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Abstract Background Since 2010, three meta-analyses have been published on the impact of thyroid autoimmunity (TAI) on pregnancy outcomes in infertile women treated with assisted reproductive technology (ART). The initially observed high risk for miscarriage became very low in the most recent meta-analysis, published in 2016. Objective To investigate whether the lower risk for miscarriage in the latest meta-analysis was associated with the increased use of intracytoplasmic sperm injection (ICSI) in recent studies. Data Source MEDLINE was searched from January 1990 to May 2017. Study Selection Data from case-control and cohort studies on ART (in vitro fertilization/ICSI) pregnancy outcomes in women with and without TAI. Only studies in which women were treated with ICSI were included. Data Extraction and Synthesis Four studies were retained, including 1855 ICSI cycles (290 with and 1565 without TAI). In women with a clinical pregnancy (114 ICSI cycles with TAI and 651 without), there was no difference in miscarriage or live birth rates: respective combined odds ratios, 0.95 [95% confidence interval (CI), 0.48 to 1.87] and 1.12 (95% CI, 0.62 to 2.03), respectively. Age did not differ between women with and without TAI: combined mean difference of 0.13 years (95% CI, −0.51 to 0.76 years), but serum thyroid-stimulating hormone was higher in women with TAI: combined mean difference of 0.20 mIU/L (95% CI, 0.07 to 0.33 mIU/L). Conclusion Infertile women with TAI treated with ICSI had no increased risk for a first-trimester miscarriage compared with women without TAI. When women with TAI who are part of an infertile couple underwent ICSI as a type of ART, their miscarriage risk was similar to that in women without TAI.

IntroductionWith the rising use of immune checkpoint inhibitors (ICIs) in oncology, emergency physicians are increasingly confronted with their immune-related adverse events (irAEs). We described the types of irAEs presenting to the ED of a Belgian cancer centre and determined associations with the development of an irAE and other patient’s characteristics. Secondary objectives describe the therapeutic management and determine 7 and 30-day mortality.MethodsA retrospective chart review of ED visits of patients on ICI from 15 December 2016 to 6 December 2020 was performed. Clinical presentation, cancer characteristics and type of ICI were extracted by a single abstractor. We recorded any suspicion of irAE in the ED and confirmation of an irAE was based on the patient’s oncologist report. Outcome was based on mortality at date of last follow-up.Results227 patients on ICI presented to the ED, with a total of 451 visits. 54 (12%) of the visits resulted in a diagnosis of irAE. Four clinical features were associated with an irAE: gastrointestinal complaints (p=0.01), skin rashes (p=0.02), acute renal failure (p=0.002) and abnormal liver function (p=0.04). An irAE was also associated with three different factors: a cancer status in remission (OR=5.33, 95% CI 2.57 to 11.04), a combination of two ICIs (OR=4.43, 95% CI 2.09 to 9.42) and a medical history of irAE (OR=2.44, 95% CI 1.27 to 4.68). 30-day mortality was lower in the irAE group (0%) than in the non-irAE group (13%, 95% CI 9% to 19%).ConclusionsOncological patients under ICI presenting in the ED are more likely to have an irAE if they present with gastrointestinal and dermatological complaints, acute renal failure and abnormal liver function. This is also true for patients with any history of irAE, a concomitant use of two ICIs and with a cancer status in remission.

