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Introduction: Crohn's disease (CD) varies by location, potentially affecting therapy efficacy and surgery risk, although research on this topic is conflicting. This study aims to investigate the independent association between CD location and therapeutic patterns., Methods: We analyzed patients with CD diagnosed from January 2005 to May 2023 registered in the nationwide ENEIDA registry. A univariate Cox regression analysis assessed the association of disease location with biologic use and persistence (with treatment discontinuation as a failure event), as well as the use of intestinal resections. A multivariate model was constructed to evaluate the independent association of disease location with therapeutic patterns, controlling for potential confounders such as sex, age at inclusion and diagnosis, disease duration and behavior, previous surgery or biological therapy, extraintestinal manifestations, and perianal disease., Results: The study included 17,292 patients with a median follow-up period of 6 years (interquartile range 2-10 years). Ileocolonic location was associated with a higher biologic use than colonic location (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.22-1.38) and ileal disease (HR 1.21, 95% CI 1.16-1.27), independently predicting biologic use (P < 0.001). Ileal location was associated with a lower biologic persistence than ileocolonic location (HR 1.14, 95% CI 1.07-1.21) and colonic disease (HR 1.10, 95% CI 1.01-1.20), independently predicting biologic persistence (P = 0.019). Ileal disease was associated with a higher likelihood of intestinal resections than colonic (HR 2.82, 95% CI 2.45-3.25) and ileocolonic location (HR 1.13, 95% CI 1.05-1.22), independently predicting the use of surgery (P < 0.001)., Discussion: CD location with ileal predominance is associated with a distinct therapeutic pattern, including higher biologic use, lower treatment persistence, and increased rates of intestinal resections., (Copyright © 2024 by The American College of Gastroenterology.)

Heart failure (HF) is a prevalent global disease, particularly impacting developed countries. With the world's aging population, HF's impact on the quantity and quality of life is expected to grow. This review aims to ascertain the frequency, characteristics, and properties of all patient-reported outcomes measures (PROMs) studied in HF patients. We searched Ovid/Medline and Web of Science for original articles about PROMs performed in adults with HF. Using pre-established quality criteria for measurement properties, an overall rating was assigned to evaluate and compare different instruments. The quality of evidence was assessed with the COSMIN risk of bias checklist. Of 4283 records identified, we reviewed 296 full-text documents and included 64 papers, involving 30,185 participants. Thirty different PROMs were identified, with 14 specifically designed for HF being the most commonly used. Minnesota Living with Heart Failure (MLHF) and Kansas City Cardiomyopathy Questionnaire (KCCQ) were evaluated 16 and 13 times, respectively, demonstrating good psychometric properties. The MacNew Heart Disease Health-Related Quality of Life Questionnaire, a common heart disease-specific instrument, exhibited negative performances across various psychometric measures. Evidence for generic instruments was scant and unremarkable and they proved to be less responsive in HF populations. MLHF and KCCQ emerged as the most commonly used and well-supported PROMs, with robust overall evidence. They are comprehensive and accurate instruments, particularly suitable for application in clinical practice and research. Future research should explore how computer-adapted instruments can enhance precision, reduce respondent burden, and improve communication between clinicians and patients, thereby promoting more efficient and patient-centered services., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cervical cancer (CC) is the fourth most common cancer affecting women worldwide. The risk of women immunosuppressed due to AIDS or organ transplantation is well documented, as most cases are caused by persistent human papillomavirus (HPV) infection and immunosuppression can prevent clearing HPV. Although European guidelines advise that inflammatory bowel disease (IBD) women under immunosuppression should be screened for CC as regularly as high-risk patients, quality evidence is lacking in our country. We performed a retrospective case-control (2020-2021) study to analyse the risk factors associated with the appearance of low-grade (LSIL) or high-grade (HSIL) squamous intraepithelial cervical lesions in patients with IBD. We included all women aged 21-65 years , followed up at the University Hospital Fundación Alcorcón (Spain). Cases were defined as those patients with abnormalities in cervical cytology, while the control group consisted of the rest of the women. Disease characteristics, treatments and epidemiological data (smoking habit, sexual behaviour and reproductive history) were obtained. We documented the evolution of abnormalities over time and compare data between women under immunosuppressive treatment or not.

Background and Objectives: inflammatory bowel disease (IBD) has a major impact on psychological well-being. This condition is associated with a high level of anxiety and mood disorders, but stress prevalence and how an individual copes with IBD have not been sufficiently explored. The objective of this study was to assess the impact of the disease on psychological disorders and to identify coping strategies used by patients with IBD, as well as to analyze the relationship between these variables and sociodemographic and clinical variables., Methods: a cross-sectional prospective study was performed including 126 consecutive patients. Those with psychiatric conditions prior to the onset of the IBD were excluded. Independent variables were measured using a sociodemographic and clinical questionnaire. The patients completed the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale (PSS) and the BRIEF COPE questionnaire. Quality of life was measured using the nine-item IBD Quality of Life (IBDQ-9)., Results: the final cohort comprised 100 patients (37 with ulcerative colitis and 63 with Crohn's disease). The prevalence rates of the variables of stress, anxiety and depression were high (44 %, 24 % and 14 %, respectively). Stress and depression were higher in females (p < 0.05), without differences regarding other sociodemographic and clinical variables. Moreover, higher levels of anxiety and depression were found to be associated with stress and dysfunctional coping strategies (p < 0.01)., Conclusions: patients with IBD, particularly women, have high rates of psychological disorders. Those with anxiety and depression presented more stress and used more dysfunctional strategies. These conditions must be considered for a multidisciplinary management.

Introduction: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice., Methods: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score., Results: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation., Discussion: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported., (Copyright © 2023 by The American College of Gastroenterology.)

Background and Aims: Clinical trials and real-life studies with ustekinumab in Crohn's disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD., Methods: Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey-Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54., Results: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]., Conclusions: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case−control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March−July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3−5.9), occupational risk (OR: 2.9; 95%CI: 1.8−4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2−2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09−0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution.

Introduction: Viral infections can induce autoimmune diseases in susceptible patients. SARS-CoV-2 has been associated with the development of rheumatic disease, especially small vessel vasculitis and arthritis. Typically, onset occurs days to weeks after the antigenic challenge and in patients with mild COVID-19. We report a case of large vessel vasculitis (LVV) temporally related to SARS-CoV-2 infection., Case Description: An otherwise healthy 19-year-old woman presented with fatigue, malaise, and chest and low back pain. The symptoms had begun 5 weeks earlier and 1 month after mild SARS-CoV-2 infection. Serological work-up revealed a marked proinflammatory state and anaemia without signs of infectious or autoimmune disease. Computerized tomography revealed thickening and blurring of the perivascular fat of the descending thoracic and abdominal aorta, progressing along the proximal iliac and renal arteries. Fluorodeoxyglucose positron emission tomography confirmed inflammatory activity. Symptoms and laboratory values normalized after prednisolone treatment., Discussion: Recent SARS-CoV-2 infection may be a trigger for LVV, including Takayasu arteritis, as well as other rheumatic diseases. A prompt and thorough differential diagnosis is essential to exclude aortitis and LVV mimickers. Moreover, physicians should be aware of the potential spectrum of systemic and autoimmune diseases that could be precipitated by SARS-CoV-2 infection. This will allow timely diagnosis and treatment, with significant improvement in prognosis., Learning Points: SARS-CoV-2 infection can trigger large vessel vasculitis and other rheumatic diseases.Awareness of the association between COVID-19 and autoimmune phenomena allows for timely diagnosis and treatment with significant improvements in prognosis.Vasculitis and other autoimmune diseases should be kept in mind in patients who develop proinflammatory states days to weeks after an initial antigenic challenge., Competing Interests: Conflicts of Interests: The authors declare there are no competing interests., (© EFIM 2022.)

