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The article presents information about a study, called SUN project, conducted to assess the role of a Mediterranean dietary pattern on obesity risk to clarify the effect of this diet on overall health and to establish an adequate nutritional policy. The SUN project is an open enrolment cohort with currently 13,500 graduates, recruited and followed up through biennial mailed questionnaires. This analysis included 4866 participants. 50 new cases of obesity were identified during a median follow up of 28.5 months. No association was found between a higher adherence to a priori defined Mediterranean dietary pattern and the risk of obesity in a prospective assessment of a cohort based on university graduates.

The article presents a study related to consumption of olive oil and incidence of hypertension. The intake of some fatty acids has been associated with a decrease in blood pressure. Particularly, n-3 polyunsaturated fatty acids and monounsaturated fatty acids (MUFA) have shown a beneficial effect on blood pressure. MUFA rich olive oil is the major fat source in Mediterranean diets. Researchers evaluated the association between olive oil consumption and the incidence of hypertension in this study. Findings of the study suggest that moderate olive oil consumption is inversely associated with the risk of hypertension in a Spanish cohort of university graduates.

Background: Telemonitoring for inflammatory bowel disease (IBD) has not consistently demonstrated superiority over standard care; however, noninferiority may be an acceptable outcome if remote care proves to be more efficient., Objective: This study aims to compare the remission time and quality of life of patients with active IBD managed through standard care versus the TECCU (Telemonitoring of Crohn Disease and Ulcerative Colitis) app., Methods: A 2-arm, randomized, multicenter trial with a noninferiority design was conducted across 24 hospitals in Spain. The study included adult patients with IBD who were starting immunosuppressive or biological therapy. Participants were randomized into 2 groups: the telemonitoring group (G&#95;TECCU) and the standard care group (G&#95;Control). The follow-up schedule for the telemonitoring group (G&#95;TECCU) was based on contacts via the TECCU app, while the control group (G&#95;Control) adhered to standard clinical practice, which included in-person visits and telephone calls. In both groups, treatment adjustments were made based on the progression of disease activity and medication adherence, assessed using specific indices and biological markers at each check-up. The primary outcome was the duration of remission after 12 weeks, while secondary outcomes included quality of life, medication adherence, adverse events, and patient satisfaction., Results: Of the 169 patients enrolled, 158 were randomized and 150 were analyzed per protocol: telemonitoring (n=71) and control (n=79). After 12 weeks, the time in clinical remission was not inferior in the telemonitoring group (mean 4.20, SD 3.73 weeks) compared with the control group (mean 4.32, SD 3.28 weeks), with a mean difference between arms of -0.12 weeks (95% CI -1.25 to 1.01; noninferiority P=.02). The mean reduction in C-reactive protein values was -15.40 mg/L (SD 90.15 mg/L; P=.19) in the G&#95;TECCU group and -13.16 mg/L (SD 54.61 mg/L; P=.05) in the G&#95;Control group, with no significant differences between the 2 arms (P=.73). Similarly, the mean improvement in fecal calprotectin levels was 832.3 mg/L (SD 1825.0 mg/L; P=.003) in the G&#95;TECCU group and 1073.5 mg/L (SD 3105.7 mg/L; P=.03) in the G&#95;Control group; however, the differences were not statistically significant (P=.96). Quality of life improved in both groups, with a mean increase in the 9-item Inflammatory Bowel Disease Questionnaire score of 13.44 points (SD 19.1 points; P<.001) in the G&#95;TECCU group and 18.23 points (SD 22.9 points; P=.001) in the G&#95;Control group. Additionally, the proportion of patients who adhered to their medication significantly increased from 35% (25/71) to 68% (48/71) in the G&#95;TECCU group (P=.001) and from 46% (36/79) to 73% (58/79) in the G&#95;Control group (P=.001). The satisfaction rate remained stable at around 90%, although noninferiority was not demonstrated for the secondary outcomes., Conclusions: Telemonitoring patients with active IBD is not inferior to standard care for achieving and maintaining short-term remission. The TECCU app may serve as a viable alternative follow-up tool, pending confirmation of improved health outcomes and cost-effectiveness over the long-term., Trial Registration: ClinicalTrials.gov NCT06031038; https://clinicaltrials.gov/ct2/show/NCT06031038., International Registered Report Identifier (irrid): RR2-10.2196/resprot.9639., (©Mariam Aguas, Javier Del Hoyo, Raquel Vicente, Manuel Barreiro-de Acosta, Luigi Melcarne, Alejandro Hernandez-Camba, Lucía Madero, María Teresa Arroyo, Beatriz Sicilia, María Chaparro, María Dolores Martin-Arranz, Ramón Pajares, Francisco Mesonero, Miriam Mañosa, Pilar Martinez, Silvia Chacón, Joan Tosca, Sandra Marín, Luciano Sanroman, Marta Calvo, David Monfort, Empar Saiz, Yamile Zabana, Ivan Guerra, Pilar Varela, Virginia Baydal, Raquel Faubel, Pilar Corsino, Sol Porto-Silva, Eduard Brunet, Melodi González, Ana Gutiérrez, Pilar Nos. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 18.11.2024.)

