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Data on safety and tolerability of the vaccines against severe acute respiratory virus coronavirus-2 (SARS-CoV-2, or coronavirus disease-2019 [COVID-19]) in patients with myasthenia gravis (MG) are currently limited. In this study we investigated the safety of mRNA-based two-dose vaccination in a cohort of patients with MG.This investigation was a prospective observational study of messenger RNA (mRNA)-based vaccines administered to patients with MG with stable disease. Local and systemic reactogenicity after injection was monitored for each dose administered. The patients were categorized and clinically assessed following the recommendations of the Myasthenia Gravis Foundation of America.Thirty-six males and 55 females (mean age at first vaccine dose, 58.8 years; standard deviation, = 17.1 years) received vaccines. Seventy-two patients (79.1%) were taking one or more immunosuppressant(s). The most frequent adverse effects were injection-site pain, fatigue, myalgia, chills, fever, and headache. Local and systemic reactions were transient; 58.2% of the patients developed one or more reaction(s). There were no anaphylactic reactions. None of the patients had a myasthenic crisis, and two developed a mild deterioration compared with their Quantitative Myasthenia Gravis baseline score. The clinical outcome scores showed no exacerbation of MG symptoms. Patients over 65 years of age developed fewer adverse effects. COVID-19 vaccination did not induce clinical exacerbation in stable patients with MG, regardless of their age, sex, history of myasthenic crisis, or whether they were taking immunosuppressants.Our data are consistent with the mRNA COVID-19 vaccine being well tolerated in patients with well-controlled MG. The findings may contribute to decisions in vaccination campaigns in the future.

OBJECTIVE To evaluate the accuracy of transvaginal ultrasound (TVS) in diagnosing deep endometriosis (DE) involving the uterosacral ligaments (USLs), torus uterinus (TU) or posterior vaginal fornix (PVF) in women with suspected endometriosis scheduled for laparoscopic surgery. METHODS In this prospective study, consecutive women with clinically suspected pelvic endometriosis who were scheduled for laparoscopic surgery were invited to participate. TVS was performed before surgery. TVS findings were compared with those obtained at laparoscopy and confirmed histologically. The accuracy of TVS for diagnosing DE involving the USLs, TU or PVF was assessed. Additionally, the association of DE involving the USLs, TU or PVF on TVS with symptoms and with DE affecting other pelvic locations was assessed. RESULTS In total, 172 patients were included. The global sensitivity and specificity of TVS in diagnosing DE affecting the USLs, TU and/or PVF were 92% and 87%, respectively. For DE involving the USLs, the accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio and negative likelihood ratio of TVS were 89.5%, 96.6%, 82.1%, 85.0%, 95.8%, 5.41 and 0.04, respectively; the respective values for DE involving the TU were 86.6%, 83.9%, 89.4%, 89.0%, 84.4%, 7.92 and 0.18, and the respective values for DE involving the PVF were 93.6%, 87.0%, 94.6%, 71.4%, 97.9%, 16.20 and 0.14. Logistic regression analysis showed a significant association between DE affecting the USLs, TU and/or PVF and DE affecting the rectosigmoid (odds ratio, 5.43; P

These European Resuscitation Council education guidelines are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. This section provides guidance to citizens and healthcare professionals with regard to teaching and learning the knowledge, skills and attitudes of resuscitation with the ultimate aim of improving patient survival after cardiac arrest.

