Search

Abstract Purpose The present study aimed at assessing the prevalences of post-traumatic stress disorder (PTSD) (main objective), anxiety, depression, and burnout syndrome (BOS) and their associated factors in intensive care unit (ICU) staff workers in the second year of the COVID-19 pandemic. Materials and methods An international cross-sectional multicenter ICU-based online survey was carried out among the ICU staff workers in 20 ICUs across 3 continents. ICUs staff workers (both caregivers and non-caregivers) were invited to complete PCL-5, HADS, and MBI questionnaires for assessing PTSD, anxiety, depression, and the different components of BOS, respectively. A personal questionnaire was used to isolate independent associated factors with these disorders. Results PCL-5, HADS, and MBI questionnaires were completed by 585, 570, and 539 responders, respectively (525 completed all questionnaires). PTSD was diagnosed in 98/585 responders (16.8%). Changing familial environment, being a non-caregiver staff worker, having not being involved in a COVID-19 patient admission, having not been provided with COVID-19-related information were associated with PTSD. Anxiety was reported in 130/570 responders (22.8%). Working in a public hospital, being a woman, being financially impacted, being a non-clinical healthcare staff member, having no theoretical or practical training on individual preventive measures, and fear of managing COVID-19 patients were associated with anxiety. Depression was reported in 50/570 responders (8.8%). Comorbidity at risk of severe COVID-19, working in a public hospital, looking after a child, being a non-caregiver staff member, having no information, and a request for moving from the unit were associated with depression. Having received no information and no adequate training for COVID-19 patient management were associated with all 3 dimensions of BOS. Conclusion The present study confirmed that ICU staff workers, whether they treated COVID-19 patients or not, have a substantial prevalence of psychological disorders.

Abstract A recurring issue with microstructure studies is specimen lighting. In particular, microscope lighting must be deployed in such a way as to highlight biological elements without enhancing caustic effects and diffraction. We describe here a high frequency technique due to address this lighting issue. First, an extensive study is undertaken concerning asymptotic equations in order to identify the most promising algorithm for 3D microstructure analysis. Ultimately, models based on virtual light rays are discarded in favor of a model that considers the joint computation of phase and irradiance. This paper maintains the essential goal of the study concerning biological microstructures but offers several supplementary notes on computational details which provide perspectives on analyses of the arrangements of numerous objects in biological tissues.

