Comparison between tofacitinib and ustekinumab as a third-line therapy in refractory ulcerative colitis: A multicenter international study.

BACKGROUND: Ustekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third-line therapies in UC patients in whom anti-TNF and vedolizumab had failed. METHODS: This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC-related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C-reactive protein, endoscopic remission, treatment withdrawal, and adverse events. RESULTS: One-hundred seventeen UC patients were included in the study and followed for a median time of 11.6 months (q1 -q3, 5.5-18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow-up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 [95% CI: 1.06-3.50] p = 0.030). Twenty-eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow-up period (log-rank test, p < 0.054). No significant differences were observed for the secondary outcomes. Six and 22 adverse events occurred in the ustekinumab and tofacitinib groups, respectively (15% vs. 31%, p = 0.11). CONCLUSIONS: Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head-to-head clinical trials are needed as to confirm these data.

Comparative Study of the Effectiveness of Vedolizumab Versus Ustekinumab After Anti-TNF Failure in Crohn's Disease (Versus-CD): Data from the ENEIDA Registry.

BACKGROUND: Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited. AIMS: To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. METHODS: CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. RESULTS: A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02-3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00-1.62], moderate-severe activity in HBI [HR 1.79; 95% CI: 1.20-2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02-1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them. CONCLUSION: In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.

Influence of socio-affective factors on quality of life in women diagnosed with fibromyalgia.

Introduction: Fibromyalgia is a disease that involves chronic pain, with high prevalence in the female population and great impact on the bio-psycho-social sphere of people affected by it. However, few studies have analyzed the possible influence of socio-affective factors on the quality of life of people who suffer from this disease. Objective: The aim of this study was to determine the relationships between the impact of this disease on the lives of people with fibromyalgia and these variables. Specifically, we analyzed the quality of partner relationship, perceived loneliness, life satisfaction, and perceived socio-family situation. Method: A descriptive-correlational cross-sectional design was used. The sample consisted of 69 women diagnosed with fibromyalgia. The participants completed different questionnaires that measured their happiness, satisfaction with life, perceived loneliness, quality of partner relationship, socio-family valuation, and the impact of fibromyalgia. Results: The quality of partner relationship, perceived loneliness and socio-family valuation seem to be good predictors of subjective happiness, life satisfaction, and the impact that fibromyalgia has on people's lives, in the sense that the more positive the valuation of the couple relationship and of the socio-family situation, and the lower the perceived loneliness, people feel happier, more satisfied with their lives and the lower the impact that fibromyalgia has on their lives. Conclusion: The 50% of satisfaction with life can be explained from the scores obtained in perceived loneliness and the quality of partner relationship. In this sense, perceived loneliness was a good predictor of the impact of fibromyalgia on the lives of these patients.

NO Is Not the Same as GSNO in the Regulation of Fe Deficiency Responses by Dicot Plants.

Iron (Fe) is abundant in soils but with a poor availability for plants, especially in calcareous soils. To favor its acquisition, plants develop morphological and physiological responses, mainly in their roots, known as Fe deficiency responses. In dicot plants, the regulation of these responses is not totally known, but some hormones and signaling molecules, such as auxin, ethylene, glutathione (GSH), nitric oxide (NO) and S-nitrosoglutathione (GSNO), have been involved in their activation. Most of these substances, including auxin, ethylene, GSH and NO, increase their production in Fe-deficient roots while GSNO, derived from GSH and NO, decreases its content. This paradoxical result could be explained with the increased expression and activity in Fe-deficient roots of the GSNO reductase (GSNOR) enzyme, which decomposes GSNO to oxidized glutathione (GSSG) and NH3. The fact that NO content increases while GSNO decreases in Fe-deficient roots suggests that NO and GSNO do not play the same role in the regulation of Fe deficiency responses. This review is an update of the results supporting a role for NO, GSNO and GSNOR in the regulation of Fe deficiency responses. The possible roles of NO and GSNO are discussed by taking into account their mode of action through post-translational modifications, such as S-nitrosylation, and through their interactions with the hormones auxin and ethylene, directly related to the activation of morphological and physiological responses to Fe deficiency in dicot plants.

Clinical parameters affecting survival outcomes in patients with low-grade serous ovarian carcinoma: an international multicentre analysis.