Background: The usefulness of thiopurines has been poorly explored in pouchitis and other pouch disorders., Objective: To evaluate the effectiveness and safety of azathioprine as maintenance therapy in inflammatory pouch disorders., Design: This was a retrospective and multicentre study., Methods: We included patients diagnosed with inflammatory pouch disorders treated with azathioprine in monotherapy. Effectiveness was evaluated at 1 year and in the long term based on normalization of stool frequency, absence of pain, faecal urgency or fistula discharge (clinical remission), or any improvement in these symptoms (clinical response). Endoscopic response was evaluated using the Pouchitis Disease Activity Index (PDAI)., Results: In all, 63 patients were included [54% males; median age, 49 (28-77) years]. The therapy was used to treat pouchitis ( n  = 37) or Crohn's disease of the pouch ( n  = 26). The rate of clinical response, remission and non-response at 12 months were 52%, 30% and 18%, respectively. After a median follow-up of 23 months (interquartile range 11-55), 19 patients (30%) were in clinical remission, and 45 (66%) stopped therapy. Endoscopic changes were evaluated in 19 cases. PDAI score decreased from 3 (range 2-4) to 1 (range 0-3). In all, 21 patients (33%) presented adverse events and 16 (25%) needed to stop therapy., Conclusion: Azathioprine may be effective in the long term for the treatment of inflammatory pouch disorders and could be included as a therapeutic option., Competing Interests: Francisco Mesonero has served as a speaker for and received consulting fees from MSD, AbbVie, Takeda, Janssen, Pfizer, Ferring, Kern-Pharma, Dr. Falk Pharma, Galapagos, Chiesi and Faes Farma. Yamile Zabana has received support for conference attendance, speaker fees, research support and consulting fees from AbbVie, Adacyte, Almirall, Amgen, Dr. Falk Pharma, FAES Pharma, Ferring, Janssen, MSD, Otsuka, Pfizer, Shire, Takeda, Galapagos, Boehringer Ingelheim and Tillots. Agnés Fernández-Clotet has served as a speaker for and received educational funding from Dr. Falk Pharma, Janssen, Takeda, Chiesi and Pfizer. Eduardo Leo-Carnerero has served as a speaker and consultant for and received educational funding from AbbVie, Janssen, Takeda, Ferring, Gilead, Pfizer and Dr. Falk Pharma. Andrea Núñez-Ortiz has received educational funding from Janssen, Takeda, Ferring and Pfizer. Berta Caballol has served as a speaker for and received consulting fees from MSD, AbbVie, Janssen, Takeda, Ferring, Shire Pharmaceuticals and Faes Pharma. Rocío Ferreiro-Iglesias has received support for conference attendance, speaker fees, research support and consulting fees from AbbVie, Adacyte, Dr. Falk Pharma, FAES Pharma, Ferring, Janssen, MSD, Kern, Chiesi, Gebro Pharma, Pfizer, Shire, Takeda and Tillots. José Miranda-Bautista has received support for conference attendance, speaker fees, and consulting and advisory fees from AbbVie, Adacyte, Dr. Falk Pharma, FAES Pharma, Ferring, Janssen, Pfizer, Takeda and Tillots. Leyanira Torrealba has served as a speaker for and received educational funding from AbbVie, Janssen, Takeda, Ferring, Gilead, Pfizer, Dr. Falk Pharma and Tillotts Pharma. Rosa María Sáiz-Chumillas has served as a speaker for and received consulting fees from Janssen, Ferring and Faes Farma. Alicia López-García has received support for conference attendance, educational funding and speaker fees from Chiesi, AbbVie, Janssen, Ferring, Takeda, Pfizer and Tillots. Cristina Rubín de Célix has received educational funding from Ferring, Tillotts Pharma, AbbVie, Norgine, MSD, Pfizer, Takeda and Janssen and is supported by a grant from the Ministerio de Economía y Competitividad (Instituto de Salud Carlos III, Rio Hortega CM21/00025) and co-financed by the European Social Fund Plus (ESF+) ‘Co-financed by the European Union’. Eduard Brunet has served as a speaker and consultant for and received educational funding from Janssen, Takeda, Ferring, Kern-Pharma, AbbVie and Chiesi. Alejandro Hernández-Camba has served as a speaker for and received educational funding from AbbVie, Takeda, Kern Pharma, Pfizer, Janssen, Adacyte Therapeutics, Chiesi, Galapagus and Ferring. Iago Rodríguez-Lago has received financial support for travelling and educational activities from or has served as an advisory board member for AbbVie, Adacyte, Celltrion, Chiesi, Danone, Dr. Falk Pharma, Ferring, Faes Farma, Janssen, Galapagos, MSD, Otsuka Pharmaceutical, Pfizer, Roche, Takeda and Tillotts Pharma. Iago Rodríguez-Lago has also received financial support for research from Tillotts Pharma and is supported by a research grant from Gobierno Vasco – Eusko Jaurlaritza [Grant No. 2020222004]. Alfonso Elosua has served as a speaker for and has received educational funding from AbbVie, Adacyte, Takeda, FAES Farma, Ferring, Janssen and Tillots Pharma. José María Huguet has received fees for educational activities, research projects, scientific meetings and advisory boards sponsored by MSD, Ferring, AbbVie, Janssen, Biogen, Sandoz, Kern Pharma, Faes Farma and Takeda. Manuel Barreiro-de Acosta has served as a speaker, consultant and advisory member for and 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., (© The Author(s), 2024.)

Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC) but little is known when it is used as the second anti-TNF., Objectives: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients., Design: Retrospective observational study., Methods: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially)., Results: Overall, 473 UC patients were included (330 IVi and 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4% in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission., Conclusion: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy., Competing Interests: MC has served as a speaker for Takeda, Janssen, Faes Farma, and MSD; FC has served as a speaker or has received educational grants from Takeda, Janssen, MSD, and Ferring; MR has served as a speaker or has received research or educational funding or advisory fees from MSD, Abbvie, Pfizer, Takeda, and Janssen; MI has served as a speaker or has received research or educational funding or advisory fees from MSD, Janssen, Adacyte, and Takeda; LC has served as a speaker or has received research or educational funding or advisory fees from Abbvie, Dr. Falk Pharma, and Tillots Pharma; LB has served as a speaker or has received research or educational funding or advisory fees from Ikan Biotech; MBA has served as a speaker or has received research or educational funding or advisory fees 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; CG-M has received educational funding fees from AbbVie, Janssen, Pfizer, Ferring, Kern Pharma, Norgine, and Tillots Pharma; JMH has served as a speaker or has received research or educational funding or advisory fees from Merck Sharp & Dohme, Ferring, Abbvie, Janssen, Biogen, Sandoz, Kern Pharma, Faes Farma, Vifor Pharma, and Takeda; RL has served as a speaker or has received research or educational funding or advisory fees from MSD, Abbvie, Pfizer, Takeda, Janssen, and Dr. Falk; AM-C has received research or educational funding from Abbvie, Biogen, Ferring, Janssen, MSD, Takeda, Dr. Falk Pharma, and Tillotts; JPG has served as a speaker or has received research or educational funding or advisory fees from MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, and Vifor Pharma; FG has served as a speaker or has received research or educational funding or advisory fees from Faes-Farma, Galápagos, Takeda, Pfizer, Janssen, and Abbvie; PA has served as a speaker or has received research or educational funding or advisory fees from MSD, Abbvie, Takeda, Janssen, Gebro Pharma, Tillotts Pharma, and Biogen; CT has served as a speaker or has received research or educational funding or advisory fees from MSD, AbbVie, Pfizer, Takeda, Janssen, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Galapagos, and Tillots; IR-L has served as a speaker or has received research or educational funding or advisory fees from MSD, Pfizer, Abbvie, Takeda, Janssen, Tillotts Pharma, Kern, Celltrion, Roche, Ferring, Dr. Falk Pharma, Galapagos, Otsuka Pharmaceutical, and Adacyte; MM has served as a speaker and has received research or educational funding from MSD, AbbVie, Takeda, Janssen, Ferring, and Pfizer; ED has served as a speaker or has received research or educational funding or advisory fees from AbbVie, Adacyte Therapeutics, Biogen, Celltrion, Galapagos, Gilead, Janssen, Kern Pharma, MSD, Pfizer, Roche, Samsung, Takeda, and Tillots; MJG has served as a speaker or has received research or educational funding or advisory fees from Janssen, Pfizer, Abbvie, Takeda, Kern Pharma, and Ferring; MA has served as a speaker or has received research or educational funding or advisory fees from Faes, Ferring, and Janssen, and received educational grants from Janssen; JRP has served as a speaker or has received research or educational funding or advisory fees from MSD, AbbVie, and Tillots Pharma; FB received educational funding fees from AbbVie, Janssen, Pfizer, Ferring, Kern Pharma, Norgine, and Tillots Pharma. The remaining authors declared no conflicts of interest., (© The Author(s), 2024.)