Background: Cephalosporins are the cornerstone of cardiac device infection prophylaxis. Owing to fears of cross-reactivity, penicillin-allergic patients are exposed to potentially more-toxic drugs, with decreased efficacy. We evaluated the safety of a cefazolin test dose (CTD) in self-reported penicillin-allergic patients. Methods: In this single-centre study, we evaluated consecutive patients with chart documentation of penicillin allergy undergoing cardiac device implantation, over a 2-year period. A CTD was performed if no cephalosporin allergy or severe anaphylactic reaction to penicillin had been documented. Patients were given 2 doses of 100 mg IV cefazolin, and if no allergic reaction occurred after 5 minutes, the full dose (1800 mg) was administered in the electrophysiology laboratory just before the implantation procedure. Results: A total of 2200 patients were included. The frequency of reported penicillin allergy was 9.3% (n = 204). In 80% of cases, the type of allergic reaction was not reported in medical notes or was unknown by the patient. A CTD was performed in 67.6% of patients with a penicillin allergy (n = 138). A total of 5 adverse events occurred (3.6% of patients [95% confidence interval, 1.1%-6.1%]) — 4 skin rashes and 1 tongue edema. These 5 patients became asymptomatic after antihistaminic and corticosteroid IV treatment. Even if the test dose was negative, 79% of patients also were administered vancomycin before the procedure, as it requires a 1-hour infusion prior to the CTD in the implantation procedure room. Conclusion: A CTD in most penicillin-allergic patients appears to be safe and allows its use per recommended guidelines. Résumé: Contexte: Les céphalosporines sont la pierre angulaire de la prophylaxie des infections des dispositifs cardiaques. En raison du risque appréhendé de réactivité croisée, les patients allergiques à la pénicilline se trouvent exposés à des médicaments potentiellement plus toxiques, qui s’avèrent aussi moins efficaces. Nous avons évalué l’innocuité d’une dose d’essai de céfazoline chez des patients qui s’étaient dits allergiques à la pénicilline. Méthodologie: Dans cette étude monocentrique, nous avons suivi pendant deux ans des patients consécutifs dont le dossier médical faisait état d’une allergie à la pénicilline et chez qui un dispositif cardiaque devait être implanté. Une dose d’essai de céfazoline a été administrée aux patients sans antécédents documentés d’allergie aux céphalosporines ou de réaction anaphylactique sévère à la pénicilline. Deux doses de 100 mg de céfazoline ont été administrées par voie intraveineuse. En l’absence de réaction allergique après cinq minutes, les patients recevaient la dose complète (1 800 mg) au laboratoire d’électrophysiologie juste avant l’implantation du dispositif cardiaque. Résultats: Au total, 2 200 patients ont été inscrits à l’étude. Le taux de signalement de l’allergie à la pénicilline était de 9,3 % (n = 204). Dans 80 % des cas, le type de réaction allergique n’a pas été précisé dans les notes médicales ou était inconnu du patient. Une dose d’essai de céfazoline a été administrée à 67,6 % des patients allergiques à la pénicilline (n = 138). Au total, cinq événements indésirables se sont produits (3,6 % des patients [intervalle de confiance à 95 % : 1,1-6,1 %]) – quatre éruptions cutanées et un œdème de la langue. Les cinq patients touchés par ces événements sont devenus asymptomatiques après avoir reçu un antihistaminique et un corticostéroïde par voie intraveineuse. Même en l’absence de réaction allergique à la dose d’essai, 79 % des patients ont reçu de la vancomycine avant l’intervention, cet agent devant être administré par perfusion durant une heure avant la dose d’essai de céfazoline dans la salle d’intervention. Conclusion: Chez la plupart des patients allergiques à la pénicilline, une dose d’essai de céfazoline semble sans danger et permet d’avoir recours à ce médicament conformément aux lignes directrices.

Summary: Background: Preoperative COVID-19 has been associated with excess postoperative morbi-mortality. Consequently, guidelines were developed that recommended the postponement of surgery for at least 7 weeks after the infection. We hypothesised that vaccination against the SARS-CoV-2 and the large predominance of the Omicron variant attenuated the effect of a preoperative COVID-19 on the occurrence of postoperative respiratory morbidity. Methods: We conducted a prospective cohort study in 41 French centres between 15 March and 30 May 2022 (ClinicalTrials NCT05336110), aimed at comparing the postoperative respiratory morbidity between patients with and without preoperative COVID-19 within 8 weeks prior to surgery. The primary outcome was a composite outcome combining the occurrence of pneumonia, acute respiratory failure, unexpected mechanical ventilation, and pulmonary embolism within the first 30 postoperative days. Secondary outcomes were 30-day mortality, hospital length-of-stay, readmissions, and non-respiratory infections. The sample size was determined to have 90% power to identify a doubling of the primary outcome rate. Adjusted analyses were performed using propensity score modelling and inverse probability weighting. Findings: Of the 4928 patients assessed for the primary outcome, of whom 92.4% were vaccinated against the SARS-CoV-2, 705 had preoperative COVID-19. The primary outcome was reported in 140 (2.8%) patients. An 8-week preoperative COVID-19 was not associated with increased postoperative respiratory morbidity (odds ratio 1.08 [95% CI 0.48–2.13]; p = 0.83). None of the secondary outcomes differed between the two groups. Sensitivity analyses concerning the timing between COVID-19 and surgery, and the clinical presentations of preoperative COVID-19 did not show any association with the primary outcome, except for COVID-19 patients with ongoing symptoms the day of surgery (OR 4.29 [1.02–15.8]; p = 0.04). Interpretation: In our Omicron-predominant, highly immunised population undergoing general surgery, a preoperative COVID-19 was not associated with increased postoperative respiratory morbidity. Funding: The study was fully funded by the French Society of Anaesthesiology and Intensive Care Medicine (SFAR).

