Mala conducta como principal causa para la retractación. Un estudio descriptivo de las publicaciones retractadas y sus autores

Objective : To analyze the causes of retracted publications and the main characteristics of their authors. Method : A descriptive cross-sectional study was designed including all retracted publications from January 1st, 2013-December 31st, 2016 indexed in PubMed. The causes of retraction were classified as: data management, authorship issues, plagiarism, unethical research, journal issues, review process, conflict of interest, other causes, and unknown reasons. Then, misbehaviour was classified as misconduct, suspicion of misconduct or no misconduct suspicion. Results : 1,082 retracted publications were identified. The retraction rate for the period was 2.5 per 10,000 publications. The main cause of retraction was misconduct (65.3%), and the leading reasons were plagiarism, data management and compromise of the review process. The highest proportion of retracted publications corresponded to Iran (15.52 per 10,000), followed by Egypt and China (11.75 and 8.26 per 10,000). Conclusions : Currently, misconduct is the main cause of retraction. Specific strategies to limit this phenomenon must be implemented. It would be useful to standardize reasons and procedures for retraction. The development of a standard retraction form to be permanently indexed in a database might be relevant.Objetivo : Analizar las causas de las retractaciones y las características fundamentales de sus autores. Método : Se diseñó un estudio descriptivo, transversal, que incluyó todas las publicaciones con retractación entre el 1 de enero de 2013 y el 31 de diciembre de 2016 indexadas en PubMed. Las causas de la retractación fueron clasificadas como manejo de datos, asuntos de autoría, plagio, investigación no ética, asuntos de las revistas, proceso de revisión, conflictos de intereses, otras causas y razones desconocidas. Tras esto, la conducta indebida fue clasificada como mala conducta, sospecha de mala conducta y sin sospecha de mala conducta. Resultados : Se identificaron 1.082 publicaciones retractadas. La proporción de publicaciones retractadas fue de 2,5 por cada 10.000 publicaciones para el periodo evaluado. La principal causa de retractación fue la mala conducta (65,3%), y las causas principales fueron plagio, manejo de los datos y compromiso del proceso de revisión. La mayor proporción de publicaciones retractadas correspondió a Irán (15,52 por 10.000), seguido de Egipto y China (11,75 y 8,26 por 10.000, respectivamente). Conclusiones : Actualmente, la mala conducta es la principal causa de retractación. Deberían implementarse estrategias específicas para limitar este fenómeno. Sería de utilidad uniformar los motivos y procedimientos para la retractación. Podría ser apropiado el desarrollo de un formulario estándar de retractación que sea indexado permanentemente en una base de datos.S

Tratamiento de la recurrencia de la infección por VHC en pacientes trasplantados hepáticos. Optimización del proceso