(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.

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.)

Aims: Merkel cell carcinoma (MCC) is an aggressive primary neuroendocrine tumor of the skin, associated with Merkel cell polyomavirus (MCPyV) in 49-89% of cases, depending on the country of origin and the techniques of detection. The presence of MCPyV defines heterogeneity in MCC; MCPyV-negative cases bear a much higher mutational load, with a distinct ultraviolet signature pattern featuring C > T transitions, as a consequence of exposure to ultraviolet light radiation. MCC stroma has not been thoroughly studied, although MCC patients benefit from therapy targeting PD1/PDL1., Methods and Results: In this study, using Tissue Microarrays and immunohistochemistry, we have analyzed a series of 219 MCC cases in relation to the presence of MCPyV, and confirmed that the presence of MCPyV is associated with changes not only in the neoplastic cells, but also in the composition of the tumor stroma. Thus, MCPyV, found in 101/176 (57,4%) analyzable cases, exhibits changes in its tumor morphology, the density of the inflammatory infiltrate, the phenotype of the neoplastic cells, and the cell composition of the tumor stroma. MCPyV presence is negatively correlated with a higher level of p53 expression, and associated with a very high frequency (86%) of HLA-I expression loss, a higher apoptotic index, and a stroma richer in T-cells, cytotoxic T-cells, macrophages, PDL1-positive macrophages, and B-cells., Conclusions: Our findings provide evidence of the basic heterogeneity of MCC, supporting the hypothesis that the presence of MCPyV may induce a rich inflammatory response, which is at least partially avoided through loss of HLA-I antigen expression. On the other hand, MCPyV-negative cases show a much higher frequency of stronger p53 expression and, probably, p53 alterations., Competing Interests: Miguel Piris declares having received lecture fees and advisory board fees from Takeda, Janssen, and Celgene. Otherwise, the authors declare that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. This does not alter our adherence to PLOS ONE policies on sharing data and materials

