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Dietary shifts replacing animal protein (AP) with plant protein (PP) sources have been associated with lowering cardiometabolic risk (CMR), but underlying mechanisms are poorly characterized. This nutritional intervention aims to characterize the metabolic changes induced by diets containing different proportions of AP and PP sources in males at CMR. This study is a 4-week, crossover, randomized, controlled-feeding trial in which 19 males with CMR followed two diets providing either 36 % for the control diet (CON-D) or 64 % for the flexitarian diet (FLEX-D) of total protein intake from PP sources. Plasma nontargeted metabolomes (LC-MS method) were measured in the fasted state and after a high-fat challenge meal at the end of each intervention arm. Lipogenesis and protein synthesis fluxes, flow-mediated dilatation (FMD) and gluco-lipidic responses were assessed after the challenge meal. Data were analyzed with mixed models, and univariate and multivariate models for metabolomics data. In both arms CMR improved with time, with decreased body weight (−0.9 %), insulin resistant (−34 %, HOMA-IR, Homeostatic Model Assessment for Insulin Resistance) and low-density lipoproteins (LDL)-cholesterol (−11 %). Diet had no effect on FMD or metabolic fluxes, but a trend (0.05 < p ≤ 0.1) was observed for a stronger decrease in HOMA-IR and lower postprandial glucose after FLEX-D vs CON-D. The abundance of 21 and 37 metabolites differed between diets at fasted and fed states, respectively, including food intake biomarkers of AP (methylhistidine, eicosapentaenoic acid, hydroxyprolines) and PP sources (trigonelline, N-acetyl-ornithine). In fasted or fed states, indole acrylic acid and indole propionic acid, both products of tryptophan catabolism, were higher after FLEX-D vs CON-D, while the indispensable amino acids-related metabolites alpha-aminoadipic acid, hydroxymethylbutyric acids and propionylcarnitine were lower. In the postprandial state only, the ω-oxidation products dodecanedioic, tetradecanedioic and hexadecanedioic acids were higher after FLEX-D vs CON-D. Despite little changes in risk factors after 4 wk, this study evidenced subtle metabolic adaptations in amino acids and lipid metabolism and gut microbiota activity occurring after higher PP source intake that may be beneficial to CMR. NCT04236518. NCT04236518 on ClinicalTrials.gov. [ABSTRACT FROM AUTHOR]

Malnutrition can develop in patients with obesity suffering from acute or chronic illness or after obesity surgery, promoting sarcopenic obesity. A better understanding of this pathophysiology and the development of new therapeutics for chronic diseases, that are often complicated with malnutrition and obesity, justify the development of new animal experimental models close to the human physiology. This study aims to characterize the effects of obesity and underfeeding on Yucatan obese minipigs, assessing its validity as a preclinical model for obesity-related malnutrition. Sixteen 30-month-old Yucatan minipigs were divided into two groups for 8 weeks: a standard diet group (ST, n = 5) and an obesogenic diet group (OB, n = 11). After 8 weeks, the OB group was further divided into two sub-groups: a standard diet group (OB-ST, n = 5) and a low-calorie/low-protein diet group (OB-LC/LP, n = 6) for 8 weeks. Body composition by CT-Scan and blood parameters were monitored, and trapezius muscle biopsies were collected to analyse signaling pathways involved in protein turnover and energy metabolism. At W8, OB-ST animals exhibited significantly higher body weight (+37.7%, p = 0.03), muscle mass (+24.9%, p = 0.02), and visceral fat (+192.0%, p = 0.03) compared to ST. Trapezius cross sectional area (CSA) normalized to body weight was lower in OB-ST animals (−15.02%, p = 0.017). At W16, no significant changes were observed in protein turnover markers, although REDD1 increased in OB-ST (96.4%, p = 0.02). After 8 weeks of low-caloric/low protein diet, OB-LC/LP showed decreased body weight (−9.8%, p = 0.03), muscle mass (−6.5%, p = 0.03), and visceral fat (−41.5%, p = 0.03) compared to OB-ST animals. Trapezius fiber CSA significantly decreased in OB-LC/LP (−36.1%, p < 0.0001) and normalized to body weight (−25.4%, p < 0.0001), combined to higher ubiquitinated protein content (+38.3%, p = 0.02). Our data support that the Yucatan minipig model mimics nutritional and skeletal muscle phenotypes observed in obese patients, with or without protein-energy malnutrition. It also reproduces muscle atrophy observed in chronic diseases or post-obesity surgery, making it a promising preclinical model for obesity-related malnutrition. [ABSTRACT FROM AUTHOR]

• 73 circulating microRNAs at first trimester of pregnancy were associated with PE. • Five miRNAs were replicated in an independent prospective birth cohort. • Plasma miR-194-5p and miR-1278 are less abundant at first trimester in PE cases. • Combining miR-194-5p, miR-1278 and PE classic risk factors improved PE prediction. To identify first trimester circulating microRNAs associated with preeclampsia (PE) and assess their predictive value in two independent cohorts Circulating microRNAs were quantified from plasma samples collected at first trimester of pregnancy in women from Gen3G (discovery; N = 385 normotensives/22 PE) and 3D (replication; N = 260 normotensives/24 PE) prospective birth cohorts. MicroRNAs associated with PE in Gen3G were identified using DESeq2 (p-value ≤ 0.05). Replicated microRNAs (selection criteria: p-value ≤ 0.05 in Gen3G, same direction of association, nominal one-side p-value ≤ 0.1 in 3D) were included in a stepwise logistic regression model to assess their predictive values alone and in combination with PE risk factors. Seventy-three circulating microRNAs were associated with PE (p-value ≤ 0.05) in Gen3G. Five microRNAs were replicated in 3D and included in a stepwise logistic regression model with PE clinical risk factors (maternal age, body mass index and mean arterial pressure (MAP) at first trimester, parity, and smoking status) and gestational age at first visit. The best model included miR-194-5p, miR-1278, maternal age, MAP at first trimester and parity and results in an area under the curve (AUC) of 0.861 [CI 95 %: 0.787–0.935] in Gen3G. Compared to risk factors only, the addition of microRNAs improves the AUC (from 0.826 to 0.861; p = 0.03). In 3D, the best model reached an AUC of 0.842 [CI 95 %: 0.769–0.914]. Circulating miR-194-5p and miR-1278 enhance early detection of women at risk of PE and offer great potential as predictors of PE in combination with classic risk factors. [ABSTRACT FROM AUTHOR]

Colon adenocarcinoma mainly occurs in older patients. Oxaliplatin-based adjuvant chemotherapy improved disease-free survival after stage III colon cancer resection, but this improvement was not demonstrated in older patients. The purpose of ADAGE-PRODIGE 34, randomized open phase III trial is to compare in patients over 70 years oxaliplatin plus fluoropyrimidine with fluoropyrimidine alone in fit patients (Group 1) and fluoropyrimidine with observation in frail patients (Group 2) after resection of stage III colon adenocarcinoma. We report a preliminary tolerance analysis on 50% of the first patients enrolled. The analysis was conducted on 491 patients (378 in Group 1 and 113 in Group 2). Patients in Group 2 were older and showed more frailty criteria than those in Group 1. Cumulative grade 3–5 toxicities were more frequent in patients treated with oxaliplatin in Group 1 or with fluoropyrimidine in Group 2 than in patients treated with fluoropyrimidine in Group 1. At least one course was deferred in more than half of the patients in all groups. Early treatment cessation was more frequent in Group 2. No safety concerns were raised for the continuation of accrual. The frailty criteria distribution suggests that the investigator's evaluation for group allocation was accurate. [ABSTRACT FROM AUTHOR]

