Mucosal Eosinophil Abundance in Non-Inflamed Colonic Tissue Is Associated with Response to Vedolizumab Induction Therapy in Inflammatory Bowel Disease

Vedolizumab is used as a treatment for patients with inflammatory bowel disease (IBD), but induction therapy leads to clinical response and remission in approximately 55% and 30% of patients with IBD, respectively. In this study, we aimed to explore the predictive value of mucosal eosinophils and serum eotaxin-1 regarding response to vedolizumab induction therapy. Eighty-four (84) patients with IBD (37 Crohn’s disease [CD], 47 ulcerative colitis [UC]) were included. For 24 patients with IBD, histopathology was assessed for eosinophil counts in non-inflamed colonic tissue prior to vedolizumab treatment. For 64 patients with IBD, serum eotaxin-1 levels were quantified prior to (baseline) and during vedolizumab treatment. Serum samples of 100 patients with IBD (34 CD, 66 UC) from the GEMINI 1 and 2 trials were used for external validation. Baseline mucosal eosinophil numbers in non-inflamed colonic tissue were significantly higher in responders to vedolizumab induction therapy when compared to primary non-responders (69 [34–138] vs. 24 [18–28] eosinophils/high-power field, respectively, p < 0.01). Baseline serum eotaxin-1 levels in the discovery cohort were significantly elevated in responders, compared to primary non-responders (0.33 [0.23–0.44] vs. 0.20 [0.16–0.29] ng/mL, p < 0.01). Prediction models based on mucosal eosinophil counts and serum eotaxin-1 showed an area under the curve (AUC) of 0.90 and 0.79, respectively. However, the predictive capacity of baseline serum eotaxin-1 levels could not be validated in the GEMINI cohort. Mucosal eosinophil abundance in non-inflamed colonic tissue was associated with response to vedolizumab induction therapy in patients with IBD. Future studies are warranted to further validate the potential value of mucosal eosinophils and serum eotaxin-1 as biomarkers for response to vedolizumab therapy

Mucosal eosinophil abundance in non-inflamed colonic tissue predicts response to vedolizumab induction therapy in inflammatory bowel disease

Vedolizumab is used as a treatment for patients with inflammatory bowel disease (IBD), but induction therapy leads to clinical response and remission in approximately 55% and 30% of patients with IBD, respectively. In this study, we aimed to explore the predictive value of mucosal eosinophils and serum eotaxin-1 regarding response to vedolizumab induction therapy. Eighty-four (84) patients with IBD (37 Crohn’s disease [CD], 47 ulcerative colitis [UC]) were included. For 24 patients with IBD, histopathology was assessed for eosinophil counts in non-inflamed colonic tissue prior to vedolizumab treatment. For 64 patients with IBD, serum eotaxin-1 levels were quantified prior to (baseline) and during vedolizumab treatment. Serum samples of 100 patients with IBD (34 CD, 66 UC) from the GEMINI 1 and 2 trials were used for external validation. Baseline mucosal eosinophil numbers in non-inflamed colonic tissue were significantly higher in responders to vedolizumab induction therapy when compared to primary non-responders (69 [34–138] vs. 24 [18–28] eosinophils/high-power field, respectively, p < 0.01). Baseline serum eotaxin-1 levels in the discovery cohort were significantly elevated in responders, compared to primary non-responders (0.33 [0.23–0.44] vs. 0.20 [0.16–0.29] ng/mL, p < 0.01). Prediction models based on mucosal eosinophil counts and serum eotaxin-1 showed an area under the curve (AUC) of 0.90 and 0.79, respectively. However, the predictive capacity of baseline serum eotaxin-1 levels could not be validated in the GEMINI cohort. Mucosal eosinophil abundance in non-inflamed colonic tissue was associated with response to vedolizumab induction therapy in patients with IBD. Future studies are warranted to further validate the potential value of mucosal eosinophils and serum eotaxin-1 as biomarkers for response to vedolizumab therapy

Microstructural Evolution of Secondary Phases in the Cast Duplex Stainless Steels CD3MN and CD3MWCuN

The isothermal formation behavior of secondary phases in two types of duplex stainless steels (DSS), CD3MN and CD3MWCuN, was characterized. Samples were heat treated from 1 minute to 30 days at temperatures from 700°C to 900°C. Small carbide (M23C6) and nitride (Cr2N) precipitates, together with the intermetallic phases sigma and chi, were observed using scanning electron microscopy (SEM) and confirmed by transmission electron microscopy (TEM) analyses. Based on SEM analysis, time-temperature-transformation (TTT) curves for the sigma and chi phases were determined by measuring their volume fractions from backscattered electron micrographs of heat-treated and quenched sample cross sections. Resulting TTT curves showed that the maximum formation temperature for chi is lower than that for sigma, while the time to reach 1 vol pct formation is much less for sigma than it is for chi. The thermodynamic driving forces associated with the sigma and chi formation were assessed using Thermo-Calc