Chronic cortisol excess induces several alterations on protein, lipid and carbohydrate metabolism resembling those found in the metabolic syndrome. However, patients exposed to prolonged high levels of cortisol in Cushing syndrome (CS) present exceeding cardiometabolic alterations not reflected by conventional biomarkers. Using 3 ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) platforms, we aimed to characterise the serum metabolome of 25 patients with active endogenous CS and 25 control subjects matched by propensity score (sex, BMI, diabetes mellitus type 2 (T2D), high blood pressure (HBP) and dyslipidaemia) to search for potential disease-specific biomarkers and pathways associated to the clinical comorbidities. A total of 93 metabolites were significantly altered in patients with CS. Increased levels of sulfur amino acids (AA), triacylglycerols, glycerophospholipids, ceramides and cholesteryl esters were observed. Contrarily, concentrations of essential and non-essential AA, polyunsaturated fatty acids, conjugated bile acids and second messenger glycerolipids were decreased. Twenty-four-hour urinary free cortisol (24h-UFC) independently determined the concentration of 21 lipids and 4 AA. A metabolic signature composed by 10 AA and 10 lipid metabolites presented an AUC-ROC of 95% for the classification of CS patients. Through differential network analysis, 152 aberrant associations between metabolites involved in the Lands cycle and Kennedy pathway were identified. Our data indicates that chronic hypercortisolemia confers a unique lipidomic signature and several alterations in numerous AA even when compared to patients with similar metabolic comorbidities providing novel insights of the increased cardiometabolic burden of CS. KEY MESSAGES: • Cortisol excess induces metabolic alterations beyond conventional biomarkers. • The hypercortisolism extent determines the concentration of 21 lipids and 5 aa. • Cortisol excess confers a unique metabolic signature of 20 metabolites. • Kennedy and Lands cycle are profoundly disturbed by cortisol excess.

Informed by a series of systematic reviews, scoping reviews and evidence updates from the International Liaison Committee on Resuscitation, the 2021 European Resuscitation Council Guidelines present the most up to date evidence-based guidelines for the practice of resuscitation across Europe. The guidelines cover the epidemiology of cardiac arrest; the role that systems play in saving lives, adult basic life support, adult advanced life support, resuscitation in special circumstances, post resuscitation care, first aid, neonatal life support, paediatric life support, ethics and education.

Aim. - To characterize the urinary metabolomic fingerprint and multi-metabolite signature associated with type 2 diabetes (T2D), and to classify the population into metabotypes related to T2D. Methods. - A metabolomics analysis using the 1 H-NMR-based, non-targeted metabolomic approach was conducted to determine the urinary metabolomic fingerprint of T2D compared with non-T2D participants in the PREDIMED trial. The discriminant metabolite fingerprint was subjected to logistic regression analysis and ROC analyses to establish and to assess the multi-metabolite signature of T2D prevalence, respectively. Metabotypes associated with T2D were identified using the k-means algorithm. Results. - A total of 33 metabolites were significantly different (P < 0.05) between T2D and non-T2D participants. The multi-metabolite signature of T2D comprised high levels of methylsuccinate, alanine, dimethylglycine and guanidoacetate, and reduced levels of glutamine, methylguanidine, 3-hydroxymandelate and hippurate, and had a 96.4% AUC, which was higher than the metabolites on their own and glucose. Amino-acid and carbohydrate metabolism were the main metabolic alterations in T2D, and various metabotypes were identified in the studied population. Among T2D participants, those with a metabotype of higher levels of phenylalanine, phenylacetylglutamine, p-cresol and acetoacetate had significantly higher levels of plasma glucose. Conclusion. - The multi-metabolite signature of T2D highlights the altered metabolic fingerprint associated mainly with amino-acid, carbohydrate and microbiota metabolism. Metabotypes identified in this patient population could be related to higher risk of long-term cardiovascular events and therefore require further studies. Metabolomics is a useful tool for elucidating the metabolic complexity and interindividual variation in T2D towards the development of stratified precision nutrition and medicine

Diese Leitlinien des European Resuscitation Council basieren auf dem internationalen wissenschaftlichen Konsens 2020 zur kardiopulmonalen Reanimation mit Behandlungsempfehlungen (International Liaison Committee on Resuscitation 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations [ILCOR] 2020 CoSTR). Dieser Abschnitt bietet Bürgern und Angehörigen der Gesundheitsberufe Anleitungen zum Lehren und Lernen der Kenntnisse, der Fertigkeiten und der Einstellungen zur Reanimation mit dem Ziel, das Überleben von Patienten nach Kreislaufstillstand zu verbessern.