In most cases, Roux-en-Y gastric bypass (RYGBP) is an efficient intervention to lose weight, change eating behavior and improve metabolic outcomes in obese patients. We hypothesized that weight loss induced by RYGBP in obese Yucatan minipigs would induce specific modifications of the gut–brain axis and neurocognitive responses to oral sucrose stimulation in relationship with food intake control. An integrative study was performed after SHAM (n = 8) or RYGBP (n = 8) surgery to disentangle the physiological, metabolic and neurocognitive mechanisms of RYGBP. BOLD fMRI responses to sucrose stimulations at different concentrations, brain mRNA expression, cecal microbiota, and plasma metabolomics were explored 4 months after surgery and integrated with WGCNA analysis. We showed that weight loss induced by RYGBP or SHAM modulated differently the frontostriatal responses to oral sucrose stimulation, suggesting a different hedonic treatment and inhibitory control related to palatable food after RYGBP. The expression of brain genes involved in the serotoninergic and cannabinoid systems were impacted by RYGBP. Cecal microbiota was deeply modified and many metabolite features were differentially increased in RYGBP. Data integration with WGCNA identified interactions between key drivers of OTUs and metabolites features linked to RYGBP. This longitudinal study in the obese minipig model illustrates with a systemic and integrative analysis the mid-term consequences of RYGBP on brain mRNA expression, cecal microbiota and plasma metabolites. We confirmed the impact of RYGBP on functional brain responses related to food reward, hedonic evaluation and inhibitory control, which are key factors for the success of anti-obesity therapy and weight loss maintenance. [ABSTRACT FROM AUTHOR]

We aimed to review current literature on the impact of Preoperative Identification (POI) of the Adamkiewicz Artery (AKA) in solid pediatric Posterior Thoracic Tumors (PTT), comprising a spectrum of neuroblastic tumors and neuroblastoma, with particular focus on Complete Macroscopic Excision (CME) and Neurologic Complications/Sequelae (NCS). A systematic review in accordance with PRISMA guidelines was undertaken. The study included reports on pediatric patients providing available data on POI of the AKA in PTT. Among 838 records screened, 33 full-texts underwent evaluation, and 8 papers were included. Among 49 tumors (N = 49 patients), 30 were neuroectodermic tumors. Spinal angiography (SA) was undertaken in four studies for 32 (65%) patients. No SA-related morbidity was recorded. Otherwise, a combination of CT and/or MRI imaging was described. The lack of detailed reporting on CT/MRI imaging, hindered a feasible detailed comparative analysis among non-SA imaging modality techniques. The overall success rate of AKA POI was 65%, 71% with SA and 33% with non-SA studies. CME was achieved in 73% of SA and 80% non-SA groups. Overall, 5 children experienced NCS, 60% of those who had dumbbell tumors. All NCS occurred in patients without successful POI of the AKA. Furthermore, no SA patient had NCS, while 33% of the non-SA sustained NCS. Successful POI of the AKA may play a key role in prevention of NCS. SA showed the utility of deploying POI, without added morbidity. Furthermore, SA appeared to have a preventive impact on NCS. SA may have a key role on CME which may also be operator dependent. [ABSTRACT FROM AUTHOR]

Single-grain OSL dating of quartz is a popular approach to OSL dating, even when incomplete bleaching is not likely to be significant. However, little testing of the accuracy of single-grain dating has been published; particularly for samples older than 50 ka. In this study, we investigate the accuracy of single-grain quartz OSL dating, when a significant number of individual grains are no longer able to accurately measure the burial dose because of saturation effects. We compare standard multi-grain OSL results with those obtained from single-grain OSL measurements for five OIS substage 5e (Eemian) samples (∼128 ka). We show that for these samples, standard multi-grain quartz dose estimation results in dose estimates in good agreement with the predicted doses (four of the five samples recover age control), but that standard frequentist single-grain dating procedures significantly underestimate the age controls, i.e. the measured to predicted dose range between 0.42 ± 0.03 and 0.84 ± 0.06, where the underestimation increases with increasing relative number of grains in saturation. Attempting to remove the inevitable bias in the dose estimation resulting from a significant number of saturated grains (by using the D c criterion) reduced the underestimation, i.e. the measured to predicted dose ratio range between 0.63 ± 0.05 and 0.94 ± 0.08, but only the sample with the smallest absorbed dose is consistent with the age control. Using Bayesian analysis ("BayLum") the ratio of measured to predicted dose range between 0.75 ± 0.07 and 1.14 ± 0.08, but only two of the five samples agree with the independent age control. Our results have implications for the evaluation of single-grain OSL dating of quartz in the 100–200 Gy natural dose range. [ABSTRACT FROM AUTHOR]

• Debt as a material transaction, a power relation and a lived experienced. • Debt bondage results from chronic debt, not employment scarcity. • Market debt and interpersonal debts may feed each other rather than substitute. • Debt as exploitation but also protection and emancipation. • Market debts may promote emancipation when they are articulated and subordinated to other forms of interdependence, which ensure the protection and recognition of debtors, and some form of equality. This paper proposes the concept of the 'socio-economy of debt' to explore the ambivalence of debt, its multiple facets and its capacity to exploit, protect or emancipate. This socio-economy of debt conceives of debt as a material transaction (defined in terms of prices, modalities of repayment, and collaterals), as well as a power relationship (inseparable from an overall set of interdependencies, protection and social differentiation) and as a social and moral experience (imbued with subjectivities, felt-obligations and also aspirations). This framework sheds a new light on the issue of "debt bondage", applied to seasonal migrants from South-India. These workers are tied to their employer through a wage advance while enjoying widened access to market debts. Paradoxically, such widened choice has reinforced their dependence on their employers and other forms of interpersonal debt. These various forms of debt, both market and interpersonal, bring about various forms of exploitation, and the dispossession of time and bodies. But these debts equally allow those workers to break with the past and imagine a new future, partially liberated not from caste hierarchies but from their local forms of expression. They offer a source of hope, confidence and courage to act. It also allows some debtors to make investments and improve their lives. Within this analytical framework, it is not the market or non-market-based quality of a debt that explain its emancipatory or alienating potential, as long argued by economic anthropology, but how a particular debt bond is articulated with other forms of interdependence and protection. [ABSTRACT FROM AUTHOR]

