Second and third trimester estimation of gestational age using ultrasound or maternal symphysis-fundal height measurements: A systematic review.

Background Accurate assessment of gestational age (GA) is important for managing pregnancies at an individual level and monitoring preterm birth rates at a population level. Objectives As many women first seek antenatal care in late pregnancy, our aim was to assess the methodology of studies reporting equations for estimating GA after 20 weeks’ gestation using ultrasound or symphysis-fundal height (SFH) measurements. Search strategy Six electronic databases were searched for studies published from January 1970 to April 2021. Selection criteria Studies were included if they contained a formula using SFH or ultrasound-measured biometry to estimate GA after 20 weeks in healthy singleton pregnancies. Data collection and analysis Two reviewers and a statistician reviewed study design, statistical methods, and reporting methods using 29 criteria. Each article was awarded an overall quality score, predefined as the percentage of the 29 criteria scored at low risk of bias. 95% prediction intervals were calculated for studies that used recommended first trimester dating to confirm true GA. Main results The search yielded 4209 results. Ninety-seven full-text articles were included in the analysis. The mean quality score was 32% (range 7%–97%). Only 10 articles scored low risk in 18 or more criteria. Their formulas estimated GA using one or more ultrasound-measured biometry parameters and SFH measurements. Twenty-three articles used recommended first trimester dating. A single-parameter formula using transcerebellar diameter (TCD) gave the lowest 95% prediction interval. Conclusions There is considerable methodological heterogeneity in studies developing equations for estimating GA. Formulas using ultrasound-based measurements more accurately estimated GA after 20 weeks than formulas using SFH measurement. While the clinical priority remains promotion of early engagement with antenatal care, we suggest unified standards for GA and growth assessment

Targeting colorectal cancer via its microenvironment by inhibiting IGF-1 receptor-insulin receptor substrate and STAT3 signaling

The tumor microenvironment (TME) exerts critical pro-tumorigenic effects through cytokines and growth factors that support cancer cell proliferation, survival, motility and invasion. Insulin-like growth factor-1 (IGF-1) and Signal transducer and activator of transcription 3 (STAT3) stimulate colorectal cancer (CRC) development and progression via cell autonomous and microenvironmental effects. Using a unique inhibitor, NT157, which targets both IGF-1 receptor (IGF-1R) and STAT3, we show that these pathways regulate many TME functions associated with sporadic colonic tumorigenesis in CPC-APC mice, in which cancer development is driven by loss of the Apc tumor suppressor gene. NT157 causes a substantial reduction in tumor burden by affecting cancer cells, cancer-associated fibroblasts (CAF) and myeloid cells. Decreased cancer cell proliferation and increased apoptosis were accompanied by inhibition of CAF activation and decreased inflammation. Furthermore, NT157 inhibited expression of pro-tumorigenic cytokines, chemokines and growth factors, including IL-6, IL-11 and IL-23 as well as CCL2, CCL5, CXCL7, CXCL5, ICAM1 and TGFβ; decreased cancer cell migratory activity and reduced their proliferation in the liver. NT157 represents a new class of anti-cancer drugs that affect both the malignant cell and its supportive microenvironment