Introduction Dipeptidyl peptidase-3 (DPP3) is a protease involved in the degradation of several cardiovascular mediators. Adrenomedullin (bio-ADM) is a peptide essential for regulation of endothelial barrier function. In different shock-pathologies, both biomarkers are associated with disease severity, organ dysfunction and mortality. Associations with outcome in critically ill COVID-19 patients are unknown. The objectives of the present study were to investigate associations of bio-ADM and “circulating DPP3” (cDPP3) with short-term outcome in critically ill COVID-19 patients (n=80). Methods A multicentre prospective cohort study was performed. The primary end-point was 28-day mortality. Secondary end-points included different severities of acute kidney injury (AKI). Results cDPP3 levels were mainly associated with 28-day mortality; Area under the receiver operating characteristics (AUROCs) of 0.69 (0.56–0.82, p=0.023), 0.77 (0.64–0.90, p

IntroductionWe sought to develop a novel method for a fully automated, robust quantification of protein biomarker expression within the epithelial component of high-grade serous ovarian tumors (HGSOC). Rather than defining thresholds for a given biomarker, the objective of this study in a small cohort of patients was to develop a method applicable to the many clinical situations in which immunomarkers need to be quantified. We aimed to quantify biomarker expression by correlating it with the heterogeneity of staining, using a non-subjective choice of scoring thresholds based on classical mathematical approaches. This could lead to a universal method for quantifying other immunohistochemical markers to guide pathologists in therapeutic decision-making.MethodsWe studied a cohort of 25 cases of HGSOC for which three biomarkers predictive of the response observed ex vivo to the BH3 mimetic molecule ABT-737 had been previously validated by a pathologist. We calibrated our algorithms using Stereology analyses performed by two experts to detect immunohistochemical staining and epithelial/stromal compartments. Immunostaining quantification within Stereology grids of hexagons was then performed for each histological slice. To define thresholds from the staining distribution histograms and to classify staining within each hexagon as low, medium, or high, we used the Gaussian Mixture Model (GMM).ResultsStereology analysis of this calibration process produced a good correlation between the experts for both epithelium and immunostaining detection. There was also a good correlation between the experts and image processing. Image processing clearly revealed the respective proportions of low, medium, and high areas in a single tumor and showed that this parameter of heterogeneity could be included in a composite score, thus decreasing the level of discrepancy. Therefore, agreement with the pathologist was increased by taking heterogeneity into account.Conclusion and discussionThis simple, robust, calibrated method using basic tools and known parameters can be used to quantify and characterize the expression of protein biomarkers within the different tumor compartments. It is based on known mathematical thresholds and takes the intratumoral heterogeneity of staining into account. Although some discrepancies need to be diminished, correlation with the pathologist’s classification was satisfactory. The method is replicable and can be used to analyze other biological and medical issues. This non-subjective technique for assessing protein biomarker expression uses a fully automated choice of thresholds (GMM) and defined composite scores that take the intra-tumor heterogeneity of immunostaining into account. It could help to avoid the misclassification of patients and its subsequent negative impact on therapeutic care.

Objectives: This study aimed to evaluate the performance of FilmArray Pneumonia Panel Plus (FA-PP) for the detection of typical bacterial pathogens in respiratory samples from patients hospitalized in intensive care units (ICUs). Methods: FA-PP was implemented for clinical use in the microbiology laboratory in March 2020. A retrospective analysis on a consecutive cohort of adult patients hospitalized in ICUs between March 2020 and May 2020 was undertaken. The respiratory samples included sputum, blind bronchoalveolar lavage (BBAL) and protected specimen brush (PSB). Conventional culture and FA-PP were performed in parallel. Results: In total, 147 samples from 92 patients were analysed; 88% had coronavirus disease 2019 (COVID-19). At least one pathogen was detected in 46% (68/147) of samples by FA-PP and 39% (57/147) of samples by culture. The overall percentage agreement between FA-PP and culture results was 98% (93–100%). Bacteria with semi-quantitative FA-PP results ≥105 copies/mL for PSB samples, ≥106 copies/mL for BBAL samples and ≥107 copies/mL for sputum samples reached clinically significant thresholds for growth in 90%, 100% and 91% of cultures, respectively. FA-PP detected resistance markers, including mecA/C, blaCTX-M and blaVIM. The median turnaround time was significantly shorter for FA-PP than for culture. Conclusions: FA-PP may constitute a faster approach to the diagnosis of bacterial pneumonia in patients hospitalized in ICUs.

