Ensuring optimal lipid oxidation during physical activity in overweight and obese patients using a capillary glycerol sensor.

AIM: To describe lipid oxidation during physical activity (PA) in overweight and obese patients using a real-time capillary glycerol sensor and to propose a personalized strategy to optimize lipolysis. METHODS: Healthy adult volunteers with a BMI >25 kg/m2 were recruited. All participants performed 27 sessions of 30-min PA covering all possible combinations of exercises (low, moderate, high intensities) and pre-exercise meals (high-carbohydrate, high-fat, or fasting) with 3 replicates. Glycerol measurements were performed five times during each session: at T0, T20, T30, T45, and T60. The evolution of capillary glycerolemia during PA was modeled by a nonlinear mixed-effects model. We developed a personalized PA recommendation based on the first 2 glycerolemia measurements that indicates whether a change in activity type is preferable. RESULTS: Thirteen patients were included in the study and 1232 capillary glycerolemia measurements were performed. Hyperglycemic and hyperlipidemic meals were associated with lower baseline glycerolemia (p < 0.0001 for both) compared to fasting. In contrast, the type of meal was not significantly associated with PA-induced lipolysis (p = 0.52 and p = 0.76 for high-carbohydrate and hyperlipidemic meal respectively). Compared with exercises done at low and moderate intensities, high intensity exercises were associated with a higher PA-induced lipolysis (p = 0.0002). Specific strength exercises were associated with a lower PA-induced lipolysis (p < 0.0001). The 2 initial glycerolemia measurements appeared to be a pertinent criterion which help the personalization of PA programs for such individuals (c-index 0.67). CONCLUSION: The inter-individual lipolysis responses to PA and the availability of a real-time capillary blood glycerol sensor may enable the personalization of PA programs, thus promoting optimal lipolysis in subjects with overweight and obesity.

Development of a model to predict the age at breast cancer diagnosis in a global population.

Knowing the mean age at diagnosis of breast cancer (BC) in a country is important for setting up an efficient BC screening program. The aim of this study was to develop and validate a model to predict the mean age at diagnosis of BC at the country level. To develop the model, we used the CI5plus database from the IARC, which contains incidence data for 122 selected populations for a minimum of 15 consecutive years from 1993 to 2012 and data from the World Bank. The standard model was fitted with a generalized linear model with the age of the population, growth domestic product per capita (GDPPC) and fertility rate as fixed effects and continent as a random effect. The model was validated in registries of the Cancer Incidence in Five Continents that are not included in the CI5plus database (1st validation set: 1950-2012) and in the most recently released volume (2nd validation set: 2013-2017). The intercept of the model was 30.9 (27.8-34.1), and the regression coefficients for population age, GDPPC and fertility rate were 0.55 (95% CI: 0.53-0.58, p < 0.001), 0.46 (95% CI: 0.26-0.67, p < 0.001) and 1.62 (95% CI: 1.42-1.88, p < 0.001), respectively. The marginal R2 and conditional R2 were 0.22 and 0.81, respectively, suggesting that 81% percent of the variance in the mean age at diagnosis of BC was explained by the variance in population age, GDPPC and fertility rate through linear relationships. The model was highly accurate, as the correlations between the predicted age from the model and the observed mean age at diagnosis of BC were 0.64 and 0.89, respectively, and the mean relative error percentage errors were 5.2 and 3.1% for the 1st and 2nd validation sets, respectively. We developed a robust model based on population age and continent to predict the mean age at diagnosis of BC in populations. This tool could be used to implement BC screening in countries without prevention programs.

Early morning immune checkpoint blockade and overall survival of patients with metastatic cancer: An In-depth chronotherapeutic study.

INTRODUCTION: Recent retrospective studies suggest potential large patient's benefit through proper timing of immune checkpoint blockers (ICB). The association between ICB treatment timing and patient survival, neoplastic response and toxicities was investigated, together with interactions with performance status (PS) and sex. METHODS: A cohort of patients with metastatic or locally advanced solid tumors, who received pembrolizumab, nivolumab, atezolizumab, durvalumab, or avelumab, alone or with concomitant chemotherapy, between November 2015 and March 2021, at the Centre Leon Bérard (France), was retrospectively studied. RESULTS: 361 patients were investigated (80% non-small cell lung cancer patients, mean [SD] age: 63 [11] years, 39% of women, 83% PS0-1 at first infusion, 19% received concomitant chemotherapy). ICB were administered from 07:25 to 17:21 and optimal morning/afternoon cut-off was 11:37. Morning infusions were associated with increased OS as compared to afternoon (median 30.3 vs 15.9 months, p = 0.0024; HR 1.56 [1.17-2.1], p = 0.003). A strong PS-timing interaction was found (PS0-1 patients, HR=1.53 [1.10-2.12], p = 0.011; PS2-3 patients, HR=0.50 [0.25-0.97], p = 0.042). Morning PS0-1 patients displayed increased OS (median 36.7 vs 21.3 months, p = 0.023), partial/complete response rate (58% vs 41%, p = 0.027), and grade1-3 toxicities (49% vs 34%, p = 0.028). Mortality risk ratio between infusions at worst time-of-day, estimated at 13:36 [12:48-14:23], and in early morning was equal to 4.8 ([2.3-10.1], p = 0.008). Timing differences in toxicities resulted significant only in female patients (women vs men: p < 0.001 vs 0.4). CONCLUSIONS: Early morning ICB infusion was associated with increased OS, response, and toxicities in patients with PS0-1 as compared to later infusions within the day. Prospective randomized trials are needed to confirm this retrospective study.

