Taxonomic and phenotypic analysis of bifidobacteria isolated from IBD patients as potential probiotic strains.

BACKGROUND: Inflammatory Bowel Diseases (IBD) are a major public health issue with unclear aetiology. Changes in the composition and functionality of the intestinal microbiota are associated with these pathologies, including the depletion of strict anaerobes such as Feacalibacterium prausnitzii. Less evidence is observed for depletion in other anaerobes, among which bifidobacteria. This study characterized the taxonomic and functional diversity of bifidobacteria isolated from the human intestinal microbiota in active and non-active IBD patients by a culturomics approach and evaluated if these bifidobacteria might be used as probiotics for gut health. RESULTS: A total of 341 bifidobacteria were isolated from the intestinal microbiota of IBD patients (52 Crohn's disease and 26 ulcerative colitis patients), with a high proportion of Bifidobacterium dentium strains (28% of isolated bifidobacteria). In ulcerative colitis, the major species identified was B. dentium (39% of isolated bifidobacteria), in active and non-active ulcerative colitis. In Crohn's disease, B. adolescentis was the major species isolated from non-active patients (40%), while similar amounts of B. dentium and B. adolescentis were found in active Crohn's disease patients. The relative abundance of B. dentium was increased with age, both in Crohn's disease and ulcerative colitis and active and non-active IBD patients. Antibacterial capacities of bifidobacteria isolated from non-active ulcerative colitis against Escherichia coli LF82 and Salmonella enterica ATCC 14028 were observed more often compared to strains isolated from active ulcerative colitis. Finally, B. longum were retained as strains with the highest probiotic potential as they were the major strains presenting exopolysaccharide synthesis, antibacterial activity, and anti-inflammatory capacities. Antimicrobial activity and EPS synthesis were further correlated to the presence of antimicrobial and EPS gene clusters by in silico analysis. CONCLUSIONS: Different bifidobacterial taxonomic profiles were identified in the microbiota of IBD patients. The most abundant species were B. dentium, mainly associated to the microbiota of ulcerative colitis patients and B. adolescentis, in the intestinal microbiota of Crohn's disease patients. Additionally, the relative abundance of B. dentium significantly increased with age. Furthermore, this study evidenced that bifidobacteria with probiotic potential (antipathogenic activity, exopolysaccharide production and anti-inflammatory activity), especially B. longum strains, can be isolated from the intestinal microbiota of both active and non-active Crohn's disease and ulcerative colitis patients.

Saccharomyces cerevisiae I-3856 in irritable bowel syndrome with predominant constipation.

BACKGROUND: Probiotics are a promising solution for managing irritable bowel syndrome (IBS). Saccharomyces cerevisiae (S. cerevisiae) I-3856 has already demonstrated beneficial effects in IBS subjects, particularly in IBS with predominant constipation (IBS-C). AIM: To confirm the efficacy of S. cerevisiae I-3856 in the management of gastrointestinal symptoms in IBS-C. METHODS: A randomized, double-blind, placebo-controlled clinical study was performed in a total of 456 subjects. After a run-in period, subjects were randomly assigned to the group receiving S. cerevisiae I-3856 (8 × 109 CFU daily) or the placebo for 8 wk, and they performed daily self-evaluations of gastrointestinal symptoms. The primary objective was to assess the effect of the probiotic on abdominal pain. The secondary objectives were the evaluation of other gastrointestinal symptoms, bowel movement frequency and consistency, and quality of life (QOL). RESULTS: A significantly higher proportion of abdominal pain responders was reported in the Probiotic group (45.1% vs 33.9%, P = 0.017). A nonsignificant difference in the area under the curve for abdominal pain over the second month of supplementation was observed in subjects receiving probiotic vs placebo [P = 0.073, 95%CI: -0.59 (-1.23; 0.05)]. No statistically significant differences were reported in the evolution of bowel movement frequency and stool consistency between the groups. After 8 wk of supplementation, the overall QOL score was significantly higher in the Probiotic group than in the Placebo group [P = 0.047, 95%CI: 3.86 (0.52; 7.20)]. Furthermore, exploratory analyses showed statistically significant and clinically relevant improvements in QOL scores in abdominal pain responders vs nonresponders. CONCLUSION: The results of this clinical study confirmed the abdominal pain alleviation properties of S. cerevisiae I-3856 in IBS-C. Abdominal pain relief was associated with improved QOL. ClinicalTrials.gov identifier: NCT03150212.

Are Nutritional Guidelines Followed in the Pediatric Intensive Care Unit?

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.

FETOS: A Self-Questionnaire for Functional Evaluation in Thoracic Outlet Syndrome.