Background: A multidisciplinary approach and Doppler ultrasound (DU) assessment for the creation and maintenance of arteriovenous fistulas (AVF) for haemodialysis can improve prevalence and patency. The aim of this study was to analyse the impact of a new multidisciplinary vascular access (VA) clinic with routine DU., Material and Methods: We analysed the VA clinic results from 2014 and 2015, before and after the implementation of a multidisciplinary team protocol (vascular surgeon/nephrologist) with routine DU in preoperative mapping and prevalent AVF., Results: We analysed 345 and 364 patients from 2014 and 2015 respectively. The number of surgical interventions was similar in both periods (p=.289), with a trend towards an increase in preventive surgical repair of AVF in 2015 (17 vs. 29, p=.098). 155 vs. 169 new AVF were performed in 2014 and 2015, with a significantly lower primary failure rate in 2015 (26.4 vs. 15.3%, p=.015), and a non-significant increase in radiocephalic AVF, 25.8 vs. 33.2% (n=40 vs. 56), p=.159. The concordance between the indication at the clinic and the surgery performed also increased (81.3 vs. 93.5%, p=.001). Throughout 2015 fewer complementary imaging test were requested from the clinic (78 vs. 35, p <.001), with a corresponding reduction in costs (€87,716 vs. €59,445)., Conclusions: Multidisciplinary approach with routine DU can improve VA results, with a decrease in primary failure rate, higher likelihood of radiocephalic AVF, better management of dis-functioning AVF and lower radiological test costs., (Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Infliximab (IFX) therapy intensification in ulcerative colitis (UC) is more common than established in pivotal studies., Objectives: To establish the frequency and form of intensification for UC in clinical practice, as well as predictors, and to compare outcomes between intensified and non-intensified treatment., Methods: A retrospective study of 10 hospitals and 144 patients with response to infliximab (IFX) induction. Predictive variables for intensification were analyzed using a Cox regression analysis. Outcome, loss of response to IFX, and colectomy were compared between intensified and non-intensified therapy., Results: Follow-up time from induction to data collection: 38 months [interquartile range (IQR), 20-62]. Time on IFX therapy: 24 months (IQR, 10-44). In all, 37% of patients required intensification. Interval was shortened for 36 patients, dose was increased for 7, and 10 subjects received both. Concurrent thiopurine immunosuppressants (IMM) and IFX initiation was an independent predictor of intensification [Hazard ratio, 0.034; p, 0.006; CI, 0.003-0.371]. In patients on intensified therapy IFX discontinuation for loss of response (30.4% vs. 10.2%; p, 0.002), steroid reintroduction (35% vs. 18%; p, 0.018), and colectomy (22% vs. 6.4%; p, 0.011) were more common. Of patients on intensification, 17% returned to receiving 5 mg/kg every 8 weeks., Conclusions: Intensification is common and occasionally reversible. IMM initiation at the time of induction with IFX predictsnon-intensification. Intensification, while effective, is associated with poorer outcome.

The activation of nuclear factor kappa B (NFκB) transcription factor family is considered to have a key role in diffuse large B-cell lymphoma (DLBCL) pathogenesis and is associated with a specific molecular subtype, the activated B-cell-like (ABC) subtype. We evaluated the expression of NFκB by immunohistochemistry in a large series of DLBCL cases. The five different NFκB family members (NFκB1, NFκB2, RELA, RELB, and REL) showed a heterogeneous expression pattern with the vast majority of cases being positive for at least one factor. Two independent series of tumor samples were classified into germinal center B-cell-like (GCB) or ABC subtypes using different approaches, immunohistochemistry, or gene expression profiling, and the expression of NFκB family members was assessed. Notably, no significant differences regarding the expression of the different NFκB members were detected between the two subtypes, suggesting that NFκB signaling is a prominent feature not only in the ABC subtype, but also in the GCB tumors. Of the five transcription factors, only REL expression had a significant clinical impact on R-CHOP-treated diffuse large B-cell lymphoma, identifying a subgroup of patients with superior clinical outcome.

