Serum and Urine Metabolomic Profiling of Newly Diagnosed Treatment-Naïve Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation. METHODS: Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses. RESULTS: A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters. CONCLUSIONS: This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.

Prevalence of interpersonal violence against children in sport in six European countries.

BACKGROUND: Investigating prevalence of child abuse in sport is a relatively new field of research, born from the need for credible data on this phenomenon. OBJECTIVE: To establish prevalence rates of interpersonal violence against children in sport in six European countries. PARTICIPANTS AND SETTING: The sample (N = 10,302) consists of individuals aged 18-30 who had participated in organized sport prior to age 18 (49.3 % male, 50 % female). METHODS: A self-report questionnaire was developed (the Interpersonal Violence Against Children in Sport Questionnaire or IVACS-Q) to measure prevalence of five categories of interpersonal violence (neglect, psychological violence, physical violence, non-contact sexual violence, and contact sexual violence) against children who participate in sport. Validation testing (published separately) showed reasonable levels of convergent and divergent validity. Prevalence rates are calculated by national context, whether inside or outside sport, and by sex (male/female). RESULTS: Prevalence of IVACS inside sport differed by category: psychological violence (65 %, n = 6679), physical violence (44 %, n = 4514), neglect (37 %, n = 3796), non-contact sexual violence (35 %, n = 3565), and contact sexual violence (20 %, n = 2060). Relatively small geographical differences were found. Across all categories, males (79 %, n = 4018) reported significantly more experiences inside sport than females (71 %, n = 3653) (χ2(1) = 92.507, p < .000). Strong correlations were found between experiencing violence inside and outside sport. CONCLUSIONS: Interpersonal violence against children in sport is widespread. The sector's approach to prevention must recognize the risks to female and male children (and all children) and the additional vulnerabilities of abused children. Further comparative and longitudinal research within sport is required.

Impact of Prolonged Ischemia on the Immunohistochemical Expression of Programmed Death Ligand 1 (PD-L1).

Antibodies targeting programmed death receptor 1 or programmed death ligand 1 (PD-L1) have become a standard of care to treat different cancers; for some of these tumors, there is a correlation between tissue expression of PD-L1 and response rates in patients. Although most of the analytical challenges in the evaluation of PD-L1 expression have been standardized, preanalytical issues have been less explored. The objective of this study was to evaluate the impact of time of ischemia on the performance of 2 commonly used antibodies against PD-L1. Sixteen tonsillectomy samples were kept in ischemia for <30 minutes from sample obtention (control) and 1, 3, 6, 12, and 24 hours at room temperature before formalin fixation and paraffin embedding. Selected areas were inserted into TMA paraffin recipient blocks stained with SP142 and SP263 antibodies and evaluated by 2 blind observers. The proportion of suboptimally stained samples was significantly higher for samples with cold ischemia times 6 hours or over ( P <0.0001). False-negative results were 25% in samples exposed to 6 hours of ischemia and raised to 34% for samples remaining in ischemia for 12 or 24 hours. When all observations were pooled, SP142 provided suboptimal results in 24% of observations and SP263 in 12.5%; this is a statistically significant difference ( P =0.042). In conclusion, the quality of staining for PD-L1 in tonsil samples varies with the time of cold ischemia. The SP142 antibody presented a significantly lower tolerance to prolonged cold ischemia than SP263. These results reveal the relevance of controlled preanalytical processing of samples.

A cosmic stream of atomic carbon gas connected to a massive radio galaxy at redshift 3.8.

The growth of galaxies in the early Universe is driven by accretion of circum- and intergalactic gas. Simulations have predicted that steady streams of cold gas penetrate the dark matter halos of galaxies and provide the raw material necessary to sustain star formation. We report a filamentary stream of gas that extends for 100 kiloparsecs and connects to the massive radio galaxy 4C 41.17. We detected the stream using submillimeter observations of the 3P1 to 3P0 emission from the [C i] line of atomic carbon, a tracer of neutral atomic or molecular hydrogen gas. The galaxy contains a central gas reservoir that is fueling a vigorous starburst. Our results show that the raw material for star formation can be present in cosmic streams outside galaxies.