BACKGROUND: Women with low-grade ovarian serous carcinoma (LGSC) benefit from surgical treatment; however, the role of chemotherapy is controversial. We examined an international database through the Ovarian Cancer Association Consortium to identify factors that affect survival in LGSC. METHODS: We performed a retrospective cohort analysis of patients with LGSC who had had primary surgery and had overall survival data available. We performed univariate and multivariate analyses of progression-free survival and overall survival, and generated Kaplan-Meier survival curves. RESULTS: Of the 707 patients with LGSC, 680 (96.2%) had available overall survival data. The patients' median age overall was 54 years. Of the 659 patients with International Federation of Obstetrics and Gynecology stage data, 156 (23.7%) had stage I disease, 64 (9.7%) had stage II, 395 (59.9%) had stage III, and 44 (6.7%) had stage IV. Of the 377 patients with surgical data, 200 (53.0%) had no visible residual disease. Of the 361 patients with chemotherapy data, 330 (91.4%) received first-line platinum-based chemotherapy. The median follow-up duration was 5.0 years. The median progression-free survival and overall survival were 43.2 months and 110.4 months, respectively. Multivariate analysis indicated a statistically significant impact of stage and residual disease on progression-free survival and overall survival. Platinum-based chemotherapy was not associated with a survival advantage. CONCLUSION: This multicentre analysis indicates that complete surgical cytoreduction to no visible residual disease has the most impact on improved survival in LGSC. This finding could immediately inform and change practice.

Rescue Therapies for Steroid-refractory Acute Severe Ulcerative Colitis: A Review.

BACKGROUND: One-third of patients with acute severe ulcerative colitis [ASUC] are steroid-refractory. We aimed to review the different options for the management of steroid-refractory ASUC, including not only the standard treatment [cyclosporine and infliximab], but also most recently developed agents [such as vedolizumab, ustekinumab, and tofacitinib]. METHODS: We performed a bibliographical search to identify studies focusing on the treatment of steroid-refractory ASUC. RESULTS: Cyclosporine and infliximab currently represent the mainstays of salvage therapy and they are generally considered comparable. However, long-term persistence is higher in infliximab therapy, and many clinicians prefer to use infliximab given its ease of use. However, cost of cyclosporine is lower. Sequential rescue therapy after cyclosporine or infliximab failure [with infliximab and cyclosporine, respectively] could be considered in referral centres for highly selected cases. Tofacitinib, due to its rapid effect, represents an attractive rescue option mainly in biologic-experienced patients. The good safety profile of vedolizumab and ustekinumab makes them ideal candidates for use as maintenance therapy in combination with cyclosporine as induction therapy, especially for patients previously exposed to anti-TNFs or thiopurines. CONCLUSIONS: Although cyclosporine and infliximab still represent the mainstays of salvage therapy for steroid-refractory ASUC, new therapeutic agents may also play a role. Tofacitinib, due to its rapid effect, is an attractive therapeutic rescue option. Vedolizumab and ustekinumab, as maintenance therapy in combination with the fast-acting cyclosporine as induction therapy, may represent a promising bridging strategy, especially in patients with previous failure to thiopurines and/or anti-TNF agents.

Increased risk of MAFLD and Liver Fibrosis in Inflammatory Bowel Disease Independent of Classic Metabolic Risk Factors.

BACKGROUND & AIMS: There is conflicting evidence regarding the prevalence of and risk factors for metabolic-associated fatty liver disease (MAFLD) in patients with inflammatory bowel disease (IBD). We aimed to determine MAFLD prevalence and risk factors in IBD patients. METHODS: Cross-sectional, case-control study included all consecutive IBD patients treated at 2 different university hospitals. Controls were subjects randomly selected from the general population and matched by age, sex, type 2 diabetes status, and body mass index in a 1:2 ratio. MAFLD was confirmed by controlled attenuation parameter. Liver biopsies were collected when MAFLD with significant liver fibrosis was suspected. In addition, age- and fibrosis stage-paired non-IBD patients with biopsy-proven MAFLD served as a secondary control group. RESULTS: Eight hundred thirty-one IBD patients and 1718 controls were included. The prevalence of MAFLD and advanced liver fibrosis (transient elastography ≥9.7 kPa) was 42.00% and 9.50%, respectively, in IBD patients and 32.77% and 2.31%, respectively, in the general population (P < .001). A diagnosis of IBD was an independent predictor of MAFLD (adjusted odds ratio, 1.99; P < .001) and an independent risk factor for advanced liver fibrosis (adjusted odds ratio, 5.55; P < .001). Liver biopsies were obtained from 40 IBD patients; MAFLD was confirmed in all cases, and fibrosis of any degree was confirmed in 25 of 40 cases (62.5%). Body mass index and type 2 diabetes prevalence were significantly lower in IBD-MAFLD patients than in severity-paired patients with biopsy-proven MAFLD. CONCLUSIONS: MAFLD and liver fibrosis are particularly prevalent in IBD patients, regardless of the influence of classic metabolic risk factors.

Idiopathic Thrombocytopaenic Purpura associated with Inflammatory Bowel Disease: a multicentre ECCO CONFER case series.

BACKGROUND: Idiopathic thrombocytopaenic purpura [ITP] is an acquired haematological disorder with an incidence of 1-6 per 100 00/year. ITP and inflammatory bowel disease [IBD] comorbidity has been reported in the literature, but insights regarding the course, outcome and optimal management are limited by its rarity. The current study aimed to evaluate the clinical presentation and outcome of ITP in patients with IBD. METHODS: This multicentre retrospective case series was performed as part of the ECCO Collaborative Network of Exceptionally Rare case reports [CONFER] project. Cases of patients with ITP and IBD were collected by participating investigators. Clinical data were recorded in a standardized collection form. RESULTS: This report includes 32 patients with concurrent ITP and IBD: ten were females, and the median age was 32.0 years (interquartile range [IQR] 20.5-39.5). Fourteen patients had a diagnosis of Crohn's disease [CD] and the other 18 ulcerative colitis [UC]. The diagnosis of IBD preceded the ITP in 26 patients (median time between diagnoses was 7.0 years [IQR, 1.5-9.5]). Among those patients, 17 were in clinical remission at ITP diagnosis. Thirteen patients were treated with mesalamine, four with oral corticosteroids, one with rectal corticosteroids, two with azathioprine and five with anti-tumour necrosis factor agents. The median platelet count was 35 000/microliter [IQR, 10 000-70 000]. Eight patients had rectal bleeding, 13 had skin purpura, three had epistaxis, six had mucosal petechiae and 13 were asymptomatic. Regarding ITP treatment, 19 were treated with corticosteroids, one with anti-RhD immunoglobulin, 12 with intravenous immunoglobulins [IVIGs], four with thrombopoietin, three with rituximab and six patients eventually required splenectomy. Ten patients needed no treatment directed to the ITP. Three patients required colectomy during long-term follow-up, due to IBD or cancer but not to massive bleeding as a complication of ITP. One of eight patients who presented with rectal bleeding required splenectomy, and none required urgent colectomy. Two patients died during the follow-up, one of them due to bleeding complications located in the upper gastrointestinal tract. Median follow-up time was 6.5 years [IQR, 3-10]. With long-term follow-up, all patients had platelet counts above 50 000/microliter, and 24 were in IBD clinical remission. CONCLUSION: Most ITP cases in this series occurred after the IBD diagnosis and responded well to regular ITP treatment. The course of the ITP in the IBD patients followed an expected course, including response to medical therapy and low rates of splenectomy.

Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn's Disease: Real World Evidence From the ENEIDA Registry.

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.

Riñón único funcionante y su seguimiento en Pediatría

Contexto: el riñón único funcionante (RUF) es una entidad que puede ser de tipo congénito y es causada por una agenesia renal unilateral o un riñón displásico multiquístico, o adquirido de forma secundaria a una nefrectomía unilateral, condicionando al paciente a un seguimiento estricto rutinario, así como en la implementación de algunas pautas de prevención en los pacientes pediátricos. Objetivo: analizar la importancia del seguimiento en los pacientes pediátricos con RUF. Metodologí:a se hace una revisión de la literatura mostrando desde la embriología, fisiología, etiología, aspectos clínicos y estudios diagnósticos en pacientes con RUF para así, posteriormente, ofrecer unas pautas de seguimiento y manejo en pacientes pediátricos. Resultados: los pacientes con RUF pueden presentar hiperfiltración glomerular compensatoria, seguida de lesión glomerular con hipertensión, albuminuria y reducción de la tasa de filtración glomerular, sin embargo, para prevenir el daño renal se deben realizar seguimientos clínico, paraclínico e imagenológico cuidadosos de todo paciente con RUF, según la condición lo amerite. Conclusiones: se hace necesaria la unificación de pautas de seguimiento en los pacientes pediátricos con RUF y hacer énfasis en aquellos factores de riesgo que predisponen a compromiso renal.