Abstract Intranuclear birefringent inclusions (IBI) found in various cell types in paraffin-embedded tissue sections have long been considered to be a tissue processing artifact, although an association with biological processes has been suggested. We applied polychromatic polarization microscopy to image their spatial organization. Our study provides evidence that IBI are caused by liquid paraffin-macromolecular crystals formed during paraffin-embedding procedures within cells and potentially reflect an active transcriptional status.

Abstract Chemogenomics, also called proteochemometrics, covers a range of computational methods that can be used to predict protein–ligand interactions at large scales in the protein and chemical spaces. They differ from more classical ligand-based methods (also called QSAR) that predict ligands for a given protein receptor. In the context of drug discovery process, chemogenomics allows to tackle the question of predicting off-target proteins for drug candidates, one of the main causes of undesirable side-effects and failure within drugs development processes. The present study compares shallow and deep machine-learning approaches for chemogenomics, and explores data augmentation techniques for deep learning algorithms in chemogenomics. Shallow machine-learning algorithms rely on expert-based chemical and protein descriptors, while recent developments in deep learning algorithms enable to learn abstract numerical representations of molecular graphs and protein sequences, in order to optimise the performance of the prediction task. We first propose a formulation of chemogenomics with deep learning, called the chemogenomic neural network (CN), as a feed-forward neural network taking as input the combination of molecule and protein representations learnt by molecular graph and protein sequence encoders. We show that, on large datasets, the deep learning CN model outperforms state-of-the-art shallow methods, and competes with deep methods with expert-based descriptors. However, on small datasets, shallow methods present better prediction performance than deep learning methods. Then, we evaluate data augmentation techniques, namely multi-view and transfer learning, to improve the prediction performance of the chemogenomic neural network. We conclude that a promising research direction is to integrate heterogeneous sources of data such as auxiliary tasks for which large datasets are available, or independently, multiple molecule and protein attribute views.

Cytochrome P450 2D6 (CYP2D6) gene polymorphisms influence the exposure to tramadol (T) and its pharmacologically active metabolite, O-demethyl tramadol (O-dT). Tramadol has been considered as a candidate probe drug for CYP2D6 phenotyping. The objective of the CYTRAM study was to investigate the value of plasma O-dT/T ratio for CYP2D6 phenotyping. European adult patients who received IV tramadol after surgery were included. CYP2D6 genotyping was performed and subjects were classified as extensive (EM), intermediate (IM), poor (PM), or ultra-rapid (UM) CYP2D6 metabolizers. Plasma concentrations of tramadol and O-dT were determined at 24 h and 48 h. The relationship between O-dT/T ratio and CYP2D6 phenotype was examined in both a learning and a validation group. Genotype data were obtained in 301 patients, including 23 PM (8%), 117 IM (39%), 154 EM (51%), and 7 UM (2%). Tramadol trough concentrations at 24 h were available in 297 patients. Mean value of O-dT/T ratio was significantly lower in PM than in non-PM individuals (0.061 ± 0.031 versus 0.178 ± 0.09, p < 0.01). However, large overlap was observed in the distributions of O-dT/T ratio between groups. Statistical models based on O-dT/T ratio failed to identify CYP2D6 phenotype with acceptable sensitivity and specificity. Those results suggest that tramadol is not an adequate probe drug for CYP2D6 phenotyping.