COVID-19 Infection among Nursing Students in Spain: The Risk Perception, Perceived Risk Factors, Coping Style, Preventive Knowledge of the Disease and Sense of Coherence as Psychological Predictor Variables: A Cross Sectional Survey.

The exploration of patterns of health beliefs about COVID-19 among nursing students may be beneficial to identify behaviors, attitudes and knowledge about contagion risk. We sought to analyze the variables of risk perception, perceived risk factors, coping style, sense of coherence and knowledge of preventive measures as possible predictors of having suffered from COVID-19. Participants were nursing students from 13 universities in Spain. Sociodemographic and health variables were collected. To test the independent variables, the Perception Risk Coping Knowledge (PRCK-COVID-19) scale was created and validated because there was no specific survey for young people adapted to the pandemic situation of COVID-19. It was validated with adequate psychometric properties. A total of 1562 students (87.5% female, mean age 21.5 ± 5.7 years) responded. The high perception of the risk of contagion, the high level of knowledge and a coping style focused on the situation were notable. Significant differences by gender were found in the coping styles, problem-focused, avoidance and knowledge scales, with women scoring higher in all categories. The multiple regression analysis was significant (F = 3.68; p < 0.001). The predictor variables were the coping styles subscale search for support and the intrinsic and extrinsic perceived risk factors. Our model predicts that nursing students with a social support-based coping style are at a higher risk of becoming infected with COVID-19, based on their own health belief model.

Differential Effects of Anti-TNFα and Anti-α4ß7 Drugs on Circulating Dendritic Cells Migratory Capacity in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is an idiopathic and chronic disorder that includes ulcerative colitis (UC) and Crohn's disease (CD). Both diseases show an uncontrolled intestinal immune response that generates tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells that play a key role in tolerance maintenance in the gastrointestinal mucosa. Although it has been reported that DC recruitment by the intestinal mucosa is more prominent in IBD patients, the specific mechanisms governing this migration are currently unknown. In this study, the expression of several homing markers and the migratory profile of circulating DC subsets towards intestinal chemo-attractants were evaluated and the effect of biological drugs with different mechanisms of action, such as anti-TNFα or anti-integrin α4ß7 (vedolizumab), on this mechanism in healthy controls (HCs) and IBD patients was also assessed. Our results revealed that type 2 conventional DCs (cDC2) express differential homing marker profiles in UC and CD patients compared to HCs. Indeed, integrin ß7 was differentially modulated by vedolizumab in CD and UC. Additionally, although CCL2 displayed a chemo-attractant effect over cDC2, while biological therapies did not modulate the expression of the homing markers, we paradoxically found that anti-TNF-treated cDC2 increased their migratory capacity towards CCL2 in HCs and IBD. Our results therefore suggest a key role for cDC2 migration towards the intestinal mucosa in IBD, something that could be explored in order to develop novel diagnostic biomarkers or to unravel new immunomodulatory targets in IBD.

Characterization of Factors Predicting a Favorable Opinion of Research Applications Submitted for an Ethical Review Process.

