourists in the post-Covid 19 era. METHODS: A theory-based structural equation model will be carried out of activation of norms, that measure variables: sanitary, socioeconomic, and safety. Precisely, we will measure how those three attributes affect the managers-guests' health in rural areas and their search for happiness at the rural destination. Based on the above, a field of study has been 215 rural tourist accommodations in the Extremadura region (Spain) and a sample population of 443 guests. Data were organised through the SEM-PLS path modelling. RESULTS: The results achieved statistically show the need to undertake a new model of healthier and safer tourism consumption that values the tourist resources of rural areas, especially nearby and sustainable destinations, based on the guiding principles of safety, health, and happiness. CONCLUSIONS: The first conclusion is that promoting tourist destinations under safe and healthy conditions has become a priority objective in the tourism industry. The second conclusion that follows from the first is that the variables safety and health and the pursuit of happiness are essential factors in promoting tourist destinations for rural hotel managers and rural tourists. The third conclusion related to the first two is that the opportunity that this study provides to develop strategies of an innovative, sustainable, and creative nature based on the relationships of the new trinomial of health, safety and happiness, from the perspective of happiness management.

Clostridium paraputrificum bacteremia in a 64-year-old woman with colon carcinoma.

Here we report a case of bacteremia caused by Clostridium paraputrificum in a 64-year-old woman with colon carcinoma and gastrointestinal disease. Using the new EUCAST 2022 clinical breakpoints for Clostridium perfringens, the isolate was susceptible to metronidazole and vancomycin, but resistant to benzylpenicillin, meropenem, and clindamycin. Thus, treatment with metronidazole should be considered in all patients with Clostridium bacteremia until antibiotic susceptibility is determined to minimize the risk of treatment failure.

Feasibility and potential advantages using VMAT in SRS metastasis treatments.

BACKGROUND: Utilization of stereotactic radiosurgery (SRS) for brain metastases (BM) has become the technique of choice as opposed to whole brain radiation therapy (WBRT). The aim of this work is to evaluate the feasibility and potential benefits in terms of normal tissue (NT) and dose escalation of volumetric modulated arc therapy (VMAT) in SRS metastasis treatment. A VMAT optimization procedure has therefore been developed for internal dose scaling which minimizes planner dependence. MATERIALS AND METHODS: Five patient-plans incorporating treatment with frame-based SRS with dynamic conformal arc technique (DA) were re-planned for VMAT. The lesions selected were between 4-6 cm3. The same geometry used in the DA plans was maintained for the VMAT cases. A VMAT planning procedure was performed attempting to scale the dose in inner auxiliary volumes, and to explore the potential for dose scaling with this technique. Comparison of dose-volume histogram (DVH) parameters were obtained. RESULTS: VMAT allows a superior NT sparing plus conformity and dose scaling using the auxiliary volumes. The VMAT results were significantly superior in NT sparing, improving both the V10 and V12 values in all cases, with a 2-3 cm3 saving. In addition, VMAT improves the dose coverage D95 by about 0.5 Gy. The objective of dose escalation was achieved with VMAT with an increment of the Dmean and the Dmedian of about 2 Gy. CONCLUSIONS: This work shows a benefit of VMAT in SRS treatment with significant NT sparing. A VMAT optimization procedure, based on auxiliary inner volumes, has been developed, enabling internal dose escalation.

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.

Phytoremediation of highly contaminated mining soils by Jatropha curcas L. and production of catalytic carbons from the generated biomass.