La infección por el virus de la hepatitis C (VHC) es la causa más frecuente de hepatopatía crónica y la primera causa de cirrosis hepática, hepatocarcinoma y trasplante hepático (TH) en nuestro medio, con una prevalencia en España del 2,5% y afectando al 3% de la población mundial. La reinfección por el VHC tras el TH se produce desde el momento de la reperfusión del injerto y a las 72 horas del TH ya se consiguen niveles de ARN-VHC en sangre similares a los pre-TH. Aunque la velocidad de progresión de la fibrosis en los pacientes trasplantados por VHC es muy variable, esta acontece de forma mucho más acelerada que en los pacientes inmunocompetentes.Esta mayor aceleración en la progresión de la fibrosis en los pacientes portadores de trasplante hepático hace que la principal causa de pérdida del injerto y de muerte de estos pacientes sea la insuficiencia hepática secundaria a la recurrencia de la cirrosis por VHC, lo que condiciona que la supervivencia del paciente y del injerto están reducidas en los pacientes infectados por VHC frente a los no-infectados, con una supervivencia del 70% a los 5 años. El tratamiento antiviral es el principal elemento capaz de modificar la evolución natural de estos pacientes. La curación tras tratamiento antiviral se define con respuesta viral sostenida (RVS) (negatividad del ARN-VHC en sangre mediante PCR sensible a las 24 semanas de haber terminado el tratamiento antiviral). La optimización del tratamiento de la recurrencia de la infección por VHC en los pacientes trasplantados hepáticos es de gran interés, ya que esto permite mejorar la indicación del tratamiento antiviral, limitar efectos secundarios y disminuir costes, mejorando las tasas de RVS y de supervivencia de este grupo de pacientes. Los tres estudios que conforman esta tesis abordan específicamente el manejo del tratamiento de la recurrencia de la infección por VHC en los pacientes trasplantados hepáticos. El estudio 1 evalúa la el momento de la indicación del tratamiento antiviral, el estudio 2 aborda la elaboración de un modelo pronóstico, con el fin específico de identificar de manera temprana, con una combinación de factores basales y dinámicos precoces, que pacientes no van a responder al tratamiento antiviral estándar, evitar toxicidad o deben ser re-dirigidos a nuevas estrategias terapéuticas que incluyan fármacos más eficaces. Finalmente, el estudio 3 se centra en un parámetro viral muy concreto y de la máxima importancia como es el establecimiento de la definición temporal de la curación de la infección de la infección por VHC, especialmente en los pacientes trasplantados, en los que las alteraciones de la bioquímica hepática pueden estar en relación a otros procesos y el poder establecer de forma precoz y definitiva la curación de la infección adquieren gran trascendencia. Los resultados nos permitieron demostrar que el tratamiento de la recidiva del VHC en la fase aguda de la recurrencia es igual de seguro y eficaz que en la fase de hepatitis crónica activa, pero no aumenta las tasas de curación. La estrategia para la elaboración de un modelo para pronosticar la RVS nos permitió crear una pocket-chart de fácil uso con las siguientes variables: edad del donante, genotipo de la IL28B del receptor y la respuesta viral rápida. También pudimos demostrar que el establecimiento de la RVS era igual de eficaz a la semana 24 que a la 12 tras la finalización del tratamiento.Resumen Infeccion with hepatitis C virus (HCV) is the leading cause of chronic liver disease and hepatocellular carcinoma and is the main indication for liver transplantation (LT) in our area. Prevalence in Spain is 2.5% and 3% over the world. Recurrent HCV infection of the allograft is universal in the anti-HCV-positive candidates. The graft is infected at reperfusión, and at 72 hours post-transplant RNA-HCV levels are similar to pre-LT levels. Fibrosis deposition in LT patients is variable, but is accelerated in LT recipients compared with patients who are not immunosuppressed. The natural history of chronic hepatitis C is accelerated in LT recipients, and is the main cause of graft lost and death. Survival is reduced in HCV-LT patients in comparison with non-HCV patients. Antiviral treatment is the main element able to modify the natural evolution of these patients. Treatment response is defined as a sustained virological response (SVR), (absence of HCV RNA from serum by a sensitive PCRbased assay 24 week after antiviral treatment). Improvement of HCV recurrent management is of great interest, because it allows to enhance treatment indication, minimize side effects and reduce costs improving SVR rates and survival in HCV-LT patients. The 3 studies that comprise this thesis addresses the manegment of HCV recurrence in LT patients. The first study addresses the timing of antiviral indication, the second study works about prognosis models to identify with basal and early on-treatment factors pacients who are going to respond to antiviral tratament, and who not, in order to avoid toxicity, and identify patients who shouls be re-directed to other treatments. The third study is focused on a very specific viral parameter; re-definition of SVR, early determination of treatment response may simplify patient care and reduce costs associated with monitoring but, most importantly, in the particular setting of LT patients, early assessment of post-treatment response is of special importance because this population is at risk of developing complications, and early exclusion of relapse facilitates their recognition and prompt treatment. The result of these studies have allowed to demonstrate that treatment in the acute phase of HCV-recurrence is as safe as in the chronic phase, but it doesn't improve SVR rates. The prognostic model allow us to build an easy use pocket-chart with the following variables: donor age, recipient IL28B genotype and rapid virological response. We were able to establish that HCV-RNA testing at 12 weeks after completion of treatment in liver transplant recipients is as useful as testing at 24 weeks to establish SVR

Does retraction after misconduct have an impact on citations? A pre–post study

Background: Retracted articles continue to be cited after retraction, and this could have consequences for the scientific community and general population alike. This study was conducted to analyse the association of retraction on citations received by retracted papers due to misconduct using two-time frames: during a postretraction period equivalent to the time the article had been in print before retraction; and during the total postretraction period. Methods: Quasiexperimental, pre-post evaluation study. A total of 304 retracted original articles and literature reviews indexed in MEDLINE fulfilled the inclusion criteria. Articles were required to have been published in a journal indexed in MEDLINE from January 2013 through December 2015 and been retracted between January 2014 and December 2016. The main outcome was the number of citations received before and after retraction. Results were broken down by journal quartile according to impact factor and the most cited papers during the preretraction period were specifically analysed. Results: There was an increase in postretraction citations when compared with citations received preretraction. There were some exceptions however: first, citations received by articles published in first-quartile journals decreased immediately after retraction (p<0.05), only to increase again after some time had elapsed; and second, postretraction citations decreased significantly in the case of articles that had received many citations before their retraction (p<0.05). Conclusions: The results indicate that retraction of articles has no association on citations in the long term, since the retracted articles continue to be cited, thus circumventing their retraction