Purpose: Peripheral T-cell lymphomas (PTCL) are a heterogeneous entity of neoplasms with poor prognosis, a lack of effective therapies, and a largely unknown molecular pathology. Deregulated NF-κB activity has been associated with several lymphoproliferative diseases, but its importance in T-cell lymphomagenesis is poorly understood. We investigated the function of the NF-κB-inducing kinase (NIK), in this pathway and its role as a potential molecular target in T-cell lymphomas., Experimental Design: We used immunohistochemistry to analyze the expression of different NF-κB members in primary human PTCL samples and to study its clinical impact. With the aim of inhibiting the pathway, we used genetic silencing of NIK in several T-cell lymphoma cell lines and observed its effect on downstream targets and cell viability., Results: We showed that the NF-κB pathway was activated in a subset of PTCLs associated with poor overall survival. NIK was overexpressed in a number of PTCL cell lines and primary samples, and a pivotal role for NIK in the survival of these tumor cells was unveiled. NIK depletion led to a dramatic induction of apoptosis in NIK-overexpressing cell lines and also showed a more pronounced effect on cell survival than inhibitor of kappa B kinase (IKK) knockdown. NIK silencing induced a blockage of both classical and alternative NF-κB activation and reduced expression of several prosurvival and antiapoptotic factors., Conclusions: The results of the present study indicate that NIK could be a promising therapeutic target in these aggressive malignancies., (©2013 AACR.)

SPIB is an Ets transcription factor that is expressed exclusively in mature B cells, T-cell progenitors, and plasmacytoid dendritic cells. In the present study, we developed a novel mAb against the SPIB protein and characterized its expression in major hematolymphoid neoplasms, including a series of 45 cases of blastic plasmacytoid dendritic cell (BPDC) neoplasms and their potential cutaneous mimics. We found that SPIB is expressed heterogeneously among B- and T-cell lymphoma types. Interestingly, SPIB is expressed in a large proportion of nongerminal center type DLBCLs. In cutaneous neoplasms, SPIB is overexpressed in all BPDC neoplasms, but none of its cutaneous mimics. SPIB remains overexpressed in all cases that lack 1 or 2 of the markers used for BPDC neoplasms (ie, CD4, CD56, TCL1, and CD123). We conclude that SPIB expression can be used as a tool for diagnosing BPDC neoplasms, but it needs to be tested in conjunction with the growing arsenal of markers for human plasmacytoid dendritic cells.

Metastatic disease is the primary cause of death in cutaneous malignant melanoma (CMM) patients. To understand the mechanisms of CMM metastasis and identify potential predictive markers, we analyzed gene-expression profiles of 34 vertical growth phase melanoma cases using cDNA microarrays. All patients had a minimum follow-up of 36 months. Twenty-one cases developed nodal metastatic disease and 13 did not. Comparison of gene expression profiling of metastatic and nonmetastatic melanoma cases identified 243 genes with a >2-fold differential expression ratio and a false discovery rate of <0.2 (206 up-regulated and 37 down-regulated). This set of genes included molecules involved in cell cycle and apoptosis regulation, epithelial-mesenchymal transition (EMT), signal transduction, nucleic acid binding and transcription, protein synthesis and degradation, metabolism, and a specific group of melanoma- and neural-related proteins. Validation of these expression data in an independent series of melanomas using tissue microarrays confirmed that the expression of a set of proteins included in the EMT group (N-cadherin, osteopontin, and SPARC/osteonectin) were significantly associated with metastasis development. Our results suggest that EMT-related genes contribute to the promotion of the metastatic phenotype in primary CMM by supporting specific adhesive, invasive, and migratory properties. These data give a better understanding of the biology of this aggressive tumor and may provide new prognostic and patient stratification markers in addition to potential therapeutic targets.

