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B-cell and T-cell responses were measured to assess the stability and duration of vaccine-induced immunity. Responses to BNT162b2 and mRNA-1273 peaked early and declined over 6 to 8 months. The response to Ad26.CoV2.S reached a lower peak but continued without evidence of notable decline for 8 months. Response levels correlating with protection have not yet been defined.

Among couples undergoing up to six cycles of in vitro fertilization (IVF) at one large infertility center, the overall live-birth rate was 72% with an optimistic analysis (assuming that women lost to follow-up had the same chance of pregnancy as women who continued treatment) and 51% with a conservative analysis (assuming that there were no live births among women lost to follow-up). These rates decreased significantly with increasing maternal age. Among couples undergoing up to six cycles of in vitro fertilization (IVF) at one large infertility center, the overall live-birth rate was 72% with an optimistic analysis and 51% with a conservative analysis. When a couple presents to a physician for a fertility evaluation and requires in vitro fertilization (IVF), their main question is whether this treatment will result in a baby. The statistic commonly quoted to couples is the outcome per cycle according to maternal age. The primary reason for the frequent use of this cross-sectional statistic is the simplicity with which it can be calculated. The national reporting systems in North America, Europe, the Middle East, Australia, and New Zealand are cross-sectional and list IVF outcomes as pregnancies per cycle. However, this statistic has limited value for individual patients because it . . .

Abstract Context Pericyte populations abundantly express tyrosine kinases (eg, platelet-derived growth factor receptor-β [PDGFR-β]) and impact therapeutic response. Lenvatinib is a clinically available tyrosine kinase inhibitor that also targets PDGFR-β. Duration of therapeutic response was shorter in patients with greater disease burden and metastasis. Patients may develop drug resistance and tumor progression. Objectives Develop a gene signature of pericyte abundance to assess with tumor aggressiveness and determine both the response of thyroid-derived pericytes to lenvatinib and their synergies with thyroid carcinoma-derived cells. Design Using a new gene signature, we estimated the relative abundance of pericytes in papillary thyroid carcinoma (PTC) and normal thyroid (NT) TCGA samples. We also cocultured CD90+;PAX8- thyroid-derived pericytes and BRAFWT/V600E-PTC-derived cells to determine effects of coculture on paracrine communications and lenvatinib response. Results Pericyte abundance is significantly higher in BRAFV600E-PTC with hTERT mutations and copy number alterations compared with NT or BRAFWT-PTC samples, even when data are corrected for clinical-pathologic confounders. We have identified upregulated pathways important for tumor survival, immunomodulation, RNA transcription, cell-cycle regulation, and cholesterol metabolism. Pericyte growth is significantly increased by platelet-derived growth factor-BB, which activates phospho(p)-PDGFR-β, pERK1/2, and pAKT. Lenvatinib strongly inhibits pericyte viability by down-regulating MAPK, pAKT, and p-p70S6-kinase downstream PDGFR-β. Critically, lenvatinib significantly induces higher BRAFWT/V600E-PTC cell death when cocultured with pericytes, as a result of pericyte targeting via PDGFR-β. Conclusions This is the first thyroid-specific model of lenvatinib therapeutic efficacy against pericyte viability, which disadvantages BRAFWT/V600E-PTC growth. Assessing pericyte abundance in patients with PTC could be essential to selection rationales for appropriate targeted therapy with lenvatinib.

Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM. Evidence from mice and humans indicates that peripartum cardiomyopathy (PPCM) is a vascular disease caused by excessive anti-angiogenic signalling in the peripartum period of pregnancy and that pre-eclampsia and multiple gestation are important risk factors for the development of PPCM. Heart disease in pregnancy The cause of a form of heart disease called peripartum cardiomyopathy (PPCM), which can affect women late in pregnancy and after giving birth, has proved elusive. Zoltan Arany and colleagues now show, using an innovative mouse model and human studies, that PPCM is a vascular disease, caused by angiogenic imbalances triggered by pregnancy. A mouse model lacking the transcriptional coactivator PCG-1α in cardiac tissue displays a phenotype similar to PPCM. The authors propose a two-hit mechanism for the condition, in which the anti-angiogenic signalling during late pregnancy combines with an underlying susceptibility caused by insufficient pro-angiogenic defences in the heart. This work offers a possible explanation for the observed link between PPCM and pre-eclampsia, and points to possible pro-angiogenic treatments for the condition, such as recombinant human VEGF121.