Prevalence of sexual dysfunction after breast cancer compared to controls, a study from CONSTANCES cohort.

PURPOSE: Sexuality, a substantial factor in quality of life, may be altered after breast cancer (BC) treatments as they intimately afflict femininity. This study aimed to assess the prevalence of sexual dysfunction in women with a history of BC and to compare it with women without a BC history. METHODS: The French general epidemiological cohort CONSTANCES includes more than 200,000 adults. All inclusion questionnaires from CONSTANCES non-virgin adult female participants were analyzed. Women reporting a history of BC were compared to controls in univariate analysis. Multivariate analysis was performed to highlight any demographic risk factor for sexual dysfunction. RESULTS: Among the 2,680 participants who had a history of BC, 34% did not engage in sexual intercourse (SI) in the month preceding the completion of the questionnaire (n = 911), 34% had pain during SI (n = 901) and 30% were not satisfied with their sex life (n = 803). Sexual dysfunction was significantly more frequent in women who had a history of BC: they had less sexual interest (OR 1.79 [1.65;1.94], p < 0.001), experienced more pain during SI (OR 1.10 [1.02;1.19], p < 0.001) and were more dissatisfied with their sex life (OR 1.58 [1.47;1.71], p < 0.001). This stayed true after adjustment on multiple demographic factors such as age, menopausal status, body mass index and depression. CONCLUSIONS: Overall, in this real-life study in a large national cohort, history of BC appeared to be a risk factor for sexual disorders. IMPLICATIONS FOR CANCER SURVIVORS: Efforts to detect sexual disorders in BC survivors and offer quality support must be pursued.

Extended antibiotic prophylaxis after pancreatoduodenectomy reduces postoperative abdominal infection in high-risk patients: Results from a retrospective cohort study.

BACKGROUND: Preoperative biliary stenting before pancreatoduodenectomy is associated with a greater risk of bacteribilia and thus could lead to more frequent and severe surgical site infections. We hypothesized that an extended antibiotic prophylaxis could reduce the risk of surgical site infections for these high-risk patients compared with standard antibiotic prophylaxis. METHODS: All consecutive patients who underwent pancreatoduodenectomy between January 1, 2010 and December 31, 2016 were included in a tricentric retrospective cohort and classified according to the risk of surgical site infections (high or low) and the type of antibiotic prophylaxis (standard or extended). Extended antibiotic prophylaxis was defined by the use of high-rank ß-lactams >2 days after surgery. Standard antibiotic prophylaxis concerned all single dose of low-rank ß-lactams antibiotic prophylaxis. The primary outcome was postoperative surgical site infections. RESULTS: Three hundred and eight patients were included; 146 (47%) were high-risk patients, and 81 (55%) received extended antibiotic prophylaxis, mostly composed of piperacilline-tazobactam and gentamicin. There were significantly fewer surgical site infections in high-risk patients receiving extended antibiotic prophylaxis versus standard antibiotic prophylaxis (odds ratio = 0.4; 95% confidence interval, 0.2-0.8; P = .011), even after adjusting on age, sex, and duration of the surgical procedure (adjusted odds ratio = 0.3; 95% confidence interval, 0.1-0.7; P = .0071). There was no statistical difference in 28-day mortality (P = .32) or 90-day mortality (P = .13). Microorganisms identified in bile culture were more often sensitive to antibiotic prophylaxis in high-risk extended antibiotic prophylaxis group than in high-risk standard antibiotic prophylaxis group (64% versus 38%; P = .01). CONCLUSION: Extended antibiotic prophylaxis is associated with a reduced risk of surgical site infections for high-risk patients with no significant reduction on 28-day mortality. Additional studies are required to determine the optimal duration of extended antibiotic prophylaxis for these patients.

Prospective external validation of a new non-invasive test for the diagnosis of non-alcoholic steatohepatitis in patients with type 2 diabetes.