Spontaneous portosystemic shunt embolization in liver transplant recipients with recurrent hepatic encephalopathy

Angiogenesis; Portal hypertension; Collateral vesselsAngiogénesis; Hipertensión portal; Vasos colateralesAngiogènesi; Hipertensió portal; Vasos col·lateralsIntroduction and objectives Spontaneous portosystemic shunts (SPSS) are a common cause of recurrent hepatic encephalopathy (HE). Shunt occlusion is an effective and safe procedure when performed in patients with cirrhosis and preserved liver function. We aimed to describe our experience with SPSS embolization after liver transplantation (LT). Patients We identified five patients who underwent SPSS embolization after LT. Clinical, biochemical and technical procedure data were collected. Results At presentation, all patients had developed graft cirrhosis and HE after LT. Median Model for End-stage Liver Disease (MELD) at embolization was 9 (range 7-12), median Child-Pugh was 8 (range 7-9). Splenorenal and mesocaval shunt were the most frequent types of SPSS found. Three patients have been completely free of HE. Of the two patients who had HE recurrence after embolization, one patient had two episodes of HE which was controlled well with medications. The other patient required three embolizations because of recurrent HE. Median follow-up was 4.4 years (range 1.0-5.0) and MELD score at last follow up was 13 (range 10-18) and median Child-Pugh score B, 7 points (range 5-12). Conclusions SPSS can be considered as a cause of HE after LT. SPSS embolization is feasible and safe in LT recipients.Isabel Campos-Varela's research activity is funded by grant PI19/00330, funded by Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF) - A way to build Europe. Macarena Simón-Talero is a recipient of the Juan Rodés grant JR17/00029 from Instituto de Salud Carlos III, Spain. CIBERehd is supported by Instituto de Salud Carlos III. The work was independent of all funding

A notable proportion of liver transplant candidates with alcohol-related cirrhosis can be delisted because of clinical improvement

Background & Aims To what extent patients with alcohol-related decompensated cirrhosis can improve until recovery from decompensation remains unclear. We aimed to investigate the probability of recovery and delisting due to improvement in patients with alcohol-related decompensated cirrhosis on the waiting list (WL) for liver transplantation (LT). Methods We conducted a registry-based, multicenter, retrospective study including all patients admitted to the LT WL in Catalonia (Spain) with the indication of alcohol-, HCV-, cholestasis- or non-alcoholic steatohepatitis-related decompensated cirrhosis between January 2007 and December 2018. Competing-risk analysis was used to investigate variables associated with delisting due to improvement in patients with alcohol-related decompensated cirrhosis. Criteria for delisting after improvement were not predefined. Outcomes of patients after delisting were also studied. Results One-thousand and one patients were included, 420 (37%) with alcohol-related decompensated cirrhosis. Thirty-six (8.6%) patients with alcohol-related decompensated cirrhosis were delisted after improvement at a median time of 29 months after WL admission. Lower model for end-stage liver disease (MELD) score, higher platelets and either female sex or lower height were independently associated with delisting due to improvement, while time of abstinence did not reach statistical significance in multivariate analysis (p = 0.055). Five years after delisting, the cumulative probability of remaining free from liver-related death or LT was 76%, similar to patients with HCV-related decompensated cirrhosis delisted after improvement. Conclusions A significant proportion of LT candidates with alcohol-related cirrhosis can be delisted due to improvement, which is predicted by low MELD score and higher platelet count at WL admission. Women also have a higher probability of being delisted after improvement, partially due to reduced early access to LT for height discrepancies. Early identification of patients with potential for improvement may avoid unnecessary transplants. Lay summary Patients with alcohol-related cirrhosis can improve until being delisted in approximately 9% of cases. Low model for end-stage liver disease score and high platelet levels at admission predict delisting after improvement, and women have higher probabilities of being delisted due to improvement. Long-term outcomes after delisting are generally favorable

High intrapatient variability of tacrolimus exposure associated with poorer outcomes in liver transplantation