ObjectiveThe Comprehensive Score for Financial Toxicity (COST) is a validated instrument measuring the economic burden experienced by patients with cancer. We evaluated the frequency of financial toxicity at different COST levels and stratified risk factors and associations with cost-coping strategies by financial toxicity severity.MethodsWe analyzed previously collected survey data of gynecologic oncology patients from two tertiary care institutions. Both surveys included the COST tool and questions assessing economic and behavioral cost-coping strategies. We adapted a proposed grading scale to define three groups: no/mild, moderate, and severe financial toxicity and used χ2, Fisher’s exact test, and Wilcoxon rank sum test to compare groups. We used Poisson regression to calculate crude and adjusted risk ratios for cost-coping strategies, comparing patients with moderate or severe to no/mild financial toxicity.ResultsAmong 308 patients, 14.9% had severe, 32.1% had moderate, and 52.9% had no/mild financial toxicity. Younger age, non-white race, lower education, unemployment, lower income, use of systemic therapy, and shorter time since diagnosis were associated with worse financial toxicity (all p<0.05). Respondents with moderate or severe financial toxicity were significantly more likely to use economic cost-coping strategies such as changing spending habits (adjusted risk ratio (aRR) 2.7, 95% CI 1.8 to 4.0 moderate; aRR 3.6, 95% CI 2.4 to 5.4 severe) and borrowing money (aRR 5.5, 95% CI 1.8 to 16.5 moderate; aRR 12.7, 95% CI 4.3 to 37.1 severe). Those with severe financial toxicity also had a significantly higher risk of behavioral cost-coping through medication non-compliance (aRR 4.6, 95% CI 1.2 to 18.1).ConclusionsAmong a geographically diverse cohort of gynecologic oncology patients, nearly half reported financial toxicity (COST <26), which was associated with economic cost-coping strategies. In those 14.9% of patients reporting severe financial toxicity (COST <14) there was also an increased risk of medication non-compliance, which may lead to worse health outcomes in this group.

BACKGROUND:First deliveries in women older than 35, 40, or 45 years are at increased risk for adverse pregnancy outcomes compared with those in younger women. However, specific relationships between each additional year of maternal age and pregnancy risks remain unclear, and absolute risks at each maternal age are not known. METHODS:Using a population-based cohort of nulliparous women in British Columbia, Canada, from 2004 to 2014 (n = 203,414), We examined relationships between maternal age (modeled flexibly to allow curvilinear shapes) and pregnancy outcomes using logistic regression. We plotted absolute predicted risks to display curves from age 20 to 50 estimated for two risk profiles(1) population average values of all risk factors; (2) a low-risk profile without preexisting diabetes/hypertension, smoking, prior spontaneous/therapeutic abortion, diagnosed infertility, inadequate prenatal care, low income, rural residence, or obesity. RESULTS:Risks of hypertensive disorders increased gradually until age 35, then accelerated. Risk of multiple gestations, major congenital anomalies, and maternal mortality or severe morbidity increased slowly until age 30, then accelerated. Cesarean delivery and gestational diabetes risks increased linearly with age. While indicated preterm delivery increased rapidly with maternal age, spontaneous preterm delivery did not. Stillbirth, neonatal mortality, and infant mortality had j-shaped relationships with maternal age, with nadirs near 30. Despite age-related increases, risks of severe outcomes remained low for women 35 and 40< 1–2% for severe maternal morbidity and 5–7% for fetal–infant composite. CONCLUSIONS:This study provides risks for specific maternal ages to inform clinical counseling and public health messaging regarding the potential implications of delayed childbearing.

Background: Prior studies have examined the association between fine particulate matter [PM ≤2.5μm in aerodynamic diameter (PM2.5 )] and fetal growth with either limited spatial or temporal resolution. Objectives: In this study, we examined the association between PM2.5 exposure during pregnancy and fetal growth measures (ultrasound parameters and birth weight) in a pregnancy cohort using spatiotemporally resolved PM2.5 in Eastern Massachusetts, USA. Methods: We used ultrasound measures of biparietal diameter (BPD), head circumference, femur length, and abdominal circumference (AC), in addition to birth weight, from 9,446 pregnancies that were delivered at the Beth Israel Deaconess Medical Center from 2011–2016. We used linear mixed-effects models to examine the associations of PM2.5 in two exposure windows (the first 16 wk of pregnancy and the cumulative exposure up until the assessment of fetal growth) with anatomic scans (ultrasound measures at<24 wk ), growth scans (ultrasound measures at≥24wk ), and birth weight. All models were adjusted for sociodemographic characteristics, long-term trends, and temperature. Results: Higher PM2.5 exposure in the first 16 wk was associated with smaller fetal growth measures, where associations were particularly strong for BPD, AC, and birth weight. For example, a 5-μg/m3 increase in PM2.5 was associated with a lower mean BPD z -score of −0.19 (95% CI: −0.31 , −0.06 ) before 24 wk, a lower mean AC z -score of −0.15 (95% CI: −0.28 , −0.01 ) after 24 wk, and a lower mean birth weight z -score of −0.11 (95% CI: −0.20 , −0.01 ). Analyses examining the associations with cumulative PM2.5 exposure up until the assessment of fetal growth produced attenuated associations. Conclusions: Higher gestational exposure to PM2.5 was associated with smaller fetal growth measures at levels below the current national standards.