End-stage kidney disease is frequently associated with left ventricular hypertrophy (LVH), a condition more prevalent in the elderly, that may increase mortality after renal transplantation (RTx). Previous studies suggested that mTOR inhibitors (mTORi) can improve LVH, but this has never been tested in elderly kidney transplant recipients. In this prospective randomized clinical trial, we analyzed the impact of Everolimus (EVL) on the reversal of LVH after RTx in elderly recipients (≥60 years) submitted to different immunosuppressive regimens: EVL/lowTacrolimus (EVL group, n = 53) or mycophenolate sodium/regularTacrolimus (MPS group, n = 47). Patients performed echocardiograms (Echo) up to 3 months after RTx and then annually. At baseline, mean age was 65±3 years in both groups and LVH was observed in 63.6% of patients in EVL group and in 61.8% of MPS group. Last Echo was performed at mean time of 47 and 49 months after RTx in EVL and MPS groups, respectively (P = .34). LVH regression was observed in 23.8% (EVL group) and 19% (MPS group) of patients (P = 1.00). Mean eGFR, blood pressure, and use of RAS blockers were similar between groups throughout follow-up. EVL did not improve LVH in this cohort, and this lack of benefit may be attributed to concomitant use of TAC, senescence, or both., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

(1) Aims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). (2) Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-ץ-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. (3) Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18−20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50−0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66−0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20−22%] vs. 14% [95% CI 13−16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. (4): Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM.

Background: Previous studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain., Methods: Prospective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients., Results: We included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses., Conclusions: Compared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe., Competing Interests: AG has served as speaker, consultant and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Tillotts Pharma, Chiesi and Otsuka Pharmaceutical. ER has provided scientific advice/participated in medical meetings/received research funding from/received payment for presentations and advice from: MSD, Schering-Plow, Ferring, Abbvie, Takeda, Janssen, Fresenius Kabi, Pfizer. IV has served as a speaker, or has received research or education funding from Abbvie, MSD, Pfizer, Takeda, Janssen, Tillotts Pharma, Ferring and Shire Pharmaceuticals. MM has served as speaker or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Biogen, Tillotts Pharma, Chiesi and Adacyte. JPG has served as speaker, consultant, and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene, Gilead/Galapagos, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, and Vifor Pharma. YZ has received support for conference attendance, speaker fees, research support and consulting fees from Abbvie, Adacyte, Almirall, Amgen, Dr. Falk, FAES Pharma, Ferring, Janssen, MSD, Otsuka, Pfizer, Shire, Takeda and Tillots. XC has received grants for research from Abbvie, MSD, Vifor fees for advisory boards form Abbvie, MSD, Takeda, Pfizer, Janssen and VIFOR and has given lectures for Abbvie, MSD, Janssen, Pfizer, Takeda, Shire and Allergan. FB has served as a speaker, a consultant and advisory member for or has received research funding from MSD, Abbvie, Takeda, Janssen, Pfizer, Biogen, Amgen, Ferring, Faes Farma, Tillotts Pharma, Falk Pharma, Chiesi, Gebro Pharma, Vifor Pharma. MM-M has served as speaker, consultant and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Takeda, Janssen, Shire Pharmaceuticals and Otsuka Pharmaceutical. MR has served as speaker, consultant or advisory member for MSD, Abbvie, Pfizer, Takeda, Janssen, Ferring and Chiesi. MP has served as speaker or has received research funding from Abbvie, Takeda and Janssen. IR-L has received financial support for traveling and educational activities from or has served as an advisory board member for MSD, Pfizer, Abbvie, Takeda, Janssen, Tillotts Pharma, Shire Pharmaceuticals, Roche, Celltrion, Faes Farma, Ferring, Dr. Falk Pharma, Otsuka Pharmaceutical and Adacyte. Financial support for research from Tillotts Pharma. RL has served as a speaker, or has received research or education funding from MSD, Abbvie, Pfizer, Takeda, Janssen and Dr. Falk. LA has served as speaker, or has received research or education funding from MSD, Abbvie, Kern Pharma, Ferring, FaesFarma, Shire Pharmaceuticals, Pfizer, Takeda, Janssen, Tillotts Pharma, and Otsuka Pharmaceutical. FA-A has served as speaker, consultant and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Tillotts Pharma, Chiesi and Dr. Falk. LR has served as a speaker, or has received education funding from MSD, Abbvie, Adacyte, Takeda, Pfizer, Janssen and Ferring. MB-d has served as a speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Gillead, Celgene, Pfizer, Sandoz, Biogen, Fresenius, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte and Vifor Pharma. ED has served as a speaker, or has received research or education funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Gilead, Janssen, Kern Pharma, MSD, Pfizer, Roche, Samsung, Takeda, Tillots, Thermofisher. RF has served as a speaker, or has received research or education funding or advisory fees from AbbVie, Janssen, Takeda, Adacyte Therapeutics, Sanofi, GlaxoSmithKline, Almirall. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gutiérrez, Zapater, Ricart, González-Vivó, Gordillo, Olivares, Vera, Mañosa, Gisbert, Aguas, Sánchez-Rodríguez, Bosca-Watts, Laredo, Camps, Marín-Jiménez, Zabana, Martín-Arranz, Muñoz, Navarro, Sierra, Madero, Vela, Pérez-Calle, Sainz, Calvet, Arias, Morales, Bermejo, Fernández-Salazar, Van Domselaar, De Castro, Rodríguez, Muñoz-Villafranca, Lorente, Rivero, Iglesias, Herreros, Busquets, Riera, Martínez-Montiel, Roldón, Roncero, Hinojosa, Sierra, Barrio, De Francisco, Huguet, Merino, Carpio, Ginard, Muñoz, Piqueras, Almela, Argüelles-Arias, Alcaín, Bujanda, Manceñido, Lucendo, Varela, Rodríguez-Lago, Ramos, Sempere, Sesé, Barreiro-de Acosta, Domènech and Francés.)