Introduction: In Spain, biomedical research applications must receive a positive ethical opinion from Research Ethics Committees (RECs) before being executed. There is limited information on how to optimize the ethical review process to reduce delays. This study was performed to characterize variables predicting favorable opinions at the first ethical review performed by a REC. Material and Methods: The study assessed all research applications revised by a REC in 2019-2020. Data was extracted from REC's database of La Rioja, Spain. Variables collected covered three areas: (i) principal investigator's profile; (ii) study design; and (iii) ethical review process. A model based on multiple logistic regression analysis was created to identify variables explaining favorable opinions in first rounds of ethical review processes. Results: The sample included 125 applications (41 submitted in 2019, and 84 in 2020). At the first review, nine (7%) applications were rejected, 56 (45%) were approved, and the remaining 60 (48%) required at least two reviews prior to approval. When comparing both years, a 2-fold increase in the number of applications submitted, and a difference in the ratio of applications with a favorable vs. non-favorable opinion were observed. Furthermore, a model predicted 71% of probability of obtaining a favorable opinion in the first ethical review. Three variables appeared as being explanatory: if the principal investigator is either the group leader or the department's head (OR = 17.39; p < 0.001), and if the informed consent (OR = 11.79; p = 0.01), and methods and procedures (OR = 34.15; p < 0.001) are well done. Conclusions: These findings confirm an increase in the number of submissions and a difference in the ratio of applications approved by year. Findings observed also confirm deficiencies in "informed consent" and in "methods and procedures" are the two main causes of delay for favorable ethical opinions. Additionally, findings highlight the need that group leaders and heads of departments should be more involved in guiding and supervising their research teams, especially when research applications are led by less experienced researchers. Based on these findings, it is suggested that an adequate mentoring and targeted training in research could derive in more robust research applications and in smoother ethical review processes.

Role of Empathy and Lifelong Learning Abilities in Physicians and Nurses Who Work in Direct Contact with Patients in Adverse Working Conditions.

Empathy and lifelong learning are two professional competencies that depend on the four principles of professionalism: humanism, altruism, excellence, and accountability. In occupational health, there is evidence that empathy prevents work distress. However, in the case of lifelong learning, the evidence is still scarce. In addition, recent studies suggest that the development of lifelong learning varies in physicians and nurses and that it is sensitive to the influence of cultural stereotypes associated with professional roles. This study was performed with the purpose of determining the specific role that empathy and lifelong learning play in the reduction in occupational stress. This study included a sample composed by 40 physicians and 40 nurses with high dedication to clinical work in ambulatory consultations from a public healthcare institution in Paraguay. Somatization, exhaustion, and work alienation, described as indicators of occupational stress, were used as dependent variables, whereas empathy, lifelong learning, gender, discipline, professional experience, civil status, and family burden were used as potential predictors. Three multiple regression models explained 32% of the variability of somatization based on a linear relationship with empathy, lifelong learning, and civil status; 73% of the variability of exhaustion based on a linear relationship with empathy, somatization, work alienation, and discipline; and 62% of the variability of work alienation based on a linear relationship with lifelong learning, exhaustion, and discipline. These findings indicate that empathy and lifelong learning play important roles in the prevention of work distress in physicians and nurses. However, this role varies by discipline.

Burnout in International Medical Students: Characterization of Professionalism and Loneliness as Predictive Factors of Burnout.

BACKGROUND: Burnout is a common mental problem in medical students. For those who are following medical studies abroad there is a higher risk of suffering this syndrome, due to the combination of academic stress and the stress derived from their new living situation. This study was performed with the purpose of testing the following hypothesis: in medical students enrolled in medical programs abroad, abilities associated with professionalism and family support play a protective role in the prevention of suffering burnout. METHODS: A cross-sectional study was performed in the Faculty of Medicine of the University of Zagreb, where a fully English medical program is offered. The general version of the Maslach Burnout Inventory (MBI-GS) was used as a dependent variable, while Jefferson Scales of empathy, teamwork, and physician lifelong learning and the Social and Emotional Loneliness Scale for Adults were used as predictive variables. In addition, information related to sex, country of birth, native language, age, academic achievement, and living situation were collected in a socio-demographic form. Linear regression models were applied to identify predictors of burnout. RESULTS: In a sample composed of 188 medical students (38 Croatians and 144 foreigners from 28 countries), 18% of the global score in the MBI-GS was explained by lifelong learning and family loneliness. A separate analysis for each domain of the MBI-GS allowed the creation of three models: the first model explained 19% of the variance of the "exhaustion" domain by "country of birth", "living with parents", "academic year", and "cynicism"; a second model explained 24% of the variance of the "cynicism" domain by "academic year", "empathy", "lifelong learning", and "exhaustion"; and finally, a third model explained 24% of the variance of the "professional efficacy" domain by "lifelong learning", "family loneliness", and "cynicism". All obtained models presented an effect size between medium and large, as well as matching the required conditions for statistical inference. CONCLUSIONS: These findings confirm the important role that family plays as a source of support for medical students. Empathy and lifelong learning, two specific elements of medical professionalism, appear as protective factors in the prevention of burnout in international students.