Metabolomics and proteomics, like other omics domains, usually face a data mining challenge in providing an understandable output to advance in biomarker discovery and precision medicine. Often, statistical analysis is one of the most difficult challenges and it is critical in the subsequent biological interpretation of the results. Because of this, combined with the computational programming skills needed for this type of analysis, several bioinformatic tools aimed at simplifying metabolomics and proteomics data analysis have emerged. However, sometimes the analysis is still limited to a few hidebound statistical methods and to data sets with limited flexibility. POMAShiny is a web-based tool that provides a structured, flexible and user-friendly workflow for the visualization, exploration and statistical analysis of metabolomics and proteomics data. This tool integrates several statistical methods, some of them widely used in other types of omics, and it is based on the POMA R/Bioconductor package, which increases the reproducibility and flexibility of analyses outside the web environment. POMAShiny and POMA are both freely available at https://github.com/nutrimetabolomics/POMAShiny and https://github.com/nutrimetabolomics/POMA, respectively., Author summary Metabolomics and proteomics are two growing areas in human health and personalized medicine fields. Often, one of the main applications of metabolomics and proteomics is the discovery of novel biomarkers and new therapeutic targets in these areas. However, these data are extremely complex and hard to analyse, since they have a large number of features, several missing values, and often important clinical variables to consider in the analyses. Therefore, powerful and versatile tools are needed to provide efficient methods for data visualization and exploration, as well as a wide range of robust statistical methods to meet all data and users requirements. Although powerful tools do exist for the analysis of these data, many of them are still limiting the analyses in terms of visualization and statistical analysis. To address this limitation and complement the existing tools, we have developed a web-based application, named POMAShiny, for the data analysis of metabolomics and proteomics. This novel and versatile tool offers a wholly interactive and easy-to-use environment for the analysis of these data, including numerous methods for preprocessing, data visualization and statistical analysis. The POMAShiny open-source tool is extremely flexible and portable, as it can be installed locally and freely accessed online at https://webapps.nutrimetabolomics.com/POMAShiny.

These European Resuscitation Council education guidelines, are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. This section provides guidance to citizens and healthcare professionals with regard to teaching and learning the knowledge, skills and attitudes of resuscitation with the ultimate aim of improving patient survival after cardiac arrest.

ObjectiveThe diagnosis of pelvic inflammatory disease (PID) is challenging. Testing forChlamydia trachomatis(CT) andNeisseria gonorrhoeae(NG) in the lower genital tract is recommended, since a positive result supports the diagnosis. The aim of this study was to investigate the prevalence of CT/NG infection in women suspected of having PID and the usefulness of a rapid molecular test to detect CT/NG.MethodsThis observational study included 3 groups of patients: mild-to-moderate PID (n=33), severe PID (n=29) and non-specific lower abdominal pain (NSAP) (n=13). CT/NG infection were analyzed using a standard and a rapid test. A cost analysis was carried out.ResultsThe presence of CT/NG was determined in 75 endocervical and urine samples. Endocervical samples of 19 patients (25.3%) were CT/ NG positive (two cases of co-infection). NG was not detected in urine in one case. Concordance between rapid and standard tests was 100%. However, the mean time to achieve results was shorter with the rapid test: 2.22vs.24.37 hours, respectively (p< 0.001). No significant differences were observed in the presence of CT/NG in mild-to-moderate compared to severe PID. Costs differed according only to disease severity but to the presence of CT/NG. Only one patient with NSAP was positive for CT.ConclusionsRapid molecular tests could help with the diagnosis of PID in sexually active women in clinical settings in which a standard technique is not available. Nonetheless, a positive test for CT/NG may not be determinant of the clinical management. The only cost difference relates to disease severity.