We aim to describe the incidence and source of contagion of COVID-19 in patients with IBD, as well as the risk factors for a severe course and long-term sequelae. This is a prospective observational study of IBD and COVID-19 included in the ENEIDA registry (53,682 from 73 centres) between March-July 2020 followed-up for 12 months. Results were compared with data of the general population (National Centre of Epidemiology and Catalonia). A total of 482 patients with COVID-19 were identified. Twenty-eight percent were infected in the work environment, and 48% were infected by intrafamilial transmission, despite having good adherence to lockdown. Thirty-five percent required hospitalization, 7.9% had severe COVID-19 and 3.7% died. Similar data were reported in the general population (hospitalisation 19.5%, ICU 2.1% and mortality 4.6%). Factors related to death and severe COVID-19 were being aged ≥ 60 years (OR 7.1, 95% CI: 1.8-27 and 4.5, 95% CI: 1.3-15.9), while having ≥2 comorbidities increased mortality (OR 3.9, 95% CI: 1.3-11.6). None of the drugs for IBD were related to severe COVID-19. Immunosuppression was definitively stopped in 1% of patients at 12 months. The prognosis of COVID-19 in IBD, even in immunosuppressed patients, is similar to that in the general population. Thus, there is no need for more strict protection measures in IBD.

Background: A recently registered device containing 80 mg of adalimumab (ADA) allows an alternative dose escalation regimen with ADA 80 mg every other week (EOW) given as a single subcutaneous injection instead of 40 mg every week. The ADASCAL study evaluated the preferences and satisfaction of inflammatory bowel disease (IBD) patients after switching their ADA regimen from 40 mg weekly to 80 mg EOW given with a single-dose pen., Methods: In this multicentre cross-sectional study, patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW completed the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4), a four-item questionnaire [a Likert-type 5-point scale for preferences, two closed questions for convenience and a 100-point visual analogue scale (VAS) to assess which escalated ADA regimen patients would prefer to continue] and two Health-Related Quality of Life (HRQoL) questionnaires: the generic European Quality of Life-5 Dimensions (EQ-5D) and disease-specific Spanish version of the Inflammatory Bowel Disease Questionnaire (SIBDQ-9)., Results: In total, 77 patients (64 Crohn's disease and 13 ulcerative colitis) were included. The TSQM score showed a notably high global satisfaction [83.4, standard deviation (SD) = 14.1] of patients with ADA 80 mg EOW given with a single-dose pen, with high TSQM scores for individual components: effectiveness (77.6, SD = 16.9), convenience (83.7, SD = 14.5) and side effects (86.1, SD = 23.4). Most of the patients (74%) preferred the ADA EOW regimen (59.7% had strong preference, 14.3% slight preference). ADA EOW interferes less with daily activity (59.7%) and with travel plans (81.8%). Most patients (77%) would prefer to continue with ADA EOW (mean VAS score of 84.7, SD = 24.1, where 100 indicates a preference for ADA EOW). Patients reported high HRQoL scores on both the EQ-5D (72.3, SD = 20.1) and SIBDQ-9 (75.1, SD = 14.7)., Conclusion: IBD patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW reported a higher preference for the EOW regimen and therefore most decided to continue with a single self-injection EOW., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. C.T. has served as a speaker, consultant and advisory board member for or has received research funding from MSD, AbbVie, Pfizer, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Galapagos and Tillots. M.P.M.-M. has served as speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Pfizer, Kern Pharma, Takeda, Janssen, Shire Pharmaceuticals and Otsuka Pharmaceutical. M.B.-d.-A. has served as a speaker, consultant and advisory member for or has received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Gilead, Celgene, Pfizer, Sandoz, Biogen, Fresenius, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte and Vifor Pharma. I.V. has served as a speaker, consultant and advisory member for and has received funding from MSD, AbbVie, Pfizer, Ferring, Shire Pharmaceuticals, Takeda and Janssen. R.L. has served as a speaker, or has received research or education funding from MSD, AbbVie, Pfizer, Takeda, Janssen and Dr. Falk Pharma. P.V. has served as a speaker, consultant or advisory member for MSD, AbbVie, Ferring, Faes Farma, Takeda and Janssen. B.C. has served as a speaker, consultant and advisory board member for MSD, AbbVie, Ferring, Shire, Takeda and Janssen. R.F.-I. has served as a speaker, consultant and advisory board member for MSD, AbbVie, Pfizer, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Adacyte and Tillots. J.L.P.C. has served as a speaker, consultant and advisory board member for MSD, AbbVie, Ferring, Faes Farma, Takeda and Janssen. C.A. has served as a speaker for Janssen and has prepared promotional material for Falk Pharma. These activities were not related to the present work. The remaining authors have no conflicts of interest to declare., (© The Author(s), 2021.)

Background and Aims: The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life., Methods: Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16., Results: A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection., Conclusions: Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The long-term outcome of patients after antitumour necrosis factor alpha (anti-TNF) discontinuation is not well known., Aims: To assess the risk of relapse in the long-term after anti-TNF discontinuation., Methods: This was an extension of the evolution after anti-TNF discontinuation in patients with inflammatory bowel disease (EVODIS) study (Crohn's disease or ulcerative colitis patients treated with anti-TNFs in whom these drugs were withdrawn after achieving clinical remission) based in the same cohort of patients whose outcome was updated. Clinical remission was defined as a Harvey-Bradshaw index ≤4 points in Crohn's disease, a partial Mayo score ≤2 in ulcerative colitis and the absence of fistula drainage despite gentle finger compression in perianal disease., Results: This was an observational, retrospective, multicenter study. A total of 1055 patients were included. The median follow-up time was 34 months. The incidence rate of relapse was 12% per patient-year (95% confidence interval [CI] = 11-14). The cumulative incidence of relapse was 50% (95% CI = 47-53): 19% at one year, 31% at 2 years, 38% at 3 years, 44% at 4 years and 48% at 5 years of follow-up. Of the 60% patients retreated with the same anti-TNF after relapse, 73% regained remission. Of the 75 patients who did not respond, 48% achieved remission with other therapies. Of the 190 patients who started other therapies after relapse, 62% achieved remission with the new treatment., Conclusions: A significant proportion of patients who discontinued the anti-TNF remained in remission. In case of relapse, retreatment with the same anti-TNF was usually effective. Approximately half of the patients who did not respond after retreatment achieved remission with other therapies., (© 2021 John Wiley & Sons Ltd.)

Background and Aims: Although commonly used in inflammatory bowel disease [IBD], thiopurines frequently cause intolerance, and switching to a second thiopurine has only been reported in some small series. Ours aims in this study were to evaluate the safety of switching to a second thiopurine in a large cohort, and to assess the impact of age on tolerance., Methods: Adult IBD patients from the ENEIDA registry, who were switched to a second thiopurine due to adverse events [excluding malignancies and infections], were identified. At the beginning of thiopurine treatment, patients were divided by age into two groups: 18-50 and over 60 years of age. The rate and concordance of adverse events between the first and second thiopurines, treatment intolerance, and persistence with the second thiopurine were evaluated., Results: A total of 1278 patients [13% over 60 years of age] were switched to a second thiopurine. At 12 months, the cumulative probability of switch intolerance was 43%, and persistence with treatment was 49%. Independent risk factors of switch intolerance were age over 60 years (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.07-2.07; p = 0.017) , previous gastrointestinal toxicity [OR 1.4; 95% CI 1.11-1.78; p = 0.005], previous acute pancreatitis [OR 6.78; 95% CI 2.55-18.05; p <0.001], and exposure to the first thiopurine <6 months [OR 1.59; 95% CI 1.14-2.23; p = 0.007]., Conclusions: In a large series in clinical practice, switching to a second thiopurine proved to be a valid strategy. Tight monitoring of elderly IBD patients switching to a second thiopurine because of adverse events is recommended., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: Declaration of competing interest The authors declare no conflict of interest.