In the last decades, the role of microbiota–gut–brain axis has emerged in the regulation of eating behavior and in the pathophysiology of anorexia nervosa (AN) that remains poorly understood. Particularly, a gut-derived dysregulation of immune response has been proposed leading to immunoglobulins directed against appetite-regulating peptides. However, intestinal permeability in patients with anorexia nervosa has been poorly documented. In the present prospective case–control study, we thus compared intestinal permeability, appetite-regulating peptides and their reactive immunoglobulins measured in severely malnourished women with AN (n = 17; 28 [21–35] y; 14.9 [14.1–15.2] kg/m2) to healthy volunteers (HV, n = 34; 26 [23–35] y; 22.3 [20.6–23.6] kg/m2). Patients with AN exhibited an increased urinary lactulose/mannitol ratio, both in 0–5 h (0.033 [0.013–0.116]) and 5–24 h samples (0.115 [0.029–0.582]), when compared to HV (0.02 [0.008–0.045], p = 0.0074 and 0.083 [0.019–0.290], p = 0.0174, respectively), suggesting an increased intestinal permeability. Urinary excretion of sucralose and plasma zonulin were not different. The levels of plasma total ghrelin and desacyl-ghrelin were increased in patients with AN compared to HV, whereas plasma leptin concentration was decreased. In addition, αMSH remained unchanged compared to HV. Finally, we did not observe any modification of the levels of total or free αMSH, leptin or ghrelin-reactive immunoglobulin G and M, as well as for their affinity properties. Only, a weak decrease of the dissociation constant (kd) for acyl-ghrelin-reactive IgG was observed in patients with AN (p = 0.0411). In conclusion, severely malnourished patients with AN show a higher intestinal permeability than HV without evidence of an effect on appetite regulating peptides-reactive immunoglobulins. [ABSTRACT FROM AUTHOR]

Parts of Central Asia have been dominated by high dust flux since the start of the Quaternary. The resulting loess-palaeosol deposits are important archives for landscape and climate changes, but there is a lack of chronological data for the subaerial deposits of Southern Tajikistan. Our study presents a high-resolution luminescence chronology for the Khonako II section in the Khovaling region. Thirty-seven samples were collected from the first ∼8 m of the section, corresponding to the Holocene soil and the upper part of the Loess 1 (L1) unit. We applied quartz OSL dating to the coarse-silt fraction (40–63 μm) and polymineral pIRIR 200,290 dating to the very fine sand fraction (63–90 μm). The polymineral pIRIR 200,290 signal has satisfactory characteristics. The quartz dose response curve displays a non-single exponential growth above ∼100 Gy, thus, the D e values were estimated by fitting a single exponential function plus linear component to the dose response data. To assess the pIRIR 200,290 residual dose at deposition, we used the offset between our quartz and polymineral chronologies from Khonako II and equivalent doses measured on modern dust samples from Tajikistan and Uzbekistan. The resulting 9.2 ± 0.4 Gy dose was then subtracted from the pIRIR 200,290 doses for final age calculation. The quartz OSL and pIRIR ages are then generally consistent. The obtained high-resolution luminescence chronology shows that the upper part of the L1 unit accumulated during the end of marine isotope stage (MIS) 3 and through MIS 2 (39–20 ka). The average dust accumulation rates (DAR) increased from ∼31 cm ka−1 to 41 cm ka−1 between MIS 3 and MIS 2. The DAR reached a peak of ∼71 cm ka−1 at 21 ka. A hiatus of ∼7–9 ka was then identified between the end of the last glacial maximum (LGM) and the beginning of the Holocene, and the average DAR decreased during the Holocene. Our results indicate a continuous high dust flux in the Khovaling plateau over the last 39 ka, but reworking processes and potential deflation events mark the LGM-Holocene transition. High-resolution luminescence dating studies in Tajikistan are therefore important to detect potential discontinuities in the sequences and provide an independent timescale for interpreting the climate proxies and calculating dust accumulation rates. [ABSTRACT FROM AUTHOR]

• There is a lack of efficient integrated machine quality assurance tools when third-party systems are associated to the linac. • A basic cone alignment test was developed for SRS cones. • A Winston-Lutz test variant is suggested for the smallest cones. • A cone alignment test is suggested as a pre-treatment QA for SRS treatments. The Varian TrueBeam STx linac can be equipped with BrainLAB stereotactic cones and ExacTrac imaging system for SRS treatments. However, these two third-party systems lack integration in a self-performance diagnosis tool dedicated to the SRS platform. The aim of this work was to design and automate essential geometric tests considering the complete set of cones with diameter range from 4 to 15 mm. EPID-based tests were focused on the cone alignment, the radiation isocentricity and the isocenters congruence. Images acquired with or without the BrainLAB pointer were analysed using the Hough transform and morphological filtering operations, after assessment of the algorithm accuracy using simulated images. The new Machine QA program was experimented over one year. A subpixel resolution of 0.02 mm was found for the circular-field center detection algorithm. The tests results did not depend on the pointer location. The maximum deviations reported were in accordance with the AAPM SRS guidelines. The accurate localization of the linac radiation isocenter allowed for guidance of the ExacTrac calibration. A misalignment reaching 0.2 mm was measured for all cones but one, highlighting the benefit of systematizing this control before each patient SRS treatment. An effective in-house QA program dedicated to SRS cones was developed to supplement the standard machine performance check on our mixed SRS platform. Specific geometric tests even include the smallest 4-mm cone, which could be of great interest for future clinical indications such as the radiosurgery of functional disorders. [ABSTRACT FROM AUTHOR]

A new polishing process for metallic parts has been developed by simultaneously coupling drag finishing and electrochemical polishing. This new hybrid process, called PEMEC, enables an improvement in the surface roughness within some minutes, and at the same time, preserves the shape of the edges. This hybrid process is based on a synergistic effect between abrasive and chemical mechanisms. It has confirmed its suitability to be applied on complex and rough surfaces produced by additive manufacturing SLM parts. [ABSTRACT FROM AUTHOR]