This paper deals with the removal of heavy metals from marginal soil mixtures from the Cobre Las Cruces and Aznalcóllar mining areas containing high concentrations of metals (Cr, Fe, Ni, Cu, Zn, Cd, Hg, Pb and As) by means of phytoremediation using Jatropha curcas L., and the subsequent production of biocatalysts from the plant biomass. First, J. curcas L. was sowed in eight mixtures of these mining soils to study its adaption to these high-contaminated soils and its growth during 60 days in a greenhouse under conditions simulating the South of Spain's spring climate. Later, the most suitable soil mixtures for plant growth were used for 120-day phytoremediation under the same conditions. Heavy metal concentration in soils, roots, stems and leaves were measured by ICP-OES at the beginning, at the middle and at the end of the phytoremediation period, thus calculating the translocation and bioaccumulation factors. J. curcas L. was found to absorb great amounts of Fe (>3000 mg kg-1 plant) as well as notable amounts of Pb, Zn, Cu, Cr and Ni, and traces of As. Other metals with lower initial concentrations such as Cd, Hg and Sn were completely removed from soils. Finally, the plant biomass was subjected to pyrolysis to obtain catalytic biocarbons, assessing the optimal temperature for the pyrolytic process by means of thermogravimetric analysis and Raman spectroscopy.

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.

Stability and aggregation propensity do not fully account for the association of various germline variable domain gene segments with light chain amyloidosis.

Variable domain (VL) gene segments exhibit variable tendencies to be associated with light chain amyloidosis (AL). While few of them are very frequent in AL and give rise to most of the amyloidogenic light chains compiled at the sequence databases, other are rarely found among the AL cases. To analyze to which extent these tendencies depend on folding stability and aggregation propensity of the germline VL protein, we characterized VL proteins encoded by four AL-associated germline gene segments and one not associated to AL. We found that the AL-associated germline rVL proteins differ widely in conformational stability and propensity to in vitro amyloid aggregation. While in vitro the amyloid formation kinetics of these proteins correlate well with their folding stabilities, the folding stability does not clearly correlate with their germline's frequencies in AL. We conclude that the association of the VL genes segments to amyloidosis is not determined solely by the folding stability and aggregation propensity of the germline VL protein. Other factors, such as the frequencies of destabilizing mutations and susceptibility to proteolysis, must play a role in determining the light chain amyloidogenicity.

Drugs, Substance Use Disorder and Driving: Intervention of Health Professionals in the Treatment of Addictions.

Editorial of vol 27-3.

Editorial del vol 27-3.

Scientific publications and research groups on alcohol consumption and related problems worldwide: authorship analysis of papers indexed in PubMed and Scopus databases (2005 to 2009).

BACKGROUND: The research of alcohol consumption-related problems is a multidisciplinary field. The aim of this study is to analyze the worldwide scientific production in the area of alcohol-drinking and alcohol-related problems from 2005 to 2009. METHODS: A MEDLINE and Scopus search on alcohol (alcohol-drinking and alcohol-related problems) published from 2005 to 2009 was carried out. Using bibliometric indicators, the distribution of the publications was determined within the journals that publish said articles, specialty of the journal (broad subject terms), article type, language of the publication, and country where the journal is published. Also, authorship characteristics were assessed (collaboration index and number of authors who have published more than 9 documents). The existing research groups were also determined. RESULTS: About 24,100 documents on alcohol, published in 3,862 journals, and authored by 69,640 authors were retrieved from MEDLINE and Scopus between the years 2005 and 2009. The collaboration index of the articles was 4.83 ± 3.7. The number of consolidated research groups in the field was identified as 383, with 1,933 authors. Documents on alcohol were published mainly in journals covering the field of "Substance-Related Disorders," 23.18%, followed by "Medicine," 8.7%, "Psychiatry," 6.17%, and "Gastroenterology," 5.25%. CONCLUSIONS: Research on alcohol is a consolidated field, with an average of 4,820 documents published each year between 2005 and 2009 in MEDLINE and Scopus. Alcohol-related publications have a marked multidisciplinary nature. Collaboration was common among alcohol researchers. There is an underrepresentation of alcohol-related publications in languages other than English and from developing countries, in MEDLINE and Scopus databases.

What role geoparks play improving the health and well-being of senior tourists?

In recent years geoparks, helped by governmental policies, have become tourist destinations especially among senior visitors. The paper aimed to analyse whether geoparks contribute to improving the health of tourists older than 65 years and what were their main motives to visit geoparks. The data were collected from 398 senior tourists who visited the Villuerca- Ibores-Jara Geopark (Spain) in 2023, presenting our results using SmartPLS version 4. The results showed that senior tourists are very interested in visiting this geopark for psychotherapeutic reasons, given its high environmental and geological interest. In addition, they consider geoparks as spaces where they can socialise, which is beneficial considering the isolation that many often experience during the year. These findings are highly relevant for public authorities to protect, maintain and promote geoparks among senior tourists.