Background: Alterations in circulating amino acids, polyamines and acylcarnitines have been reported in patients with endogenous chronic hypercortisolism. However, lipid metabolites profiling and its interplay with the serum metabolome and degree of hypercortisolism in patients with active Cushing syndrome (CS) has not been previously assessed. Objective: To identify new metabolomic biomarkers associated with active CS. Methodology: Multiple UHPLC-MS platforms were used to analyze the metabolome of serum samples obtained from 25 patients with active endogenous CS and 25 controls subjects matched by propensity score (sex, BMI, T2D, DLP, HBP). Results: Metabolome of CS patients was deeply disrupted with 122 (27%) of the assessed metabolites significantly altered (p adj. 2-fold decrease). From the altered metabolites, 3 amino acids (AA), 2 acylcarnitines (ACs), 2 ceramides (CER) and 5 glycerophospholipids showed direction of effect independently associated with 24-h urinary free cortisol (MS) levels. A highly discriminant (AUC 96%) metabolome signature (n=59) characterized by lower levels of AA, ACs, polyunsaturated fatty acids (PUFA) and monoglycerophosphocolines (MGPC) together with increased levels of triacyclglycerols (TG), CER, diacylglycerophosphocholines (DGPC) and cholesteryl esters was identified and cross-validated (R2Y= 0.92, Q2Y= 0.68) using PLS-DA VIP scores >1.5. PUFA omega-6, and alanine, aspartate and glutamate metabolism resulted the most impacted canonical pathways (q-stat 19.7, 10.8 (p Conclusion: Active Cushing syndrome leads to a global proatherogenic shift in the circulating ceramides, glycerophospholipids and sphingolipids metabolites which are independently associated to the levels of urinary free cortisol being potential biomarkers of patients’ cardiovascular risk.

Objective Sports-related activity has been proposed as a risk factor for ALS, particularly among professionals playing American football and soccer, with a reported prevalence between two and forty times higher than the general population. Early onset (by two decades) was described among Italian soccer players as early as 2005. This study aims to characterise the phenotype of seven Spanish retired professional and semi-professional soccer players. Methods The cases were identified using the following sources: (i) personal archives from a leading ALS Unit, (ii) PubMed and specialised websites, and (iii) self-reports of patients in the media. Age and site of onset, survival time, history of trauma, playing position and time between retirement and first symptoms were investigated for soccer players in the Spanish league diagnosed between 2000 and 2020. Results Seven ALS cases were identified. The mean age at onset was 41.5 years (SD 9.2, median 45.5, range 31.5–51.2). Onset was bulbar in one individual, while six experienced spinal onset. Three patients had the flail arm syndrome variant. Two cases were goalkeepers, two defenders and three midfielders. Four had a history of trauma (two serious). Survival time for the two deceased patients was 71.8 months. Mean time between retirement and first symptoms was 9.4 years (SD 8.0, median 15.2, range 0.1–17.5). Conclusions Our study has the largest sample size of non-Italian league soccer professionals and semi-professionals, and our results corroborate early onset (by 23.7 years). Unlike the Italian cohorts, bulbar onset is rare, and upper limb onset is most common.

Sentinel lymph node biopsy (SLNB) can be used for nodal staging in early cervical cancer. For this purpose, the tracers most commonly used are radiotracers based on technetium. For the last decade, indocyanine green (ICG) has been used as a tracer for SLNB in other malignancies with excellent results and, more recently, a combination of ICG and a radiotracer has been shown to have the advantages of both tracers. The aim of this study was to evaluate the role of ICG-99mTc-nanocolloid in SLN detection in patients with cervical cancer. This prospective study included 16 patients with cervical cancer. The hybrid tracer was injected the day (19–21 h) before surgery for planar and SPECT/CT lymphoscintigraphy. Blue dye was administered periorificially in 14 patients. SLNs were removed according to their distribution on lymphoscintigraphy and when radioactive, fluorescent and/or stained with blue dye. Nodal specimens were pathologically analysed for metastases including by immunochemistry. Lymphoscintigraphy and SPECT/CT showed drainage in all patients. A total of 69 SLNs were removed, of which 66 were detected by their radioactivity signal and 67 by their fluorescence signal. Blue dye identified only 35 SLNs in 12 of the 14 patients (85.7%). All patients showed bilateral pelvic drainage. Micrometastases were diagnosed in two patients, and were the only lymphatic nodes involved. SLNB with ICG-99mTc-nanocolloid is feasible and safe in patients with early cervical cancer. This hybrid tracer provided bilateral SLN detection in all patients and a higher detection rate than blue dye, so it could become an alternative to the combined technique.