Surgery plays a key role in the management of Neuroblastic tumours (NB), where the standard approach is open surgery, while minimally invasive surgery (MIS) may be considered an option in selected cases. The indication(s) and morbidity of MIS remain undetermined due to small number of reported studies. The aim of this study was to critically address the contemporary indications, morbidity and overall survival (OS) and propose guidelines exploring the utility of MIS for NB. Materials & Methods: A SIOPEN study where data of patients with NB who underwent MIS between 2005 and 2018, including demographics, tumour features, imaging, complications, follow up and survival, were extracted and then analysed. A total of 222 patients from 16 centres were identified. The majority were adrenal gland origin (54%) compared to abdominal non-adrenal and pelvic (16%) and thoracic (30%). Complete and near complete macroscopic resection (>95%) was achieved in 95%, with 10% of cases having conversion to open surgery. Complications were reported in 10% within 30 days of surgery. The presence of IDRF (30%) and/or tumour volume >75 ml were risk factors for conversion and complications in multivariate analysis. Overall mortality was 8.5%. MIS for NB showed that it is a secure approach allowing more than 95% resection. The presence of IDRFs was not an absolute contraindication for MIS. Conversion to open surgery and overall complication rates were low, however they become significant if tumour volume >75 mL. Based on these data, we propose new MIS guidelines for neuroblastic tumours. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disease involving several cell types, including T cells, via the IL-23/IL-17 axis. IL-17A acts on the surrounding epithelial cells thus resulting in an inflammatory feedback loop. The development of immunocompetent models that correctly recapitulate the complex phenotype of psoriasis remains challenging, which also includes both the T cell isolation and activation methods. The purpose of this work was to develop an advanced in vitro 3D psoriatic skin model that enables the study of the impact of T cells on psoriatic epithelial cells. To reach that aim, healthy and psoriatic fibroblasts and keratinocytes were used to reproduce this tissue-engineered skin model in which activated T cells, isolated beforehand from human whole blood, have been incorporated. Our study showed that isolation of T cells with the EasySep procedure, followed by activation with PMA/ionomycin, mimicked the psoriatic characteristics in an optimal manner with the production of inflammatory cytokines important in the pathogenesis of psoriasis, as well as increased expression of Ki67, S100A7, elafin and involucrin. This psoriatic model enriched in activated T cells displayed enhanced production of IL-17A, IFN-ƴ, CCL2, CXCL10, IL-1ra, IL-6 and CXCL8 compared with the healthy model and whose increased secretion was maintained over time. In addition, anti-IL17A treatment restored some psoriatic features, including epidermal thickness and basal keratinocytes proliferation, as well as a downregulation of S100A7, elafin and involucrin expression. Altogether, our study demonstrated that this model reflects a proper psoriatic inflammatory environment and is effective for the investigation of epidermal and T cell interaction over time. The aim of this study was to provide an innovative 3D immunocompetent human psoriatic skin model. To our knowledge, this is the first immunocompetent model that uses skin cells from psoriatic patients to study the impact of IL-17A on pathological cells. Through the use of this model, we demonstrated that the T-cell enriched psoriatic model differs from T-cell enriched healthy model, highlighting efficient crosstalk between pathologic epithelial cells and T cells. This advanced preclinical model further mimics the original psoriatic skin and will prove relevant in predicting clinical outcomes, thereby decreasing inaccurate predictions of compound effects. [Display omitted] [ABSTRACT FROM AUTHOR]

This study aimed to assess the learning curve (LC) of cytoredutive surgery (CRS) of peritoneal metastasis (PM) from colorectal cancer (CRC). Information about learning curves is important for developing teaching tools and well-structured training programs for the implementation of this complex procedure in new healthcare centers. The aim of this study was to estimate how many procedures an inexperienced surgeon must perform (the length of the learning period) in order to demonstrate an acceptably low rate of locoregional recurrence. All consecutive 74 patients with CRS for CRC performed by a novice surgeon between 2012 and 2017 in a tertiary cancer center were included. The learning curve was calculated by a cumulative sum control chart (CUSUM) graph. Two groups were formed based on the length of the learning period and were compared on overall and disease free survival. The risk of locoregional recurrence decreased after surgeons had performed 19 cases, suggesting a learning period of this length. Overall survival and postoperative morbidity were not significantly different between learning and proficiency periods. Multiple linear regression analysis showed that the learning period and peritoneal cancer index are the only factors affecting disease free survival. A second learning period was observed in cases where patient care became more complex. This study confirms that learning period has negative impacts on disease-free survival. An initial experience supervised in specialized centers allow to have a short learning curve for CRS for peritoneal metastases for CRC. [ABSTRACT FROM AUTHOR]

Transcatheter edge-to-edge repair (TEER) provides an alternative option for high-risk patients with systemic tricuspid regurgitation (STR). Preliminary data of the French study has shown its feasibility and safety, but mid-term echocardiographic outcome is lacking. Echocardiographic outcome of TEER in systemic tricuspid valve regurgitation. TEER French cohort is a multicentre, longitudinal, descriptive, prospective study of patients undergoing TEER for severe STR. 14 patients with severe or greater STR undergoing percutaneous repair with the MitraClip system were enrolled in the study between May 2019 and June 2023. A transthoracic echocardiography was performed at baseline, six months, one year and two years after the procedure. TR was assessed using standard 2-dimensional color Doppler methods and graded TR using the 5-class grading scheme: mild, moderate, severe, massive, and torrential. The number of clips and their localization was analyzed. A reduction of at least 1 grade in TR was achieved in all subjects. TR grade remained moderate or less in 85% of patients at 1-year follow-up, and 83% of patients at 2-years follow-up. TR reduction was sustained at 2-years follow-up for all the 6 patients evaluated. Five patients had one-clip implantation: in the antero-septal coaptation line for 4 patients and in the antero-posterior coaptation line for 1 patient. 9 patients had two or more clips implantation: antero-septal/postero-septal in 2 patients, antero-septal/antero-posterior in 2 patient, 2 antero-septal in 4 patients, 2 antero-septal/antero-posterior in 1 patient. TR grade seemed to be lower in the group of patients with 2-clips strategy at 2-years follow-up: TR was graduated mild in 67% of patients in 2 or more clips group and moderate in 100% of patients in 1-clip group. Systemic tricuspid TEER is found to be safe and effective, with sustained effects at 2 years in patients. Patients with two or more clips implantation seem to have a better outcome in the regurgitation grade, but additional data and a bigger cohort are needed to predict the outcomes and define the optimal technical strategy. [ABSTRACT FROM AUTHOR]

The coastal sedimentary record of Galicia (NW Spain) is important to study sea-level oscillations during the Late Quaternary. The alluvial deposits preserved in the Ria de Coruña and Ria de Arousa are remnants of fluvial valleys flooded by the sea during the successive Pleistocene and Holocene transgressions. A first chronological study by Optical Stimulated Luminescence (OSL)- revealed a fast-component dominated, but dim OSL signal emitted by quartz from this area. Equivalent dose distributions, as obtained with the Analyst software, yielded large overdispersion values, which were negatively correlated to the potassium concentration in the sediment, thus suggesting the influence of beta dose rate heterogeneities. Nevertheless, for most samples many aliquots were considered in saturation, leading to a palaeodose and age underestimation – regardless of the model choice for age calculation. In this paper, we present new analyses using the open-source R package BayLum, as the so-called saturated aliquots may be incorporated in age calculation. Thus, we test this model performance and more commonly used models in retrieving large doses. Then, we discuss the implications for age calculation for these continental sediments formed during the Late Pleistocene. [ABSTRACT FROM AUTHOR]