[Severe rhabdomyolysis associated with atorvastatin. Case report]. / Rabdomiólisis severa asociada a atorvastatina. Reporte de caso.

Background: Dyslipidemia is a risk factor for the development of atherosclerosis and ischemic heart disease. Statins are safe drugs that are part of the routine treatment in patients with Acute Myocardial Infarction (AMI), however, rhabdomyolysis associated with severe myonecrosis due to statins can occur and associated complications such as acute kidney injury increase mortality. The main objective of this article is to report the case of a critically ill patient with AMI who presented severe statin-associated rhabdomyolysis documented with muscle biopsy. Description of the case: A 54-year-old man who presented with AMI, cardiogenic shock, and cardiorespiratory arrest requiring cardiopulmonary resuscitation, fibrinolysis, and successful salvage coronary angiography. However, he presented severe rhabdomyolysis associated with atorvastatin that required suspension of the drug and multi-organ support in a Coronary Care Unit. Conclusions: The prevalence of statin-associated rhabdomyolysis is low, however, the late elevation of CPK above 10 times its upper normal value in those patients with successful percutaneous coronary angiography should promptly draw attention, generate a diagnostic approach towards non-traumatic acquired causes of rhabdomyolysis and assess the suspension of statins.

Introducción: la dislipidemia es un factor de riesgo para el desarrollo de ateroesclerosis y cardiopatía isquémica. Las estatinas son fármacos seguros que forman parte del tratamiento de rutina en el paciente con infarto agudo de miocardio (IAM). Sin embargo, la rabdomiólisis asociada a mionecrosis severa por estatinas puede presentarse y las complicaciones asociadas como la lesión renal aguda incrementan la mortalidad. El objetivo principal de este artículo es reportar el caso de un paciente críticamente enfermo con IAM que presentó rabdomiólisis severa asociada a estatinas documentada con biopsia muscular. Caso clínico: hombre de 54 años que presentó IAM, choque cardiogénico y paro cardiorrespiratorio, que ameritó reanimación cardiopulmonar, fibrinólisis y angiografía coronaria de rescate exitosa. Sin embargo, presentó rabdomiólisis severa asociada a atorvastatina que requirió de suspensión del fármaco y soporte multiorgánico en una unidad de cuidados coronarios. Conclusiones: la prevalencia de la rabdomiólisis asociada a estatinas es baja, sin embargo, la elevación tardía de la CPK por arriba de 10 veces su valor superior normal en aquellos pacientes con angiografía coronaria percutánea exitosa debe llamar la atención, generar un abordaje diagnóstico hacia causas adquiridas no traumáticas de rabdomiólisis y valorar la suspensión de estatinas.

RNA-based analysis of two SMARCB1 mutations associated with familial schwannomatosis with meningiomas.

Germline mutations in the SMARCB1 gene cause familial schwannomatosis, a condition characterized by the presence of multiple schwannomas, although mutations in SMARCB1 have also been associated with rhadboid tumor predisposition syndrome 1 (RTPS1). Both schwannomatosis and RTPS1 are autosomal dominant conditions that predispose individuals to develop distinct types of tumors. We clinically and genetically characterized two families with schwannomatosis associated with SMARCB1 mutations. Eight affected members of these families developed different numbers of schwannomas and/or meningiomas at distinct ages, evidence that meningiomas are variably expressed in this condition. We identified two germline mutations in SMARCB1 associated with the familial disease, c.233-1G>A and the novel c.207_208dupTA mutation, which both proved to affect the main SMARCB1 isoforms at the RNA level distinctly. Interestingly, the c.207_208dupTA mutation had no effect on the coding sequence, pre-mRNA splicing or the level of expression of the SMARCB1 isoform 2. Furthermore, SMARCB1 isoforms harboring a premature termination codon were largely eliminated via the nonsense-mediated mRNA decay pathway. Our results highlight the importance of RNA-based studies to characterize SMARCB1 germline mutations in order to determine their impact on protein expression and gain further insight into the genetic basis of conditions associated with SMARCB1 mutations.