BACKGROUND: One of the unmet needs in patients with type 2 diabetes mellitus (T2DM) is the prediction of non-alcoholic liver disease by non-invasive blood tests, for each of the three main histological features, fibrosis, non-alcoholic steatohepatitis (NASH) and steatosis. AIMS: To validate externally the performances of a recent panel, Nash-FibroTest, for the assessment of the severity of fibrosis stages, NASH grades and steatosis grades. METHODS: We prospectively analysed 272 patients with T2DM. Standard definitions of stages and grades were used, and analyses were centralised and blinded. The performances of the FibroTest, NashTest-2 and SteatoTest-2 were assessed using the Obuchowski measure (OM), the main outcome recommended as a summary measure of accuracy includeing all pairwise stages and grades comparisons, which is not provided par the extensively used binary area under the ROC curve. RESULTS: The diagnostic performance of each component of the panel was significant. OM (SE; significance) of the FibroTest, the NashTest-2 and the SteatoTest-2 was 0.862 (0.012; P < 0.001), 0.827 (0.015; P < 0.001) and 0.794 (0.020; P < 0.01), respectively. For ballooning and lobular inflammation, OM was 0.794 (0.021; P < 0.001) and 0.821 (0.017; P < 0.001), respectively. In a post hoc analysis the FibroTest outperformed VCTE by 4.1% (2.5-6.5; P < 0.001) for reliability, with a non-significant difference for OM for fibrosis staging, 0.859 (0.012) for FibroTest vs 0.870 (0.009) for VCTE. CONCLUSIONS: From a single blood sample, the panel provides non-invasive diagnosis of the stages of fibrosis, and the grades of NASH and steatosis in patients with T2DM. TRIAL REGISTRATION NUMBER: NCT03634098.

The impact of having a baby with cleft lip and palate on parents and on parent-baby relationship: the first French prospective multicentre study.

BACKGROUND: The objective of this prospective, multidisciplinary and multicenter study was to explore the effect of a cleft lip, associated or not with a cleft palate, on parents, on parent-infant relationship, and on the baby's relational development. It also highlighted how the type of cleft and the timing of the surgery could impact this effect. METHOD: 158 infants, with Cleft lip with or without Palate, and their parents participated in this multicenter prospective cohort. Clinical evaluations were performed at 4 and 12 months postpartum. The impact on the parents and on the parent-infant relationship was evaluated by the Parenting Stress Index (PSI), the Edinburgh Post-partum Depression Scale (EPDS) and the Impact-on-Family Scale (IOFS). The relational development of the infant was assessed using the Alarm Distress Baby Scale (ADBB). The main criteria used to compare the infants were the severity of cleft and the time of surgery. RESULTS: The timing of surgery, the type of malformation or the care structure had no effect on social withdrawal behaviors of the child at 4 and 12 months postpartum (ADBB). Furthermore, early intervention significantly decreased maternal stress assessed with the PSI at 4 months. Parents for whom it had been possible to give a prenatal diagnosis were much better prepared to accept the waiting time between birth and the first surgical intervention (IOFS). Higher postpartum depression scores (EPDS) were found for both parents compared to the general population. CONCLUSION: A joint assessment of the mental health of both infants and parents is required in the follow-up of cleft lip and palate. Even if most families are remarkably resilient faced with this major cause of stress, a significant proportion of them could require help to deal with the situation, especially during this first year of follow-up. An assessment of the child's social withdrawal behaviour and of the parental stress and depression appears useful, in order to adapt care to infant and parent's needs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00993993. Registered 10/14/2009 <.

Maternal Distress and Infant Social Withdrawal (ADBB) Following Infant Cardiac Surgery for Congenital Heart Disease.

BACKGROUND: Mothers and infants are exposed to multiple stresses when cardiac surgery is required for the infant. This study reviewed infant responsiveness using a standardized objective observational measure of social withdrawal and explored its association with measures of maternal distress. METHODS: Mother-infant pairs involving infants surviving early cardiac surgery were assessed when the infant was aged two months. Infant social withdrawal was measured using the Alarm Distress Baby Scale. Maternal distress was assessed using self-report measures for maternal depression (Edinburgh Postnatal Depression Scale), anxiety (Spielberger State-Trait Anxiety Scale), and parenting stress (Parenting Stress Index-Short Form). Potential associations between infant social withdrawal and maternal distress were evaluated. RESULTS: High levels of maternal distress and infant social withdrawal were identified relative to community norms with a positive association. Such an association was not found between infant social withdrawal and the cardiac abnormality and surgery performed. CONCLUSION: The vulnerability of infants requiring cardiac surgery may be better understood when factors beyond their medical condition are considered. The findings suggested an association between maternal distress and infant social withdrawal, which may be consistent with mothers' distress placing infants subjected to cardiac surgery at substantially increased risk of social withdrawal. However, it is unclear to what extent infant withdrawal may trigger maternal distress and what the interactive effects are. Further research is warranted. Trialing a mother-infant support program may be helpful in alleviating distress and improving the well-being and outcomes for these families.