Environmental and biological factors play important roles in determining the skeletal morphology and mineralogy of modular colonial organisms such as bryozoans. The broad bathymetrical ranges of Antarctic bryozoans make them useful organisms for evaluating depth-related changes in colony morphology, including branch diameter, which has been shown to decrease with depth in various ramose colonial animals. The current study focuses on the bryozoan Fasciculipora ramosa, using 32 specimens collected at East Antarctica from 185 to 597 m deep during the CEAMARC cruise (2007–2008). In order to test for the expected inverse relationship between depth and branch diameter, measurements of branch diameters were made. Levels of Mg in the calcite skeleton were determined as this was also predicted to follow changes in branch diameter. A significant negative correlation was found between branch diameter and depth. No significant relationship was detected between branch diameter and skeletal Mg, suggesting that these variables are driven by different factors. The thickest branches were found in current-influenced sites on Adelie Bank where temperature and salinity are both lower and planktonic food supply may also be different from the other sites. Further studies are needed along a wider bathymetrical range to clarify which factors influence branch diameter as well as Mg content in F. ramosa and to test its potential as an environmental indicator.

OBJECTIVES To analyze the effect of bowel preparation prior to transvaginal ultrasound (TVS) examination on the detection of bowel involvement and the description of rectosigmoid nodules of deep infiltrating endometriosis (DIE), and to evaluate patient tolerance of bowel preparation. METHODS This was a prospective study of paired data obtained between September 2015 and March 2016 from a cohort of women referred, on suspicion of DIE but without surgical criteria, to the endometriosis unit of a tertiary university hospital. In all patients, the wall of the rectum and lower sigmoid colon was evaluated by two TVS examinations: the first was performed without bowel preparation and the second was done after the patient had followed a 3-day low-residue diet and received two 250-mL enemas, one the night before TVS and the second 1-3 h before the examination. The presence of adhesions, number and size of rectosigmoid nodules, deepest layer of the rectum affected, percentage of the circumference of the bowel affected and distance from the most caudal part of the bowel nodule to the anal verge were determined. Patient tolerance to bowel preparation was assessed using a 5-point Likert scale, in which 1 represented 'very well tolerated' and 5 represented 'very poorly tolerated'. RESULTS The mean ± SD age of the 110 patients included in the study was 36.8 ± 5.07 years. As many as 55% of those identified during the first examination (TVS alone) as having adhesions were identified at the second examination (TVS with prior bowel preparation) as having rectosigmoid nodules, and 22 additional nodules were observed on TVS following bowel preparation. These newly detected rectosigmoid nodules, initially assessed mainly as adhesions, were smaller and more superficial compared with the nodules detected on TVS alone, or located in the anterior sigmoid wall. Patient tolerance overall to bowel preparation scored a mean of 1.81 on the 5-point Likert scale. CONCLUSIONS Bowel preparation is well tolerated by patients. When bowel preparation is performed before TVS, the detection of small and superficial nodules and those in the anterior sigmoid wall is improved, allowing more detailed description of these nodules in patients with suspected endometriosis. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Background: In-hospital cardiac arrest is a major cause of death in European countries, and survival of patients remains low ranging from 20% to 25%. Aims: The purpose of this study was to assess healthcare professionals’ knowledge on cardiopulmonary resuscitation among university hospitals in 12 European countries and correlate it with the return of spontaneous circulation rates of their patients after in-hospital cardiac arrest. Methods and results: A total of 570 healthcare professionals from cardiology, anaesthesiology and intensive care medicine departments of European university hospitals in Italy, Poland, Hungary, Belgium, Spain, Slovakia, Germany, Finland, The Netherlands, Switzerland, France and Greece completed a questionnaire. The questionnaire consisted of 12 questions based on epidemiology data and cardiopulmonary resuscitation training and 26 multiple choice questions on cardiopulmonary resuscitation knowledge. Hospitals in Switzerland scored highest on basic life support ( P=0.005) while Belgium hospitals scored highest on advanced life support ( PConclusion: Differences in knowledge about resuscitation and course attendance were found between university hospitals in 12 European countries. Education in cardiopulmonary resuscitation is considered to be vital for patients’ return of spontaneous circulation rates after in-hospital cardiac arrest. A higher level of knowledge in advanced life support results in higher return of spontaneous circulation rates.