Abstract Background Chronic treatment of hypertension or heart failure very often includes an angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) as renin-angiotensin system inhibitors (RASi) treatments. To stop or not to stop these medications before major surgery remains an unresolved issue. The lack of evidence leads to conflicting guidelines with respect to RASi management before major surgery. The purpose of this study is to evaluate the impact of a strategy of RASi continuation or discontinuation on perioperative complications in patients undergoing major non-cardiac surgery. Methods This is a multicenter, open-labeled randomized controlled trial in > 30 French centers. In the experimental group, RASi will be continued while the treatment will be stopped 48 h before the surgery in the control arm. The primary endpoint is a composite endpoint of major complications after surgery. An endpoint adjudication committee will review clinical data and adjudicate efficacy endpoints while blinded to the assigned study drug group. Main analysis will be by intention-to-treat comparing the composite outcome measure at 28 days in the two groups. A total of 2222 patients are planned to detect an absolute complications difference of 5%. Discussion The results of the trial should provide robust evidence to anesthesiologists and surgeons regarding management of RASi before major non-cardiac surgery. Trial registration ClinicalTrials.gov, NCT03374449. Registered on 11 December 2017.

La démocratie administrative n'est pas un mécanisme inutile. Par conséquent, les éléments suivants sont considérés dans cet article: référendum sur l'initiative citoyenne au niveau local, organes consultatifs au niveau local qui rassemblent les fonctionnaires au niveau local et les clients finaux, les messages issus de la démocratie administrative, etc. Il souligne que la démocratie administrative favorise la participation dans la prise de décision publique par divers professionnels et la nécessité de la présence systématique de divers participants à la discussion (associations civiles, etc.). Enfin, les inconvénients de la démocratie administrative sont également observés.

Twiddler syndrome is an uncommon yet dangerous phenomenon usually resulting in lead displacement with loss of capture of cardiac implantable electronic devices. In this case report, we present an interesting case of Twiddler syndrome without lead dislodgment which was detected by an alert triggered by an increase in impedance on remote monitoring.

Background: Apical hypertrophic cardiomyopathy (aHCM) is thought to have a more benign clinical course compared to septal HCM (sHCM), but most data have been derived from Asian cohorts. Comparative data on clinical outcome in Caucasian aHCM cohorts are scarce, and the results are conflicting. The aim of this study was to estimate the prevalence and outcome of aHCM in French-Canadians of Caucasian descent.Methods and results: We conducted a retrospective, single-center cohort study. The primary endpoint was a composite of documented sustained ventricular arrhythmia (VA), appropriate ICD therapy, arrhythmogenic syncope, cardiac arrest, or all-cause mortality. A total of 301 HCM patients (65% males) were enrolled including 80/301 (27%) with aHCM and 221/301 (73%) with sHCM. Maximal wall thickness was similar in both groups. Left ventricular apical aneurysm was significantly more common in aHCM (10 vs. 0.5%; p < 0.001). The proportion of patients with myocardial fibrosis ≥ 15% of the left ventricular mass was similar between aHCM and sHCM (21 vs. 24%; p = 0.68). Secondary prevention ICDs were more often implanted in aHCM patients (16 vs. 7%; p = 0.02). The primary endpoint occurred in 26% of aHCM and 10.4% of sHCM patients (p = 0.001) and was driven by an increased incidence of sustained VA (10 vs. 2.3%; p = 0.01). Multivariate analysis identified apical aneurysm and a phenotype of aHCM as independent predictors of the primary endpoint and the occurrence of sustained ventricular tachycardia. Unexplained syncope and a family history of sudden cardiac death were additional predictors for sustained VA. Apical HCM was associated with an increased risk of ventricular arrhythmia even when excluding patients with apical aneurysm.Conclusions: The phenotype of apical HCM is much more common in French-Canadians (27%) of Caucasian descent compared to other Caucasian HCM populations. Apical HCM in French-Canadians is associated with an increased risk for ventricular arrhythmia.

Background The axillary lymph nodes (ALNs) in breast cancer patients are the body regions to where tumoral cells most often first disseminate. The tumour immune response is important for breast cancer patient outcome, and some studies have evaluated its involvement in ALN metastasis development. Most studies have focused on the intratumoral immune response, but very few have evaluated the peritumoral immune response. The aim of the present article is to evaluate the immune infiltrates of the peritumoral area and their association with the presence of ALN metastases. Methods The concentration of 11 immune markers in the peritumoral areas was studied in 149 patients diagnosed with invasive breast carcinoma of no special type (half of whom had ALN metastasis at diagnosis) using tissue microarrays, immunohistochemistry and digital image analysis procedures. The differences in the concentration of the immune response of peritumoral areas between patients diagnosed with and without metastasis in their ALNs were evaluated. A multivariate logistic regression model was developed to identify the clinical-pathological variables and the peritumoral immune markers independently associated with having or not having ALN metastases at diagnosis. Results No statistically significant differences were found in the concentrations of the 11 immune markers between patients diagnosed with or without ALN metastases. Patients with metastases in their ALNs had a higher histological grade, more lymphovascular and perineural invasion and larger-diameter tumours. The multivariate analysis, after validation by bootstrap simulation, revealed that only tumour diameter (OR = 1.04; 95% CI [1.00–1.07]; p = 0.026), lymphovascular invasion (OR = 25.42; 95% CI [9.57–67.55]; p

Immunohistochemistry (IHC) for ER, PR, HER2, and Ki67 is used to predict outcome and therapy response in breast cancer patients. The current IHC assessment, visual or digital, is based mostly on global biomarker expression levels in the tissue sample. In our study, we explored the prognostic value of digital image analysis of conventional breast cancer IHC biomarkers supplemented with their intratumoral heterogeneity and tissue immune response indicators. Surgically excised tumor samples from 101 female patients with hormone receptor-positive breast cancer (HRBC) were stained for ER, PR, HER2, Ki67, SATB1, CD8, and scanned at 20x. Digital image analysis was performed using the HALO™ platform. Subsequently, hexagonal tiling was used to compute intratumoral heterogeneity indicators for ER, PR and Ki67 expression. Multiple Cox regression analysis revealed three independent predictors of the patient's overall survival: Haralick's texture entropy of PR (HR = 0.19, p = 0.0005), Ki67 Ashman's D bimodality (HR = 3.0, p = 0.01), and CD8+SATB1+ cell density in tumor tissue (HR = 0.32, p = 0.02). Remarkably, the PR and Ki67 intratumoral heterogeneity indicators were prognostically more informative than the rates of their expression. In particular, a distinct non-linear relationship between the rate of PR expression and its intratumoral heterogeneity was observed and revealed a non-linear prognostic effect of PR expression. The independent prognostic significance of CD8+SATB1+ cells infiltrating the tumor could indicate their role in anti-tumor immunity. In conclusion, we suggest that prognostic modeling, based entirely on the computational image-based IHC biomarkers, is possible in HRBC patients. The intratumoral heterogeneity and immune response indicators outperformed both conventional breast cancer IHC and clinicopathological variables while markedly increasing the power of the model.

Open-pit mines often generate large quantities of waste rocks that are usually stored in waste rock piles (WRPs). When the waste rocks contain reactive minerals (mainly sulfides), water and air circulation can lead to the generation of contaminated drainage. An experimental WRP was built at the Lac Tio mine (Canada) to validate a new disposal method that aims to limit water infiltration into reactive waste rocks. More specifically, a flow control layer was placed on top of the pile, which represents a typical bench level, to divert water toward the outer edge. Hydrogeological sensors and geophysical electrodes were installed for monitoring moisture distribution in the pile during infiltration events. A three-dimensional (3D) time-lapse hydrogeophysical monitoring program was conducted to assess water infiltration and movement. Readings from the 192 circular electrodes buried in the WRP were used to reconstruct the 3D bulk electrical resistivity (ER) variations over time. A significant effort was devoted to assessing the spatiotemporal evolution of water ER because the bulk ER is strongly affected by water quality (and content). The water ER was used as a tracer to monitor the infiltration and flow of resistive and conductive waters. The results indicate that the inclined surface layer efficiently diverts a large part of the added water away from the core of the pile. Local and global models of water infiltration explaining both bulk and water ER variations are proposed. The results shown here are consistent with hydrogeological data and provide additional insights to characterize the behavior of the pile.

