Maternal insulin resistance, triglycerides and cord blood insulin are not determinants of offspring growth and adiposity up to 5 years: a follow-up study.

AIMS: Metabolic dysregulation in utero may influence fetal metabolism and early growth. We previously investigated relationships between maternal indices of glucose homeostasis and triglycerides as well as cord blood insulin with offspring anthropometry up to 2 years. The aim of this analysis was to follow these relationships up to the age of 5 years. METHODS: Associations between maternal metabolic variables of glucose and lipid metabolism measured at 32 weeks' gestation and cord blood insulin with growth and body composition of 162 offspring aged 3-5 years were explored. Both indirect (i.e. body weight, BMI percentiles, sum of four skinfold thicknesses) and direct (i.e. ultrasonography, magnetic resonance imaging in a subgroup) measurement techniques were employed. RESULTS: Maternal metabolic indices were largely unrelated to child body composition. Cord blood insulin was negatively associated with fat mass and lean body mass at 3 years in unadjusted analyses, and the sum of four skinfold thicknesses and body fat percentage in adjusted analyses, whereas the association with lean body mass was no longer observed. An inverse relationship between cord blood insulin and weight gain up to 5 years was observed in girls only with small effect sizes. CONCLUSIONS: Results from this follow-up do not provide convincing evidence that these markers are independently related to offspring growth and adiposity in early childhood. Although cord blood insulin was weakly inversely related to weight gain in girls at 5 years, we cannot conclude that the observed changes in outcomes are clinically meaningful. (Clinical Trials Registry No: NCT00362089).

Meta-analysis of outcomes following resection of the primary tumour in patients presenting with metastatic colorectal cancer.

BACKGROUND: It is not clear whether resection of the primary tumour (when there are metastases) alters survival and/or whether resection is associated with increased morbidity. This systematic review and meta-analysis assessed the prognostic value of primary tumour resection in patients presenting with metastatic colorectal cancer. METHODS: A systematic review of MEDLINE/PubMed was performed on 12 March 2016, with no language or date restrictions, for studies comparing primary tumour resection versus conservative treatment without primary tumour resection for metastatic colorectal cancer. The quality of the studies was assessed using the MINORS and STROBE criteria. Differences in survival, morbidity and mortality between groups were estimated using random-effects meta-analysis. RESULTS: Of 37 412 initially screened articles, 56 retrospective studies with 148 151 patients met the inclusion criteria. Primary tumour resection led to an improvement in overall survival of 7·76 (95 per cent c.i. 5·96 to 9·56) months (risk ratio (RR) for overall survival 0·50, 95 per cent c.i. 0·47 to 0·53), but did not significantly reduce the risk of obstruction (RR 0·50, 95 per cent c.i. 0·16 to 1·53) or bleeding (RR 1·19, 0·48 to 2·97). Neither was the morbidity risk altered (RR 1·14, 0·77 to 1·68). Heterogeneity between the studies was high, with a calculated I2 of more than 50 per cent for most outcomes. CONCLUSION: Primary tumour resection may provide a modest survival advantage in patients presenting with metastatic colorectal cancer.

Impact of the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on offspring neurodevelopment: 5-year follow-up of a randomized controlled trial.