OBJECTIVE: Thoracic outlet syndrome is caused by the compression of blood vessels and nerves leading to the upper limbs; the level of functional discomfort in activities of daily living can be significant. This discomfort has been evaluated using a variety of nonspecific scales, prompting the development a specific self-questionnaire ("Functional Evaluation in Thoracic Outlet Syndrome). Here, the scale's test-retest reliability, sensitivity to change, and criterion validity were assessed. DESIGN: Between May 2015 and July 2017, a total of 37 patients were assessed during an intensive rehabilitation program. The Functional Evaluation in Thoracic Outlet Syndrome self-questionnaire comprises 16 items rated on a 4-point scale: impossible, major discomfort, moderate discomfort, or no difficulty. A total score is then calculated and the usual level of discomfort is rated on a numerical scale. The questionnaire was completed on day (D)1, D2, and the day of discharge. RESULTS: The questionnaire showed very good test-retest reliability, with an overall correlation coefficient above 0.91. The overall score was highly sensitive to change, with a significant median improvement (-5.89) between D1 and discharge (P < 0.001). Of the 16 items, 9 showed significant scalability in their individual sensitivity to change. The criterion validity was moderate: the coefficient for the correlation with the numerical scale was 0.68 on D1 (P < 0.001), 0.55 on D2 (P < 0.001), and 0.69 at discharge (P < 0.001). CONCLUSIONS: The Functional Evaluation in Thoracic Outlet Syndrome self-questionnaire is a quick, simple way of assessing the impact of thoracic outlet syndrome on activities of daily living. The overall score and most of the items displayed good reproducibility and sensitivity to change.

Extended myositis-specific and -associated antibodies profile in systemic sclerosis: A cross-sectional study.

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® and D-tek® 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-TIF1γ 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 ß, 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.

Gender does not impact the short- or long-term outcomes of home-based pulmonary rehabilitation in patients with COPD.

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.

High-intensity focused ultrasound (HIFU) therapy for benign thyroid nodules: a 3-year retrospective multicenter follow-up study.

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.

Long-Term Effectiveness of a Home-Based Pulmonary Rehabilitation in Older People with Chronic Obstructive Pulmonary Disease: A Retrospective 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.

Expression and Prognostic Significance of Neurotrophins and Their Receptors in Canine Mammary Tumors.

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.

Randomized, double-blind trial of F14512, a polyamine-vectorized anticancer drug, compared with etoposide phosphate, in dogs with naturally occurring lymphoma.

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.

Antithymocyte globulin in pediatric allogeneic hematopoietic stem cell transplantation: Infusion time and tolerability.

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.

Prognostic significance of the renal resistive index in the primary prevention of type II diabetes.

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.

Influence Of Socioeconomic Deprivation On Short- And Long-Term Outcomes Of Home-Based Pulmonary Rehabilitation In Patients With Chronic Obstructive Pulmonary Disease.

Background: Pulmonary rehabilitation (PR) improves exercise tolerance and quality of life in patients with chronic obstructive pulmonary disease (COPD), regardless of disease severity. Socioeconomic deprivation has been linked to the incidence of COPD; however, little is known about its impact on PR outcomes. Methods: In this retrospective observational study, 459 COPD patients were enrolled and dichotomized into socially deprived (n=276) and non-socially deprived (n=183) groups based on a cut-off of 30.17 in the EPICES questionnaire (Evaluation of Deprivation and Inequalities in Health Centers), which evaluates socioeconomic disadvantage. The PR program consisted of once-weekly home sessions for 8 weeks, and consisted of an individualized plan of retraining exercises, physical activities, therapeutic education, and psychosocial and motivational support. Exercise tolerance, anxiety and depression, and quality of life were assessed using the 6 min stepper test (6MST), Hospital Anxiety and Depression Scale (HADS), and Visual Simplified Respiratory Questionnaire (VSRQ). Assessments were made before the PR program (baseline) and then at 2 (T2), 8 (T8), and 14 (T14) months after baseline. Results: Compared with the non-socially deprived group, socially deprived patients were younger, more frequently women, active smokers, and living alone, and belonged to lower socioprofessional categories. At baseline, 6MST, VSRQ, and HADS measures were lower for the socially deprived than the non-socially deprived group. At T2, T8, and T14, there were no significant between-group differences in any outcome, and the percentage of patients showing clinically important improvements was the same in both groups. Conclusion: Home-based PR is effective for COPD patients in the short and long term, regardless of socioeconomic status.

Ten-Year Outcome of Islet Alone or Islet After Kidney Transplantation in Type 1 Diabetes: A Prospective Parallel-Arm Cohort Study.

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.

Global Lung Initiative spirometry references in healthy 3-15-year-old French children.

Global Lung Initiative spirometry references satisfactorily fit data of healthy 3- to 15-year-old French children http://bit.ly/2Z2922R.

Dyspnea Is a Specific Symptom in Parkinson's Disease.