Adverse drug reactions, also called side effects, range from mild to fatal clinical events and significantly affect the quality of care. Among other causes, side effects occur when drugs bind to proteins other than their intended target. As experimentally testing drug specificity against the entire proteome is out of reach, we investigate the application of chemogenomics approaches. We formulate the study of drug specificity as a problem of predicting interactions between drugs and proteins at the proteome scale. We build several benchmark datasets, and propose NN-MT, a multi-task Support Vector Machine (SVM) algorithm that is trained on a limited number of data points, in order to solve the computational issues or proteome-wide SVM for chemogenomics. We compare NN-MT to different state-of-the-art methods, and show that its prediction performances are similar or better, at an efficient calculation cost. Compared to its competitors, the proposed method is particularly efficient to predict (protein, ligand) interactions in the difficult double-orphan case, i.e. when no interactions are previously known for the protein nor for the ligand. The NN-MT algorithm appears to be a good default method providing state-of-the-art or better performances, in a wide range of prediction scenario that are considered in the present study: proteome-wide prediction, protein family prediction, test (protein, ligand) pairs dissimilar to pairs in the train set, and orphan cases.

Diagnosis of arrhythmic disorders is challenging because of their short-lasting, intermittent character. Conventional technologies of noninvasive ambulatory rhythm monitoring are limited by modest sensitivity. We present a novel form of wearable electrocardiogram (ECG) sensors providing an alternative tool for long-term rhythm monitoring with the potential of increased sensitivity to detect intermittent or subclinical arrhythmia. The objective was to assess the signal quality and R-R coverage of a wearable ECG sensor system compared to a standard 3-lead Holter. In this phase-1 trial, healthy individuals underwent 24-h simultaneous rhythm monitoring using the OMsignal system together with a 3-lead Holter recording. The OMsignal system consists of a garment (bra or shirt) with integrated sensors recording a single-lead ECG and an acquisition module for data storage and processing. Head-to-head signal quality was assessed regarding adequate P-QRS-T distinction and was performed by three electrophysiologists blinded to the recording technology. The accuracy of signal coverage was assessed using Bland-Altman analysis. Fifteen individuals underwent simultaneous 24-h recording. Signal quality and accuracy of the OMgaments was equivalent to Holter-monitoring (84% vs 93% electrophysiologists rating, p = 0.06). Signal coverage of R-R intervals showed a very close overlay between the OMsignal system and Holter signals, mean difference in heart rate of 2 5 bpm. The noise level of OMgarments was comparable to Holter recording. OMgarments provide high signal quality for adequate rhythm analysis, representing a promising novel technology for long-term non-invasive ECG monitoring.

Pathology has recently entered the era of personalized medicine. This brings new expectations for the accuracy and precision of tissue-based diagnosis, in particular, when quantification of histologic features and biomarker expression is required. While for many years traditional pathologic diagnosis has been regarded as ground truth, this concept is no longer sufficient in contemporary tissue-based biomarker research and clinical use. Another major change in pathology is brought by the advancement of virtual microscopy technology enabling digitization of microscopy slides and presenting new opportunities for digital image analysis. Computerized vision provides an immediate benefit of increased capacity (automation) and precision (reproducibility), but not necessarily the accuracy of the analysis. To achieve the benefit of accuracy, pathologists will have to assume an obligation of validation and quality assurance of the image analysis algorithms. Reference values are needed to measure and control the accuracy. Although pathologists' consensus values are commonly used to validate these tools, we argue that the ground truth can be best achieved by stereology methods, estimating the same variable as an algorithm is intended to do. Proper adoption of the new technology will require a new quantitative mentality in pathology. In order to see a complete and sharp picture of a disease, pathologists will need to learn to use both their analogue and digital eyes.