STUDY QUESTION Is the length of the anogenital distance (AGD) a biomarker of ovarian reserve and response to controlled ovarian stimulation (COS)? SUMMARY ANSWER Shorter AGD is associated with presence of poor ovarian response. WHAT IS KNOWN ALREADY Organ development during prenatal life is influenced by the prevailing intrauterine environment, and it has been suggested that nutritional, environmental and toxic factors could affect ovarian reserve set prenatally. AGD is a biomarker of prenatal-hormonal environment and observational studies have shown an association between its length and reproductive parameters in both sexes. STUDY DESIGN, SIZE, DURATION This was a prospective cohort study of 437 women treated with IVF/ICSI conducted in a tertiary-care university hospital between January and December 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS All women underwent their first COS for IVF/ICSI and reached criteria for oocyte retrieval. Based on the number of oocytes obtained, patients were divided into three groups: poor responders (≤3 oocytes) (n = 50), normoresponders (4-15 oocytes) (n = 332) and high responders (>15 oocytes) (n = 55). Before retrieval, the following patient data were recorded: age, body mass index (BMI), ovarian reserve markers (anti-Mullerian hormone [AMH], antral follicle count [AFC] and follicular stimulation hormone [FSH]), cause of infertility, total doses of gonadotropins used and ovarian sensitivity index (OSI). Patients with previous pregnancies, polycystic ovary syndrome (PCOS), endometriosis and previous ovarian or genital surgery were excluded. Anthropometric biomarkers of AGDAC (anus-clitoris) and AGDAF (anus-fourchette) were measured in all patients under sedation on the day of retrieval and before proceeding to oocyte pick-up. Multiple linear regression analyses were used to examine the association between both AGD and ovarian reserve markers, the total units of gonadotropins used, the number of oocytes obtained and the OSI. Logistic regression was used to predict poor response in COS for IVF/ICSI, while accounting for confounders such as age and BMI. MAIN RESULTS AND THE ROLE OF CHANCE Baseline FSH, AMH, AFC and age were significantly different among the three groups of ovarian response, as were the units of gonadotropin used, and the ovarian sensitivity index (OSI) (P < 0.001). Both AGDAC and AGDAF measurements were positively correlated with AMH levels (r = 0.38 and r = 0.21; P < 0.05), AFC (r = 0.41 and r = 0.20; P < 0.05), the OSI (r = 0.24 and r = 0.19; P < 0.05) and the number of oocytes retrieved (r = 0.29 and r = 0.28, respectively; P < 0.05). Conversely, there was a negative correlation between both AGD measurements and the doses of gonadotropins used (r= -0.19 and r= -0.15; P < 0.05). The area under the curve (AUC) for prediction of poor response of AGDAC was 0.70 (95% CI 0.66, 0.75), which was comparable to the classic ovarian reserve markers, such as AFC and AMH. AGDAF showed a significantly worse predictive capacity for poor ovarian response (AUC 0.60 [95% CI 0.55, 0.60]) than AMH and AFC. LIMITATIONS, REASONS FOR CAUTION The population used for the study was a highly selected group of infertile women who underwent COS for IVF, so the findings of this research may not be applicable for general population. Besides, measurement or selection biases might have been possible and must be considered. WIDER IMPLICATIONS OF THE FINDINGS The findings of this study suggest that in utero exposure to certain hormonal environments could affect the ovarian reserve set prenatally. STUDY FUNDING/COMPETING INTEREST(S) None. The authors have no competing interests to declare.