BACKGROUND: Dyspnea is a multidimensional sensation that is reported in Parkinson's disease (PD). The multidimensional dyspnea profile (MDP) questionnaire can help to distinguish the perceptive dimension and the emotion response. OBJECTIVE: The aim was to assess the clinical features associated with dyspnea using the MDP questionnaire in order to determine which aspects of the symptom was linked with anxiety, depression or motor severity of the disease. METHODS: Non-demented patients were asked whether they experienced shortness of breath in the last month. In case of positive answer, dyspnea was assessed by the MDP. MDS-UPDRS, global cognitive performance, non-motor symptoms and quality of life were assessed. RESULTS: 60/163 patients were dyspneic since 4.6±2.4 years. The most frequent best sensory quality (SQ) described were: hyperpnoea (35%), physical breathing effort (25%) and air hunger (20%). Hyperpnoea and air hunger had the highest SQ intensity. Anxiety had the highest intensity in the emotional domain. CONCLUSION: Dyspnea is a frequent symptom in PD, with specific presentations and two main aspects: one related with anxiety and another with ventilation control impairment.

No impact of sports practice before or after atrial fibrillation ablation on procedure efficacy in athletes: a case-control study.

AIMS: Limited data exist on the efficacy of catheter ablation (CA) for sport-related atrial fibrillation (AF). Impact of sports practice resumption post-CA remains unknown. We aimed to determine AF CA efficacy in athletes vs. non-athletes, and to assess the impact of sport practice resumption. METHODS AND RESULTS: From 1153 first-time AF CA performed between 2009 and 2017, 73 athletes were matched with 73 sedentary patients based on age, sex, and closest CA procedure date. Athletes were defined as performing ≥6 h/week of vigorous sports to achieve ≥2000 h accumulated lifetime sports activity. They were mostly males (93.2%) with a mean age of 55 ± 9.8 years. Before CA, athletes practiced 10.2 ± 3.9 h/week of vigorous exercise vs. 4.6 ± 3.4 after CA. Within first year after CA, physical activity was stopped in 12 (16.4%) athletes, lowered in 45 (61.9%), and resumed at same intensity in 16 (21.9%). Athletes and non-athletes suffered from same AF recurrence rates during 5-year follow-up after CA: 38 (52.0%) vs. 35 (47.9%), respectively [adjusted hazard ratio (HR) on age, body mass index (BMI), obstructive sleep apnoea (OSA), and reduced left ventricular ejection fraction (LVEF), 1.17 (0.70-1.97, P = 0.54)]. No significant impact of physical activity resumption status was found regarding AF recurrence rates at 1-year and beyond (P = 0.60). Procedure effectiveness was significantly lower in athletes with non-paroxysmal AF [adjusted on age, BMI, reduced LVEF, and OSA HR 2.36 (confidence interval 1.19-4.70), P = 0.01]. CONCLUSION: Sports practice before and after CA has no significant impact on AF recurrence rates in athletes within 5-year after AF CA.

Carfilzomib Weekly plus Melphalan and Prednisone in Newly Diagnosed Transplant-Ineligible Multiple Myeloma (IFM 2012-03): A Phase I Trial.

PURPOSE: Carfilzomib is a novel generation proteasome inhibitor. The Carmysap trial demonstrated that twice-weekly KMP (carfilzomib, melphalan, prednisone) might challenge the MPV (melphalan, prednisone, bortezomib) standard. We sought to study KMP weekly, allowing to increase carfilzomib's dose with maintained efficacy and improved safety profile. PATIENTS AND METHODS: IFM2012-03, a phase I multicenter study of KMP weekly in elderly patients with newly diagnosed multiple myeloma (eNDMM), aimed to determine the MTD of carfilzomib. Carfilzomib was given intravenously at 36, 45, 56, and 70 mg/m2/day on days 1, 8, 15, and 22 with melphalan and prednisone, for nine 35-day induction cycles, followed by carfilzomib maintenance for 1 year. Three dose-limiting toxicities (DLT) determined MTD at the lower dose. RESULTS: Thirty eNDMMs were treated, 6 per cohort at 36, 45, and 56 mg/m2 and 12 at 70 mg/m². There was one DLT at 36 mg/m2 (lymphopenia), one at 45 mg/m2 (lysis syndrome), two at 56 mg/m2 (cardiac insufficiency and febrile neutropenia), and two at 70 mg/m2 (vomiting and elevated liver enzymes). The safety profile was acceptable; however, specific attention must be paid to the risk of cardiovascular events, especially for elderly patients. The overall response rate was 93.3%, with 46.6% complete response. CONCLUSIONS: The MTD dose of carfilzomib was 70 mg/m2 in this KMP weekly study in eNDMM. Response rates, and especially CR rate, were remarkable in this population, and would benefit from being assessed in a larger-scale study. The IFM2012-03 study demonstrated that the MTD of carfilzomib weekly is 70 mg/m2 in eNDMM, and 56 mg/m2 for patients older than 75 years. Carfilzomib used weekly in combination has a good efficacy and safety profile in eNDMM.