ABO Blood System and COVID-19 Susceptibility: Anti-A and Anti-B Antibodies Are the Key Points.

The implication of the ABO blood group in COVID-19 disease was formulated early, at the beginning of the COVID-19 pandemic more than 2 years ago. It has now been established that the A blood group is associated with more susceptibility and severe symptoms of COVID-19, while the O blood group shows protection against viral infection. In this review, we summarize the underlying pathophysiology of ABO blood groups and COVID-19 to explain the molecular aspects behind the protective mechanism in the O blood group. A or B antigens are not associated with a different risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than that of other antigens. In this case, the cornerstone is natural anti-A and anti-B antibodies from the ABO system. They are capable of interfering with the S protein (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2; host cell receptor), thereby conferring protection to patients with sufficient antibodies (O blood group). Indeed, the titers of natural antibodies and the IgG isotype (specific to the O blood group) may be determinants of susceptibility and severity. Moreover, older adults are associated with a higher risk of bad outcomes due to the lack of antibodies and the upregulation of ACE2 expression during senescence. A better understanding of the role of the molecular mechanism of ABO blood groups in COVID-19 facilitates better prognostic stratification of the disease. Furthermore, it could represent an opportunity for new therapeutic strategies.

Perceptions and Profiles of Young People Regarding Spa Tourism: A Comparative Study of Students from Granada and Aachen Universities.

Spa tourism has undergone important changes in recent decades, actively embracing wellness and wellbeing. However, this transition is taking place in different ways in Europe, and this has led to varying perceptions of thermalism that have little to do with its original conception. The main aim of this study was to analyse current perceptions of spa tourism amongst university students, so as to identify profiles and compare the differences between two study cases: Granada (Spain) and Aachen (Germany). For this purpose, we applied a methodology that combines artificial intelligence techniques with questionnaires containing both quantitative and qualitative variables. This enabled us to identify and characterize a series of profiles, so as to acquire detailed knowledge of the perceptions of these students regarding spa tourism in Granada and Aachen. On the basis of the results, the interviewees were grouped together into seven profiles from which we deduced that young Germans from Aachen visit spas more frequently and have a more realistic perception of the thermal sector than young Spanish people from Granada. This situation could limit present and future demand for spas in southern Spain. With this in mind, in this paper we present an updated assessment of the demand for spas amongst university students, in order to design effective geomarketing strategies in two cities with long spa traditions.

Trends in the use of antihistamines with reference to drivers between 2015 and 2019: A population-based registry analysis.

BACKGROUND: First-generation antihistamines are considered driving-impairing medicines (DIM), while second- and third-generation antihistamines are relatively safe for driving. OBJECTIVES: The aim of this study was to know the trend of consumption of antihistamines and other DIMs in Spain between 2015 and 2019. METHODS: This is a population-based registry study. The population distribution by age and gender has been taken into account, as well the treatment duration with these medicines and the concomitant use of other DIMs. Adjusted consumption for licensed drivers is also presented. RESULTS: Between 2015 and 2019, antihistamines were dispensed to 12.1% of the population and 9.25% of drivers. Oral antihistamines are the most consumed with 85.83%, and generally more used by women than men. Regardless of systemic antihistamines, the second-generation were the most consumed (8.9%) followed by the third-generation (2.07%) and the first-generation (0.61%). Subacute use was predominant in second -generation antihistamines (4.96%) and third-generation (1.26%), while acute use was predominant in third-generation antihistamines. On the other hand, only 0.36% of the population consumed antihistamines daily. The concomitant use of antihistamines with other DIMS was considerable, especially anxiolytics, opioids, other analgesics and antipyretics and antidepressants. The results in drivers were similar than in the general population. CONCLUSIONS: The use of antihistamines has increased in recent years, however, in Spain, the use of less sedatives predominates, which is safe for driving. Finally, it is important to consider that concomitant use with other DIMs was frequent, which may affect the fitness to drive.