Prediction of the early response to spironolactone in resistant hypertension by the combination of matrix metalloproteinase-9 activity and arterial stiffness parameters.

AIMS: The aim of this study was to determine whether arterial stiffness assessed with the biochemical parameter active matrix metalloproteinase (MMP)-9 and the clinical parameters pulse pressure (PP) and pulse wave velocity predicts the response to spironolactone in resistant hypertension (RH). METHODS AND RESULTS: Ambulatory blood pressure (BP) and active MMP-9 (measured by zymography and ELISA) were measured at baseline, and patients were classified as having pseudo-RH or RH. Patients with RH received spironolactone and the response was determined after 8 weeks by ambulatory BP monitoring: those who achieved BP goals were considered controlled (CRH) and those who did not were considered uncontrolled (UCRH). Plasma active MMP-9 was significantly higher in patients with RH than with pseudo-RH, and correlated with 24 h systolic BP and PP. Receiver operating characteristic analysis indicated that active MMP-9 could predict the response to spironolactone, and its combination with 24 h PP and pulse wave velocity significantly improved this prediction. Moreover, plasma of patients with UCRH induced the MMP-9 expression pathway. CONCLUSION: We propose active MMP-9 as a useful biomarker to identify patients with RH who will not respond to spironolactone. Combining MMP-9 activity with classical arterial stiffness parameters improves the prediction of the clinical response to spironolactone and might contribute to guide the most appropriate therapeutic decisions for patients with RH.

Non-academic factors influencing the development of empathy in undergraduate nursing students: a cross-sectional study.

BACKGROUND: Empathy is described as a core competence of nursing. There is abundant research evidence supporting that empathy varies according to personal characteristics and targeted training. The aim of this study was to characterize non-academic factors (personal and environmental) influencing the development of empathy in undergraduate nursing studies who are not receiving a targeted training in empathetic abilities in their nursing schools. METHODS: A cross-sectional study was performed in the three nursing schools located in Cusco city, Peru (two private and one public). The Jefferson Scales of Empathy, Attitudes toward Physician-Nurse Collaboration, and Lifelong Learning, the Emotional Loneliness Scale for Adults, and the Scale of Life Satisfaction, were applied as the main measures. Also, information regarding gender, nursing school, and age, were collected. After psychometric properties were assessed, all measures were used in the development of a multivariate regression model to characterize factors of influence in empathy. RESULTS: In a sample composed by 700 undergraduate nursing students (72 males and 628 females), a multivariate linear regression model was created. This model explained the 53% of variance of empathy and fitted all conditions necessary for inference estimations. Teamwork abilities, loneliness, age, sex, subjective well-being, and nursing school, appeared as factors influencing the development of empathy in patients' care. CONCLUSIONS: Findings have indicated that, in absence of a targeted training, individual characteristics and characteristics associated with social and family environments play an important role of influence in the development of empathy in nursing students. These findings are also in consonance with others previously reported in different cultural settings including high-, middle- and low-income countries.

Inter-Professional Collaboration and Occupational Well-Being of Physicians Who Work in Adverse Working Conditions.