Discrepancies concerning the prognostic significance of cancer vascularization can be partly explained by biases due to quantification protocols. We recently recommended a swift, inexpensive and automatic analysis of 2,700 dpi slide scanner images of the whole immunostained sections. Another team, proposed, quite at the same time, to work at 4,000 dpi. The aim of the present paper is to check if information contained in images scanned at 2,700 and 4,000 dpi are relevant and equivalent, when compared to the low magnification of the microscope, in order to propose the best compromise between precision and time expense. To evaluate precisely the amount of information gained or lost according to the resolution used, we compared the number and size of blood vessel profiles, manually detected, on twenty one Hodgkin lymphoma acquired with a scanner (2,700 and 4,000 dpi) and with a microscope (16,000 dpi). Results obtained at 4,000 dpi were equivalent to the estimation performed at microscopical level either by a biologist or a pathologist, while tiny vessels were lost at 2,700 dpi. Scanning whole histological sections at 4,000 dpi provides a relevant method for evaluating tumour vascularization, which can be easily automated and standardized.

Ventriculostomy-related infection (VRI) is a serious complication of external ventricular drain (EVD) but its natural history is poorly studied. We prospectively tracked the bacteria pathways from skin towards ventricles to identify the infectious process resulting in ventriculostomy-related colonization (VRC), and VRI. We systematically sampled cerebrospinal fluid (CSF) on a daily basis and collected swabs from both the skin and stopcock every 3.0 days for microbiological analysis including in 101 neurosurgical patient. Risk factors for positive event defined as either VRC or VRI were recorded and related to our microbiological findings. A total of 1261 CSF samples, 473 skin swabs, and 450 stopcock swabs were collected. Skin site was more frequently colonized than stopcock (70 (60%) vs 34 (29%), p = 0.023), and earlier (14 ±1.4 vs 24 ±1.5 days, p

Relative abundance of tumour angiogenesis has been shown to be of clinical relevance in cancers of various locations such as the ovary. Nevertheless, several problems are encountered when quantifying tumour microvessels: (i) as many other tumour markers, vascularity pattern is often heterogeneous within the tumour mass and even within the same histological section. As a consequence, an adequate acquisition method must be developed for accurate field sampling. (ii) Manual microvessel counting is long, tedious and subject to poor reproducibility. Introduction in routine practice requires a fast, reproducible and reliable automatic image processing. In this study we present an original procedure combining a slide scanner image acquisition and a fully automatic image analysis sequence. The slide scanner offers the advantage of recording an image of the whole histological section for subsequent automatic blood vessel detection and hot spot area location. Microvessel density and surface fraction were measured for the whole section as well as within hot spots. Different immunostaining methods were tested in order to optimise the procedure. Moreover, the method proposed was submitted to a quality control procedure, with reference to interactive identification of microvessels at scanner level. This experiment showed that 93 to 97% of blood vessels were detected, according to the staining protocol used. Colour figures can be viewed on http://www.esacp.org/acp/2003/25‐2/kim.htm.

Hadamard transform atmospheric pressure ion mobility-MS and rapid UHPLC-MS methods were investigated for analysis of closely related isomeric flavonoids and their glycosides using a test set of seven standards. On a time scale of a few minutes, the flavonoid aglycones were all separated by ion mobility, but not by UHPLC. The glycosides were better resolved by IMS but not completely separated by both methods. The results suggest that IMS provides sufficient resolution for separation of isomeric polyphenols such as flavonoids in high-throughput metabolomics studies.

The aim of the present study is to propose alternative automatic methods to time consuming interactive sorting of elements for DNA ploidy measurements. One archival brain tumour and two archival breast carcinoma were studied, corresponding to 7120 elements (3764 nuclei, 3356 debris and aggregates). Three automatic classification methods were tested to eliminate debris and aggregates from DNA ploidy measurements (mathematical morphology (MM), multiparametric analysis (MA) and neural network (NN)). Performances were evaluated by reference to interactive sorting. The results obtained for the three methods concerning the percentage of debris and aggregates automatically removed reach 63, 75 and 85% for MM, MA and NN methods, respectively, with false positive rates of 6, 21 and 25%. Information about DNA ploidy abnormalities were globally preserved after automatic elimination of debris and aggregates by MM and MA methods as opposed to NN method, showing that automatic classification methods can offer alternatives to tedious interactive elimination of debris and aggregates, for DNA ploidy measurements of archival tumours.