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

Research potential and limitations of trace analyses of cremated remains

Human cremation is a common funeral practice all over the world and willpresumably become an even more popular choice for interment in thefuture. Mainly for purposes of identification, there is presently agrowing need to perform trace analyses such as DNA or stable isotopeanalyses on human remains after cremation in order to clarify pendingquestions in civil or criminal court cases. The aim of this study was toexperimentally test the potential and limitations of DNA and stableisotope analyses when conducted on cremated remains.For this purpose, tibiae from modern cattle were experimentally crematedby incinerating the bones in increments of 100 degrees C until a maximumof 1000 degrees C was reached. In addition, cremated human remains werecollected from a modern crematory. The samples were investigated todetermine level of DNA preservation and stable isotope values (C and Nin collagen, C and O in the structural carbonate, and Sr in apatite).Furthermore, we assessed the integrity of microstructural organization,appearance under UV-light, collagen content, as well as the mineral andcrystalline organization. This was conducted in order to provide ageneral background with which to explain observed changes in the traceanalyses data sets. The goal is to develop an efficacious screeningmethod for determining at which degree of burning bone still retains itsoriginal biological signals. We found that stable isotope analysis ofthe tested light elements in bone is only possible up to a heat exposureof 300 degrees C while the isotopic signal from strontium remainsunaltered even in bones exposed to very high temperatures. DNA-analysesseem theoretically possible up to a heat exposure of 600 degrees C butcan not be advised in every case because of the increased risk ofcontamination. While the macroscopic colour and UV-fluorescence ofcremated bone give hints to temperature exposure of the bone’s outersurface, its histological appearance can be used as a reliable indicatorfor the assessment of the overall degree of burning

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

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

Imaging in living cells using ν

The boron-rich cobaltabisdicarbollide (COSAN) and its 8,8′-I2 derivative (I2-COSAN), both of purely inorganic nature, are shown to accumulate within living cells, where they can be detected using νB–H Raman microspectroscopy. This demonstrates an alternative method for cell labelling and detection. The inorganic, boron-based molecule cobaltabisdicarbollide, [3,3′-Co(1,2-C2B9H11)2]−, commonly known as COSAN, comprises of a cobalt atom sandwiched by two carboranyl clusters.1 This structure exhibits both electrostatic interactions, via a dispersed negative ionic charge covering the whole molecule,2 and non-bonding intermolecular interactions between its weakly polarized B–H and C–H bonds.3 This duality imparts the molecular property of being simultaneously hydrophobic and hydrophilic, and makes COSAN soluble in both water and oils. The polarized lipid molecules that make up biological membranes also possess amphiphilic properties, and can assemble into membranes and vesicles formed from lipid bilayers. COSAN has also been shown to form small nano-vesicles and above a critical aggregation concentration (cacvesicle ≈ 0.01 mM), begin to form micelles.4 However, unlike lipid bilayer membranes, the membranes of COSAN vesicles are monolayered. Recently, [3,3′-Co(8-I-1,2-C2B9H10)2]−, I2-COSAN, has also been found to self-assemble into a lyotropic lamellar phase with sufficient curvature to create closed vesicles.5 These similarities in physicochemical properties to biological lipids suggest that COSAN molecules may be compatible with living cells, and could be used to label cells in a similar manner to lipophilic dyes. Here, we use Raman microspectroscopy to show the accumulation of COSAN and I2-COSAN in living cells. As a first step in this work, COSAN or I2-COSAN was added directly to Dulbecco's Modified Eagle medium (DMEM) with Human Embryonic Kidney (HEK293) cells. When the cells were concentrated by low speed centrifugation, washed and incubated in new DMEM medium, visual inspection showed accumulation of COSAN or I2-COSAN (orange in colour) within cell pellets (Fig. 1). This observation indicated that these COSAN molecules could be taken up by living cells