Background: The Solitary functioning kidney (SFK) is an entity that can be congenital type caused by unilateral renal agenesis or multicystic dysplastic kidney, or acquired secondary to unilateral nephrectomy conditioning to a strict routine follow-up, as well as the implementation of some prevention guidelines in pediatric patients. Purpose: To analyze the importance of follow-up in pediatric patients with a single functioning kidney. Methodology: A review of the literature is made showing embryology, physiology, etiology, clinical aspects and diagnostic studies in patients with SFK in order to subsequently offer guidelines for follow-up and management in pediatric patients. Results: Patients with SFK may present compensatory glomerular hyperfiltration, followed by glomerular injury with hypertension, albuminuria and reduced glomerular filtration rate, however, to prevent renal damage a careful clinical, paraclinical and imaging follow-up of every patient with SFK should be performed as the condition warrants. Conclusions: It is necessary to unify follow-up guidelines in pediatric patients with SFK and to emphasize those risk factors that predispose to renal compromise.

A shoot derived long distance iron signal may act upstream of the IMA peptides in the regulation of Fe deficiency responses in Arabidopsis thaliana roots.

When plants suffer from Fe deficiency, they develop morphological and physiological responses, mainly in their roots, aimed to facilitate Fe mobilization and uptake. Once Fe has been acquired in sufficient quantity, the responses need to be switched off to avoid Fe toxicity and to conserve energy. Several hormones and signaling molecules, such as ethylene, auxin and nitric oxide, have been involved in the activation of Fe deficiency responses in Strategy I plants. These hormones and signaling molecules have almost no effect when applied to plants grown under Fe-sufficient conditions, which suggests the existence of a repressive signal related to the internal Fe content. The nature of this repressive signal is not known yet many experimental results suggest that is not related to the whole root Fe content but to some kind of Fe compound moving from leaves to roots through the phloem. After that, this signal has been named LOng-Distance Iron Signal (LODIS). Very recently, a novel family of small peptides, "IRON MAN" (IMA), has been identified as key components of the induction of Fe deficiency responses. However, the relationship between LODIS and IMA peptides is not known. The main objective of this work has been to clarify the relationship between both signals. For this, we have used Arabidopsis wild type (WT) Columbia and two of its mutants, opt3 and frd3, affected, either directly or indirectly, in the transport of Fe (LODIS) through the phloem. Both mutants present constitutive activation of Fe acquisition genes when grown in a Fe-sufficient medium despite the high accumulation of Fe in their roots. Arabidopsis WT Columbia plants and both mutants were treated with foliar application of Fe, and later on the expression of IMA and Fe acquisition genes was analyzed. The results obtained suggest that LODIS may act upstream of IMA peptides in the regulation of Fe deficiency responses in roots. The possible regulation of IMA peptides by ethylene has also been studied. Results obtained with ethylene precursors and inhibitors, and occurrence of ethylene-responsive cis-acting elements in the promoters of IMA genes, suggest that IMA peptides could also be regulated by ethylene.

To grow or not to grow under nutrient scarcity: Target of rapamycin-ethylene is the question.

To cope with nutrient scarcity, plants generally follow two main complementary strategies. On the one hand, they can slow down growing, mainly shoot growth, to diminish the demand of nutrients. We can call this strategy as "stop growing." On the other hand, plants can develop different physiological and morphological responses, mainly in their roots, aimed to facilitate the acquisition of nutrients. We can call this second strategy as "searching for nutrients." Both strategies are compatible and can function simultaneously but the interconnection between them is not yet well-known. In relation to the "stop growing" strategy, it is known that the TOR (Target Of Rapamycin) system is a central regulator of growth in response to nutrients in eukaryotic cells. TOR is a protein complex with kinase activity that promotes protein synthesis and growth while some SnRK (Sucrose non-fermenting 1-Related protein Kinases) and GCN (General Control Non-derepressible) kinases act antagonistically. It is also known that some SnRKs and GCNs are activated by nutrient deficiencies while TOR is active under nutrient sufficiency. In relation to the "searching for nutrients" strategy, it is known that the plant hormone ethylene participates in the activation of many nutrient deficiency responses. In this Mini Review, we discuss the possible role of ethylene as the hub connecting the "stop growing" strategy and the "searching for nutrients" strategy since very recent results also suggest a clear relationship of ethylene with the TOR system.