In the last decade, the role of the microbiota–gut–brain axis in eating behavior and anxiety-depressive disorders has gained increasing attention. Although a gut microbiota dysbiosis has been reported in anorectic patients, its pathophysiological role remains poorly understood. Thus, we aimed to characterize the potential role of gut microbiota by evaluating the effects of its depletion in the Activity-Based Anorexia (ABA) mouse model both in male and female mice. Male and female C57Bl/6 mice were submitted (ABA group) or not (CT group) to the ABA protocol, which combines access to a running wheel with a progressive limited food access. Gut microbiota was previously depleted or not by a cocktail of antibiotics (ATB) delivered by oral gavages. We monitored body composition, anxiety-like behavior, leptin and adiponectin plasma levels, hypothalamic and hippocampal neuropeptides mRNA levels, as well as dopamine (DRD) and serotonin (5HT1 and 4) receptors mRNA expression. In response to the ABA model, the body weight loss was less pronounced in ATB-treated ABA compared to untreated ABA, while food intake remained unaffected by ATB treatment. ATB-treated ABA exhibited increased fat mass and decreased lean mass compared to untreated ABA both in male and female mice, whereas but plasma adipokine concentrations were affected in a sex-dependent manner. Only male ABA mice showed a reduced anticipatory physical activity in response to ATB treatment. Similarly, anxiety-like behavior was mainly affected in ATB-treated ABA male mice compared to ATB-treated ABA female mice, which was associated with male-specific alterations of hypothalamic CRH mRNA and hippocampal DRD and 5-HT1A mRNA levels. Our study provides evidence that ATB-induced gut microbiota depletion triggers alterations of nutritional and behavioral responses to the activity-based anorexia model in a sex-dependent manner. [ABSTRACT FROM AUTHOR]

Malnutrition affects 5–10% of elderly people living in the community. A few studies suggest that nutritional intervention may reduce health care costs. The present study included malnourished elderly patients living at home. It aimed to compare health care costs between patients that were prescribed ONS by their general practitioner and those who were not, and to assess the effect of ONS prescription on the risk of hospitalisation. This prospective multicentre observational study included malnourished patients ≥70 years old who lived at home. Patients were defined as malnourished if they presented with one or more of the following criteria: weight loss ≥5% in 1 month, weight loss ≥10% in 6 months, BMI <21 kg/m2, albuminemia <35 g/L or Short-Form MNA ≤ 7. Their general practitioners prescribed an ONS, or not, according to their usual practice. Health care costs were recorded during a 6-month period. Other collected data were diseases, disability, self-perception of current health status, quality of life (QoL), nutritional status, appetite and compliance to ONS. A propensity score method was used to compare costs and risk of hospitalisation to adjust for potential confounding factors and control for selection bias. We analysed 191 patients. At baseline, the 133 patients (70%) who were prescribed ONS were more disabled (p < 0.001) and had poorer perception of their health (p = 0.02), lower QoL (p = 0.04) and lower appetite (p < 0.001) than the 58 patients (30%) who were not prescribed ONS. At 6 months, appetite had improved more in the ONS prescription group (p = 0.001). Weight change was not different between groups. Patients prescribed ONS were more frequently hospitalised (OR 2.518, 95% CI: [1.088; 5.829] hosp; p = 0.03). Analyses of adjusted populations revealed no differences in health care costs between groups. In the ONS prescription group, we identified that health care costs were lower (p = 0.042) in patients with an energy intake from ONS ≥ 500 kcal/d (1389 ± 264 €) vs. < 500 kcal/d (3502 ± 839 €). The risk of hospitalisation was reduced 3 and 5 times when the intake from ONS was ≥30 g of protein/day or ≥500 kcal/d, respectively. ONS prescription in malnourished elderly patients generated no extra heath care cost. High energy and protein intake from ONS was associated with a reduced risk of hospitalisation and health care costs. [ABSTRACT FROM AUTHOR]

Separation anxiety is one of the most commonly diagnosed behavioral disorders in domestic dogs and a principal reason for relinquishment of dogs to animal shelters. While pharmacologic and behavioral interventions can be effective in treating this disorder, they require a significant investment of time and effort on the part of the owner to be successful. Failures in compliance are frequent. In this case report, a mixed-breed dog presented with hyper-attachment to the owner and severe separation anxiety that was poorly responsive to pharmacologic and behavior-modification treatment. While continuing the pharmacologic treatment, the dog was provided a novel behavioral intervention. This intervention relied on a newly developed device consisting of machine learning–enabled computer vision and a positive reinforcement mechanism, which was used as part of a counter-conditioning and desensitization program in both the owner's presence and, subsequently, absence. This treatment was able to significantly reduce the signs of separation anxiety within 12 weeks of therapy, allowing the dog's owner to leave her apartment for 30 minutes without the dog showing any signs of separation anxiety. Interactive devices that present cognitive challenges requiring engagement may provide a valuable tool for addressing separation distress in dogs. [ABSTRACT FROM AUTHOR]

Background: It has not been investigated whether the quick sepsis-related organ failure assessment score (qSOFA), a new bedside tool for early sepsis detection, may help accelerating antibiotic initiation in ED patients with sepsis.Methods: In this prospective pre/post quasi-experimental single-ED study, patients admitted with a suspected bacterial infection were managed using standard triage procedures only (baseline) or in association with qSOFA (intervention, with prioritization of patients with a qSOFA ≥ 2).Results: A total of 151/328 (46.0%) and 185/350 (52.8%) patients with definite bacterial infection met the criteria for sepsis in the baseline and intervention periods, respectively. The sensitivity and specificity of a qSOFA ≥ 2 for sepsis prediction were 17.3% (95% confidence interval [CI], 13.6%-21.7%) and 98.8% (95% CI, 97.0%-99.5%). Eleven (7.3%) and 28 (13.5%) patients with sepsis in the baseline and intervention periods received a first antibiotic dose within one hour following triage (primary endpoint, absolute difference 6.2%, 95% CI [-0.5%, 12.7%], P = 0.08). The proportions of patients with sepsis receiving a first antibiotic dose within three hours following triage (39.7% [50/151] versus 36.8% [68/185], absolute difference - 2.9%, 95% CI [-13.3%, 7.3%], P = 0.65), requiring ICU admission, or dying in the hospital were similar in both periods. The median ED occupation rate at triage was 104.3% (interquartile range [IQR], 80.4%-128.3%), with a median number of 157 ED visits per day (IQR, 147-169).Conclusions: A qSOFA-based triage procedure does not improve antibiotic timing and outcomes in patients with sepsis admitted to a high-volume ED. The qSOFA value at triage was poorly sensitive for early sepsis detection. Trial registration (ClinicalTrials.gov): NCT03299894. [ABSTRACT FROM AUTHOR]