Background The suitability of the United States National Academy of Medicine guidelines for gestational weight gain in women with gestational diabetes remains uncertain, raising global concerns. This study aimed to evaluate the association of gestational weight gain with pregnancy and birth outcomes and to determine optimal ranges for gestational weight gain per pre-pregnancy body mass index category in women with gestational diabetes. Methods An epidemiological analysis between 2009–2018 analyzed a large Belgian cohort of singleton pregnancies with gestational diabetes and gestational age 38–40 weeks. Multivariate logistic regression assessed associations between gestational weight gain and relevant pregnancy and birth outcomes, with and without adjustment for confounding variables, including maternal age, origin, education, mode of conception, parity, gestational age at delivery, social deprivation, and year of delivery. Potential optimal weight gain ranges were calculated by minimizing the combined risk of small- and large-for-gestational-age infants (SGA, LGA). Results A total of 13,060 women with gestational diabetes were included. Compared to recommended weight gain, gestational weight gain above guidelines occurred in 26.9% and was associated with an increased risk of gestational hypertension (aOR 1.41, 95% CI 1.20–1.66, p  < 0.001), emergency caesarean section (aOR 1.45, 95% CI 1.25–1.69, p  < 0.001), LGA infants (aOR 1.84, 95% CI 1.63–2.08, p  < 0.001), and macrosomia (aOR 1.78, 95% CI 1.55–2.04, p  < 0.001). Weight gain less than recommended (40.2%) was associated with a decreased risk of gestational hypertension (aOR 0.81, 95% CI 0.69–0.96, p  = 0.015), LGA infants (aOR 0.58, 95% CI 0.50–0.66, p  < 0.001), and macrosomia (aOR 0.57, 95% CI 0.49–0.65, p  < 0.001), but at the expense of an increased risk of SGA infants (aOR 1.68, 95% CI 1.45–1.96, p  < 0.001) and low birth weight (aOR 2.28, 95% CI 1.57–3.32, p  < 0.001). Based on current analysis, the optimal ranges for gestational weight gain would be 9 to 14 kg for women with a normal weight, 1 to 9 kg for women with overweight, and -7 to 1 kg for women with obesity. Conclusions This Belgian study suggests that optimal gestational weight gain for singleton at-term pregnancies complicated by gestational diabetes should be lower than current recommendations, highlighting the need to reevaluate gestational weight gain guidelines in this context.

Background The prognostic value of body composition in cancer patients has been widely studied during the last decade. The main finding of these studies is that sarcopenia, or skeletal muscle depletion, assessed by CT imaging correlates with a reduced overall survival (OS). By contrast, the prognostic value of fat mass remains ill-defined. This study aims to analyze the influence of body composition including both muscle mass and adipose tissue on OS in a homogeneous population of advanced colorectal cancer (CRC) patients. Methods Among 235 patients with chemorefractory advanced CRC included in the SoMore and RegARd-C trials, body composition was assessed in 217 patients on baseline CT images. The relationship between body composition (sarcopenia, muscle density, subcutaneous and visceral fat index and density), body mass index (BMI) and OS were evaluated. Results Patients with a higher BMI had a better OS (≥30 versus < 30, HR: 0.50; 0.33–0.76). Those with low muscle index and muscle density had an increased mortality (HR: 2.06; 1.45–2.93 and HR: 1.54; 1.09–2.18, respectively). Likewise, low subcutaneous and visceral fat index were associated with an increased risk of dying (HR: 1.63; 1.23–2.17 and 1.48; 1.09–2.02 respectively), as were a high subcutaneous and visceral adipose tissue density (HR: 1.93; 1.44–2.57 and 2.40; 1.79–3.20 respectively). In multivariate analysis, a high visceral fat density was the main predictor of poor survival. Conclusions Our results confirm the protective role of obesity in CRC patients at an advanced stage, as well as the negative prognostic impact of muscle depletion on survival. More importantly, our data show for the first time that visceral adipose tissue density is an important prognostic factor in metastatic CRC. Trial registration NCT01290926 , 07/02/2011 and NCT01929616 , 28/08/2013.

Background. Anti-cancer treatment and the cancer population have evolved since the last European Organisation for Research and Treatment of Cancer (EORTC) fungemia survey, and there are few recent large epidemiological studies. Methods. This was a prospective cohort study including 145 030 admissions of patients with cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of fungemia were analyzed. Results. Fungemia occurred in 333 (0.23%; 95% confidence interval [CI], .21–.26) patients, ranging from 0.15% in patients with solid tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297 evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%) patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological malignancies. Fungemia including polymicrobial infection was due to: Candida spp. in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%) patients. Favorable overall response was achieved in 113 (46.5%) patients by week 2. After 4 weeks, the survival rate was 64% (95% CI, 59%–70%) and was not significantly different between Candida spp. Multivariable logistic regression identified baseline septic shock (odds ratio [OR] 3.04, 95% CI, 1.22–7.58) and tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66–5.24), while antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06–.62) and remission of underlying cancer (OR, 0.18; 95% CI, .06–.50) were protective. Conclusions. Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC centers but was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better survival.