Liver transplantation; Tacrolimus; Liver diseasesTrasplante de hígado; Tacrolimús; Enfermedades del hígadoTrasplantament hepàtic; Tacrolimús; Malalties del fetgeTacrolimus (TAC) is a dose-dependent immunosuppressor with considerable intrapatient variability (IPV) in its pharmacokinetics. The aim of this work is to ascertain the association between TAC IPV at 6 months after liver transplantation (LT) and patient outcome. This single-center cohort study retrospectively analyzed adult patients who underwent transplantation from 2015 to 2019 who survived the first 6 months with a functioning graft. The primary end point was the patient’s probability of death and the secondary outcome was the loss of renal function between month 6 and the last follow-up. TAC IPV was estimated by calculating the coefficient of variation (CV) of the dose-corrected concentration (C0/D) between the third and sixth months post-LT. Of the 140 patients who underwent LT included in the study, the low-variability group (C0/D CV < 27%) comprised 105 patients and the high-variability group (C0/D CV ≥ 27%) 35 patients. One-, 3-, and 5-year patient survival rates were 100%, 82%, and 72% in the high-variability group versus 100%, 97%, and 93% in the low-variability group, respectively (p = 0.005). Moreover, significant impaired renal function was observed in the high-variability group at 1 year (69 ± 16 ml/min/1.73 m2 vs. 78 ± 16 ml/min/1.73 m2, p = 0.004) and at 2 years post-LT (69 ± 17 ml/min/1.73 m2 vs. 77 ± 15 ml/min/1.73 m2, p = 0.03). High C0/D CV 3–6 months remained independently associated with worse survival (hazard ratio = 3.57, 95% CI = 1.32–9.67, p = 0.012) and loss of renal function (odds ratio = 3.47, 95% CI = 1.30–9.20, p = 0.01). Therefore, high IPV between the third and sixth months appears to be an early and independent predictor of patients with poorer liver transplant outcomes.Isabel Campos-Varela’s research activity is funded by grant PI19/00330 from Instituto de Salud Carlos III. CIBERehd is supported by Instituto de Salud Carlos III. The work was independent of all funding

Safety of Drugs Used during the First Wave of COVID-19: A Hospital-Registry-Based Study

COVID-19; Adverse drug reactions; HydroxychloroquineCOVID-19; Reaccions adverses als medicaments; HidroxicloroquinaCOVID-19; Reacciones adversas a los medicamentos; HidroxicloroquinaThe emergency of the coronavirus disease 2019 (COVID-19) pandemic led to the off-label use of drugs without data on their toxicity profiles in patients with COVID-19, or on their concomitant use. Patients included in the COVID-19 Patient Registry of a tertiary hospital during the first wave were analyzed to evaluate the adverse drug reactions (ADRs) with the selected treatments. Twenty-one percent of patients (197 out of 933) had at least one ADR, with a total of 240 ADRs. Patients with ADRs were more commonly treated with multiple drugs for COVID-19 infection than patients without ADRs (p &lt; 0.001). They were younger (median 62 years vs. 70.1 years; p &lt; 0.001) and took less medication regularly (69.5% vs. 75.7%; p = 0.031). The most frequent ADRs were gastrointestinal (67.1%), hepatobiliary (10.8%), and cardiac disorders (3.3%). Drugs more frequently involved included lopinavir/ritonavir (82.2%), hydroxychloroquine (72.1%), and azithromycin (66.5%). Although most ADRs recovered without sequelae, fatal cases were described, even though the role of the disease could not be completely ruled out. In similar situations, efforts should be made to use the drugs in the context of clinical trials, and to limit off-label use to those drugs with a better benefit/risk profile in specific situations and for patients at high risk of poor disease prognosis

The Treatment With the SGLT2 Inhibitor Empagliflozin Modifies the Hepatic Metabolome of Male Zucker Diabetic Fatty Rats Towards a Protective Profile