Inter-professional collaboration, empathy and lifelong learning, components of medical professionalism, have been associated with occupational well-being in physicians. However, it is not clear whether this role persists in adverse working conditions. This study was performed to assess whether this is the case. These three abilities, and the self-perception of somatization, exhaustion and work alienation, were measured in a sample of 60 physicians working in a hospital declared to be in an institutional emergency. A multiple regression model explained 40% of the variability of exhaustion, with a large effect size (Cohen's-f2 = 0.64), based on a linear relationship with teamwork (p = 0.01), and more dedication to academic (p < 0.001) and management activities (p < 0.003). Neither somatization nor alienation were predicted by empathy or lifelong learning abilities. Somatization, exhaustion, or alienation scores either explained empathy, inter-professional collaboration or lifelong learning scores. These findings indicate that, in adverse working environments, physicians with a greater sense of inter-professional collaboration or performing multi-task activities are more exposed to suffering exhaustion.

Design of the EBE-ST Questionnaire among Nursing Students: Multicenter Study from Eight Universities in Spain.

BACKGROUND: Twenty years after the degree in nursing was introduced in Spain, the subject of evidence-based nursing is still unstructured and unestablished in most faculties. Moreover, there are hardly any rigorous studies at a national level that evaluate the current state of this competence in our faculties. Understanding the starting point is essential for the curricular design to ensure that evidence-based practice is implemented among future professionals. AIM: To design and validate an evidence-based nursing competency questionnaire for fourth-year nursing students. METHODS: A specific questionnaire was developed and validated (EBE-ST). A cross-sectional survey design with psychometric validation of an instrument. Participants were 304 senior year nursing students from eight universities in Spain (2020). RESULTS: The EBE-ST questionnaire is composed of 33 items that determine eight factors. It presents adequate reliability and validity (alpha = 0.882), measuring knowledge, attitudes and the practical application of evidence-based practice. CONCLUSIONS: We have created an instrument with good psychometric properties to measure evidence-based practice competence among senior nursing students. The heterogeneity of knowledge regarding evidence-based nursing in our country suggests that further reflection is warranted on the incorporation of this topic during undergraduate training. We have designed and validated an evidence-based nursing competency questionnaire specific to nursing students.

Cardiovascular Risk Stratification Based on Oxidative Stress for Early Detection of Pathology.

Aims: Current cardiovascular (CV) risk prediction algorithms are able to quantify the individual risk of CV disease. However, CV risk in young adults is underestimated due to the high dependency of age in biomarker-based algorithms. Because oxidative stress is associated with CV disease, we sought to examine CV risk stratification in young adults based on oxidative stress to approach the discovery of new markers for early detection of pathology. Results: Young adults were stratified into (i) healthy controls, (ii) subjects with CV risk factors, and (iii) patients with a reported CV event. Plasma samples were analyzed using FASILOX, a novel approach to interrogate the dynamic thiol redox proteome. We also analyzed irreversible oxidation by targeted searches using the Uniprot database. Irreversible oxidation of cysteine (Cys) residues was greater in patients with reported CV events than in healthy subjects. These results also indicate that oxidation is progressive. Moreover, we found that glutathione reductase and glutaredoxin 1 proteins are differentially expressed between groups and are proteins involved in antioxidant response, which is in line with the impaired redox homeostasis in CV disease. Innovation: This study, for the first time, describes the oxidative stress (reversible and irreversible Cys oxidation) implication in human plasma according to CV risk stratification. Conclusion: The identification of redox targets and the quantification of protein and oxidative changes might help to better understand the role of oxidative stress in CV disease, and aid stratification for CV events beyond traditional prognostic and diagnostic markers. Antioxid. Redox Signal. 35, 602-617.

Lunasin Peptide is a Modulator of the Immune Response in the Human Gastrointestinal Tract.