Cardiac catheterization (CC) has largely improved the diagnosis and treatment of congenital heart disease in children over the last decades, but it leads to exposure to low doses of X-rays. Children have a greater radiation sensitivity, however, little is known about the long-term radiation associated cancer risks. This study aims to assess the risk of lympho-hematopoietic malignancies among children diagnosed and/or treated with CC. The COCCINELLE cohort includes children from 15 French paediatric cardiology departments who underwent a first CC between 2000–2013, before 16 years old. The cohort was linked with national registries to identify cancer cases and collect information on predisposing factors to cancer (PF). Individual cumulative doses to active bone marrow (ABM) were calculated with the PCXMC software, based on detailed dosimetric information retrieved from reports of 1,139 CC procedures. Standardised incidence ratios (SIRs) and relative risks (RR) of haematological malignancies associated with the 2-year lagged ABM dose were calculated. The cohort included 17,104 children, followed 6.5 years on average. 22,227 CC procedures were collected, with a mean individual ABM cumulative dose of 3.0 mGy. 38 lympho-hematopoietic malignancies were counted (23 lymphoma and 15 leukemia). A significant excess of cancer incidence was observed (SIR = 3.8 [95% confidence interval 2.9; 4.9]), which wasn't anymore observed after excluding patients with PF (SIR = 1.3 [0.6; 2.7]). The ABM dose wasn't significantly associated with the risk of lympho-hematopoietic malignancies (RR/mGy = 1.00 [0.88; 1.10]) or lymphoma (RR/mGy = 1.03 [0.90; 1.14]) after adjustment for attained age, gender and PF. No significant increase of cancer incidence was observed after excluding patients with PF and no dose-response relationship was observed between the risk of lympho-hematopoietic malignancies or lymphoma and cumulative ABM dose arising from CC procedure. The extension of the COCCINELLE study and the European Harmonic project will help to better assess health effects of CC exposure during childhood. [ABSTRACT FROM AUTHOR]

Systemic tricuspid valve regurgitation (TR) is often encountered in patients with atrial correction of transposition of the great arteries (acTGA) or congenitally corrected transposition of the great arteries (ccTGA). When at least moderate, it is related to impaired functional capacity, heart failure and mortality. Management is a matter of debate as medical management is limited and valvular surgery at risk. Among adults with severe and symptomatic systemic mitral regurgitation at high risk for surgery, percutaneous edge-to-edge repair is now proposed as a reasonable alternative. We hypothetised that percutaneous management of systemic TR may be feasible and safe. A monthly national dedicated multidisciplinary meeting was therefore organized, including cardiologists and surgeons dedicated to adults with CHD. All concerned patients were evaluated and a decision was taken and thereafter offered to each patients. So far, 9 patients, of whom 1 female, with a median age of 41 ± 14 years, were included, 4 with acTGA and 5 with ccTGA. The procedures were performed in 4 French tertiary CHD centers between May 2019 and June 2022, following institutional review board approval. The XTR MitraClip device (Abbott, Santa Clara, CA) was used, 1 MitraClip was used in 5 patients, 2 in 2 and 3 in 1. The procedure was not possible in 1 patient, because of impossibility to achieve appropriate orientation of the clip on the tricuspid valve. No complication was reported. At 6 months of follow-up, we noticed a decrease in the TR of at least 1 grade in 8 patients. NYHA functional class improved in 5 patients and diuretics doses decreased in 4. Transcatheter edge-to-edge repair appears as a feasible and safe procedure in patients with significant systemic TR. Further studies need to be performed to precise the optimal position of percutaneous reduction of systemic TR in the management of these patients. [ABSTRACT FROM AUTHOR]

Comprehensive Geriatric Assessment (CGA), is used in older patients with cancer to identify frailties, which can interfere with specialized treatment, and to help with therapeutic care. Functional Status (FS) is a domain of CGA in which Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) are evaluation tools. Our study reviewed the data available on the most frequently used tools to assess ADL and IADL in a geriatric oncology setting and their predictive values on overall survival (OS), toxicity, treatment feasibility or decision and postoperative complications. This review was based on a systematic search of the MEDLINE® database for articles published in English and French between January 1, 2010, and December 31, 2017. In the final analysis, 40 out of 4061 studies were included. The most common ADL and IADL scales used are the Katz ADL (KL-ADL) in 25 studies and the Lawton IADL (IADL 8) in 22 studies. FS is predictive of OS in 11 out of 24 studies, chemotoxicity in 2 out of 7 studies, treatment feasibility in 2 out of 5 studies, treatment decisions in 2 out of 3 studies, and postoperative complications in 4 out of 6 studies. FS is of prognostic value in a geriatric oncology setting despite heterogeneous methodology and inclusion criteria, in the studies included. Additional research is needed to explore more precisely the prognostic value of FS in overall survival, toxicity, treatment feasibility or decision and postoperative complications, in older cancer patients. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This matched cohort study aims to determine whether teenagers with a history of childhood sexual abuse (CSA) are at greater risk of consulting for a pregnancy and related complications than teenagers from the general population. It also aims to compare provoked abortion, live births, and fetal losses of participants who were sexually abused in childhood and those of the general population. A total of 661 girls (aged 13–18 years) with a corroborated by Child Protection Services CSA report between 2001 and 2010 were matched to 661 girls from the general population upon age, biological sex, urban Child Protection Services area, and public drug insurance admissibility at reporting date. Pregnancy consultations and complications during pregnancy and delivery were documented using diagnoses from public health insurance administrative databases from January 1996 to March 2013. Socioeconomic status was controlled. Results indicate that compared with participants from the general population, those with a history of CSA were 4.6 times more likely to consult for at least one pregnancy, 5.3 times more likely to consult for at least one complication during pregnancy or delivery, and on average 5.2 and 3.3 times more likely to consult for at least one live birth and provoked abortion, respectively. There were too few observations to compare fetal losses between groups. Medical interventions for teenage pregnancies and related complications should take into consideration a possible history of CSA to reinforce gynecological follow-up and treatment for girls who were sexually abused and to prevent unfavorable outcomes. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Identifying malware has always been a great challenge. Much money and time has been invested by companies and governments to mitigate the impact of these threats. Nowadays, with the increasing amount of data available, it is possible to use more precise classification techniques. However, most large datasets that include malicious and non-malicious softwares are not public, which hinders the quest for solutions based in technologies that rely on the availability of large amounts of data, such as deep learning. To overcome this limitation, this article introduces a new large dataset for malware classification, which was made publicly available. We then propose a model to train a multiclass classification recurrent neural network (RNN), more specifically a long short-term memory neural network (LSTM) on our dataset. This model for analyzing unstructured malware data is then tested on unseen programs and the accuracy obtained reaches 67.60%, including six classes with five different types of malware. [ABSTRACT FROM AUTHOR]

To describe the clinical and microbiological characteristics and outcomes after antibiotic treatment of a national cohort of patients with Lyme arthritis confirmed by PCR testing on synovial fluid and by serology, when available. Using the French National Reference Center for Borrelia database, patients with a positive PCR on synovial fluid for Borrelia were identified. Patient clinical and biological characteristics were reviewed from patient records. Long-term outcomes after treatment were studied through a questionnaire and with follow-up data. Among 357 synovial fluid testing by PCR between 2010 and 2016, 37 (10.4%) were positive for Borrelia. Patients' median age was 36 years (range 6–78) with 61% of men and 28% patients under 18. The presentation was monoarticular in 92% and the knee was involved in 97%. Contrary to the Borrelia species repartition in European ticks, B. burgdorferi sensu stricto was the most prevalent species found in synovial fluid (54%) followed by B. azfelii (29%) and B. garinii (17%). Antibiotic treatments were mainly composed of doxycycline (n = 24), ceftriaxone (n = 10) and amoxicillin (n = 6), for a median duration of 4 weeks (range 3–12). Despite a properly conducted treatment, 34% of patients (n = 12) developed persistent synovitis for at least 2 months (median duration 3 months, range 2–16). Among those, 3 developed systemic inflammatory oligo- or polyarthritis in previously unaffected joints with no signs of persistent infection (repeated PCR testing negative), which mandated Disease-Modifying Antirheumatic Drugs (DMARD) introduction, leading to remission. In France and contrary to ticks ecology, Lyme arthritis is mainly caused by B. burgdorferi sensu stricto. Despite proper antibiotic therapy, roughly one third of patients may present persistent inflammatory synovitis and a small proportion may develop systemic arthritis. In such cases, complete remission can be reached using DMARD. [ABSTRACT FROM AUTHOR]