A Population-Based Registry Analysis on Hospitalized COVID-19 Patients with Previous Cardiovascular Disease: Clinical Profile, Treatment, and Predictors of Death.

A high percentage of patients with COVID-19 (coronavirus disease 2019) have previous cardiovascular disease (CVD). The findings presented here came from an epidemiological population-based registry study (real-world data) that enrolled all in-hospital COVID-19 patients with previous CVD from 1 March to 31 May 2020. Death, other comorbidities, hospital stay variables, ventilation type, and main clinical outcomes were evaluated. In Castile and Leon, 35.83% of the 7307 in-hospital COVID-19 patients who participated in this study had previous CVD, particularly arrhythmias (48.97%), cerebrovascular disease (25.02%), ischemic heart disease (22.8%), and chronic heart failure (20.82%). Of the patients, 21.36% were men and more than 90% were over 65 years of age, and the mortality rate achieved 32.93%. The most used medicines were antibiotics (91.41%), antimalarials (73.3%), steroids (46.64%), and antivirals (43.16%). The main predictors of death were age over 65 years (OR: 5), ventilation needs (OR: 2.81), treatment with anti-SIRS (systemic inflammatory response syndrome) medicines (OR: 1.97), antivirals (OR: 1.74) or steroids (OR: 1.68), SIRS (OR: 5.75), SARS (severe acute respiratory syndrome) (OR: 2.44), or AKI (acute kidney injury) (OR: 1.63) occurrence. Chronic heart failure and cerebrovascular disease were associated with a worse clinical course of COVID-19, especially in men older than 65 years with diabetes who developed SIRS, SARS, or AKI.

The association of telomere length with substance use disorders: a systematic review and meta-analysis of observational studies.

BACKGROUND AND AIMS: Several recent studies have investigated the relationship between telomere length and substance use disorders with inconsistent results. We aimed to assess this association and to identify moderators of the relationship. METHODS: Systematic review and meta-analysis. Selection criteria were observational studies reporting telomere length in people with a substance use disorder compared with a control group. Studies focused solely on nicotine addiction, employing other study designs, and non-human studies were excluded. Study selection and data extraction were independently conducted by two researchers following a standardized protocol and included studies until December 2019. Standardized mean differences were used as the effect size index [d; 95% confidence interval (CI)] and random-effects models were used for the meta-analysis. Cochran's Q-statistic, I2 index, visual inspection of the forest plot and a 95% prediction interval were applied to verify study heterogeneity. Subgroup analyses and meta-regressions were conducted to explore heterogeneity. Small study effects were examined using the 'funnel plot', the Egger test, Duval & Tweedie's trim-and-fill method and the precision-effect test-precision-effect estimate with standard error (PET-PEESE) method. The risk of bias and the quality of evidence were assessed. RESULTS: Ten studies (12 analysis units with 2671 cases and 4532 controls) met the selection criteria. An overall effect size of moderate magnitude was found (d+  = -0.63; 95% CI = -1.00 and -0.26; P = 0.0008). A potential small study effect was detected, as well as large heterogeneity between studies (Q-statistic P < 0.001, I2  = 97.3%). Selection of controls, reporting laboratory quality control procedures and total sample size significantly affected the effect size. The quality of the evidence was very low, based on risk of bias analysis and the grading of recommendations assessment, development and evaluation (GRADE) system. CONCLUSIONS: People with substance use disorders appear to have shorter telomere length than controls; however, this finding should be interpreted with caution due to the poor quality of the evidence.

Predictive Modeling of Poor Outcome in Severe COVID-19: A Single-Center Observational Study Based on Clinical, Cytokine and Laboratory Profiles.