Background: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients., Methods: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent., Results: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug., Conclusions: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Anti-tumor necrosis factor agents (anti-TNFs) are efficacious at preventing the postoperative recurrence (POR) of Crohn disease, as demonstrated in 2 randomized controlled trials. However, real-life data for infliximab or adalimumab in this setting are scarce. Our aim was to assess both the efficiency of anti-TNFs at preventing early POR of Crohn disease in clinical practice and the associated risk factors for POR., Methods: Patients in whom anti-TNFs were prescribed for the prevention of POR within 3 months after ileocolonic resection and who had an endoscopic assessment within 18 months were identified from the ENEIDA registry. Clinical and endoscopic features were collected within 18 months after surgery., Results: In total, 152 patients were included (55 treated with infliximab, 97 with adalimumab, and 39% with concomitant immunosuppressants). Anti-TNF treatment was started after a median time of 29 days (IQR 13-44) after surgery. Eighty-two percent of patients had at least one risk factor for POR, and 82% had been exposed to anti-TNFs before the index surgery. Overall, 34% had endoscopic POR (as defined using a Rutgeerts endoscopic score > i1); 14% had advanced endoscopic POR (>i2); and 20% had clinical POR, with no differences between infliximab and adalimumab. In the multivariate analysis, only perianal disease (odds ratio 2.73, 95% confidence interval [CI] 1.26-5.91) and rectal involvement (odds ratio 2.79, 95% CI 1.09-7.14) were independent predictors of endoscopic POR., Conclusions: In clinical practice, anti-TNFs for the prevention of POR of Crohn disease are frequently used in patients experienced with anti-TNFs and with concomitant immunosuppressants. The efficacy of infliximab and adalimumab for POR prevention is similar and in accordance with the results obtained in randomized controlled trials., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cystic echinococcosis (CE) is a zoonosis endemic in Spain caused by the larval stage of the cestode Echinococcus granulosus and is one of the 18 neglected tropical diseases recognized by the WHO. The aim of this study was to describe the epidemiological and clinical data of CE in a surgical referral hospital., Methods: A retrospective descriptive study of all adults' patients diagnosed with CE and followed at Vall d'Hebron University Hospital in Barcelona, Spain, between 2000 and 2015., Results: We found 151 cases, 78 (51.7%) women, and median age at diagnosis was 68 (range, 15-92) years. Diagnosis was a radiological finding in 97 (64.2%) and the most frequent location was the liver [135 (89.4%) patients]. Nearly 80% of the cysts were calcified and serology was positive in 48 (51.6%). The WHO-IWGE classification was only available in 70 of the 104 (67.3%) cases of liver cysts that had an ultrasound. First therapeutic plan was "watch and wait" followed by surgery. International recommendations were not always followed, particularly in CE4 and CE5 stages, and 20% needed a change of treatment because of progression or recurrence. Patients treated surgically were younger, more symptomatic, and had larger and less calcified cysts in multiple sites. Serology was not useful for CE diagnosis and neither serology nor calcification of the cyst helped to predict viability., Conclusions: The formation of multidisciplinary teams in reference hospitals could help to improve CE diagnosis, its management, and follow-up, since international recommendations are not usually followed.

The number of organs retrieved from donation after circulatory death (DCD) donors has continued to rise in recent years. The functional superiority of DCD organs is achieved when the lungs are perfused with cold perfusion and livers with normothermic regional perfusion (NRP). Thus, a precise surgical technique is required to combine thoracic and abdominal organ procurement. The technique used at our center consists of a rapid laparotomy and middle sternotomy, then the abdominal aorta (Ao) and abdominal inferior vena cava (VC) are cannulated and the descending thoracic Ao is cross-clamped. NRP is started at that point. As a variation of previously described techniques, the thoracic vena cava is not initially clamped in order to improve the return of blood volume to the NRP circuit. The pulmonary artery is cannulated to flush the lungs and the left atrial appendage is opened for drainage. After 120 minutes, NRP perfusion is stopped and the organs are flushed with cold preservation solution. In 2016, 3 livers and 6 lungs were harvested at our center using the technique described. After a minimum follow-up of 1 year, no evidence of biliary complications was observed. The combined procurement of lungs after room temperature perfusion and liver after NRP without initial clamping of the thoracic VC is feasible, with excellent function post-transplantation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We aimed to evaluate the safety and efficacy of low doses of anti-T-lymphocyte globulin (ATG)-based immunosuppression in preserving renal function and preventing liver rejection in liver transplant (LT) recipients with pretransplant renal dysfunction. We designed a prospective single-center cohort study analyzing patients with pre-LT renal dysfunction defined as eGFR<60 mL/min/1.73m 2 , who underwent induction therapy with ATG ( ATG group, n=20) . This group was compared with a similar retrospective cohort treated with basiliximab ( BAS group, n=20 ). An economic analysis between both induction therapies was also undertaken. In the ATG group, 45% and 50% of patients had recovered their renal function without acute cellular rejection (ACR) episodes at day 7 and 1 month after LT, respectively, versus 40% and 55% of patients in the BAS group (p=1). Renal function improved in both groups over time and no differences between groups were observed regarding one-year eGRF and one-year probability of ACR. Cost per patient of the ATG course was 403€ (r: 126-756) versus 2,524€ of the basiliximab course (p=0.001). In conclusion, induction with low dose of ATG or basiliximab in patients with pretransplant renal dysfunction is a good strategy for preserving posttransplant renal function; however the use of low-dose ATG resulted in a substantial reduction in drug costs. This trail is registered with ClinicalTrials.gov number: NCT01453218.

This brief report presents the results of 20 adult and pediatric patients treated with the use of biodegradable SX-Ella biliary stents placed by means of a transhepatic approach for the treatment of benign biliary strictures after liver transplantation. Stent insertions were always feasible (100%), and only 1 case of acute pancreatitis was observed (5%). The overall clinical success rate of the procedure, including anastomotic and nonanastomotic strictures, was 75%, and was higher in the anastomotic stricture group (81.25%) than in the nonanastomotic stricture group (50%)., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

BACKGROUND The characteristics of liver donors have changed over the last decade owing to the shortage of organs and high mortality on the waiting list, leading to wider use of extended-criteria donors, including older donors. The aim of this study was to evaluate the effect of matching donor-recipient age on morbidity at 1 year post-transplant and on long-term patient and graft survival. MATERIAL AND METHODS Retrospective study from a prospectively-obtained database including adult patients who had received a primary liver transplant (LT) from whole graft of brain-dead donors. Recipients were divided into 2 age groups: <60 years and ≥60 years. Both groups were sub-divided according to donor age (younger than 60 years and 60 years or older). A propensity score analysis was performed to further adjust for baseline differences between recipients and donors. RESULTS We analyzed 642 patients who had LT performed between January 2000 and December 2013. No differences were observed in 1-year morbidity (hospital stay, rejection, surgical complications, and retransplant) between groups. Although patient and graft survival was significantly impaired in the older donor/older recipient group on Kaplan-Meier analysis (p=0.004), the propensity score analysis showed that donor age ≥60 years did not increase the risk of death for recipients aged ≥60 (HR1.40, p 0.074) and <60 years (HR 1.47, p 0.070). CONCLUSIONS Older donor age did not negatively affect survival regardless of recipient age, and comparable outcomes were achieved without an increased rate of complications.