BACKGROUND/OBJECTIVES: Evidence regarding the effect of n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy on offspring's neurodevelopment is not conclusive. SUBJECTS/METHODS: In this analysis, the effect of a reduced n-6:n-3 LCPUFA ratio in the diet of pregnant/lactating women (1.2 g n-3 LCPUFA together with an arachidonic acid (AA)-balanced diet between 15th wk of gestation-4 months postpartum vs control diet) on child neurodevelopment at 4 and 5 years of age was assessed. A child development inventory (CDI) questionnaire and a hand movement test measuring mirror movements (MMs) were applied and the association with cord blood LCPUFA concentrations examined. RESULTS: CDI questionnaire data, which categorizes children as 'normal', 'borderline' or 'delayed' in different areas of development, showed no significant evidence between study groups at 4 (n=119) and 5 years (n=130) except for the area 'letters' at 5 years of age (P=0.043). Similarly, the results did not strongly support the hypothesis that the intervention has a beneficial effect on MMs (for example, at 5 years: dominant hand, fast: adjusted mean difference, -0.08 (-0.43, 0.26); P=0.631). Children exposed to higher cord blood concentrations of docosahexaenoic acid, eicosapentaenoic acid and AA, as well as a lower ratio of n-6:n-3 fatty acids appeared to show beneficial effects on MMs, but these results were largely not statistically significant. CONCLUSIONS: Our results do not show clear benefits or harms of a change in the n-6:n-3 LCPUFA ratio during pregnancy on offspring's neurodevelopment at preschool age. Findings on cord blood LCPUFAs point to a potential influence on offspring development.

The relationship between breast milk leptin and adiponectin with child body composition from 3 to 5 years: a follow-up study.

BACKGROUND: Research indicates that breast milk contains bioactive components that influence metabolism in infancy and may play a role in the prevention of obesity in early childhood. In our initial study, 147 breastfeeding mother/child pairs were followed from birth to 2 years of age to examine the relationship between breast milk leptin and total adiponectin (collected at 6 weeks and 4 months postpartum) and infant body composition. Higher breast milk total adiponectin was related to greater fat mass and weight gain in children at 1 and 2 years of age, whereas leptin showed no association. OBJECTIVES/METHODS: In this follow-up, we examined the relationship between both adipokines and children's body weight, body mass index percentiles, sum of four skin-folds, percentage of body fat, fat mass and lean body mass at 3, 4 and 5 years of age. RESULTS: Breast milk adipokines were largely unrelated to child anthropometric measures. CONCLUSION: Our results do not provide significant evidence that breast milk adipokines can predict adiposity in preschool children.

The Role of PD-L1 Expression and Intratumoral Lymphocytes in Response to Perioperative Chemotherapy for Urothelial Carcinoma.

Introduction: Immunological pathways are relevant for the effectiveness of conventional cytotoxic chemotherapy. Recently, checkpoint inhibition of the PD-1/PD-L1 axis has been shown to be therapeutically relevant in urothelial carcinoma. Objective: To monitor PD-L1 expression on tumor cells and intratumoral infiltration with CD8 positive lymphocytes during perioperative chemotherapy for urothelial cancer and to evaluate their use as potential predictive markers for chemotherapy. Patients and Methods: Sixty-four patients with muscle-invasive urothelial cancer were included in the analysis. Twenty-two patients received preoperative chemotherapy and 42 were treated in an adjuvant setting for locally advanced disease or lymph node metastases. PD-L1 status and the density of infiltration with CD8-positive cells were assessed by immunohistochemistry and analysed for their association with survival (adjuvant group) and response to chemotherapy (preoperative group). For PD-L1 positivity we used a cutoff of 10% positive tumor cells. Results: In the adjuvant group, 11 of 42 patients (26.2%) had PD-L1 positive tumor cells. Twenty-six of 42 (61.9%) patients were highly infiltrated with CD8 + lymphocytes. There was no significant evidence of an association with overall survival for PD-L1 status nor for CD8 infiltration density (p = 0.63 and 0.71). In the preoperative group, eight of the 22 (36.4%) patients were PD-L1 positive and 13 (59%) were highly infiltrated with CD8 + lymphocytes before chemotherapy. There was no evidence of associations with response or survival. Eight patients showed a pathological response to preoperative treatment. These had a significantly longer overall survival than non-responders (p = 0.01). In the preoperative group the pre-treatment expression of the immunologic markers could be compared to the post-treatment status. Only one patient showed a changed PD-L1 status and three patients a changed CD8 status. Conclusions: The tumoral expression of PD-L1 in urothelial carcinoma does not seem to be largely influenced by chemotherapy. Our data do not provide evidence that tumoral expression of PD-L1 and CD8 are useful as prognostic or predictive markers. Small sample size is the major limitation of our study.