Abstract Background To assess the outcome of patients with biliary atresia (BA) who underwent a surgical shunt (SS) for severe portal hypertension (PH) following a Kasai procedure. Methods We collected and analyzed the data and outcomes of patients with BA who underwent SS for severe PH following a Kasai procedure between 1974 and 2014, focusing on complications related to the procedure, overall survival (OS), and transplant-free survival (TFS). Results SS was performed at a median age of 5.5 years [2–13.5] in 38 patients. Conjugated bilirubin level (cBL) was ≤ 20 μmol/l in 24 patients at time of SS. Median follow-up was 15 years [1–32]. OS at 5 and 10 years was 91% and 87% respectively. TFS at 5 and 10 years was 84% and 70% respectively. Long-term complications included hepatic encephalopathy in 9 patients, and hepatopulmonary syndrome in 3. At last follow-up, 10/14 patients without LT and 18/ 24 who had a delayed LT at a median delay of 11 years [1.5–22] were alive. Conclusion Surgical shunt for severe portal hypertension in biliary atresia may delay the need for liver transplantation. However complications are indications for transplantation. Level of evidence Type of study: Therapeutic. Level of evidence III. [ABSTRACT FROM AUTHOR]

Abstract We introduce a new R package 'BayLum' devoted to the analysis of OSL data and to construct chronological models in a Bayesian framework. Our contribution presents a summary of the statistical models, and introduces the main functions implemented in the package. Highlights • Introduction of a new R package. • Bayesian methodology and MCMC samplers. • Bayesian modelling of OSL ages. • Chronological modelling. [ABSTRACT FROM AUTHOR]

Abstract Since 2013, new excavations have focused on the northern part of the Toca da Janela da Barra do Antonião (TJBA-N) rockshelter, which is located on the edge of the Serra da Capivara National Park in Brazil. Ten sediment samples were dated by multigrain quartz OSL and three samples by feldspar IRSL. Multigrain OSL ages on quartz were assessed using the Central Age Model (CAM) and a Bayesian model built with the R BayLum statistics package. Ages are in good stratigraphic agreement and ages from quartz and feldspars, when available, are internally consistent. Furthermore, we produced a Bayesian model (BayLum) based on OSL ages obtained for the six sediment samples of the main stratigraphy that included stratigraphic constraints and a covariance matrix of errors. Two gaps in sedimentation were detected and can be correlated with climatic changes during the MIS 3 and during the MIS 3 to MIS 2 transition. Finally, our results provide a chronological framework for a new important Pleistocene-Holocene sequence in the region. Highlights • The chronostratigraphy of TJBA-N rockshelter is proposed. • A Bayesian model based on OSL ages is presented. • Two gaps in sedimentation are detected. • TJBA-N is an important Pleistocene-Holocene sequence for the peopling of America. [ABSTRACT FROM AUTHOR]

Abstract Background Encapsulated follicular variant of papillary thyroid carcinoma has recently been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features on the basis of its highly indolent behavior, as proposed by an international group of experienced thyroid pathologists. Methods All patients from 9 high-volume endocrine surgery departments who underwent surgery between 2005 and 2015 and whose final surgical pathology revealed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (>10 mm) were included in this study. The primary outcome was to determine the potential for recurrent disease in these patients. Results Among the 363 patients with noninvasive follicular thyroid neoplasm with papillary-like nuclear features, 76% were female with a median age of 50 years (5–86 years); 345 patients (95%) underwent total thyroidectomy. A total of 65 patients had an associated micropapillary thyroid carcinoma. In the group of 133 patients who underwent prophylactic lymph node dissection (37%), 1 patient had a micrometastasis but with an associated micropapillary thyroid carcinoma. Over a median follow-up period of 5 years, 1 patient with an associated micropapillary thyroid carcinoma had recurrent disease at 6 years. All patients with noninvasive follicular thyroid neoplasm with papillary-like nuclear features without micropapillary thyroid carcinoma had no lymph node metastasis or recurrent disease. Conclusion We found that noninvasive follicular thyroid neoplasm with papillary-like nuclear features presents with indolent behavior. However, the identification of an associated micropapillary thyroid carcinoma should be carefully evaluated because it could be a factor for lymph node metastasis and/or of recurrence. [ABSTRACT FROM AUTHOR]

Résumé L'insuffisance mitrale (IM) est la deuxième forme la plus répandue de cardiopathie valvulaire. Elle est classé comme primitive (dégénérative) ou secondaire (fonctionnelle). L'IM secondaire est la conséquence d'une maladie du myocarde. L'IM primitive est une maladie valvulaire dégénérative due à une déterioration de l'appareil valvulaire mitral (prolapsus des feuillets, rupture de cordage etc.). Il couvre toutes les étiologies dans lesquelles des lésions intrinsèques affectent un ou plusieurs composants de l'appareil valvulaire mitral. La prise en charge thérapeutique par excellence de l'IM primitive sévère est une intervention chirurgicale destinée à réparer ou parfois à remplacer la valve mitrale. Cependant, les patients considérés à haut risque en raison de leur âge ou de la présence de comorbidités (50 % de tous les patients) ne sont pas éligibles pour la chirurgie. Des techniques de cathétérisme interventionnel ont été développées pour corriger l'IM par voie percutanée. La seule intervention de ce type qui a été évaluée dans les IM primitive ou secondaire, est la procédure de réparation bord à bord utilisant le MitraClip® (Abbott Vascular, Menlo Park, Californie). Le MitraClip® offre une alternative à la réparation chirurgicale ouverte ou au remplacement par une voie mini-invasive. L"étude EVEREST II a montré que MitraClip® était plus sûr que la chirurgie, bien qu'il soit moins efficace pour réduire l'IM. Un nombre important de patients âgés n'est pas admissible à une chirurgie de la valve mitrale en raison du risque chirurgical prohibitif. Pour ces patients, le MitraClip® peut offrir une alternative thérapeutique efficiente très sécurisante que l'origine de l'IM soit primitive ou secondaire. Actuellement, la réparation percutanée de bord-à-bord par MitraClip® est la première technique percutanée acceptée dans les recommandations de l'ESC : une procédure percutanée de réparation bord-à-bord peut être envisagée chez les patients répondant aux critères échographiques d'éligibilité et qui sont jugés inopérables ou à risque chirurgical prohibitif par un collège de médecins (heart team des valvulopathies) (classe de recommandations IIb, niveau de preuve C). Ainsi, actuellement et en raison de leur fragilité, chez les personnes âgées, le MitraClip® peut constituer une bonne alternative à la chirurgie mitrale lorsqu'elle est indiquée pour une IM qu'elle soit primitive ou secondaire. Abstract Mitral regurgitation (MR) is the second most common form of valvular heart disease. It is classified as either primary (degenerative) or secondary (functional). Secondary MR is the consequence of myocardium disease. Primary MR from degenerative valve disease is due to a primary disruption of the mitral valve apparatus from either prolapsed or flail leaflets. It covers all aetiologies in which intrinsic lesions affect one or several components of the mitral valve apparatus. Gold-standard therapeutic management of severe primary MR is surgery usually to repair but sometime to replace the mitral valve. However patients considered to be at high-risk due to their age or the presence of comorbidities – accounting for 50% of all patients – are not eligible for surgery. Catheter-based interventions have been developed to correct MR percutaneously. The only such intervention which has been evaluated in organic MR is the edge-to-edge procedure using the MitraClip® (Abbott Vascular, Menlo Park, CA). MitraClip® offers an alternative to open surgical repair or replacement via a minimally invasive route and it was shown in the EVEREST II study that MitraClip® was safer than surgery even though it was less effective in reducing MR. A substantial number of patients are ineligible for mitral valve surgery because of prohibitive surgical risk. For those patients, MitraClip® may offer an alternative treatment option. Percutaneous edge-to-edge repair is the first percutaneous option accepted in the 2012 ESC guidelines: Percutaneous edge-to-edge procedure may be considered in patients with symptomatic severe primary MR who fulfill the echo criteria of eligibility, are judged inoperable or at high surgical risk by a 'heart team', and have a life expectancy greater than 1 year (recommendation class IIb, level of evidence C). Because of its frailty, MitraClip® in the elderly may be a good alternative to mitral surgery when indicated for primary or secondary MD. [ABSTRACT FROM AUTHOR]