Background: Anti-TNF treatment is effective for Crohn's disease (CD); however, some patients did not achieve remission with these drugs., Aims: To evaluate the short-term effectiveness of a second anti-TNF in CD patients who did not achieve remission with the first one and to assess its durability., Methods: Patients who did not achieve remission with their first anti-TNF were included. The short-term response of the second anti-TNF was assessed, the long-term response was evaluated in patients who achieved remission (Kaplan-Meier). Cox-regression was performed to identify predictors of loss of efficacy., Results: In all, 118 CD patients received a second anti-TNF after primary failure of the first. The first anti-TNF was discontinued because of non-response in 54% of patients and partial response in 46%. Fifty-one percent of patients achieved remission in the short-term. The probability of remission was lower in patients for whom the drug indication was perianal disease (OR=0.3, 95% CI=0.1-0.7, P=0.005). The dose was increased in 33% of patients, and 37% achieved/regained remission. The probability of maintaining remission was 76%, 68% and 64% at 12, 18 and 24 months, respectively., Conclusions: Approximately half of the patients achieved remission with a second anti-TNF after primary failure of the first, this strategy was less effective in patients with perianal disease., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Despite now being an infrequent complication in liver transplantation (LT) recipients, acute liver failure is still associated with high mortality., Case Report: Here we report a case of acute liver failure 11 months after AB0-compatible LT in a hepatitis C-positive 50-year-old male recipient caused by late antibody-mediated rejection (AMR). De novo donor-specific antibodies appeared later in a previously negative donor-recipient crossmatch, leading to a rapid deterioration of liver function., Conclusions: We highlight the importance of an accurate diagnosis and an early therapeutic intervention. The analysis of this case brings novel and generalizable insights to the differential diagnosis of acute liver failure after LT., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT)., Methods: We retrospectively reviewed the combined experience at Toronto General Hospital and Hospital Vall d'Hebron managing HCC recurrence after LT (n = 121) between 2000 and 2012. We analyzed prognostic factors by uni- and multi-variate analysis. Median follow-up from LT was 29.5 (range 2-129.4) months. Median follow-up from HCC recurrence was 12.2 (range 0.1-112.5) months., Results: At recurrence, 31.4 % were treated with curative-intent treatments (surgery or ablation), 42.1 % received palliative treatment, and 26.4 % received best supportive care. The 1-, 3-, and 5-year survivals, respectively, after HCC recurrence were 75, 60, and 31 %, vs. 60, 19, and 12 %, vs. 52, 4, and 5 % (p < 0.001). By multivariate analysis, not being amenable to a curative-intent treatment [hazard ratio (HR) 4.7, 95 % confidence interval (CI) 2.7-8.3, p < 0.001], α-fetoprotein of ≥100 ng/mL at the time of HCC recurrence (HR 2.1, 95 % CI 1.3-2.3, p = 0.002) and early recurrence (<12 months) after LT (HR 1.6, 95 % CI 1.1-2.5, p = 0.03) were found to be poor prognosis factors. A prognostic score was devised on the basis of these three independent variables. Patients were divided into three groups, as follows: good prognosis, 0 points (n = 22); moderate prognosis, 1 or 2 points (n = 84); and poor prognosis, 3 points (n = 15). The 1-, 3-, and 5-year actuarial survival for each group was 91, 50, and 50 %, vs. 52, 7, and 2 %, vs. 13, 0, and 0 %, respectively (p < 0.001)., Conclusions: Patients with HCC recurrence after transplant amenable to curative-intent treatments can experience significant long-term survival (~50 % at 5 years), so aggressive management should be offered. Poor prognosis factors after recurrence are not being amenable to a curative-intent treatment, α-fetoprotein of ≥100 ng/mL, and early (<1 year) recurrence after LT.

Background: Liver transplantation (LT) is the treatment of choice for chronic and acute liver failure; however, the status of long-term survivors and allograft function is not well known., Aim: To evaluate the clinical outcome and allograft function of survivors 20 years post-LT, cause of death during the same period and risk factors of mortality., Methods: A retrospective study was conducted from prospective, longitudinal data collected at a single center of adult LT recipients surviving 20 years. A comparative sub-analysis was made with patients who were not alive 20 years post-transplantation to identify the causes of death and risk factors of mortality., Results: Between 1988 and 1994, 132 patients received 151 deceased-donors LT and 28 (21%) survived more than 20 years. Regarding liver function in this group, medians of AST, ALT and total bilirubin at 20 years post-LT were 33 IU/L (13-135 IU/L), 27 (11-152 IU/L) and 0.6 mg/dL (0.3-1.1 mg/dL). Renal dysfunction was observed in 40% of patients and median eGFR among 20-year survivors was 64 mL/min/1.73 m(2) (6-144 mL/min/1.73 m(2)). Sixty-one percent of 20-year survivors had arterial hypertension, 43% dyslipidemia, 25% de novo tumors and 21% diabetes mellitus. Infections were the main cause of death during the 1st year post-transplant (32%) and between the 1st and 5th year post-transplant (25%). After 5th year from transplant, hepatitis C recurrence (22%) became the first cause of death. Factors having an impact on long-term patient survival were HCC indication (p = 0.049), pre-transplant renal dysfunction (p = 0.043) and long warm ischemia time (p = 0.016); furthermore, post-transplant factors were diabetes mellitus (p = 0.001) and liver dysfunction (p = 0.05) at 1 year., Conclusion: Our results showed the effect of immunosuppression used during decades on long-term outcome in our LT patients in terms of morbidity (arterial hypertension, diabetes mellitus, dyslipidemia and renal dysfunction) and mortality (infections and hepatitis C recurrence).