Background and Objective: Maternal obesity is an epidemic health problem that is aggravated by excessive gestational weight gain (GWG) and postpartum weight retention. Current US Institute of Medicine (now US National Academy of Medicine) guidelines (2009) for GWG need to be evaluated against the current rise in obesity in the general and pregnant population. We wanted to study the relation between GWG and pregnancy and birth outcomes and to relate this to the current recommendations for GWG. Methods: Population-based study. We performed an epidemiological analysis in a cohort of Belgian pregnant women with singleton live births at term (≥37 weeks) between 2009 and 2014 (n = 337,590). Logistic regression was used to determine the optimal GWG in relation to relevant pregnancy and birth outcomes. Results: The prevalence of maternal obesity significantly increased from 10.3% in 2009 to 11.4% in 2014. The mean (SD) body mass index at the start of the pregnancy significantly increased from 23.9 (4.5) in 2009 to 24.2 (4.6) in 2014. Excessive GWG was frequent, especially in overweight (56.8%) and obese (52.9%) pregnant women. In the logistic regression model, the amount of GWG associated with the lowest incidence of both large-for-gestational-age and small-for-gestational-age infants was 21 kg in underweight women, 14 kg in normal weight, 8 kg in overweight, 0 kg in obese class I, –4 kg in obese class II and –5 kg in obese class III. Conclusion: The prevalence of maternal obesity has risen in Belgium between 2009 and 2014. Current GWG guidelines, based on historic observational data, are probably too liberal for class II and III obese women in which better outcomes are being predicted for lower weight gain than recommended.

Background According to the WHO Multicentre Growth Reference Study Group recommendations, boys and girls have different growth trajectories after birth. Our aim was to develop gender-specific fetal growth curves in a low-risk population and to compare immediate birth outcomes. Methods First, second, and third trimester fetal ultrasound examinations were conducted between 2002 and 2012. The data was selected using the following criteria: routine examinations in uncomplicated singleton pregnancies, Caucasian ethnicity, and confirmation of gestational age by a crown-rump length (CRL) measurement in the first trimester. Generalized Additive Model for Location, Scale and Shape (GAMLSS) was used to align the time frames of the longitudinal fetal measurements, corresponding with the methods of the postnatal growth curves of the WHO MGRS Group. Results A total of 27,680 complete scans were selected from the astraia© ultrasound database representing 12,368 pregnancies. Gender-specific fetal growth curves for biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) were derived. The HC and BPD were significantly larger in boys compared to girls from 20 weeks of gestation onwards ( p  < 0.001) equating to a 3-day difference at 20–24 weeks. Boys were significantly heavier, longer, and had greater head circumference than girls ( p  < 0.001) at birth. The Apgar score at 1 min ( p  = 0.01) and arterial cord pH ( p  < 0.001) were lower in boys. Conclusions These longitudinal fetal growth curves for the first time allow integration with neonatal and pediatric WHO gender-specific growth curves. Boys exceed head growth halfway of the pregnancy, and immediate birth outcomes are worse in boys than girls. Gender difference in intrauterine growth is sufficiently distinct to have a clinically important effect on fetal weight estimation but also on the second trimester dating. Therefore, these differences might already play a role in early fetal or immediate neonatal management.

