Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Evaluation of the Impact of Functional Hypogonadism in Body Composition and Weight Loss in Men Undergoing Bariatric Surgery.

Introduction: Obesity and hypogonadism are linked in a vicious cycle: low testosterone levels favor weight gain and adiposity induces hypogonadism. We aimed to investigate if low levels of testosterone in pre-operative of bariatric surgery impacts postoperative weight loss (WL) and body composition (BC).

Material And Methods: A prospective, observational study included male patients who qualified for bariatric surgery.

The effect of high-fibre diets on glycaemic control in women with diabetes in pregnancy: A systematic review and meta-analysis.

Unlabelled: Dietary fibre improves glycaemic control in type 2 diabetes, but its therapeutic role in women with diabetes in pregnancy is unclear. We assessed the effect of dietary fibre on markers of glycaemic control in women with diabetes in pregnancy.

Methods: We searched four databases (Cochrane Library, MEDLINE, Embase and Web of Science) to identify RCTs exploring the effect of dietary fibre, high-fibre diets or fibre supplementation on fasting blood glucose (FBG), 2-h postprandial blood glucose (PBG) and requirement for insulin therapy, among other glycaemic makers in pregnant women with diabetes.

Associations of High BMI and Excessive Gestational Weight Gain With Pregnancy Outcomes in Women With Type 1 Diabetes: A Systematic Review and Meta-analysis.

Background: The increased risk of pregnancy complications in type 1 diabetes is mainly attributed to maternal hyperglycemia. However, it is unclear whether other potentially modifiable factors also contribute to risk in this population.

Purpose: We sought to assess whether high BMI and excessive gestational weight gain (GWG) are associated with perinatal complications in type 1 diabetes.

The Role of Hypogonadism in the Body Composition of Obese Men in the Preoperative Period of Bariatric Surgery.

Objective: To describe clinical characteristics, hormonal profile and body composition of obese men in preoperative of bariatric surgery.

Methods: Cross-sectional, population-based study. Patients evaluated from June 2019 to December 2021 in 2 obesity referral centers.

Pharmacokinetics and coagulation biomarkers in children and adults with hemophilia A receiving emicizumab prophylaxis every 1, 2, or 4 weeks.

Background: Emicizumab is a bispecific antibody that bridges activated factor (F)IX and FX, mimicking the function of missing activated FVIII and thus improving hemostasis in people with hemophilia A. The efficacy and safety of emicizumab were demonstrated in 4 phase III clinical trials (HAVEN 1-4).

Objectives: Here, we describe pharmacokinetics (PKs), pharmacodynamics (PDs), and exploratory safety biomarkers in HAVEN 1 to 4.

GDF15 linked to maternal risk of nausea and vomiting during pregnancy.

GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG.

Nutrients as Risk Factors and Treatments for Gestational Diabetes.

Gestational diabetes (GDM), traditionally defined as any form of glucose intolerance first detected in pregnancy [...

[Implant of embolic protection filters in duplicated vena cava].

We present the case of a patient with venous thromboembolic disease and contraindication to anticoagulation, where the incidental finding of a duplication of the inferior vena cava was made. This observation determined the need to implant two embolic protection filters. Although this vascular anomaly is rarely present, it is important to keep this possibility in mind to ensure that proper protection is provided when inferior vena cava filters are implanted.

Associations of appetitive traits with growth velocities from infancy to childhood.

Several studies have reported associations between appetitive traits and weight gain during infancy or childhood, but none have directly compared these associations across both age periods. Here, we tested the associations between appetitive traits and growth velocities from birth to childhood. Appetitive trait data were collected using the Children's Eating Behaviour Questionnaire (CEBQ) in 149 children from the Cambridge Baby Growth Study at age 9-17 years.

Pregnancy glucagon-like peptide 1 predicts insulin but not glucose concentrations.

Aims: Incretin hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory peptide (GIP) cause increased insulin secretion in non-pregnant adults, but their role in pregnancy, where there are additional metabolically-active hormones from the placenta, is less clear. The aim of the present study was to assess if fasting and post-load incretin concentrations were predictive of pregnancy insulin and glucose concentrations.

Methods: Pregnant women (n = 394) with one or more risk factors for gestational diabetes were recruited at 28 weeks for a 75 g oral glucose tolerance test (OGTT).

Fetally-encoded GDF15 and maternal GDF15 sensitivity are major determinants of nausea and vomiting in human pregnancy.

Human pregnancy is frequently accompanied by nausea and vomiting that may become severe and life-threatening, as in hyperemesis gravidarum (HG), the cause of which is unknown. Growth Differentiation Factor-15 (GDF15), a hormone known to act on the hindbrain to cause emesis, is highly expressed in the placenta and its levels in maternal blood rise rapidly in pregnancy. Variants in the maternal gene are associated with HG.

Leptin and IGF-1 in Infancy Are Associated With Variants in DHCR7 and CYP2R1 That Relate With Type 1 Diabetes and 25OHD.

Context: Vitamin D has been variably implicated in risk of developing type 1 diabetes based on cohorts of at-risk individuals. Emergent type 1 diabetes in childhood is putatively preceded by altered growth.

Objective: We explored whether polymorphisms in vitamin D metabolism genes modify risk of type 1 diabetes via effects on growth in a prospective, population-based cohort of infants.

Butyrate in Human Milk: Associations with Milk Microbiota, Milk Intake Volume, and Infant Growth.

Butyrate in human milk (HM) has been suggested to reduce excessive weight and adipo-sity gains during infancy. However, HM butyrate's origins, determinants, and its influencing mechanism on weight gain are not completely understood. These were studied in the prospective longitudinal Cambridge Baby Growth and Breastfeeding Study (CBGS-BF), in which infants ( = 59) were exclusively breastfed for at least 6 weeks.