Fluorescently labelled vedolizumab to visualise drug distribution and mucosal target cells in inflammatory bowel disease

Objective:Improving patient selection and development of biological therapies such as vedolizumab in IBD requires a thorough understanding of the mechanism of action and target binding, thereby providing individualised treatment strategies. We aimed to visualise the macroscopic and microscopic distribution of intravenous injected fluorescently labelled vedolizumab, vedo-800CW, and identify its target cells using fluorescence molecular imaging (FMI). Design: Forty three FMI procedures were performed, which consisted of macroscopic in vivo assessment during endoscopy, followed by macroscopic and microscopic ex vivo imaging. In phase A, patients received an intravenous dose of 4.5 mg, 15 mg vedo-800CW or no tracer prior to endoscopy. In phase B, patients received 15 mg vedo-800CW preceded by an unlabelled (sub)therapeutic dose of vedolizumab. Results: FMI quantification showed a dose-dependent increase in vedo-800CW fluorescence intensity in inflamed tissues, with 15 mg (153.7 au (132.3-163.7)) as the most suitable tracer dose compared with 4.5 mg (55.3 au (33.6-78.2)) (p=0.0002). Moreover, the fluorescence signal decreased by 61% when vedo-800CW was administered after a therapeutic dose of unlabelled vedolizumab, suggesting target saturation in the inflamed tissue. Fluorescence microscopy and immunostaining showed that vedolizumab penetrated the inflamed mucosa and was associated with several immune cell types, most prominently with plasma cells. Conclusion: These results indicate the potential of FMI to determine the local distribution of drugs in the inflamed target tissue and identify drug target cells, providing new insights into targeted agents for their use in IBD. Trial registration number:NCT04112212.</p

Türkiye’de bulunan yoğun bakımlarda sabun, kağıt havlu ve alkol bazlı el dezenfektanı yeterli mi?: Phokai çalışması sonuçları

Introduction: Hand hygiene is one of the most effective infection control measures to prevent the spread of healthcare-associated infections (HCAI). Water, soap, paper towel and hand disinfectant must be available and adequate in terms of effective hand hygiene. The adequacy of hand hygiene products or keeping water-soap and paper towel is still a problem for many developing countries like Turkey. In this multicenter study, we analyzed the adequacy in number and availability of hand hygiene products.Materials and Methods: This study was performed in all intensive care units (ICUs) of 41 hospitals (27 tertiary-care educational, 10 state and four private hospitals) from 22 cities located in seven geographical regions of Turkey. We analyzed water, soap, paper towel and alcohol-based hand disinfectant adequacy on four different days, two of which were in summer during the vacation time (August, 27th and 31st 2016) and two in autumn (October, 12th and 15th 2016).Results: The total number of ICUs and intensive care beds in 41 participating centers were 214 and 2357, respectively. Overall, there was no soap in 3-11% of sinks and no paper towel in 10-18% of sinks while there was no alcohol-based hand disinfectant in 1-4.7% of hand disinfectant units on the observation days. When we compared the number of sinks with soap and/or paper towel on weekdays vs. weekends, there was no significant difference in summer. However, on autumn weekdays, the number of sinks with soap and paper towel was significantly lower on weekend days (p<0.0001, p<0.0001) while the number of hand disinfectant units with alcohol-based disinfectant was significantly higher (p<0.0001).Conclusion: There should be adequate and accessible hand hygiene materials for effective hand hygiene. In this study, we found that soap and paper towels were inadequate on the observation days in 3-11% and 10-18% of units, respectively. Attention should be paid on soap and paper towel supply at weekends as well

La Relación Entre la Motivación Docente y Variables de la Organización: Revisión de la Literatura

Abstract Teacher motivation plays a central role in education because ofitsimpacton student motivation. Previous reviews of teacher motivation have focused on individual variables and psychopathology indicators. However, it is also important to understand the effect of organizational variableson teacher motivationbecause these highlightthe contextthat the teacher is a part of(i.e.,the school). The literature review in this paper analysed studies related to teacher motivation and a pre-defined group of organizational variablesthat werepublished between 1990 and 2014 in several electronic databases.The study found that organizational culture was the most studied variable associated with teacher motivationand most studies in this area were published between 2010 and 2014.Further,there was a prevalence of quantitative studies. This paper concludes with the theoreticaland practical implications of the results,as well assuggestions for future research directions

Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2\u2009cm; P\u20091.5\u2009cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8\u2009cm vs 652.8\u2009cm (94% vs 85% by 10 years; P\u2009=\u20090.020; 80% vs 50% at 10 years; P\u2009=\u20090.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8\u2009cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs

Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: Study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background: A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods: Thismulticentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2- week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged usingMRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8Gy in radiotherapy-naive patients, and 15 × 2.0Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-termoncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion: This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections