LifeinU™ Bacillus subtilis CU1 (BSCU1) has been previously shown to be effective in stimulating mucosal immune responses and supporting resistance to common infectious disease episodes in the elderly. The current clinical study aimed at exploring potential pathways by which BSCU1 could beneficially modulate the immune system and contribute to protection against infection in the general population. A total of 88 participants from three different age groups were supplemented with BSCU1 (2 × 109 cfu/day) for 4 weeks. The effect of the intervention on mucosal immunity was assessed by faecal sIgA levels. In addition, a series of complementary immunoassays were selected, including immune phenotyping, gene expression, basal cytokine levels, cytokine levels in lipopolysaccharide (LPS)-stimulated whole blood and phagocytosis assay. Although no significant effect was observed on faecal sIgA levels after intervention, BSCU1 showed a positive effect on a consistent set of markers of the peripheral innate immune system in adults and the elderly. Percentages of peripheral blood myeloid cells as well as the expression of the activation marker CD69 on monocytes were significantly increased after probiotic intervention. BSCU1 supplementation resulted in significant enrichment of clusters of genes involved in response to type I interferon and phagocytosis pathway. Consistently, ex vivo stimulation of whole blood with LPS resulted in a statistically significant increase in pro-inflammatory cytokines (interleukin (IL)-1beta, IL-6, interferon-gamma, IL-12, tumour necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1alpha, IL-8) and phagocytosis assays showed increased capacity of monocytes to engulf bacteria as well as higher phagosome maturation. BSCU1 supplementation also had a positive effect on low-grade inflammation as significant reduction in basal levels of several serum cytokines (IL-10, TNF-alpha, MIP-1alpha, IL-8) were observed in the elderly subgroup. Overall, BSCU1 primed immune cells for a better response to microbial challenges and reduced low-grade inflammation associated with aging. Registered at ClinicalTrials.gov with the identifier NCT05403398.

Supplementary Figure 1. Complementary survival curves for the whole cohort (n=30). (A) Event Free Survival (EFR); (B) Time to new treatment (TTNT); (C) Duration of response (DOR). Supplementary Figure 2. Progression Free Survival and Overall Survival according to cytogenetic risk (n=30). (A) PFS according to cytogenetic risk; (B) OS according to cytogenetic risk.

Abstract Background Cardiovascular disease (CVD) is responsible for 35% of total deaths worldwide. Sex hormones, such as oestrogen and progesterone, have a cardiovascular protective role in women. After menopause, women are more prone to hypertension and vascular stiffness, accelerated vascular aging and risk for CVD. Menaquinone-7 (MK-7) is a fat-soluble vitamin K2 and serves as cofactor for vitamin K-dependent protein carboxylation. The vitamin K-dependent matrix Gla protein (MGP) is synthesized in the vasculature and has shown to inhibit vascular calcification and stiffness. Purpose To investigate effects of MK-7 on vascular stiffness in pre/peri- versus post-menopausal women. Methods In a double-blind placebo-controlled clinical intervention trial (NCT02404519), 166 women (age 40-70; dephosphorylated-undercarboxylated MGP (dp-ucMGP) > 400 pmol/L at baseline) received daily 180 µg of MK-7 (n=83) or a matching placebo (n=83) for one year. Blood was sampled during intake (inclusion/exclusion), at baseline and at the end of the study to determine dp-ucMGP levels. Regional carotid-femoral (cf-PWV) and carotid-radial (cr-PWV) pulse wave velocities, vessel wall characteristics (e.g., intima-media thickness, arterial diameter, and local carotid artery PWV (caPWV), and arterial blood pressure were measured at baseline and after one year of vitamin K2 supplementation. Pre/peri- and post-menopausal women were sub-divided according to arterial stiffness (high b-stiffness index: > overall median 9.83). Results Post-hoc analyses showed a significant decrease in dp-ucMGP plasma levels of MK-7 supplemented pre/peri-menopausal (n=34; -8.58% ± 27.65; p=0.009) and post-menopausal women (n=48; -13.40% ± 27.45; p<0.001). At baseline, vascular parameters were significantly increased in post-menopausal women compared to pre/peri-menopausal women, e.g., intima media thickness (p=0.013), carotid artery diameter (p=0.007), and caPWV (p=0.012). MK-7 treatment significantly attenuated vascular stiffness in post-menopausal women (Young’s modulus; placebo +49.14% ± 77.38; MK-7 +9.38% ± 67.10; p=0.044). Post-menopausal women with a high stiffness index showed significantly improved vascular markers after MK-7 treatment, e.g., decreased blood pressure at brachialis (-3.03% ± 9.04; p=0.012), decreased blood pressure at carotid artery (-4.49% ± 11.66; p=0.008), increased distensibility coefficient (+13.25% ± 32.34; p=0.040), and increased compliance coefficient (±12.66% ± 32.64; p=0.040). Conclusions Our results confirm that hormonal changes affect the vasculature, and that post-menopausal women suffer from increased vascular stiffness reflected by functional vascular damage. Further, MK-7 supplementation significantly attenuates arterial stiffness in post-menopausal women, in which women with increased stiffness benefit most on blood pressure. Further research is needed to unravel the mechanisms by which MK-7 executes this beneficial role in post-menopausal women.

Dans la sclérodermie systémique (ScS) et les myopathies inflammatoires idiopathiques (MII), les auto-anticorps sont utilisés dans la pratique quotidienne comme biomarqueurs des phénotypes cliniques. Cette étude vise à estimer la prévalence des anticorps spécifiques des myosites (ASM) et des anticorps associés aux myosites (AAM) en utilisant deux tests immunoblots différents dans une cohorte de patients atteints de ScS bien caractérisés, puis à étudier leurs associations cliniques. Dans cette étude transversale, les sérums de 300 patients ont été testés de façon consécutive, avec réalisation simultanée des tests immunoblots « myosites » Euroimmun® et D-tek®. La prévalence des ASM/AAM, ASM et AAM était respectivement de 17,0 %, 8,0 % et 9,7 %. En combinant les résultats des deux tests, des anticorps anti-PM/Scl 100 étaient présents chez 5,0 % (intervalle de confiance à 95 % : 2,8 ; 8,1) ; anti-PM/Scl 75 et anti-TIF1γ chez 3,7 % (1,8 ; 6,5) ; anti-Ku chez 3,0 % (1,4 ; 5,6) ; anti-MDA5 chez 1,3 % (0,4 ; 3,4) ; anti-Mi-2 β, anti-NXP2, anti-PL-7 et anti-SRP chez 0,7 % (0,08 ; 2,4) ; anti-EJ et anti-PL-12 chez 0,3 % (0,01 ; 1,8) des patients. Aucune réactivité anti-SAE1, Jo-1 ou OJ n’a été observée. Les anticorps anti-PM/Scl 75 étaient associés à la pneumopathie interstitielle (80 % contre 42 %) et la myosite (27 % contre 3 %) ; les anticorps anti-Ku étaient associés avec la myosite (33 % contre 3 %). Dans cette étude transversale portant sur 300 patients atteints de ScS, la prévalence des ASM/AAM, des ASM et des AAM, testés à partir de deux immunoblots différents, était respectivement de 17,0 %, 8,0 % et 9,7 %. La positivité des AAM était associée à la pneumopathie interstitielle et à la myosite, mais cette étude n’a pas mis en évidence d’association clinique avec les ASM.

Postpartum haemorrhage (PPH) is one of the leading causes of maternal morbidity and mortality world-wide. The arrival of intrauterine balloon devices has revolutionised PPH management. However, it seems interesting to know the situations of failure to improve the management. The objective is to define the factors related to failure of intrauterine balloon tamponade (IUBT) in women with a postpartum haemorrhage (PPH) after vaginal delivery, and especially blood loss after placement to avoid delaying management. Retrospective cohort study was conducted in 2 centers. All PPH after vaginal deliveries treated by IUBT were included. Two groups were defined (successes and failures) and compared. Failure was defined as the need of invasive procedure. Calculated area under receiver operating characteristic (ROC) curves and thresholds of bleeding at 10 min were also calculated for prediction of failure. 127 women were included. The overall success rate was 78.0 % (95 % CI 70.7-85.1 %). Blood loss at 10 min was factor prognostic of early IUBT failure. The ROC curve of blood loss at 10 min for prediction of failure of IUBT had an area under the curve of 0.876 (95 % CI 0.782-0.970). The predictive positive value of blood loss at 10 min were respectively 0.53, 0.8 and 0.94 for blood loss of 100, 200 and 250 mL. Physicians should be alerted if blood loss are more than 200 mL at 10 min after placement of IUBT and considered invasive procedure if more than 250 mL to avoid delaying management of PPH.

Background: French (2014) and American (2017) pediatric guidelines recommend starting enteral nutrition (EN) early in pediatric intensive care. The aims of this study were to compare the applicability of the guidelines in the pediatric intensive care unit (PICU) and to identify risk factors of non-application of the guidelines. Methods: This retrospective, single-center study was conducted in a medical–surgical PICU between 2014 and 2016. All patients from 1 month to 18 years old with a length of stay >48 h and an exclusive EN at least 1 day during the PICU stay were included. The outcome variable was application of the 2014 and 2017 guidelines, defined by energy intakes ≥90% of the recommended intake at least 1 day as defined by both guidelines. The risk factors of non-application were studied comparing “optimal EN” vs. “non-optimal EN” groups for both guidelines. Results: In total, 416 children were included (mortality rate, 8%). Malnutrition occurred in 36% of cases. The mean energy intake was 34 ± 30.3 kcal kg −1 day −1 . The 2014 and 2017 guidelines were applied in 183 (44%) and 296 (71%) patients, respectively ( p < 0.05). Following the 2017 guidelines, enteral energy intakes were considered as “satisfactory enteral intake” for 335 patients (81%). Hemodynamic failure was a risk factor of the non-application of both guidelines. Conclusion: In our PICU, the received energy intake approached the level of intake recommended by the American 2017 guidelines, which used the predictive Schofield equations and seem more useful and applicable than the higher recommendations of the 2014 guidelines. Multicenter studies to validate the pediatric guidelines seem necessary.

Objective: In systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM), auto-antibodies are used in daily practice as potent biomarkers of clinical phenotypes. This study aimed at estimating the prevalence of myositis-specific (MSA) and myositis-associated (MAA) auto-antibodies in a well-characterised SSc patients cohort using two different immunoblot assays, and studying their clinical associations. Methods: In this cross-sectional study, the sera of 300 consecutive patients were tested at the same time with myositis antibodies Euroimmun (R) and D-tek (R) immunoblot assays. Results: Prevalence of MSA/MAA, MSA and MAA were 17.0%, 8.0% and 9.7%, respectively. When combining results of both tests, anti-PM/Scl 100 were found in 5.0% (95% confidence interval 2.8; 8.1); anti-PM/Scl 75 and anti-TIF1 gamma in 3.7% (1.8; 6.5); anti-Ku 3.0% (1.4; 5.6); anti-MDA5 in 1.3% (0.4; 3.4); anti-Mi-2 beta, anti-NXP2, anti-PL-7 and anti-SRP in 0.7% (0.08; 2.4); anti-EJ and anti-PL-12 in 0.3% (0.01; 1.8) of patients. No reactivity against SAE1, Jo-1 or OJ was observed. Anti-PM/Scl 75 antibodies were associated with interstitial lung disease (80% vs. 42%) and myositis (27% vs. 3%); anti-Ku antibodies were associated with myositis (33% vs. 3%). Conclusion: In this cross-sectional study of 300 SSc patients, the prevalence of MSA/MAA, MSA and MAA using immunoblot assays were 17.0%, 8.0% and 9.7%, respectively. MAA positivity was associated with ILD and myositis, but this study did not highlight any clinical associations with MSA positivity. (C) 2020 Societe francaise de rhumatologie. Published by Elsevier Masson SAS.

Antithymocyte globulin is a major drug in transplantation. rATG has been successfully used to prevent graft‐versus‐host disease in allogeneic HSCT. However, its first infusion is associated with reactions ranging from simple fevers to distributive shocks and may interfere with the transplant conditioning. To evaluate the impact of rATG infusion rate on clinical tolerability, we conducted a retrospective study of all pediatric allogeneic HSCT patients who received rATG (Thymoglobulin®) as part of their conditioning at Lille University Hospital from 2003 to 2018. Until 2012, patients received rATG with a theoretical infusion time of 12 hours (12H group, n = 33). From 2012, they had a theoretical infusion time of 4 hours (4H group, n = 43). Patients from the 12H arm presented more ≥ grade 3 infusion‐related reactions at first dose (70% versus 44%, P = .027), had significantly higher fever (median of 39.6°C versus 39.2°C, P = .002), and needed a greater use of symptomatic treatments. However, they received a slightly higher first dose of rATG (median of 2.7 versus 2.3 mg/kg, P = .042). In view of these results, a rATG infusion time of 4 hours can be a relevant option for pediatric transplant centers to avoid interference with the conditioning regimen and facilitate medical surveillance.

Background Outcomes of high-intensity focused ultrasound (HIFU), as a non-surgical treatment option for benign symptomatic thyroid nodules, has mainly been based on single-center studies and short-term follow-up. Therefore, we assessed the safety, and long-term efficacy of HIFU in benign thyroid nodules among four centers with expertise in thyroid mini-invasive procedures. Patients and methods Retrospective three year follow-up study in four European centers, treating solid benign thyroid nodules causing pressure symptoms and/or cosmetic concerns. Nodule volume reduction was assessed at 1, 3, 6, 12, 24, and 36 months post-treatment. Technical efficacy, defined as a volume reduction rate (VVR) >50% was evaluated at 6, 12, 24 and 36 months. Predictive factors of efficacy were assessed using logistic models. Complications and side effects were classified according to the Interventional Radiology Guidelines and changes in local symptoms were scored on a visual-analog scale. Results Sixty-five patients (mean age 51.1 ± 14.0 years; 86.2% women) with a single thyroid nodule and a mean baseline nodule volume of 9.8 ± 10.3 mL were treated with a mean energy of 7.1 ± 3.1 kJ (range: 2.0 to 15.5 kJ). Median nodule volume reduction was 31.5% (IQR: −38.6% to −23.1%) at 12 months and 31.9% (IQR: −36.4% to −16.1%) at 36 months. Technical efficacy was obtained in 17.2% of cases at 6 months, 17.8% at 12 months, 3.4% at 24 months, and 7.4% at 36 months. The number of treated pixels and the mean energy delivered were positively correlated to VRR at 1, 6 and 12 months. The risk of treatment failure decreased by 4.3% for each additional unit of energy delivered. The procedure duration was inversely correlated with treatment failure (OR 1.043, 95% CI: 1.011–1.083; p = 0.014). Improvement of cervical pressure symptoms or cosmetic complaints were observed in less than 15% of the cases at 12, 24 and 36 months. Horner’s syndrome occurred in one case (1.5%) and minor complications, not requiring treatment, in three (4.6%) patients. No change in thyroid function was registered. Conclusions HIFU carried a low risk of complications. A single treatment resulted in a 30–35% thyroid nodule volume decrease within one year, reduction that remained stable for 2 years. Outcomes varied significantly between centers with different HIFU expertise. Focus on improved HIFU technology, adequate training, and appropriate selection of patients is needed to achieve efficacy comparable to other thermal ablation procedures.

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Objective. - The study aimed to evaluate the impact of the single nucleotide polymorphism (SNP) rs7903146 on the transcription factor 7-like 2 (TCF7L2) gene in stress-related hyperglycaemia (SRH), defined as blood glucose >= 11 mmol/L in at least two blood samples during the first 3 days in the intensive care unit (ICU), and on 28-day and 1-year mortality, and incidence of type 2 diabetes (T2D) at 6 months and 1 year in patients hospitalized in the ICU. Methods. - This prospective observational (non-interventional) multicentre READIAB study, carried out during 2012-2016 in six French ICUs, involved adult patients admitted to ICUs for at least two organ failures; patients admitted for < 48 h were excluded. During the 3-day ICU observational period, genetic testing, blood glucose values and insulin treatment were recorded. Main results. - The association of rs7903146 with SRH was assessed using logistic regression models. Cox proportional hazards regression models assessed the associations between rs7903146 and mortality and between SRH and mortality, both at 28 days and 1 year. A total of 991 of the 1000 enrolled patients were included in the READIAB-G4 cohort, but 242 (24.4%) had preexisting diabetes and were excluded from the analyses. SRH occurred within the first 3 days in the ICU for one-third of the non-diabetes patients. The association between the rs7903146 polymorphism and SRH did not reach significance (P = 0.078): OR(per one T copy): 1.24, 95% CI: 0.98-1.58. A significant association was found between rs7903146 and 28-day mortality after adjusting for severity scores (P = 0.026), but was no longer significant at 1 year (P = 0.61). At 28 days, mortality was increased in patients with SRH (HR: 2.09, 95% CI: 1.43-3.06; P < 0.001), and remained significant at 1 year after adjusting for severity scores (HR: 1.73, 95% Cl: 1.32-2.28; P < 0.001). On admission, non-diabetes patients with SRH had a higher incidence of T2D at 6 months vs. those without SRH (16.0% vs. 7.6%, RR: 2.11, 95% CI: 1.07-4.20; P= 0.030). At 1 year, these figures were 13.4% vs. 9.2%, RR: 1.45, 95% CI: 0.71-2.96; P = 0.31). Moreover, the rs7903146 polymorphism was not significantly associated with T2D development at either 6 months (P= 0.72) or 1 year (P= 0.64). Conclusion. - This study failed to demonstrate any significant association between rs7903146 and SRH. Nevertheless, the issue remains an important challenge, as SRH may be associated with increased rates of both mortality and T2D development. (C) 2019 Published by Elsevier Masson SAS.

Pulmonary rehabilitation, whether performed at home or in a specialised centre, is effective in the management of COPD. As gender-related differences in COPD were previously reported, we aimed to evaluate the impact of gender on pulmonary rehabilitation outcomes in the short, medium and long term. In this retrospective observational study of 170 women and 310 men with COPD, we compared the outcomes of an 8-week home-based pulmonary rehabilitation programme including an individualised plan of retraining exercises, physical activities, therapeutic education, and psychosocial and self-management support. Exercise tolerance, anxiety, depression, and quality of life (QOL) were assessed using the 6-min stepper test (6MST), Hospital Anxiety and Depression Scale (HADS) and Visual Simplified Respiratory Questionnaire (VSRQ), respectively. Assessments were carried out before, immediately after the pulmonary rehabilitation programme (T2) and at 8 (T8) and 14 months (T14). At baseline, women were younger (mean 62.1 versus 65.3 years), more often nonsmokers (24.7% versus 7.7%) and had a higher body mass index (28 versus 26.4 kg·m−2). They more often lived alone (50.6% versus 24.5%) and experienced social deprivation (66.7% versus 56.4%). They had significantly lower exercise tolerance (−34 strokes, 6MST) and higher anxiety and depression (+3.2 HADS total score), but there were no between gender differences in QOL (VSRQ). Both groups showed similar improvements in all outcome measures at T2, T8 and T14 with a tendency for men to lose QOL profits over time. Despite some differences in baseline characteristics, women and men with COPD had similar short-, medium- and long-term benefits of a home-based pulmonary rehabilitation programme.

The renal resistive index has been demonstrated to predict the progression of renal disease and recurrence of major cardiac events in high-risk cardiovascular patients, in addition to other comorbidities. We aimed to assess the prognostic significance of the renal resistive index in type 2 diabetic patients for primary prevention. From 2008 to 2011, patients with type 2 diabetes underwent cardiovascular evaluation, including renal resistive index assessment by renal Doppler ultrasound. The incidence of all-cause death, cardiovascular events, dialysis requirement or a twofold increase in creatinine was recorded. Survival curves were estimated by the Kaplan-Meier method. Two hundred sixty-six patients were included; 50% of the patients were men, an HbA1C level of 8.1 +/- 1.7% (65 +/- 13.6 mmol/mol) and a serum creatinine level of 8 [7-9] mg/L. The mean 24-hour systolic blood pressure, 24-hour diastolic blood pressure, and 24-hour pulse pressure were 133.4 +/- 16.7, 76.5 +/- 9.4, and 56.9 +/- 12.4 mm Hg, respectively. The median renal resistive index was 0.7 [0.6-0.7] with a threshold of 0.7 predictive of monitored events. After adjustment of the 24-hour pulse pressure, age and 24-hour heart rate, a renal resistive index >= 0.70 remained associated with all-cause death (hazard ratio: 3.23 (1.16-8.98); P = .025) and the composite endpoint of major clinical events (hazard ratio: 2.37 (1.34-4.18); P = .003). An elevated renal resistive index with a threshold of 0.7 is an independent predictor of a first cardiovascular or renal event in type 2 diabetic patients. This simple index should be implemented in the multiparametric staging of diabetes.

Accumulating data highlight the role of neurotrophins and their receptors in human breast cancer. This family includes nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), both synthetized as proneurotrophins (proNGF and proBDNF). (pro)NGF and (pro)BDNF initiate their biological effects by binding to both their specific receptors TrkA and TrkB, respectively, and the common receptor p75NTR. Currently, no data are available about their expression and potential role in canine mammary tumors. The aim of this study was to investigate expression of proNGF and BDNF as well as their receptors TrkA, TrkB, and p75NTR in canine mammary carcinomas, and to correlate them with clinicopathological parameters (grade, histological type, lymph node status, recurrence, and distant metastasis) and survival. Immunohistochemistry was performed on serial sections of 96 canine mammary carcinomas with antibodies against proNGF, BDNF, TrkA, TrkB, and p75NTR. Of the 96 carcinomas, proNGF expression was detected in 71 (74%), BDNF in 79 (82%), TrkA in 94 (98%), TrkB in 35 (37%), and p75NTR in 44 (46%). No association was observed between proNGF, BDNF, or TrkA expression and either clinicopathological parameters or survival. TrkB and p75NTR expression were associated with favorable clinicopathological parameters as well as better overall survival.

Impact of age on bladder cancer management practices: a general population study

Background:Long-term effectiveness of pulmonary rehabilitation (PR) is still uncertain in older people with severe chronic obstructive pulmonary disease (COPD). The objective was to compare the effects of home-based PR in people with COPD above and below the age of 70 years. Methods:In this retrospective study, 480 people with COPD were recruited and divided into those ≤70 (n=341) and those >70 years of age (n=139). All participants underwent an 8 weeks of home-based PR, consisting of a weekly supervised 90-minute home session. Six-minute stepper test (6MST), timed-up and go test (TUG), Hospital Anxiety and Depression Scale, and Visual Simplified Respiratory Questionnaire (VSRQ) were assessed at baseline (M0), at 2 (M2), 8 (M8), 14 (M14) months after baseline. Results:The older group was described by fewer current smokers (p <0.001), more long-term oxygen therapy use (p = 0.024), higher prevalence of comorbidities (p<0.001), lower 6MST score and higher TUG score (p<0.001), compared to the younger group. Both groups improved every outcome at M2 compared to baseline. At M2, 88% of people ≤70 years of age and 79% of those above 70 were considered as responders in at least one evaluated parameter (p = 0.013). Both groups maintained the benefits at M14, except for the VSRQ score and the number of responders to this outcome in the older group. Conclusion:Regardless of the age, personalized home-based PR was effective for people with COPD in the short term. Above 70 years, an ageing effect appeared on the long-term effectiveness of quality of life benefit.

Purpose: F14512 is an epipodophyllotoxin derivative from etoposide, combined with a spermine moiety introduced as a cell delivery vector. The objective of this study was to compare the safety and antitumor activity of F14512 and etoposide phosphate in dogs with spontaneous non-Hodgkin lymphoma (NHL) and to investigate the potential benefit of F14512 in P-glycoprotein (Pgp) overexpressing lymphomas. Experimental Design: Forty-eight client-owned dogs with intermediate to high-grade NHL were enrolled into a randomized, double-blind trial of F14512 versus etoposide phosphate. Endpoints included safety and therapeutic efficacy. Results: Twenty-five dogs were randomized to receive F14512 and 23 dogs to receive etoposide phosphate. All adverse events (AEs) were reversible, and no treatment-related death was reported. Hematologic AEs were more severe with F14512 and gastrointestinal AEs were more frequent with etoposide phosphate. F14512 exhibited similar response rate and progression-free survival (PFS) as etoposide phosphate in the global treated population. Subgroup analysis of dogs with Pgp-overexpressing NHL showed a significant improvement in PFS in dogs treated with F14512 compared with etoposide phosphate. Conclusion: F14512 showed strong therapeutic efficacy against spontaneous NHL and exhibited a clinical benefice in Pgp-overexpressing lymphoma superior to etoposide phosphate. The results clearly justify the evaluation of F14512 in human clinical trials.