[Abstract] The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in patients with Type 2 Diabetes Mellitus (T2DM)) trial evidenced the potential of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of patients with diabetes and cardiovascular disease. Recent evidences have shown the benefits of the SGLT2 inhibitor empagliflozin on improving liver steatosis and fibrosis in patients with T2DM. Metabolomic studies have been shown to be very useful to improve the understanding of liver pathophysiology during the development and progression of metabolic hepatic diseases, and because the effects of empagliflozin and of other SGLT2 inhibitors on the complete metabolic profile of the liver has never been analysed before, we decided to study the impact on the liver of male Zucker diabetic fatty (ZDF) rats of a treatment for 6 weeks with empagliflozin using an untargeted metabolomics approach, with the purpose to help to clarify the benefits of the use of empagliflozin at hepatic level. We found that empagliflozin is able to change the hepatic lipidome towards a protective profile, through an increase of monounsaturated and polyunsaturated glycerides, phosphatidylcholines, phosphatidylethanolamines, lysophosphatidylinositols and lysophosphatidylcholines. Empagliflozin also induces a decrease in the levels of the markers of inflammation IL-6, chemerin and chemerin receptor in the liver. Our results provide new evidences regarding the molecular pathways through which empagliflozin could exert hepatoprotector beneficial effects in T2DM.This work was supported by Boehringer Ingelheim Pharma GmbH and Co., by the National Institute of Health “Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III” Madrid, Spain (PI15/00681, PI17/00409, PI18/00821, PI20/00902, RETICS Programme RD16/0012/0014 and CIBER de Enfermedades Cardiovasculares (CIBERCV)); European Regional Development Fund (FEDER) and European Union framework MSCA-RISE-H2020 Programme (Project number 734899). AH-A was funded by predoctoral research grants from Xunta de Galicia and FPU Program of the Spanish Ministry of Science, Innovation and Universities (Spain); MF-S was funded by the predoctoral research grants “Programa Científico do Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS) (Spain) and Xunta de Galicia; and AV-L was funded by the predoctoral research grant from the PFIS Program of the Spanish Ministry of Science and Instituto de Salud Carlos III (Spain

Mild cognitive decline. A position statement of the Cognitive Decline Group of the European Innovation Partnership for Active and Healthy Ageing (EIPAHA)

Introduction Mild cognitive impairment (MCI) is a term used to describe a level of decline in cognition which is seen as an intermediate stage between normal ageing and dementia, and which many consider to be a prodromal stage of neurodegeneration that may become dementia. That is, it is perceived as a high risk level of cognitive change. The increasing burden of dementia in our society, but also our increasing understanding of its risk factors and potential interventions, require diligent management of MCI in order to find strategies that produce effective prevention of dementia. Aim To update knowledge regarding mild cognitive impairment, and to bring together and appraise evidence about the main features of clinical interest: definitions, prevalence and stability, risk factors, screening, and management and intervention. Methods Literature review and consensus of expert opinion. Results and conclusion MCI describes a level of impairment in which deteriorating cognitive functions still allow for reasonable independent living, including some compensatory strategies. While there is evidence for some early risk factors, there is still a need to more precisely delineate and distinguish early manifestations of frank dementia from cognitive impairment that is less likely to progress to dementia, and furthermore to develop improved prospective evidence for positive response to intervention. An important limitation derives from the scarcity of studies that take MCI as an endpoint. Strategies for effective management suffer from the same limitation, since most studies have focused on dementia. Behavioural changes may represent the most cost-effective approach

COVID-19 Clinical Profile in Latin American Migrants Living in Spain: Does the Geographical Origin Matter?

COVID-19; Latin America; SeverityCOVID-19; Amèrica Llatina; GravetatCOVID-19; América Latina; GravedadThe aim of this study was to describe and compare the clinical characteristics of hospitalized patients with COVID-19 pneumonia according to their geographical origin. This is a retrospective case-control study of hospitalized patients with confirmed COVID-19 pneumonia treated at Vall d’Hebron University Hospital (Barcelona) during the first wave of the pandemic. Cases were defined as patients born in Latin America and controls were randomly selected among Spanish patients matched by age and gender. Demographic and clinical variables were collected, including comorbidities, symptoms, vital signs and analytical parameters, intensive care unit admission and outcome at 28 days after admission. Overall, 1080 hospitalized patients were registered: 774 (71.6%) from Spain, 142 (13.1%) from Latin America and the rest from other countries. Patients from Latin America were considered as cases and 558 Spanish patients were randomly selected as controls. Latin American patients had a higher proportion of anosmia, rhinorrhea and odynophagia, as well as higher mean levels of platelets and lower mean levels of ferritin than Spanish patients. No differences were found in oxygen requirement and mortality at 28 days after admission, but there was a higher proportion of ICU admissions (28.2% vs. 20.2%, p = 0.0310). An increased proportion of ICU admissions were found in patients from Latin America compared with native Spanish patients when adjusted by age and gender, with no significant differences in in-hospital mortality.Isabel Campos-Varela’s research activity is funded by grant PI19/00330 from Instituto de Salud Carlos III. CIBERehd is supported by Instituto de Salud Carlos III. The work was independent of all funding. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors