Effectiveness of Helicobacter pylori Treatments According to Antibiotic Resistance.

INTRODUCTION: Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance. METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included. RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results. DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.

Evaluation of Genetic Variants Associated with the Risk of Thiopurine-Related Pancreatitis: A Case Control Study from ENEIDA Registry.

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry.

This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed.  A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70-145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient's age, and patients' origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders. What is Known: • Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness. What is New: • Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy. • PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.

Machine Learning-Driven Classification of Urease Inhibitors Leveraging Physicochemical Properties as Effective Filter Criteria.

Urease, a pivotal enzyme in nitrogen metabolism, plays a crucial role in various microorganisms, including the pathogenic Helicobacter pylori. Inhibiting urease activity offers a promising approach to combating infections and associated ailments, such as chronic kidney diseases and gastric cancer. However, identifying potent urease inhibitors remains challenging due to resistance issues that hinder traditional approaches. Recently, machine learning (ML)-based models have demonstrated the ability to predict the bioactivity of molecules rapidly and effectively. In this study, we present ML models designed to predict urease inhibitors by leveraging essential physicochemical properties. The methodological approach involved constructing a dataset of urease inhibitors through an extensive literature search. Subsequently, these inhibitors were characterized based on physicochemical properties calculations. An exploratory data analysis was then conducted to identify and analyze critical features. Ultimately, 252 classification models were trained, utilizing a combination of seven ML algorithms, three attribute selection methods, and six different strategies for categorizing inhibitory activity. The investigation unveiled discernible trends distinguishing urease inhibitors from non-inhibitors. This differentiation enabled the identification of essential features that are crucial for precise classification. Through a comprehensive comparison of ML algorithms, tree-based methods like random forest, decision tree, and XGBoost exhibited superior performance. Additionally, incorporating the "chemical family type" attribute significantly enhanced model accuracy. Strategies involving a gray-zone categorization demonstrated marked improvements in predictive precision. This research underscores the transformative potential of ML in predicting urease inhibitors. The meticulous methodology outlined herein offers actionable insights for developing robust predictive models within biochemical systems.

Unveiling Novel Urease Inhibitors for Helicobacter pylori: A Multi-Methodological Approach from Virtual Screening and ADME to Molecular Dynamics Simulations.

Helicobacter pylori (Hp) infections pose a global health challenge demanding innovative therapeutic strategies by which to eradicate them. Urease, a key Hp virulence factor hydrolyzes urea, facilitating bacterial survival in the acidic gastric environment. In this study, a multi-methodological approach combining pharmacophore- and structure-based virtual screening, molecular dynamics simulations, and MM-GBSA calculations was employed to identify novel inhibitors for Hp urease (HpU). A refined dataset of 8,271,505 small molecules from the ZINC15 database underwent pharmacokinetic and physicochemical filtering, resulting in 16% of compounds for pharmacophore-based virtual screening. Molecular docking simulations were performed in successive stages, utilizing HTVS, SP, and XP algorithms. Subsequent energetic re-scoring with MM-GBSA identified promising candidates interacting with distinct urease variants. Lys219, a residue critical for urea catalysis at the urease binding site, can manifest in two forms, neutral (LYN) or carbamylated (KCX). Notably, the evaluated molecules demonstrated different interaction and energetic patterns in both protein variants. Further evaluation through ADMET predictions highlighted compounds with favorable pharmacological profiles, leading to the identification of 15 candidates. Molecular dynamics simulations revealed comparable structural stability to the control DJM, with candidates 5, 8 and 12 (CA5, CA8, and CA12, respectively) exhibiting the lowest binding free energies. These inhibitors suggest a chelating capacity that is crucial for urease inhibition. The analysis underscores the potential of CA5, CA8, and CA12 as novel HpU inhibitors. Finally, we compare our candidates with the chemical space of urease inhibitors finding physicochemical similarities with potent agents such as thiourea.

Adaptation and validation of an abbreviated version of the SIPAT integrated psychosocial risk scale in patients with liver cirrhosis candidates for liver transplantation (SIPAT-11). / Adaptación y validación de una versión abreviada de la escala SIPAT de riesgo psicosocial integrado en pacientes con cirrosis hepática candidatos a trasplante hepático (SIPAT-11).

INTRODUCTION: Patients with liver cirrhosis who are candidates for liver transplantation must be evaluated both clinically and socially in order to obtain the optimal outcomes and avoid futile therapeutic measures. For the evaluation of the social aspects in these patients, no validated scale in Spanish is available. The SIPAT (Stanford Integrated Psychosocial Assessment for Transplantation) scale is an instrument that measures the social, family and psychological aspects in candidates for solid organ transplantation. The objective of this study is to adapt and validate an abbreviated version of the SIPAT scale in Spanish for patients with liver cirrhosis. MATERIAL AND METHODS: Prospective observational study carried out in the Hepatology Unit of the La Fe Unversity Hospital in Valencia, by questionnaire validation methodology. To analyze the reliability of the questionnaire, the internal consistency of all variables was calculated, for variability an exploratory factor analysis, and for stability the test-retest test was carried out. RESULTS: 96 patients who were admitted for decompensated cirrhosis to the Hepatology Unit of the La Fe Hospital in Valencia between November 1, 2017 and January 31, 2017 were selected. 84% were men, the mean age was 60.01 (SD 10.12) years. In 73.2% of those admitted, the etiology of cirrhosis was alcoholic. 14.4% had a Child's stage A, 57.7% B and 27.8% C. The internal consistency of all variables reached a Cronbach's Alpha of 0.766. In the exploratory factor analysis, 6 dimensions of the questionnaire were identified that explain 84.27% of the total variability. To see the stability of the instrument, the measurement was repeated at 2 and 6 months of follow-up, obtaining in the test-retest a kappa agreement of 0.612 and 0.565 respectively. CONCLUSION: The SIPAT-11 questionnaire has good psychometric characteristics in cirrhotic patients who are candidates for liver transplantation. It is easy to complete and can be administered by professionals who are not specialists in the area of ​​Mental Health.

Influence of social support and stressful life events on adherence to colorectal cancer screening using faecal occult blood test in Spanish medium risk population.

INTRODUCTION: Colorectal cancer (CRC) is the second cause of cancer-related deaths worldwide. Five-year survival rate in Spain is 57%. The most important prognostic factor is the stage of the tumor at the diagnosis. CRC can be early diagnosed, but the adherence to screening programs is low (<50%). This study aims to ascertain the influence of social support and stressful life events on the adherence to the population screening of CRC with fecal occult blood test in Spanish average risk population. METHODS: Multicenter case-control study. We conducted a simple random sampling among individuals invited to participate in the colorectal cancer screening program. We analyzed epidemiological and social variables associated with lifestyle and behavioral factors. We performed a descriptive and a bivariant analyses and a logistic regression analysis. RESULTS: Four hundred and eight patients (237 cases and 171 controls) were included. Multivariant analyses showed independent association between higher adherence to the screening program and older age (OR: 1.06; 95% CI: 1.01-1.10), stable partner (OR: 1.77, 95% CI: 1.08-2.89) and wide social network (OR: 1.68; 95% CI: 1.07-2.66). Otherwise, lower adherence was associated to perceiving barriers to participate in the program (OR: 0.92; 95% CI: 0.88-0.96). We find a statistically significant association between lower adherence and high impact stressful life events in the bivariant analyses, and the tendency was maintained (OR: 0.63, 95% CI: 0.37-1.08) in the multivariant. CONCLUSION: Social variables decisively influence the adherence to colorectal cancer screening. The implementation of social interventions that improve social support, reduce impact of stressful life events and the design of screening programs that decrease the perceived barriers, will contribute to increase the participation on these programs. Secondary, the colorectal cancer diagnosis will be made in early-stages with the consequent mortality reduction.

Bismuth quadruple three-in-one single capsule three times a day increases effectiveness compared with the usual four times a day schedule: results from the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain. AIM: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg). METHODS: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection. RESULTS: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection. CONCLUSIONS: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety.

Sponge-nested polymer monoliths: Versatile materials for the solid-phase extraction of bisphenols.

Polymer monoliths are promising materials for sample preparation due to their high porosity, pH stability, and simple preparation. The use of melamine formaldehyde foams has been reported as an effective support to prepare highly robust silica and polymer monoliths. Herein, divinylbenzene monoliths based on a 50:50 (%, w/w) crosslinker/porogen ratio have been nested within a melamine-formaldehyde sponge, resulting in monoliths with a surface area higher than 400 m2 /g. The extraction performance of these monoliths was evaluated for the extraction of endocrine-disrupting bisphenols from aqueous solutions. We evaluated for the first time the versatility of sponge-nested polymer monoliths by comparing three different extraction modes (vortex mixing, magnetic stirring, and orbital shaking). Vortex mixing showed a comparable recovery of bisphenols (39%-81%) in a shorter extraction time (30 min, instead of 2 h). In addition, the robustness of the sponge-nested polymer monoliths was demonstrated for the first time by reshaping a larger monolithic cube (0.125 cm3 ) into four smaller pieces (4 × 0.03125 cm3 ) leading to a 16%-21% increase in extraction efficiency. This effect was attributed to an increase in the effective contact area with the sample, obtaining a higher analyte extraction capacity.

Inadequate social support decreases survival in decompensated liver cirrhosis patients.

INTRODUCTION: Inadequate social support is associated with higher mortality both in the general population and in patients with chronic diseases. There are no studies that have described social support in liver cirrhosis and its impact on prognosis. OBJECTIVES: To analyze the impact social support has in the survival of patients with decompensated cirrhosis. METHODS: Prospective multicentric cohort study (2016-2019). Patients with decompensated liver cirrhosis were included. Epidemiological, clinical and social variables were collected, using the validated Medical Outcomes Study Social Support Survey, with a 12-month follow-up. RESULTS: A total of 127 patients were included, of which 79.5% were men. The most common etiology of cirrhosis was alcohol (74.8%), mean age was 60 years (SD 10.29), mean MELD was 15.6 (SD 6.3) and most of the patients had a Child-Pugh B (53.5%) or C (35.4%). In the assessment of social support, we observed that most of the patients (92.2%) had adequate global support. At the end of the follow-up (median 314 days), 70.1% of the patients survived. The 1-year survival rate in patients with inadequate global social support was 30%, compared to 73.5% in the presence of social support. In multivariate Cox regression analysis, inadequate social support predicted survival with an adjusted HR of 5.5 (95% CI 2,3-13,4) independently of MELD (HR 1.1, 95% CI 1-1.2), age (HR 1, 95% CI 1-1.1) and hepatocarcinoma (HR 10.6, 95% CI 4.1-27.4). CONCLUSION: Adequate social support improves survival in liver cirrhosis, independently of clinical variables. Social intervention strategies should be considered for their management.

International on-line questionnaire about severe lower gastrointestinal bleeding management: Do we have it clear? / Encuesta internacional on-line sobre el manejo de la hemorragia digestiva baja grave. ¿Lo tenemos claro?