Objective: This report presents the results of a prospective randomized study that compared 2 grafts of different diameter: 6 mm, and 8 mm tapered to 6 mm at the arterial site, placed in the upper arm for hemodialysis in a selected population of patients younger than 71 years without diabetes., Methods: Seventy consecutive patients younger than 71 years without diabetes who required an upper arm graft between January 1997 and January 2002 and without previous access in the same limb were randomly allocated to receive either a 6-mm graft or 6- to 8-mm graft. Graft flow was measured every 3 months with the Doppler dilution technique. When access flow was less than 600 mL/min, fistulography was performed, and any stenosis was surgically treated with venous outflow replacement. Thrombectomy and associated stenosis treatment in the same stage was performed in all cases immediately after detection of thrombosis. Complication rate, and primary, assisted primary, and secondary patency rates were compared between the two groups with the Student t test and life table analysis., Results: Mean access flow was 975 mL/min for 6-mm grafts (range, 600-1500 mL/min; 95% confidence interval [CI], 889-1070), and for 6- to 8-mm grafts was 1397 mL/min (range, 1122-2700 mL/min; 95% CI, 1122-1672). This difference was significant (P <.01). Complication rate was 0.45 episodes per graft-year in 6-mm grafts, and 0.19 episodes per graft-year in 6- to 8-mm grafts (P <.01). At 1, 2, and 3 years, primary patency rates were 62%, 58%, and 44%, respectively, for 6-mm grafts, and 85%, 78%, and 73% for 6- to 8-mm grafts; log-rank comparison between curves was P =.0259. At 1, 2, and 3 years, secondary patency rates were 85%, 85%, and 85%, respectively, for 6-mm grafts, and 90%, 90%, and 90% for 6- to 8-mm grafts; log-rank comparison between curves was not significant, at P =.0603. At 1, 2, and 3 years, assisted primary patency rates were 84%, 79%, and 76%, respectively, for 6-mm grafts, and 90% for 6- to 8-mm grafts; log-rank comparison was P =.0414., Conclusions: The results of this study show an advantage in terms of primary and assisted primary patency rates, and complication rate for upper arm grafts with diameter 6 mm to 8 mm over grafts with 6-mm diameter in a patient population younger than 70 years without diabetes. The finding of a similar secondary patency rate in both groups is probably due to the surveillance program with sequential measurement of access flow and prompt surgical treatment of stenosis. However, we needed twice the number of rescue procedures in 6-mm grafts to achieve a similar patency rate as with large-bore grafts. These study results must be carefully evaluated, taking into consideration the small number of patients and the selected patient population.

Cutaneous malignant melanoma remains the leading cause of skin cancer death in industrialized countries. Clinical and histological variables that predict survival, such as Breslow's index, tumor size, ulceration, or vascular invasion have been identified in malignant melanoma. Nevertheless, the potential relevance of biological variables still awaits an in-depth exploration. Using tissue microarrays (TMAs), we retrospectively analyzed 165 malignant melanoma samples from 88 patients corresponding to distinct histological progression phases, radial, vertical, and metastases. A panel of 39 different antibodies for cell cycle, apoptosis, melanoma antigens, transcription factors, DNA mismatch repair, and other proteins was used. Integrating the information, the study has identified expression profiles distinguishing specific melanoma progression stages. Most of the detected alterations were linked to the control of cell cycle G1/S transition; cyclin D1 was expressed in radial cases 48% (12 of 25) with significant lost of expression in vertical cases 14% (9 of 65), P = 0.002; whereas p16(INK4a) (89% in vertical versus 71% in metastatic cases, P = 0.009) and p27(KIP1) (76% in radial versus 45% in vertical cases, P = 0.010) were diminished in advanced stages. The study also defines a combination of biological markers associated with shorter overall survival in patients with vertical growth phase melanoma, that provided a predictor model with four antibodies (Ki67, p16(INK4a), p21(CIP1), and Bcl-6). This predictor model was validated using an independent series of 72 vertical growth phase melanoma patients.