Background: Little data exists regarding the performance of elastography in EBUS-TBNA. The aim of the study was to evaluate the elastography score proposed and previously published by Izumo, in particular its capacity to perfectly identify benign lymph node, and to discriminate malignant ones. Methods: This study included patients undergoing EBUS-TBNA for mediastinal lymph nodes (LN). Before LN needle aspiration, an elastography was performed which allowed a color elastogram to be superimposed on the ultrasound image. Three blinded assessors classified these elastograms into 3 types using the score published by Izumo: type 1 (predominantly not blue), type 2 (partially blue, partially not blue), or type 3 (predominantly blue). These types were then compared with pathology results. Results: A total of 217 LN (114 patients) were analyzed: histologic findings identified 97 benign LN (44.7% of the lymph nodes) and 120 malignant LN (55.3%). There were 44 elastographies (20.2%) that were classified as type 1, 90 elastographies (41.5%) classified as type 2, and 83 elastographies (38.3%) classified as type 3. Considering type 1 as benign and type 3 as malignant, sensitivity, specificity, positive predictive value, and negative predictive value were respectively 87.0%, 68.0% , 80.0% , and 77.0%. Ten (23%) of the 44 lymph nodes with a type 1 elastogram were malignant. Conclusion: Elastography does not preclude performing TBNA of the lymph nodes. It does not preclude EBUS-TBNA when a type 1 elastogram pattern is found. All lymph nodes visualized should be sampled by EBUS-TBNA, regardless of elastography pattern.

Background Arthralgia and myalgia are described with the vascular endothelial growth factor inhibitor Bevacizumab (Bev). However, in clinical practice these pains are not spontaneously reported by patients. We aimed to evaluate the frequency of arthralgia in patients treated by Bev and identify risk factors associated with arthralgia. Methods We conducted an observational, prospective, bicentric, health data study in two French centers. Self-administered questionnaires were distributed to patients at the initiation of Bev, at 3 months and at 6 months during treatment. We included patients treated for ovarian, colorectal or lung cancers. Bev (5 to 15 mg/kg) was administered intravenously every 2 or 3 weeks with chemotherapy most of the time. Results We included 71 patients from January 2018 to November 2018 (42 patients with colorectal cancer, 22 with ovarian cancer and 7 with lung cancer). Seventy-one patients completed the questionnaire at initiation, 56 (78,9%) at 3 months and 36 (50,7%) at 6 months. The frequency of joint pain before Bev initiation was 29,6% and increase at 3 months (41,8%, p = 0,18) and significantly at 6 months (50%, p = 0,04). The functional repercussion significantly increased for elementary activities from 5,9% at initiation to 12,7% at 3 months (p 25 kg/m2 (p = 0,04), ovarian cancer (p Conclusions Bevacizumab-associated protocols are responsible for a significant increase of arthralgia frequency in women treated for an ovarian cancer. The pain appears in the first 3 months and increase during treatment. Oncologists should be aware of this side effect in order to inform the patients and propose a suitable treatment. Clinical trial identification NCT03455907. Legal entity responsible for the study Vieillard Marie-Helene. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

OBJECTIVE The long-term outcome of allogenic islet transplantation is unknown. The aim of this study was to evaluate the 10-year outcome of islet transplantation in patients with type 1 diabetes and hypoglycemia unawareness and/or a functioning kidney graft. RESEARCH DESIGN AND METHODS We enrolled in this prospective parallel-arm cohort study 28 subjects with type 1 diabetes who received islet transplantation either alone (ITA) or after a kidney graft (IAK). Islet transplantation consisted of two or three intraportal infusions of allogenic islets administered within (median [interquartile range]) 68 days (43–92). Immunosuppression was induced with interleukin-2 receptor antibodies and maintained with sirolimus and tacrolimus. The primary outcome was insulin independence with A1C ≤6.5% (48 mmol/mol). Secondary outcomes were patient and graft survival, severe hypoglycemic events (SHEs), metabolic control, and renal function. RESULTS The primary outcome was met by (Kaplan-Meier estimates [95% CI]) 39% (22–57) and 28% (13–45) of patients 5 and 10 years after islet transplantation, respectively. Graft function persisted in 82% (62–92) and 78% (57–89) of case subjects after 5 and 10 years, respectively, and was associated with improved glucose control, reduced need for exogenous insulin, and a marked decrease of SHEs. ITA and IAK had similar outcomes. Primary graft function, evaluated 1 month after the last islet infusion, was significantly associated with the duration of graft function and insulin independence. CONCLUSIONS Islet transplantation with the Edmonton protocol can provide 10-year markedly improved metabolic control without SHEs in three-quarters of patients with type 1 diabetes, kidney transplanted or not.