ObjectivesThe goal of our study was to identify preoperative factors in patients with endometrial intraepithelial neoplasia that are associated with concurrent endometrial cancer to select patients who may benefit from sentinel lymph node (SLN) assessment at the time of hysterectomy.MethodsRetrospective single institution cohort study of patients with a preoperative diagnosis of endometrial intraepithelial neoplasia who underwent hysterectomy with or without staging from January 2010 to July 2020. Modified Poisson regression was used to calculate risk ratios (RR) and 95% confidence intervals (CI).ResultsOf 378 patients with a preoperative diagnosis of endometrial intraepithelial neoplasia, 275 (73%) had endometrial intraepithelial neoplasia and 103 (27%) had invasive cancer on final pathology. Age (p=0.003), race (p=0.02), and hypertension (p=0.02) were significantly associated with concurrent endometrial cancer. The median preoperative endometrial stripe was significantly greater in the endometrial cancer group (14 mm (range 10–19)) than in the endometrial intraepithelial neoplasia group (11 mm (range 8–16); p=0.002). A preoperative endometrial stripe ≥20 mm was associated with double the risk of endometrial cancer on final pathology (crude RR 2.0, 95% CI 1.3 to 2.9) and preoperative endometrial stripe ≥15 mm was 2.5 times more likely to be associated with high risk Mayo criteria on final pathology (crude RR 2.5, 95% CI 1.2 to 5.2). Of those with concurrent endometrial cancer, 5% were stage IB, 29% had tumors >2 cm, and 1% had grade 3 histology. Only 3% of all patients underwent lymph node evaluation.ConclusionsIn a large cohort of patients with a preoperative diagnosis of endometrial intraepithelial neoplasia, less than a third had invasive cancer and even fewer had pathologic features considered high risk for nodal metastasis, arguing against the use of routine SLN dissection in these patients. Endometrial stripe ≥15 mm may be a useful preoperative marker to identify patients at higher risk for concurrent endometrial cancer and may be an important criterion for use of selective SLN dissection in carefully selected patients with endometrial intraepithelial neoplasia.

PurposeWe evaluate the cost-effectiveness of prophylactic antibiotic use to prevent catheter-associated urinary tract infections.Materials and methodsA decision tree model was used to assess the cost-effectiveness of prophylactic antibiotics in preventing catheter-associated urinary tract infections for patients with a short-term indwelling urinary catheter. The model accounted for incidence of urinary tract infections with and without the use of prophylactic antibiotics, incidence of antibiotic-resistant urinary tract infections, as well as costs associated with diagnosis and treatment of urinary tract infections and antibiotic-resistant urinary tract infections. Costs were calculated from the health care system’s perspective. We conducted one-way sensitivity analyses.ResultsThe base case analysis showed that the use of prophylactic antibiotics is cost-saving in preventing catheter-associated urinary tract infections. The use of prophylactic antibiotics resulted in lower costs and higher quality-adjusted life-years compared with no prophylactic antibiotics. Sensitivity analyses showed that the optimal strategy changes to no prophylactic antibiotics when the incidence of urinary tract infections after prophylactic antibiotics exceeds 22% or the incidence of developing urinary tract infections without prophylactic antibiotics is less than 12%. Varying the costs of prophylactic antibiotics, urinary tract infection treatment, or antibiotic-resistant urinary tract infection treatment within a reasonable range did not change the optimal strategy.ConclusionsProphylactic antibiotic use to prevent catheter-associated urinary tract infections is cost-effective under most conditions. These results were sensitive to the likelihood of developing catheter-associated urinary tract infections with and without prophylactic antibiotics. Our results are limited to the cost-effectiveness perspective on this clinical practice.

ObjectiveTo estimate absolute risks of obstetric outcomes in the USA according to maternal age at first birth from age 15 to 45 separately by maternal race.Design and settingPopulation-based cohort study.SettingVital statistics Birth Cohort-Linked Birth- Infant Death Data Files and Fetal Death Data Files in the USA.Participants16 514 849 births to nulliparous women from 2004 to 2013.Outcome measuresWe estimated absolute risks of obstetric outcomes (multiple gestations, caesarean delivery, early and late preterm birth, small for gestational age birth, stillbirth, neonatal mortality, postneonatal infant mortality) at each year of maternal age from 15 to 45 years using logistic regression in the overall population and stratified by maternal race. We modelled maternal age flexibly to allow curvilinear shapes and plotted risk curves for each outcome.ResultsIn the overall population, multiple gestations, caesarean delivery and stillbirth risks were lowest at young maternal ages with linear or quadratic increases with age. Curves for preterm birth, small for gestational age, neonatal mortality and postneonatal mortality were u or j shaped, with nadirs between 20 and 29 years, and elevated risks at both younger and older maternal ages. In race-stratified analyses, the shapes of the curves were generally similar across races. Risks increased for all women for all outcomes after age 30. However, increased risks at young maternal ages were most pronounced for white and Asian/Pacific Islander women, for whom young childbearing was least common. Conversely, risks at older ages were more pronounced for Black and American Indian/Alaska Native women, for whom delayed childbearing was least common.ConclusionOur findings confirm risks associated with first births to women younger than 20 and older than 30 years, provide easily interpretable risk curves and illuminate variability in these relationships across categories of maternal race in the USA.