BACKGROUND AND AIMS: The diagnostic and therapeutic strategy in severe lower gastrointestinal bleeding (LGIB) varies depending on the patient's clinical situation. Actual clinical practice guidelines propose different management strategies. We aim to know the attitude of the gastroenterologists from different hospitalary centers in the management of this entity. METHODS: Descriptive and observational study using an on-line questionnaire, addressed to gastroenterologists in Spain and Latin America, in December 2021. RESULTS: We included 281 anonymous questionnaires of gastroenterologists from Spain and Latin America. Diagnostic and therapeutic management of severe LGIB was heterogeneous among the participants. Regarding to the first diagnostic modalities they showed variability between performing computed tomography angiography (CTA) (44.5%), gastroscopy (33.1%), colonoscopy (20.6%) and arteriography (1.1%). The therapeutic attitude after a positive CTA mostly varied between performing arteriography (38.1%) and colonoscopy (44.1%). If negative CTA, in the majority of cases a gastroscopy was performed. If the patient needed intensive critical unit (ICU) care and to undergo colonoscopy, most participants performed an urgent colonoscopy (<24h) (31% always, 43.4% in most cases); while if the patient did not require ICU admission this percentage was lower (10% always, 33.8% in most cases). The 40.9% of the participants admitted having doubts about the management of this patients and the 98.2% considered the need for a creation of an action protocol. CONCLUSIONS: There is a high interhospitalary variability on the management of severe lower gastrointestinal bleeding among gastroenterologists. It is necessary to unify the diagnostic and therapeutic management of this pathology.

Perceived barriers and benefits in the participation in faecal occult blood test colorectal cancer screening programme.

BACKGROUND: Colorectal cancer is the second cancer-related cause of death in the world. Tumour stage at diagnosis is the principal prognosis factor of survival. However, the participation in the programme is around 50%. The aim of the study was to identify the benefits and barriers perceived by the population when participating in a colorectal cancer screening programme with faecal occult blood test. METHODS: We carried out a cases-controls study with 408 participants. We analyzed epidemiological and social variables associated with lifestyle and behavioural factors based in the Health Belief Model. We conducted a descriptive analysis, and identified variables associated to adherence by a logistic regression. RESULTS: Variables independently associated with the participation in a colorectal cancer screening programme were age (OR 1.06; 95% CI: 1.01-1.11), having a stable partner (OR 1.96; 95% CI: 1.20-3.18), the level of education (OR 1.59; 95% CI: 1.02-2.47) and two of the barriers to participate in the faecal occult blood test screening: "you don't know how to do one" (OR=0.46; 95% CI: 0.23-0.93) and "it is not that important right now" (OR=0.43; 95% CI: 0.24-0.78). CONCLUSION: The existing barriers for screening with faecal occult blood test are the best factor predicting. This is relevant when designing the intervention programmes, as they should focus on reducing perceived barriers to increase the participation in colorectal cancer screening, thereby reducing colorectal cancer mortality.

Rawl's questionnaire spanish validation for colorectal cancer screening with faecal occult blood testing. / Validación al castellano del cuestionario Rawl de cribado de cáncer colorrectal con sangre oculta en heces.

INTRODUCTION: Colorectal cancer 5-years-survival is 57%, partway due to a low rate of participation in screening programmes. Instruments analyzing causes of low adherence are needed. OBJECTIVE: To evaluate the validity and internal consistency of the Spanish version of Rawl's Questionnaire for the screening of colorectal cancer by faecal occult blood testing. TYPE OF STUDY: Questionnaire validation methodology. LOCATION: Three Primary Care Centres in Valencia. VARIABLES: Age, sex, civil status, educational level, social class, smoking, alcohol consumption, body mass index, personal and family history of cancer. RESULTS: We analyzed 408 individuals (237 cases and 171 controls). Mean age was 59.45 years (SD 5.17). Internal consistency of all variables reached a Cronbach's alfa of 0.796. The Cronbach's alfa benefit dimension of the screening was 0.871 and for the barrier dimension of the screening it was 0.817. Intraclass correlation coefficients of the test-retest for the benefit dimension of the screening was 0.809 (CI 95% 0.606-0.913) and 0.499 (CI 95% 0.126-0.750) for the barrier dimension. CONCLUSION: The Spanish version of Rawl's Questionnaire is valid, reliable and reproducible, so we have this validated instrument with which to identify barriers and benefits in a colorectal screening programme in Spain.

Tamoxifen induces apoptosis and inhibits respiratory burst in equine neutrophils independently of estrogen receptors.

Neutrophils play an important role in the exacerbation and maintenance of severe equine asthma; persistent neutrophil activity and delayed apoptosis can be harmful to surrounding tissues. Tamoxifen (TX) is a nonsteroidal estrogen receptor modulator with immunomodulatory effects and induces early apoptosis of blood and bronchoalveolar lavage neutrophils from horses with acute lung inflammation. This study investigated if the in vitro effects of tamoxifen are produced by its action on nuclear (α and ß) and membrane (GPR30) estrogen receptors in healthy equine neutrophils. Results showed that TX inhibits neutrophil respiratory burst induced by opsonized zymosan in a dose-dependent manner. Nuclear (17-ß-Estradiol) and GPR30 cell membrane (G1) estrogen receptor agonists and their antagonists (ICI 182,780 and G15, respectively) do not block or reproduce the effect of TX. Therefore, TX does not inhibit respiratory burst through estrogen receptors. TX (8.5 µM) also increased phosphatidylserine translocation, a marker of early apoptosis, which did not occur with any of the estrogen receptor agonists or antagonists. Thus, tamoxifen generates dose-dependent inhibition of respiratory burst and increased early apoptosis in healthy equine neutrophils, independently of nuclear or membrane estrogen receptors. Further studies are necessary to explore the signaling pathways of tamoxifen-induced ROS inhibition and phosphatidylserine translocation.

A long-term prospective study of the efficacy and safety of endoscopic septotomy using the LigaSure® system for the treatment of Zenker's diverticulum.

BACKGROUND AND OBJECTIVES: endoscopic septotomy of the cricopharyngeal muscle (ESCM) is a technique used for the treatment of Zenker's diverticulum (ZD). The experience with computerized vascular sealing systems (LigaSure® type) is limited. The objective of this study was to evaluate the efficacy and safety of ESCM using LigaSure®. METHODS: this was a long-term prospective study of 18 patients with ZD, who were referred to our hospital due to ESCM between 2010 and 2016. The severity of the symptoms was determined using the Dakkak-Bennett validated scale for dysphagia and the rest with numerical scales. The rates of relapse and retreatment were evaluated. RESULTS: ESCM with LigaSure® was performed in 17 cases, one case was excluded due to technical difficulties. The median age was 72 years and regurgitation, dysphagia and respiratory symptoms were found in 100%, 89% and 56% of cases, respectively. The median size of the diverticulum was 28 mm (20-60 mm). The median time of the procedure was 35 minutes (25-45 minutes). There were four complications, two hemorrhages and two perforations. The median follow-up was 13 months (range: 12-82 months). Clinical improvements were observed for all symptoms and were maintained 12 months after treatment (p < 0.05). There was no relapse during follow-up in 13 patients. A complete section was not achieved and clinical relapse occurred after a median time of seven months that required retreatment in the remaining patients. CONCLUSIONS: ESCM with LigaSure® may be a safe and effective technique in long-term follow-up situations, with low rates of relapse.

Vedolizumab, an option in patients with inflammatory bowel disease intolerant to thiopurines and refractory to biological agents. / Vedolizumab, una opción en pacientes con enfermedad inflamatoria intestinal intolerantes a tiopurinas y refractarios a biológicos.