Abstract Objective To assess the effectiveness of prolonged perioperative thoracic epidural analgesia (PEA) on long term survival of patients who underwent a complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM). Background Grade III-IV morbidity affects long term outcomes after CRS and HIPEC. As compared with opioid administered via patient-controlled analgesia (PCA), PEA reduces morbidity. Method From 2005 to 2016, 150 patients underwent CRS plus HIPEC with or without prolonged PEA. Clinical data and outcomes collected from prospective database were analyzed. Survival was assessed in terms of analgesic method using Kaplan-Meier plots and a propensity score. Results Patients 'characteristics of 59 patients in PCA group were comparable to those of 91 patients in PEA group, except for age, ASA score and fluid requirements, significantly more important in PEA group. Grade III-IV morbidity was 62.7% in PCA group compared with 36.3% in PEA group (p = 0. 0015). Median overall survival (OS) of PEA group was 54.7 months compared to 39.5 months in PCA group (p = 0. 0078). When adjusted on the covariates, using the propensity score, the PEA significantly improves OS [HR 0.40 (95% CI: 0.28–0.56)] (p < 0. 0001) and disease free survival (DFS) [HR 0.61 (95% CI: 0.45–0.81] (p < 0. 0007) Conclusions In this retrospective study of patients who underwent a complete CRS and HIPEC for colorectal peritoneal metastases, the perioperative thoracic epidural analgesia prolonged for over 72 h reduced significantly the grade III-IV morbidity and may improve OS and DFS. [ABSTRACT FROM AUTHOR]

Background The Middle East region is characterized by low levels of high-density lipoprotein cholesterol (HDL-C). To date, no genetic study has investigated the cause of low HDL-C in the Lebanese population. Objective Our objective was to study the genetic causes for hypoalphalipoproteinemia in a Lebanese family with extremely low HDL-C levels. Methods We sequenced the ABCA1 gene and evaluated cholesterol efflux, inflammatory, and metabolic profiles in the proband and his family. Results We identified the first Lebanese pathogenic variant in ABCA1 gene causing Tangier disease in a consanguineous family. The proband carried a novel homozygous pathogenic variant p.Gly592Asp in exon 14 of ABCA1 , which segregated with the disease in the family. Functional study of the p.Gly592Asp pathogenic variant revealed that lipid-free apolipoprotein A-I–dependent cholesterol efflux was completely abolished in cholesterol-loaded human monocytes-derived macrophages isolated from the proband when compared to controls. Systemic inflammatory and metabolic assessments showed that plasma cytokines (MCP-1, MIP-1α, IL-6, CRP, TNF-α), adhesion molecules (ICAM-1, VCAM-1, E-selectin), inflammatory soluble receptors (sIL-6r, sTNFRI, sTNFRII), and metabolic markers (Insulin, C-peptide) were elevated in the proband when compared to controls. Noninvasive cardiovascular investigation revealed the presence of premature artery lesions in the proband. Conclusions It is the first case of Tangier disease reported in Lebanon harboring a novel pathogenic variant in ABCA1. Further genetic research is needed in the Middle East where the consanguinity rate is elevated, to understand the cause of the highly prevalent dyslipidemia. This will help guiding the early diagnosis, management, and prevention of cardiovascular complications. Highlights • We report the first Tangier disease in Lebanon with a new causing variant in ABCA1. • The new pathogenic variant is p.Gly592Asp in ABCA1 , it segregated with the disease. • ApoA-I–dependent cholesterol efflux was abolished in the proband's macrophages. • Genetic studies are needed in the Middle East where consanguinity rate is elevated. [ABSTRACT FROM AUTHOR]

Abstract Objectives The aim of this study was to describe and analyze data from patients treated in France with the Edwards SAPIEN transcatheter heart valve (Edwards Lifesciences LLC, Irvine, California) in the pulmonary position. Background The Edwards SAPIEN valve has recently been introduced for percutaneous pulmonary valve implantation (PPVI). Methods From April 2011 to May 2017, 71 patients undergoing PPVI were consecutively included. Results The median age at PPVI was 26.8 years (range 12.8 to 70.1 years). Primary underlying diagnoses were conotruncal malformations (common arterial trunk, tetralogy of Fallot and variants; n = 45), Ross procedure (n = 18), and other diagnoses (n = 8). PPVI indication was pure stenosis in 33.8% of patients, pure regurgitation in 28.1%, and mixed lesions in 38.1%. PPVI was successfully implemented in 68 patients (95.8%). Pre-stenting of the right ventricular outflow tract was performed in 70 patients (98.6%). Early major complications occurred in 4 subjects (5.6%), including 1 death, 1 coronary compression, and 2 pulmonary valve embolizations. Three of the 4 major complications occurred in the first 15 operated patients. No significant regurgitation was recorded after the procedure. Transpulmonary gradient was significantly reduced from 34.5 to 10.5 mm Hg (p < 0.0001). No patient died during a 1-month follow-up period. At 1-year follow-up, the death rate was 2.9%, and 3 patients had undergone surgical reintervention (44%). Conclusions Early results with the Edwards SAPIEN valve in the pulmonary position demonstrate an ongoing high rate of procedural success. Graphical abstract [ABSTRACT FROM AUTHOR]