STUDY QUESTION Are the levels of circulating cell-derived microparticles (cMPs) in patients with recurrent miscarriage (RM) associated with the antiphospholipid syndrome (APS)? SUMMARY ANSWER cMPs in women with RM are not associated with antiphospholipid antibodies (aPLs). WHAT IS KNOWN ALREADY Previous studies have focused on cMP levels in RM patients. Most studies have shown higher levels of cMPs in RM patients whereas others have reported lower levels. Data regarding cMPs in patients with the APS are scanty in the literature. STUDY DESIGN, SIZE, DURATION A case-control study including three groups of patients. A total of 154 women were prospectively recruited from September 2009 to October 2013. Four patients refused to participate. The APS group consisted of 50 women that had been previously diagnosed with primary APS and had had ≥3 consecutive first trimester miscarriages. The uRM group included 52 couples with ≥3 consecutive first trimester miscarriages of unknown etiology. The fertile control (FER) group was composed of 52 healthy fertile women with no history of pregnancy losses. Miscarriage was defined as intrauterine pregnancy loss at

The study of biomarkers of dietary patterns including the Mediterranean diet (MedDiet) is scarce and could improve the assessment of these patterns. Moreover, it could provide a better understanding of health benefits of dietary patterns in nutritional epidemiology. We aimed to determine a robust and accurate biomarker associated with a high adherence to a MedDiet pattern that included dietary assessment and its biological effect. In this cross-sectional study, we included 56 and 63 individuals with high (H-MDA) and low (L-MDA) MedDiet adherence categories, respectively, all from the Prevencion con Dieta Mediterranea trial. A 1H-NMR-based untargeted metabolomics approach was applied to urine samples. Multivariate statistical analyses were conducted to determine the metabolite differences between groups. A stepwise logistic regression and receiver operating characteristic curves were used to build and evaluate the prediction model for H-MDA. Thirty-four metabolites were identified as discriminant between H-MDA and L-MDA. The fingerprint associated with H-MDA included higher excretion of proline betaine and phenylacetylglutamine, among others, and decreased amounts of metabolites related to glucose metabolism. Three microbial metabolites - phenylacetylglutamine, p-cresol and 4-hydroxyphenylacetate - were included in the prediction model of H-MDA (95% specificity, 95% sensitivity and 97% area under the curve). The model composed of microbial metabolites was the biomarker that defined high adherence to a Mediterranean dietary pattern. The overall metabolite profiling identified reflects the metabolic modulation produced by H-MDA. The proposed biomarker may be a better tool for assessing and aiding nutritional epidemiology in future associations between H-MDA and the prevention or amelioration of chronic diseases.

Summary Aim To assess the evolution of occupational asthma (OA) depending on whether the patient avoids or continues with exposure to the offending agent. Methods Study in patients diagnosed with OA using a specific inhalation challenge. Patients underwent the following examinations on the same day: clinical interview, physical examination, forced spirometry, methacholine test and determination of total IgE. Clinical improvement, deterioration or no change were defined according to the changes seen on the GINA severity scale at the time of diagnosis. Results Of the 73 patients finally included, 55 had totally ended exposure and 18 continued to be exposed at work. Clinical improvement was observed in 47% of those who had terminated exposure and in 22% of those who remained exposed; clinical deterioration was observed in 14% and 17% respectively ( p = 0.805). Logistical regression analysis, including the type of agent and the persistence or avoidance of exposure among the variables, did not show any predictive factors of clinical evolution. Similarly, the changes in FEV 1 and in bronchial hyperresponsiveness were not associated with the avoidance or continuation of exposure to the causative agent. Conclusions Avoiding exposure to the causative agent in patients with OA does not seem to improve prognosis in this disease. Despite these findings, there is insufficient evidence to recommend a change in current management guidelines.

Study Objective The objective of this study is to analyze the ultrasound findings in patients referred to an endometriosis unit with and without previous endometriosis surgeries over one-year period. Design Retrospective study including 430 patients who had a first visit and an ultrasound scan at an endometriosis referral unit from January to December 2018. Information about surgical history and ultrasound findings was collected. Setting Endometriosis referral unit in a tertiary hospital in Barcelona, Spain. Patients or Participants 430 patients referred to the endometriosis unit were included. Interventions Ultrasound scan was performed according to the protocol stablished in this unit. Measurements and Main Results 177 patients (41.2%) had a previous history of endometriosis surgery. 72.9% of them had one previous surgery and 14.7% had two whereas 12.4% had three or more. Laparoscopy was the main route, which was used in 74.6% of them. The main procedures were endometrioma decapsulation (45.6%) followed by adnexal surgery (19.8%) and deep infiltrating endometriosis nodule excision (16%). Only 2.7% of patients had a previous bowel resection. When comparing the ultrasound findings between patients who have a previous endometriosis surgery with those without, statistically significant differences were found in the presence of ovarian adhesions, ovarian endometriomas, presence of intestinal endometriotic nodules and Douglas-blockage. Conclusion More than 40% of patients referred to the endometriosis unit had had a previous surgery. They had a higher rate of presence of intestinal endometriotic nodules among other ultrasound findings. Thus, it reinforces the need of referral units in order to establish a precise treatment either medical or surgical with high-skilled surgeons.