Síndrome de opsoclonia mioclonia idiopático: Reporte de caso en una paciente de 13 meses / Idiopathic opsoclonus myoclonus syndrome: Case report in a 13-month-old female patient

Resumen El síndrome de opsoclonia mioclonía es una entidad neurológica poco frecuente que afecta a los niños en la etapa preescolar. Clínicamente se caracteriza por una triada clásica de opsoclonía, mioclonía y ataxia aguda, con una evolución progresiva o incluso de manera incompleta. Su etiología puede ser paraneoplásica, en la mayoría de los casos en asociación con neuroblastomas, así como postinfecciosa o parainfecciosa, autoinmune o idiopática. En objetivo del tratamiento es la inmunomodulación con terapia de primera línea con esteroides endovenosos aunque pudiendo asociarse a recaídas y secuelas a largo plazo en el ámbito neurológico y conductual. El síndrome de opsoclonia mioclonía representa un reto diagnóstico en los pacientes con ataxia aguda dada la variedad de presentación clínica, por tanto es importante tener una alta sospecha diagnostica para garantizar un tratamiento oportuno y evitar secuelas futuras.

Abstract Opsoclonus myoclonus syndrome is a rare neurological entity affecting preschool children. Clinically it is characterized by a classic triad of opsoclonus, myoclonus, and acute ataxia, with a progressive or even incomplete course. Its etiology can be paraneoplastic, in most cases in association with neuroblastomas, as well as postinfectious or parainfectious, autoimmune or idiopathic. The goal of treatment is immunomodulation with first-line therapy with intravenous steroids, although it can be associated with relapses and long-term neurological and behavioral sequelae. The opsoclonus myoclonus syndrome represents a diagnostic challenge in patients with acute ataxia given the variety of clinical presentations, therefore it is important to have a high diagnostic suspicion to ensure timely treatment and aoid future sequelae.

Prevalence of SARS-CoV-2 antibodies and risk factors in the pandemic epicentre of Catalonia.

To define the seroprevalence of antibodies against SARS-CoV-2 in the municipality of Vilanova del Camí (in the region of Conca d'Ódena, Barcelona, Spain) and to know the risk factors associated with positive seroprevalence. Cross-sectional descriptive study. The population of Vilanova del Camí had the opportunity to voluntarily attend two screenings (October and December 2020) for antibodies against the nucleocapsid protein of SARS-CoV-2 using a Rapid Diagnostic Test (RDT) (Salocor (Salofa Oy). Participants in the screening signed an informed consent form. From the 3,610 attendees at the screening, 2,170 patients were randomly selected. The relationship between antibody test results and other demographic (sex, age, morbidity index) and clinical (diagnoses, smoking and drugs) variables was analysed. The prevalence of antibodies against SARS-CoV-2 was 9.6% (95% CI of 8.4% to 10.9%) and was similar for men and women but increased with age. Among complex chronic patients, 14.3% had antibodies against SARS-CoV-2, and among patients with advanced chronic disease, 25% had antibodies against SARS-CoV-2. Age, AMG (Adjusted Morbidity Groups) index, COVID-19 diagnosis and contact with a COVID-19 case were risk factors for positive seroprevalence. A higher seroprevalence was detected in the October screening (12.16%) than in the December screening (8.38%). In the December screening, obesity was a risk factor for positive seroprevalence. This study demonstrates the high seroprevalence of antibodies against SARS-CoV-2 in the pandemic epicentre of Catalonia.

Actualización de resultados demográficos y terapéuticos de pacientes con Leucemia Mieloide Aguda no promielocítica en el Hospital Clínico de la Pontificia Universidad Católica de Chile / Acute myeloid leukemia. Analysis of 114 patients

BACKGROUND: Acute myeloid leukemia (AML) is the most common leukemia in adults. Aim: To Describe our population of patients with AML and report the outcomes of our treatments. MATERIAL AND METHODS: Review of electronic clinical records of 114 patients with AML with a median age of 57 years (59% men). Results: Seventeen percent of patients were classified as low risk, 38% as intermediate risk and 33% as high risk. Seventy-six percent of patients were treated with intensive chemotherapy. Five years overall survival according to cytogenetic risk was 59, 41, and 12% in low, intermediate, and high-risk patients, respectively. The outcomes were better in patients under 60 years. The median survival of patients treated with intensive chemotherapy aged less than 60 years and 60 years and above was 3.4 and 1 year, respectively. CONCLUSIONS: Our results are comparable to those reported in developed countries. Improving the survival of patients 60 years and older is our main challenge.