Currently immunosuppressive and biological agents are used in a more extensive and earlier way in patients with inflammatory bowel disease, rheumatic or dermatologic diseases. Although these drugs have shown a significant clinical benefit, the safety of these treatments is a challenge. Hepatitis B virus (HBV) reactivations have been reported widely, even including liver failure and death, and it represents a deep concern in these patients. Current guidelines recommend to pre-emptive therapy in patients with immunosuppressants in general, but preventive measures focused in patients with corticosteroids and inflammatory diseases are scarce. Screening for HBV infection should be done at diagnosis. The patients who test positive for hepatitis B surface antigen, but do not meet criteria for antiviral treatment must receive prophylaxis before undergoing immunosuppression, including corticosteroids at higher doses than prednisone 20 mg/d during more than two weeks. Tenofovir and entecavir are preferred than lamivudine because of their better resistance profile in long-term immunosuppressant treatments. There is not a strong evidence, to make a general recommendation on the necessity of prophylaxis therapy in patients with inflammatory diseases that are taking low doses of corticosteroids in short term basis or low systemic bioavailability corticosteroids such as budesonide or beclomethasone dipropionate. In these cases regularly HBV DNA monitoring is recommended, starting early antiviral therapy if DNA levels begin to rise. In patients with occult or resolved hepatitis the risk of reactivation is much lower, and excepting for Rituximab treatment, the prophylaxis is not necessary.

Background: Blood glucose control is fundamental albeit not enough to prevent diabetic macrovascular complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors are effective in improving metabolic parameters in patients with type 2 diabetes mellitus (T2DM) but little is known about its cardiovascular effects. We compared the DPP-4 inhibitor sitagliptin with bedtime NPH insulin (NPH) as add-on therapy in patients with T2DM, aiming to ascertain which drug would have additional cardioprotective effects., Methods: Thirty-five T2DM patients inadequately controlled with metformin plus glyburide were randomized to receive sitagliptin (n = 18) or NPH (n = 17) for 24 weeks. Fasting plasma glucose, HbA1c, lipid profile, C-reactive protein, active glucagon-like peptide (aGLP-1) levels, 24-hour ambulatory blood pressure measurement and comprehensive 2-dimensional echocardiogram were determined before and after treatments., Results: Both sitagliptin and NPH therapies decreased HbA1c levels after 24 weeks. Fasting plasma glucose and triglyceride levels decreased in the NPH group whereas only sitagliptin increased aGLP-1 levels. Left ventricular diastolic dysfunction (LVDD) was detected in 58.6% of twenty-nine patients evaluated. Beneficial effects in LVDD were observed in 75% and 11% of patients treated with sitagliptin and NPH, respectively (p = 0.015). Neither therapy changed C-reactive protein or blood pressure., Conclusions: Sitagliptin and bedtime NPH were similarly effective on glucose control. Improvement in LVDD in T2DM patients treated with sitagliptin was suggested, probably related to the increase of aGLP-1 levels. Therefore, DPP-4 inhibitor seems to have cardioprotective effects independent of glucose control and may have a role in the prevention of diabetic cardiomyopathy.

Aims: There is no definitive and reliable echocardiographic method for estimating the pulmonary vascular resistance (PVR) to differentiate persistent vascular disease from dynamic pulmonary hypertension. The aim of this study was to analyze the relationship between the pulmonary venous blood flow velocity-time integral (VTIpv) and PVR., Methods and Results: Eighteen patients (10 females; 4 months to 22 years of age) with congenital heart disease and left to right shunt were studied. They underwent complete cardiac catheterization, including measurements of the PVR and Qp:Qs ratio, before and after 100% oxygen inhalation. Simultaneous left inferior pulmonary venous flow VTIpv was obtained by Doppler echocardiography. The PVR decreased significantly from 5.0 ± 2.6 W to 2.8 ± 2.2 W (P = 0.0001) with a significant increase in the Qp:Qs ratio, from 3.2 ± 1.4 to 4.9 ± 2.4 (P = 0.0008), and the VTIpv increased significantly from 22.6 ± 4.7 cm to 28.1 ± 6.2 cm (P = 0.0002) after 100% oxygen inhalation. VTIpv correlated well with the PVR and Qp:Qs ratio (r = -0.74 and 0.72, respectively). Diagnostic indexes indicated a sensitivity of 86%, specificity of 75%, accuracy of 83%, a positive predictive value of 92% and a negative predictive value of 60%., Conclusion: The VTIpv correlated well with the PVR. The measurement of this index before and after oxygen inhalation may become a useful noninvasive test for differentiating persistent vascular disease from dynamic and flow-related pulmonary hypertension., (© 2013, Wiley Periodicals, Inc.)

Energy consumption constraints on computing systems are more important than ever. Maintenance costs for high performance systems are limiting the applicability of processing devices with large dissipation power. New solutions are needed to increase both the computation capability and the power efficiency. Moreover, energy efficient applications should balance performance vs. consumption. Therefore power data of components are important. This work presents the most remarkable alternatives to measure the power consumption of different types of computing systems, describing the advantages and limitations of available power measurement systems. Finally, a methodology is proposed to select the right power consumption measurement system taking into account precision of the measure, scalability and controllability of the acquisition system.

Various models using radiometric approach have been proposed to solve the problem of estimating the distance between a camera and an infrared emitter diode (IRED). They depend directly on the radiant intensity of the emitter, set by the IRED bias current. As is known, this current presents a drift with temperature, which will be transferred to the distance estimation method. This paper proposes an alternative approach to remove temperature drift in the distance estimation method by eliminating the dependence on radiant intensity. The main aim was to use the relative accumulated energy together with other defined models, such as the zeroth-frequency component of the FFT of the IRED image and the standard deviation of pixel gray level intensities in the region of interest containing the IRED image. By using the abovementioned models, an expression free of IRED radiant intensity was obtained. Furthermore, the final model permitted simultaneous estimation of the distance between the IRED and the camera and the IRED orientation angle. The alternative presented in this paper gave a 3% maximum relative error over a range of distances up to 3 m.

This paper presents a methodology for high resolution radar image generation and automatic target recognition emphasizing the computational cost involved in the process. In order to obtain focused inverse synthetic aperture radar (ISAR) images certain signal processing algorithms must be applied to the information sensed by the radar. From actual data collected by radar the stages and algorithms needed to obtain ISAR images are revised, including high resolution range profile generation, motion compensation and ISAR formation. Target recognition is achieved by comparing the generated set of actual ISAR images with a database of ISAR images generated by electromagnetic software. High resolution radar image generation and target recognition processes are burdensome and time consuming, so to determine the most suitable implementation platform the analysis of the computational complexity is of great interest. To this end and since target identification must be completed in real time, computational burden of both processes the generation and comparison with a database is explained separately. Conclusions are drawn about implementation platforms and calculation efficiency in order to reduce time consumption in a possible future implementation.