Vedolizumab (VDZ), a human monoclonal antibody that binds specifically to α4ß7-integrin, and is approved for the treatment of Crohn's disease (CD) and ulcerative colitis (UC), has demonstrated its efficacy in controlled clinical trials. OBJECTIVE: To describe a population treated with VDZ and to evaluate its long-term efficacy and safety in clinical practice. METHODS: An observational and multicentre study was carried out on patients with inflammatory bowel disease treated with VDZ for at least one year. An evaluation was performed on the activity indices, faecal calprotectin and C-reactive protein levels, hospital admissions, surgeries, and adverse events. RESULTS: A total of 73 patients were analysed (43 UC and 30 CD). More than one anti-TNF and more than one immunosuppressive was previously used by 74 and 23%, respectively, of UC patients, and 90 and 37%, respectively of CD patients. VDZ was stopped in 17 (23%) patients, 10 UC and 7 CD, due to a lack or loss of response before the first year, or due to adverse events. An intensification of the dose was required in 26 (63%) UC, and 16 (53%) CD patients. At 6 months, 70 and 42% of UC patients, and 80 and 43% of CD patients achieved a clinical response and remission, respectively. At one year, 58 and 35% of UC patients and 47 and 43% of CD patients, maintained the clinical response and remission, respectively. The C-reactive protein decreased significantly in both CD and UC patients. However, the decrease in faecal calprotectin was only achieved during follow-up in UC, but not in CD patients. Eight patients with CD that had been treated previously with ustekinumab avoided surgery at one year. A colectomy was performed on 8 (18.6%) UC patients, and 4 (13.3%) CD patients needed surgery. Six patients (8%) (5 UC and 1 CD) had adverse events. The concomitant use of corticosteroids or immunomodulators did not increase the efficacy. Those with a higher number of previous anti-TNF treatments showed less remissions in UC and responses in CD. CONCLUSIONS: After one year of VDZ, a clinical response and remission was induced in a considerable percentage of patients refractory to different biological or immunosuppressive therapies. VDZ can be considered as an alternative in those intolerant to immunosuppressives, with few adverse events.

Tamoxifen inhibits chemokinesis in equine neutrophils.

Neutrophils are terminally differentiated innate effector cells at the first line of host defense. Neutrophil migration within tissues is complex and involves several steps, during which these cells must be able to interpret a variety of chemical and physical signals. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including equine asthma. Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and bronchoalveolar lavage fluid (BALF) neutrophils, reduction of BALF neutrophil content, and improvement in animals' clinical status. Further, TX dampens chemotactic index and respiratory burst production in vitro. The aim of this study was to provide information on the effect of TX on chemokinesis in peripheral blood neutrophils from five healthy horses. Results showed that neutrophils increased migration and travelled distance in response to IL-8; but in the presence of TX, IL-8 did not produce neutrophil migration. This suggests that TX has an inhibitory effect on the kinesis of equine peripheral blood neutrophils stimulated with IL-8. However, further studies are required to fully understand the signaling pathways of TX on neutrophil chemokinesis.

Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia.

BACKGROUND: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1-positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults. METHODS: We performed genomic profiling of 1725 patients with precursor B-cell ALL and detailed genomic analysis of 154 patients with Ph-like ALL. We examined the functional effects of fusion proteins and the efficacy of tyrosine kinase inhibitors in mouse pre-B cells and xenografts of human Ph-like ALL. RESULTS: Ph-like ALL increased in frequency from 10% among children with standard-risk ALL to 27% among young adults with ALL and was associated with a poor outcome. Kinase-activating alterations were identified in 91% of patients with Ph-like ALL; rearrangements involving ABL1, ABL2, CRLF2, CSF1R, EPOR, JAK2, NTRK3, PDGFRB, PTK2B, TSLP, or TYK2 and sequence mutations involving FLT3, IL7R, or SH2B3 were most common. Expression of ABL1, ABL2, CSF1R, JAK2, and PDGFRB fusions resulted in cytokine-independent proliferation and activation of phosphorylated STAT5. Cell lines and human leukemic cells expressing ABL1, ABL2, CSF1R, and PDGFRB fusions were sensitive in vitro to dasatinib, EPOR and JAK2 rearrangements were sensitive to ruxolitinib, and the ETV6-NTRK3 fusion was sensitive to crizotinib. CONCLUSIONS: Ph-like ALL was found to be characterized by a range of genomic alterations that activate a limited number of signaling pathways, all of which may be amenable to inhibition with approved tyrosine kinase inhibitors. Trials identifying Ph-like ALL are needed to assess whether adding tyrosine kinase inhibitors to current therapy will improve the survival of patients with this type of leukemia. (Funded by the American Lebanese Syrian Associated Charities and others.).