Prognostic markers of inflammation in endometrioid and clear cell ovarian cancer.

OBJECTIVES: Cancer-related systemic inflammation has been associated with prognosis in multiple cancer types. Conversely, local inflammation, which is characterized by dense intratumoral immune infiltrates, is a favorable predictor of survival outcome. However, these survival associations are not well established in ovarian cancer, particularly in the less frequent endometrioid and clear cell endometriosis associated histotypes. METHODS: This retrospective study included 119 patients (63 endometrioid and 56 clear cell ovarian carcinomas). We performed a comprehensive survival association analysis of both systemic (neutrophil-to-lymphocyte ratio or presence of endometriosis) and local inflammation markers (CD3+ and CD8+ tumor infiltrating lymphocytes) using multivariate Cox proportional hazards models that account for confounding factors. RESULTS: Medium to high levels of intraepithelial CD8+ tumor infiltrating lymphocytes are associated with longer survival in endometrioid ovarian cancer (p=0.04). In addition, we found that intraepithelial CD8+ tumor infiltrating lymphocytes are prognostic in clear cell ovarian cancer (p=0.02), and that intraepithelial CD3+ tumor infiltrating lymphocytes are also associated with improved outcome (p=0.02). Furthermore, intratumoral CD3+ and CD8+ tumor infiltrating lymphocytes showed improved prognosis in the endometrioid subtype (p<0.1). No prognostic value was observed for systemic immune markers. CONCLUSIONS: In this study, patients with endometrioid and clear cell ovarian cancer with moderate to high CD8+ and CD3+ intraepithelial tumor infiltrating lymphocytes had longer overall survival. Higher expression of intratumoral CD3+ and CD8+ tumor infiltrating lymphocytes also showed an improved outcome in endometrioid ovarian cancer. In contrast, systemic inflammation, evaluated by neutrophil-to-lymphocyte ratio or presence of endometriosis, did not have a prognostic impact in these histologic subtypes.

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study.

BACKGROUND: Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn's disease (CD) patients in real-world clinical practice. METHODS: A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. RESULTS: A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). CONCLUSIONS: Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.

This large retrospective study demonstrated the short- and long-term effectiveness and safety of ustekinumab in patients with Crohn's disease in real-world clinical practice, including those with refractory disease.

Gastroenteropancreatic Neuroendocrine Neoplasms in Patients with Inflammatory Bowel Disease: An ECCO CONFER Multicentre Case Series.

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms [GEP-NENs] have rarely been reported in association with inflammatory bowel diseases [IBDs]. METHODS: An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collects cases of GEP-NENs diagnosed in patients with IBD. RESULTS: GEP-NEN was diagnosed in 100 IBD patients; 61% female, 55% Crohn's disease, median age 48 years (interquartile range [IQR] 38-59]). The most common location was the appendix [39%] followed by the colon [22%]. Comprehensive IBD-related data were available for 50 individuals with a median follow-up of 30 months [IQR 11-70] following NEN diagnosis. Median duration of IBD at NEN diagnosis was 84 months [IQR 10-151], and in 18% of cases NEN and IBD were diagnosed concomitantly. At diagnosis, 20/50 were stage-I [T1N0M0], and 28/50 were graded G1 [ki67 ≤2%]. Incidental diagnosis of NEN and concomitantly IBD diagnosis were associated with an earlier NEN stage [p = 0.01 and p = 0.02, respectively]. Exposure to immunomodulatory or biologic therapy was not associated with advanced NEN stage or grade. Primary GEP-NEN were more frequently found in the segment affected by IBD [62% vs 38%]. At the last follow-up data, 47/50 patients were alive, and only two deaths were related to NEN. CONCLUSIONS: In the largest case series to date, prognosis of patients with GEP-NEN and IBD seems favourable. Incidental NEN diagnosis correlates with an earlier NEN stage, and IBD-related therapies are probably independent of NEN stage and grade. The association of GEP-NEN location and the segment affected by IBD may suggest a possible role of inflammation in NEN tumorigenesis.