Background: Compensated cirrhotic patients with single hepatocellular carcinoma (HCC) ≤5 cm may benefit from both liver resection (LR) and liver transplantation (LT); however, the better 10-year actuarial survival of the two treatments remains unclear. We aimed to assess the long-term outcome of cirrhotic patients with single HCC ≤5 cm treated either with LR or LT on an intention-to-treat basis., Methods: A total of 217 cirrhotic patients with single HCC ≤5 cm were evaluated at our department: 95 were treated with LR (LR group), and 122 were included on the waiting list for LT (LT group). Patients in the LR group were divided into very early HCC (tumor size ≤2 cm) and early HCC (tumor size >2 cm). Median follow-up was 5.3 (range 0.1-18) years., Results: Tumor recurrence was 72 % in the LR group versus 16 % in the LT group (p < 0.001). 1-, 5-, and 10-year cumulative risk of recurrence was 18, 69, and 83 % in the LR group versus 4, 18, and 20 % in the LT group (p < 0.001). Ten-year actuarial survival was 33 % in the LR group versus 49 % in the LT group (p = 0.002). At HCC recurrence, 27.3 % were included on the waiting list for salvage transplantation (very early HCC group) versus 15.1 % (early HCC group) (p = 0.2). After salvage transplantation, HCC recurrence was 0 % (very early HCC group) versus 40 % (early HCC group) (p = 0.2). No significant differences were observed in 1-, 5-, and 10-year actuarial survival between the very early HCC group and the LT group (95, 55, and 50 % vs. 82, 62, and 50 %)., Conclusions: LR should be the treatment of choice for cirrhotic patients with very early HCC.

Hepatitis B virus (HBV) is a very common infection worldwide. Its reactivation in patients receiving immunosuppression has been widely described as being associated with significant morbidity and mortality unless anti-viral prophylaxis is administered. Treatment in inflammatory bowel disease (IBD) patients has changed in recent years and immunosuppression and biological therapies are now used more frequently than before. Although current studies have reported an incidence of hepatitis B in inflammatory bowel disease patients similar to that in the general population, associated liver damage remains an important concern in this setting. Liver dysfunction may manifest in several ways, from a subtle change in serum aminotransferase levels to fulminant liver failure and death. Patients undergoing double immunosuppression are at a higher risk, and reactivation usually occurs after more than one year of treatment. As preventive measures, all IBD patients should be screened for HBV markers at diagnosis and those who are positive for the hepatitis B surface antigen should receive antiviral prophylaxis before undergoing immunosuppression in order to avoid HBV reactivation. Tenofovir/entecavir are preferred to lamivudine as nucleos(t)ide analogues due to their better resistance profile. In patients with occult or resolved HBV, viral reactivation does not appear to be a relevant issue and regular DNA determination is recommended during immunosuppression therapy. Consensus guidelines on this topic have been published in recent years. The prevention and management of HBV infection in IBD patients is addressed in this review in order to address practical recommendations.

A method for estimation of respiratory rate from electrocardiogram (ECG) signals, based on variations in slopes of QRS complexes, is presented. 12 standard leads, 3 leads from vectorcardiogram (VCG), and 2 additional non-standard leads derived from VCG loops were analysed. A total of 34 slope series were studied, 2 for each analysed lead: slopes between the peak of Q and R waves, and between the peak of R and S waves. Information of QRS slopes series was combined in order to increase the robustness of estimation. Evaluation is performed over a database containing ECG and respiratory signals simultaneously recorded in 17 subjects spontaneously breathing during a tilt table test. Respiratory rate estimation is performed with information of 4 different combinations of QRS slope series. The best results in respiratory rate estimation error terms are 0.72 ± 4.34%(0.46 ± 7.59 mHz). These results outperform those obtained with other known methods, motivating the use of QRS slopes to obtain reliable respiratory rate estimates.

Antiphospholipid antibodies (aPL) and antiphospholipid syndrome (APS) have been described in primary Sjögren's syndrome (pSS) with controversial findings regarding aPL prevalence and their association with thrombotic events. We evaluated 100 consecutive pSS patients (American-European criteria) and 89 age-gender-ethnicity-matched healthy controls for IgG/IgM anticardiolipin (aCL), IgG/IgM anti-beta2-glycoprotein-I (aβ2GPI), and lupus anticoagulant (LA) (positivity according to APS Sydney's criteria). Clinical analysis followed standardized interview and physical examination assessing thrombotic and nonthrombotic APS manifestations and thrombosis risk factors. aPLs were detected in 16 % patients and 5.6 % controls (p = 0.035). LA was the most common aPL in patients (9 %), followed by aβ2GPI (5 %) and aCL (4 %). Thrombotic events occurred in five patients [stroke in two, myocardial infarction in one and deep-vein thrombosis (DVT) in four], but in none of controls (p = 0.061). Mean age at time of stroke was 35 years. Three patients with thrombotic events (including the two with stroke) had APS (Sydney's criteria) and were positive exclusively for LA. Comparison of patients with (n = 16) and without (n = 84) aPL revealed similar mean age, female predominance, and ethnicity (p > =0.387). Frequencies of livedo reticularis (25 vs. 4.8 %, p = 0.021), stroke (12.5 vs. 0 %, p = 0.024), and DVT (18.8 vs. 1.2 %, p = 0.013) were significantly higher in APL + patients. Conversely, frequencies of hypertension, dyslipidemia, diabetes, obesity, smoking, sedentarism, and hormonal contraception were similar in patients with or without aPL (p ≥ 0.253). Our study identified LA as an important marker for APS in pSS, particularly for stroke in young patients, warranting routine evaluation of these antibodies and rigorous intervention in modifiable risk factors.

Background: Methotrexate is useful in inflammatory bowel disease (IBD), but its role is secondary because of its limited experience and a supposedly unfavorable safety profile., Aim: To describe the efficacy and safety of methotrexate in a long-term real clinical practice., Methods: Retrospectively reviewed records of IBD patients treated with methotrexate in eight hospitals of Madrid (Spain)., Results: A total of 77 patients were included (80% Crohn's disease); 94% received methotrexate because of steroid dependency. Overall, 82% of the patients initially responded (28% remission). Eighty-eight percent of the patients followed maintenance treatment for a mean of 17 (range: 1-108) months. Forty percent of the patients lost response at a mean of 57 weeks after starting methotrexate. No statistically significant differences were found in the response rates in terms of the disease type, route of administration, or the Montreal Classification category. The mean methotrexate cumulative dose was 1108 mg (range: 25-6480). The main adverse events included 10 cases of gastrointestinal symptoms, four of myelotoxicity, and 10 of abnormal liver function tests, and led to methotrexate withdrawal in four (5%) patients. Transient elastography, performed in 46 patients, detected six additional cases with significant fibrosis and normal liver function tests., Conclusion: Methotrexate is useful in inducing a response in IBD, although its efficacy decreases frequently through the follow-up. Although methotrexate seems safe in the long term, in addition to biochemical controls, a more accurate method to detect liver damage should be considered.

Human herpes virus 8 (HHV8)-positive plasmablastic lymphoma (PBL) is a particularly rare and aggressive subtype of non-Hodgkin lymphoma, strongly associated with human immunodeficiency virus infection, with poor response to therapy and short survival. Characteristically, it shows proliferation of large plasmablastic cells with often eccentrically placed nuclei, with immunohistochemical assay positive for HHV8 latent nuclear antigen 1 and IgM. Primary mediastinal occurrence of a HHV8-positive PBL is rare and metastatic disease even more uncommon; tumor invasion to the heart leading to intracardiac obstruction with a rapidly fatal disease course has not been previously described.