Pneumonia is the main cause of hospital admission in COVID-19 patients. We aimed to perform an extensive characterization of clinical, laboratory, and cytokine profiles in order to identify poor outcomes in COVID-19 patients. METHODS: A prospective and consecutive study involving 108 COVID-19 patients was conducted between March and April 2020 at Hospital Clínico Universitario de Valladolid (Spain). Plasma samples from each patient were collected after emergency room admission. Forty-five serum cytokines were measured in duplicate, and clinical data were analyzed using SPPS version 25.0. RESULTS: A multivariate predictive model showed high hepatocyte growth factor (HGF) plasma levels as the only cytokine related to intubation or death risk at hospital admission (OR = 7.38, 95%CI-(1.28-42.4), p = 0.025). There were no comorbidities included in the model except for the ABO blood group, in which the O blood group was associated with a 14-fold lower risk of a poor outcome. Other clinical variables were also included in the predictive model. The predictive model was internally validated by the receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.94, a sensitivity of 91.7% and a specificity of 95%. The use of a bootstrapping method confirmed these results. CONCLUSIONS: A simple, robust, and quick predictive model, based on the ABO blood group, four common laboratory values, and one specific cytokine (HGF), could be used in order to predict poor outcomes in COVID-19 patients.

HGF, IL-1α, and IL-27 Are Robust Biomarkers in Early Severity Stratification of COVID-19 Patients.

Pneumonia is the leading cause of hospital admission and mortality in coronavirus disease 2019 (COVID-19). We aimed to identify the cytokines responsible for lung damage and mortality. We prospectively recruited 108 COVID-19 patients between March and April 2020 and divided them into four groups according to the severity of respiratory symptoms. Twenty-eight healthy volunteers were used for normalization of the results. Multiple cytokines showed statistically significant differences between mild and critical patients. High HGF levels were associated with the critical group (OR = 3.51; p < 0.001; 95%CI = 1.95-6.33). Moreover, high IL-1α (OR = 1.36; p = 0.01; 95%CI = 1.07-1.73) and low IL-27 (OR = 0.58; p < 0.005; 95%CI = 0.39-0.85) greatly increased the risk of ending up in the severe group. This model was especially sensitive in order to predict critical status (AUC = 0.794; specificity = 69.74%; sensitivity = 81.25%). Furthermore, high levels of HGF and IL-1α showed significant results in the survival analysis (p = 0.033 and p = 0.011, respectively). HGF, IL-1α, and IL 27 at hospital admission were strongly associated with severe/critical COVID-19 patients and therefore are excellent predictors of bad prognosis. HGF and IL-1α were also mortality biomarkers.

Evaluation of Cytokines as Robust Diagnostic Biomarkers for COVID-19 Detection.

Antigen tests or polymerase chain reaction (PCR) amplification are currently COVID-19 diagnostic tools. However, developing complementary diagnosis tools is mandatory. Thus, we performed a plasma cytokine array in COVID-19 patients to identify novel diagnostic biomarkers. A discovery-validation study in two independent prospective cohorts was performed. The discovery cohort included 136 COVID-19 and non-COVID-19 patients recruited consecutively from 24 March to 11 April 2020. Forty-five cytokines' quantification by the MAGPIX system (Luminex Corp., Austin, TX, USA) was performed in plasma samples. The validation cohort included 117 patients recruited consecutively from 15 to 25 April 2020 for validating results by ELISA. COVID-19 patients showed different levels of multiple cytokines compared to non-COVID-19 patients. A single chemokine, IP-10, accurately identified COVID-19 patients who required hospital admission (AUC: 0.962; 95%CI (0.933-0.992); p < 0.001)). The results were validated in an independent cohort by multivariable analysis (OR: 25.573; 95%CI (8.127-80.469); p < 0.001) and AUROC (AUC: 0.900; 95%CI (0.846-0.954); p < 0.001). Moreover, showing IP-10 plasma levels over 173.35 pg/mL identified COVID-19 with higher sensitivity (86.20%) than the first SARS-CoV-2 PCR. Our discover-validation study identified IP-10 as a robust biomarker in clinical practice for COVID-19 diagnosis at hospital. Therefore, IP-10 could be used as a complementary tool in clinical practice, especially in emergency departments.