INTRODUCTION: Lunasin is a soybean bioactive peptide with a variety of beneficial properties against chronic disorders. However, its effect in human primary intestinal cells remains unknown. Hence, this study aims to characterize its ex vivo biological activity in the human intestinal mucosa. METHODS AND RESULTS: Human intestinal biopsies, obtained from healthy controls, are ex vivo conditioned with lunasin both in the presence/absence of lipopolysaccharide (LPS). Peptide maintains its stability during biopsy culture by HPLC-MS/MS analysis. Lunasin is bioactive in the human mucosa, as it induces IL-1ß, TNF-α, IL-17A, CCL2, and PGE2/COX-2 gene expression together with an increased expression of tolerogenic IL-10 and TGFß, while it also downregulates the expression of iNOS and subunit p65 from NF-κB. Indeed, lunasin also abrogates the LPS-induced pro-inflammatory response, downregulating IL-17A, IFNγ, and IL-8 expression, and inducing IL-10 and TGFß expression. These results are also mirrored in the cell-free culture supernatants at the protein level by Multiplex. Moreover, lunasin further induces a regulatory phenotype and function on human intestinal conventional dendritic cell and macrophage subsets as assessed by flow cytometry. CONCLUSIONS: We hereby have characterized lunasin as an immunomodulatory peptide with potential capacity to prevent immune and inflammatory-mediated disorders in the human gastrointestinal tract.

Tissue Proteomic Approaches to Understand the Pathogenesis of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) has become a global disease encompassing a group of progressive disorders characterized by recurrent chronic inflammation of the gut with variable disease courses and complications. Despite recent advances in the knowledge of IBD pathophysiology, the elucidation of its etiopathology and progression is far from fully understood, requiring complex and multiple approaches. Therefore, limited clinical progress in diagnosis, assessment of disease activity, and optimal therapeutic regimens have been made over the past few decades. This review explores recent advances and challenges in tissue proteomics with an emphasis on biomarker discovery and better understanding of the molecular mechanisms underlying IBD pathogenesis. Future multi-omic studies are required for the comprehensive molecular characterization of disease biology in real time with a future impact on early detection, disease monitoring, and prediction of the clinical outcome.

Analysis of Global Oxidative Status Using Multimarker Scores Reveals a Specific Association Between Renal Dysfunction and Diuretic Therapy in Older Adults.

Aging and chronic kidney disease (CKD) are important interrelated cardiovascular risk (CVR) factors linked to oxidative stress, but this relationship has not been well studied in older adults. We assessed the global oxidative status in an older population with normal to severely impaired renal function. We determined the oxidative status of 93 older adults (mean age 85 years) using multimarker scores. OxyScore was computed as index of systemic oxidative damage by analyzing carbonyl groups, oxidized low-density lipoprotein, 8-hydroxy-2'-deoxyguanosine, and xanthine oxidase activity. AntioxyScore was computed as index of antioxidant defense by analyzing catalase and superoxide dismutase (SOD) activity and total antioxidant capacity. OxyScore and AntioxyScore were higher in subjects with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 than in peers with eGFR >60 mL/min/1.73 m2, with protein carbonyls, catalase, and SOD activity as major drivers. Older adults with a recent cardiovascular event had similar OxyScore and AntioxyScore as peers with eGFR >60 mL/min/1.73 m2. Multivariate linear regression analysis revealed that both indices were associated with decreased eGFR independently of traditional CVR factors. Interestingly, AntioxyScore was also associated with diuretic treatment, and a more pronounced increase was seen in subjects receiving combination therapy. The associations of AntioxyScore with diuretic treatment and eGFR were mutually independent. In conclusion, eGFR is the major contributor to the imbalance in oxidative stress in this older population. Given the association between oxidative stress, CKD, and CVR, the inclusion of renal function parameters in CVR estimators for older populations, such as the SCORE-OP, might improve their modest performance.

Profiling of Human Circulating Dendritic Cells and Monocyte Subsets Discriminates Between Type and Mucosal Status in Patients With Inflammatory Bowel Disease.

BACKGROUND: Intestinal dendritic cells (DC) and macrophages drive disease progression in patients with inflammatory bowel disease (IBD). We aimed to characterize the activation and homing profile of human circulating DC and monocyte subsets in healthy control patients (CP) and IBD patients. METHODS: Eighteen CP and 64 patients with IBD were categorized by diagnoses of Crohn disease (CD) and ulcerative colitis (UC), either endoscopically active (inflamed) or quiescent. Circulating type 1 conventional DC, type 2 conventional DC, plasmacytoid DC, classical monocytes, nonclassical monocytes, and intermediate monocytes were identified by flow cytometry in each individual and characterized for the expression of 18 markers. Association between DC/monocytes and IBD risk was tested by logistic regression. Discriminant canonical analyses were performed to classify the patients in their own endoscopy category considering all markers on each subset. RESULTS: CCRL1, CCR3, and CCR5 expression on circulating type 1 DC; CCRL1 expression on nonclassical monocytes; and CCR9 and ß7 expression on classical monocytes allowed us to discriminate among the different study groups. Indeed, the same markers (excluding ß7) were also associated with IBD when all DC and monocyte subsets were considered at the same time. CONCLUSIONS: Monitoring the phenotype of human circulating DC and monocyte subsets may provide novel tools as biomarkers for disease diagnosis (CD/UC) or mucosal status (inflamed/noninflamed) in the absence of an invasive colonoscopy.

Single-incision versus four-port laparoscopic cholecystectomy in an ambulatory surgery setting: A prospective randomised double-blind controlled trial.

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) can be done as a day-case procedure and may have advantages over conventional laparoscopic cholecystectomy (LC). We present the results of our study looking at post-operative pain and post-operative recovery time. METHODS: This was a single-institution randomised double-blind controlled trial. Seventy-three patients with symptomatic cholelithiasis were randomized to SILC (n = 37) or LC (n = 36). The primary endpoint was to compare post-operative pain. We also compared surgical time, procedural difficulty, adverse events, additional ports used and conversion rate, success of day surgery process, return to work, aesthetic satisfaction, quality of life and 4-year incisional hernia rate. RESULTS: In the SILC group, post-operative analgesic requirements were lower on day 7, there was an earlier return to work and cosmetic satisfaction was significantly higher. The SILC procedure presented a higher technical difficulty. Operative time, surgical complications, post-operative pain, success of the day-case process, return to normal activity, quality of life scores and incisional hernia rates were similar for both the procedures. CONCLUSIONS: SILC has advantages over LC in terms of late post-operative analgesic requirements and aesthetic results; however, it is technically harder to perform. There was no benefit in terms of day surgery outcomes.

The Immunohistochemical Expression of Programmed Death Ligand 1 (PD-L1) Is Affected by Sample Overfixation.

Humanized antibodies targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have been approved for the treatment of different cancers. Some of these antibodies show a correlation between the tissue expression of PD-L1 and response. Evaluation of PD-L1 expression presents multiple challenges, but some preanalytical issues such as tissue fixation have been scarcely evaluated. With the hypothesis that immunohistochemical staining of PD-L1 may be impacted by the time of specimen fixation, we evaluated differences in its expression in tonsil samples exposed to predefined fixation times. Random nontumoral tonsillectomy specimens were blindly evaluated in tissue microarray slides after staining with SP142 and SP263 antibodies. With fixation times ranging from 12 to 72 hours, between 2.8% and 6.1% of the samples were considered to be suboptimally stained, with no differences between the 2 antibodies within these fixation times. A significantly higher proportion of samples exposed to a fixation time of 96 hours presented suboptimal immunostaining (15.6%, P<0.0001). In addition, suboptimally stained spots were 20.8% using SP142 and 10.4% using SP263 after 96 hours of fixation (P=0.046). In conclusion, the quality of staining for PD-L1 in tonsil samples decreased with overfixation of the specimen at times >72 hours. Samples exposed to formaldehyde for longer periods presented suboptimal results for both clones, but the SP142 antibody presented a significantly lower tolerance to formalin overexposure than SP263. These results indicate the relevance of a controlled preanalytical processing of samples and particularly the length of fixation of tumor specimens.