Aim: Anti-tumor necrosis factor (TNF)-alpha agents are widely used for the treatment of both inflammatory bowel disease (IBD) and psoriasis. Psoriatic skin lesions induced by anti-TNF have been described in patients with IBD. We report a case series of psoriasis induced by anti-TNF agents in IBD patients., Methods: Systematic analysis of cases of psoriasis induced by anti-TNF in an IBD patient cohort in tertiary hospitals of Madrid., Results: A total of 21 of 1294 patients with IBD treated with anti-TNF-alpha agents developed drug-induced psoriasis (cumulative incidence 1.62%; 95% CI 1.06%-2.47%): 14 patients with infliximab and 7 with adalimumab; seventeen with Crohn's disease, 4 with ulcerative colitis. The onset of skin lesions varied in a wide range of time (after a mean 13±8 doses). The most frequent site of skin lesions was the limbs (62%) followed by the trunk (48%) and the scalp (43%). The psoriasis phenotypes were plaque psoriasis (57%), scalp (14%), palmoplantar pustulosis (14%), pustular generalized psoriasis (5%), guttate (5%) and inverse (5%). Four patients interrupted the anti-TNF treatment, and that led to the complete regression of lesions in 1 of them. The other 17 patients were maintained on anti-TNF therapy and managed with topical steroids., Conclusion: Psoriatic lesions can be induced by anti-TNF drugs. Plaque psoriasis on the extremities and trunk were the most frequent presentations in our series. Topical steroid treatment is effective in most patients. Anti-TNF discontinuance may be reserved for patients with severe psoriasis or patients without response to topical therapy., (Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

This paper proposes a novel hardware implementation of a dense recovery of stereovision 3D measurements. Traditionally 3D stereo systems have imposed the maximum number of stereo correspondences, introducing a large restriction on artificial vision algorithms. The proposed system-on-chip (SoC) provides great performance and efficiency, with a scalable architecture available for many different situations, addressing real time processing of stereo image flow. Using double buffering techniques properly combined with pipelined processing, the use of reconfigurable hardware achieves a parametrisable SoC which gives the designer the opportunity to decide its right dimension and features. The proposed architecture does not need any external memory because the processing is done as image flow arrives. Our SoC provides 3D data directly without the storage of whole stereo images. Our goal is to obtain high processing speed while maintaining the accuracy of 3D data using minimum resources. Configurable parameters may be controlled by later/parallel stages of the vision algorithm executed on an embedded processor. Considering hardware FPGA clock of 100 MHz, image flows up to 50 frames per second (fps) of dense stereo maps of more than 30,000 depth points could be obtained considering 2 Mpix images, with a minimum initial latency. The implementation of computer vision algorithms on reconfigurable hardware, explicitly low level processing, opens up the prospect of its use in autonomous systems, and they can act as a coprocessor to reconstruct 3D images with high density information in real time.

Background: Endomyocardial biopsy (EMB) is the gold standard method for the diagnosis of cellular rejection (CR) after heart transplantation (HT)., Objective: To test the hypothesis that tissue Doppler imaging (TDI) could detect CR > 3A and add diagnostic information compared to conventional Doppler., Methods: Fifty-four HT patients underwent 129 EMB and a TDI echocardiographic study within 24 hours. We compared HT patients with CR > 3A versus HT patients with CR < 3A, with a normal matched control group (13 patients). We measured TDI systolic (S), early diastolic (e'), late diastolic (a') velocities and e'/a' ratio in the left ventricular annulus, basal and medium (mid) segments of the septal (SEP), lateral (LAT), inferior (INF), anterior (ANT) walls; and in the right ventricular annulus., Results: HT patients showed CR > 3A in 39/129 (30.2%) EMB. The best isolated predictor for CR diagnosis was a'LAT, with a sensitivity of 76.3%, specificity of 73.8% (p = 0.001). In the multivariate analysis, a'LAT (p = 0.001), a'SEP (p = 0.002), e'/a' LAT ratio (p = 0.006), e'Mitral/ e'LAT ratio (p = 0.014), SINF (p = 0.009) predicted CR > 3A. We obtained a score with a sensitivity of 88.2%, accuracy of 79.6% and negative predictive value of 92.9% to diagnose CR > 3A. Conventional Doppler (mitral and pulmonary venous flow) was not relevant to predict CR > 3A., Conclusion: TDI added diagnostic information to predict CR > 3A compared to conventional Doppler. A TDI-based model could become a potential method to detect CR > 3A after heart transplantation.

Purpose: Survival post-liver transplantation (LT) has improved; however, patients are considered at the, risk of malignancy due to prolonged immunosuppression. The long-term outcome of patients developing de novo neoplasm (DN) at our centre was evaluated., Methods: Between October 1988 and December 2007, 800 LT were performed in 742 patients. Patients were divided into two study periods according to the time of LT; first: October 1988-December 1995; second: January 1996-December 2007., Results: After a mean follow-up of 5 ± 4.6 years, 71 DN (9.5%) were detected in 742 patients. The cumulative risk of DN development increased with the time from LT although no differences at 3, 5, and 10 years were found when first and second periods were compared (3, 7, 16% vs. 2, 4, 11%, respectively; p = 0.4). DN incidence was higher in the first compared with the second period (10.7 vs. 7.8%; p < 0.04); no significant differences were observed in mortality rate (50 vs. 27%; p = 0.052). Actuarial patient survival post-DN at 1, 3, and 5 years: 67, 48, 45% versus 82, 71, 65%, in the first versus second period, respectively, p < 0.04., Conclusions: DN incidence has decreased in recent years; however, as survival post-LT increases, so does the incidence of DN. Surveillance programmes are necessary to diagnose DN at early stages.

Background: The aim of this study was to analyze the evolution of biliary complications over 20 years among adult patients undergoing liver transplantation (OLT) at our institution., Patients and Methods: Between 1985 and 2007, we performed 1000 OLT in 789 adults and 211 children. To ascertain the evolution of biliary complications among adult OLT from October 1988 to September 2007, we compared the first 100 to with the last 200 adult OLT., Results: Duct-to-duct was the most common biliary anastomosis performed in both periods (1st; 89% and 2nd; 94%; P = NS). However, a T-tube was used more frequently in the first period (1st; 46% vs 2nd; 6.6%; P < .001). The remaining cases underwent a hepaticojejunostomy (1st; 11% vs 2nd; 7.6%). Biliary complications were more frequent in the first period (1st; 20% vs 2nd; 9%; P < .01). In the first period, the use of a T-tube caused 32% of complications, all of them being bile leaks; but there were none in the second period. Arterial thrombosis or strictures were related to biliary complications in 10% and 33.3% among the first and second periods, respectively. The severity of complications according to the Clavien classification was similar in both periods: IIIa, 15% versus 33.3%; IIIb, 55% versus 55.5%; and IV, 15% versus 11.1%, respectively (P = NS)., Conclusion: The biliary complication rate among adult patients post-OLT decreased over 20 years at our institution, probably owing to the abandonment of the routine use of a T-tube as well as to advances in immunosuppressive protocols, organ preservation, and preoperative patient management., (Copyright © 2011 Elsevier Inc. All rights reserved.)