Objective This study compares the patterns of visceral (VIS) and subcutaneous (SC) adipose tissue (AT)-derived metabolites from non-obese (BMI 24-26 kg/m2) and obese subjects (BMI > 40 kg/m2) with no major metabolic risk factors other than BMI. Methods SC- and VIS- AT obtained from obese (Ob) and non-obese (NOb) subjects during surgery were incubated to obtain their metabolites. Differences related to obesity or anatomical provenances of AT were assessed using an untargeted metabolomics approach based on gas chromatography-mass spectrometry. Results The overall effect of obesity on the metabolite profile resulted more remarkable than the effect of regional AT. Only the depletion of 2-ketoisocaproic (2-KIC) acid reached statistical significance for the SC-AT alone, although it was observed in both depots. Obesity induced more significant changes in several amino acids levels of the VIS-AT metabolites. On the one hand, higher released levels of glutamine and alanine were detected in the VIS- obese AT, whereas on the other, the VIS- obese AT presented a diminished uptake of essential amino acids (methionine, threonine, lysine), BCAAs, leucine, and serine. Conclusion This study shows that obesity markedly affects the amino acid metabolic signature of the AT before the clinical onset of other significant metabolic alterations aside from BMI.

Sentinel lymph node biopsy (SLNB) can be used for nodal staging in early cervical cancer. For this purpose, the tracers most commonly used are radiotracers based on technetium. For the last decade, indocyanine green (ICG) has been used as a tracer for SLNB in other malignancies with excellent results and, more recently, a combination of ICG and a radiotracer has been shown to have the advantages of both tracers. The aim of this study was to evaluate the role of ICG-This prospective study included 16 patients with cervical cancer. The hybrid tracer was injected the day (19-21 h) before surgery for planar and SPECT/CT lymphoscintigraphy. Blue dye was administered periorificially in 14 patients. SLNs were removed according to their distribution on lymphoscintigraphy and when radioactive, fluorescent and/or stained with blue dye. Nodal specimens were pathologically analysed for metastases including by immunochemistry.Lymphoscintigraphy and SPECT/CT showed drainage in all patients. A total of 69 SLNs were removed, of which 66 were detected by their radioactivity signal and 67 by their fluorescence signal. Blue dye identified only 35 SLNs in 12 of the 14 patients (85.7%). All patients showed bilateral pelvic drainage. Micrometastases were diagnosed in two patients, and were the only lymphatic nodes involved.SLNB with ICG

Methylation is a regulatory mechanism known to be associated with tumour initiation and progression. Finding genes regulated by methylation is a first step to develop therapies that target these genes, for instance to inhibit tumor development. This study addresses this problem by comparing two methods, one based on mutual information, and a new one based on clustering the coefficients of fitted curves. The methods are tested on a Cancer Colon study and the biological analysis of the resulting lists suggests that at least some of the genes selected are indeed genes regulated by methylation, opening the door to an automatic mining method.

The study of biomarkers of dietary patterns including the Mediterranean diet (MedDiet) is scarce and could improve the assessment of these patterns. Moreover, it could provide a better understanding of health benefits of dietary patterns in nutritional epidemiology. We aimed to determine a robust and accurate biomarker associated with a high adherence to a MedDiet pattern that included dietary assessment and its biological effect. In this cross-sectional study, we included 56 and 63 individuals with high (H-MDA) and low (L-MDA) MedDiet adherence categories, respectively, all from the Prevención con Dieta Mediterránea trial. A