The NeoRHEA was a single-arm phase 2 study that included patients with estrogen receptor positive / human epidermal factor receptor 2 negative early breast cancer that received 4 cycles of neoadjuvant palbociclib and endocrine therapy. The primary outcome was baseline biomarkers of treatment resistance and secondary outcome was post-treatment transcriptional and epigenetic changes of tumor, immune and stromal cells. E2F targets and G2M checkpoint proliferation-related genes gene sets were enriched in baseline samples from resistant patients., Downregulation of E2F targets and G2M checkpoint post treatment was observed in tumor, endothelial and T cells. Gene Set Enrichment Analyses (GSEA) based on genes residing in the differentially accessible peaks revealed similar effects,. Moreover, decreases in CD8 + CD103+ tissue-resident memory cell marker genes were observed post-treatment and validated by multiplex immunohistochemistry. Our data reveal that treatment with palbociclib and endocrine therapy diminishes adaptive anti-tumor immunity by decreasing T cell proliferation and the presence of tissue-resident memory T cells NCT03065621. The NeoRHEA trial showed that treatment with palbociclib and endocrine therapy decreases T cell proliferation and the presence of tissue-resident memory T cells. These results are important for the development of CDK4 selective inhibitors.

Background Excessive maternal pre-pregnancy and gestational weight gain are related to pregnancy- and birth outcomes. The interpregnancy time window offers a unique opportunity to intervene in order to acquire a healthy lifestyle before the start of a new pregnancy. Methods INTER-ACT is an e-health driven multicentre randomised controlled intervention trial targeting women at high risk of pregnancy- and birth related complications. Eligible women are recruited for the study at day 2 or 3 postpartum. At week 6 postpartum, participants are randomised into the intervention or control arm of the study. The intervention focuses on weight, diet, physical activity and mental well-being, and comprises face-to-face coaching, in which behavioural change techniques are central, and use of a mobile application, which is Bluetooth-connected to a weighing scale and activity tracker. The intervention is rolled out postpartum (4 coaching sessions between week 6 and month 6) and in a new pregnancy (3 coaching sessions, one in each trimester of pregnancy); the mobile app is used throughout the two intervention phases. Data collection includes data from the medical record of the participants (pregnancy outcomes and medical history), anthropometric data (height, weight, waist- and hip circumferences, skinfold thickness and body composition by bio-electrical impedance analysis), data from the mobile app (physical activity and weight; intervention group only) and questionnaires (socio-demographics, breastfeeding, food intake, physical activity, lifestyle, psychosocial factors and process evaluation). Medical record data are collected at inclusion and at delivery of the subsequent pregnancy. All other data are collected at week 6 and month 6 postpartum and every subsequent 6 months until a new pregnancy, and in every trimester in the new pregnancy. Primary outcome is the composite endpoint score of pregnancy-induced hypertension, gestational diabetes mellitus, caesarean section, and large-for-gestational-age infant in the subsequent pregnancy. Discussion INTER-ACT is a unique randomised controlled lifestyle intervention trial in its implementation between pregnancies and during the subsequent pregnancy, with an e-health driven approach. Trial registration ClinicalTrials.gov Identifier: NCT02989142 . Registered August 2016.

Heparanase promotes tumor growth in breast tumors. We now evaluated heparanase protein and gene-expression status and investigated its impact on disease-free survival in order to gain better insight into the role of heparanase in ER-positive (ER+) breast cancer prognosis and to clarify its role in cell survival following chemotherapy. Using pooled analysis of gene-expression data, we found that heparanase was associated with a worse prognosis in estrogen receptor-positive (ER+) tumors (log-rank p < 10−10) and predictive to chemotherapy resistance (interaction p = 0.0001) but not hormonal therapy (Interaction p = 0.62). These results were confirmed by analysis of data from a phase III, prospective randomized trial which showed that heparanase protein expression is associated with increased risk of recurrence in ER+ breast tumors (log-rank p = 0.004). In vitro experiments showed that heparanase promoted tumor progression and increased cell viability via epithelial–mesenchymal transition, stemness, and anti-apoptosis pathways in luminal breast cancer. Taken together, our results demonstrated that heparanase is associated with worse outcomes and increased cell viability in ER+ BC.