Association of GDF15 levels with body mass index and endocrine status in β-thalassaemia.

Objective: GDF15 has emerged as a stress-induced hormone, acting on the brain to reduce food intake and body weight while affecting neuroendocrine function. Very high GDF15 levels are found in thalassaemia, where growth, energy balance and neuroendocrine function are impaired. We examined the relationships between GDF15 and anthropometric measures and endocrine status in β-thalassaemia.

Association of Higher Ocrelizumab Exposure With Reduced Disability Progression in Multiple Sclerosis.

Background And Objectives: Ocrelizumab improved clinical and MRI measures of disease activity and progression in three phase 3 multiple sclerosis (MS) studies. Post hoc analyses demonstrated a correlation between the ocrelizumab serum concentration and the degree of blood B-cell depletion, and body weight was identified as the most influential covariate on ocrelizumab pharmacokinetics. The magnitude of ocrelizumab treatment benefit on disability progression was greater in lighter vs heavier patients.

Iron Supplementation in Pregnancy and Risk of Gestational Diabetes: A Narrative Review.

Pregnant women frequently supplement their diets with iron to treat any cryptic anemia, on the assumption that if anemia is not present, there will be no negative consequences. However, in women who are already iron-replete, it has been suggested that this can lead to iron overload and an increased risk of certain pregnancy complications. One such complication is gestational diabetes.

Emicizumab dose up-titration in case of suboptimal bleeding control in people with haemophilia A.

Introduction: Emicizumab promotes effective haemostasis in people with haemophilia A (PwHA). It is indicated for routine prophylaxis of bleeding episodes in PwHA with or without factor (F)VIII inhibitors.

Aim: To investigate the effect of emicizumab dose up-titration in PwHA with suboptimal bleeding control.

Associations between breast milk intake volume, macronutrient intake and infant growth in a longitudinal birth cohort: the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF).

Growth patterns of breastfed infants show substantial inter-individual differences, partly influenced by breast milk (BM) nutritional composition. However, BM nutritional composition does not accurately indicate BM nutrient intakes. This study aimed to examine the associations between both BM intake volumes and macronutrient intakes with infant growth.

Associations between maternal iron supplementation in pregnancy and offspring growth and cardiometabolic risk outcomes in infancy and childhood.

It was previously observed that maternal iron supplementation in pregnancy was associated with increased offspring size and adiposity at birth, possibly mediated through increased risk of gestational diabetes. In this study we investigated potential long-term associations of maternal iron supplementation in pregnancy with offspring growth in infancy, and growth and cardiometabolic risk factors in mid-childhood to seek evidence of nutritional programming. Using a nested case-control format, markers of growth and adiposity were measured at 3, 12 and 24 months of age in 341 infants from the Cambridge Baby Growth Study whose mothers supplemented with iron in pregnancy and 222 infants whose mothers did not.

Increased basal insulin sensitivity in late pregnancy in women carrying a male fetus: a cohort study.

Background: It has been suggested that fetal sex may be able to modify maternal metabolism and physiology during pregnancy. Recently pregnant women carrying a male fetus were reported to be more insulin sensitive than those carrying females, although related evidence is inconsistent.

Methods: In this study we administered a 75 g oral glucose tolerance test at around week 28 of pregnancy in 813 pregnant women from a contemporary birth cohort (the Cambridge Baby Growth Study), derived surrogate indices of insulin secretion and sensitivity, and related them to the fetal sex.

A Model-Based Framework to Inform the Dose Selection and Study Design of Emicizumab for Pediatric Patients With Hemophilia A.

Emicizumab is a bispecific antibody mimicking the cofactor function of activated coagulation factor VIII to prevent bleeds in patients with hemophilia A. The dose selection for the first-in-child phase III study of emicizumab was addressed by pediatric pharmacokinetic prediction using an adult/adolescent population pharmacokinetic model developed in phase I-I/II studies. The model was modified to incorporate functions describing the age-dependent increase in body weight (BW) with or without clearance maturation to account for the differences in emicizumab pharmacokinetics between adults/adolescents and children.

Low immunogenicity of emicizumab in persons with haemophilia A.

Introduction: Emicizumab is a humanised, bispecific monoclonal antibody mimicking the cofactor function of activated factor (F)VIII. It is indicated for routine prophylaxis of bleeding episodes in persons with haemophilia A (PwHA) with/without FVIII inhibitors.

Aim: To evaluate the development of anti-emicizumab antibodies and their impact on pharmacokinetics (PK), pharmacodynamics (PD), efficacy and safety in PwHA.

Extensive Study of Breast Milk and Infant Growth: Protocol of the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF).

Growth and nutrition during early life have been strongly linked to future health and metabolic risks. The Cambridge Baby Growth Study (CBGS), a longitudinal birth cohort of 2229 mother-infant pairs, was set up in 2001 to investigate early life determinant factors of infant growth and body composition in the UK setting. To carry out extensive profiling of breastmilk intakes and composition in relation to infancy growth, the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) was established upon the original CBGS.

Associations between Maternal Iron Supplementation in Pregnancy and Changes in Offspring Size at Birth Reflect Those of Multiple Micronutrient Supplementation.

It was previously observed that in a population of a high-income country, dietary multiple micronutrient supplementation in pregnancy was associated with an increased risk of gestational diabetes (GDM) and increased offspring size at birth. In this follow-up study, we investigated whether similar changes are observed with dietary iron supplementation. For this we used the prospective Cambridge Baby Growth Study with records of maternal GDM status, nutrient supplementation, and extensive offspring birth size measurements.