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1.

Objective

To examine the association of placental levels of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and chromium (Cr) with birth outcomes (birth weight, length, and head circumference, low birth weight [LBW], gestational age, preterm delivery, and small for gestational age [SGA]) in mother-child pairs from the Environment and Childhood (INMA) Project in Spain.

Methods

Metal concentrations were measured in placenta tissue samples randomly selected from five INMA cohorts. Data on birth outcomes were obtained from medical records. Associations were assessed in a sub-sample of 327 mother-infant pairs by regression models adjusted for confounding factors and for all metals simultaneously. Effect modification by sex was also evaluated.

Results

Elevated placental Cd levels (>5.79 vs. <3.30?ng/g) were associated with reduced birth weight (?111.8?g, 95%CI?=??215.6; ?8.06, p-trend?=?0.01) and length (?0.62?cm, 95%CI?=??1.20; ?0.04, p-trend?=?0.02), while a 10% increase in Cd was associated with 1.21-fold increased odds (95%CI?=?1.01; 1.43) of LBW in the global sample but with 14% lower odds (95%CI?=?0.78; 0.96) of preterm delivery in males (Pinteraction?=?0.10). Detected (vs. undetected) Hg was associated with reduced head circumference (?0.49?cm, 95%CI?=??1.00; 0.03) in females (Pinteraction?=?0.03). A 10% increase in placental Mn was associated with slight increases in gestational age (0.04 weeks, 95%CI?=?0.01; 0.07) in the global sample and in head circumference (0.05?cm, 95%CI?=??0.01; 0.10) in females (Pinteraction?=?0.03). Elevated Cr levels (>99.6 vs. <56.1?ng/g) were associated with reduced birth length (?0.68?cm, 95%CI?=??1.33; ?0.04, p-trend?=?0.02) and slightly increased gestational age (0.35 weeks, 95%CI?=??0.07; 0.77, p-trend?=?0.08) in the global sample. As and Pb were detected in few placentas (27% and 13%, respectively) and were not associated with any studied birth outcome.

Conclusions

Data suggest that in utero exposure to Cd, Hg, and Cr could adversely affect fetal growth, whereas Mn and Cr appear to have a positive effect on gestational age. Given the relatively small number of subjects, sex-specific associations should be interpreted with caution.  相似文献   
2.

Background

Pazopanib has been approved for first-line treatment of patients with metastatic renal-cell carcinoma on the basis of clinical trials that enrolled only patients with adequate renal function. Few data are available on the safety and efficacy of pazopanib in patients with renal insufficiency. This study investigated the effect of kidney function on treatment outcomes in such patients.

Patients and Methods

We retrospectively analyzed data of metastatic renal-cell carcinoma patients treated with pazopanib from January 2010 to June 2016 with respect to renal function. Patients with Modification of Diet in Renal Disease ≤ 60 mL/min/1.73 m2 (group A) were compared to patients with Modification of Diet in Renal Disease > 60 mL/min/1.73 m2 (group B) in terms of progression-free survival, toxicities, response rates, and overall survival.

Results

A total of 229 patients were included: 128 in group A and 101 in group B. Median progression-free survival was 14 months (95% confidence interval [CI], 9.4-18.5) and 17 months (95% CI, 11.4-22.8), and overall survival was 30.5 months (95% CI, 8-53) and 41.4 months (95% CI, 21-62) for group A and group B, respectively, with no significant difference (P = .6). No significant difference between the 2 groups was reported in the incidence of adverse events. Dose reductions were more frequent in group A patients (66% vs. 36%; P = .04).

Conclusion

Although the dose of pazopanib was reduced more frequently in patients with renal impairment, kidney function at therapy initiation does not adversely affect the safety and efficacy of pazopanib.  相似文献   
3.
ABSTRACT

Introduction

Fifteen percent of proliferating infantile hemangioma (IH) require intervention because of the threat to function or life, ulceration, or tissue distortion. Propranolol is the mainstay treatment for problematic proliferating IH. Other β-blockers and angiotensin-converting enzyme (ACE) inhibitors have been explored as alternative treatments.  相似文献   
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Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O6 -methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in welldifferentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.  相似文献   
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A review of the literature was performed to explore the association between prenatal education and rates of primary cesarean birth for women at low risk for cesarean birth. Most women who are nulliparous with a singleton fetus of term gestational age and in the vertex position are considered to be at low risk and favorable for a vaginal birth, yet the cesarean birth rate for women at low risk was 25.6% in 2019. It has been suggested that the rise in the cesarean birth rate among low-risk women may not be due to medical indications but, rather, to nonmedical factors, such as a provider’s or woman’s preference or lack of prenatal education. Evidence from this literature review supports the premise that prenatal education classes should be routinely incorporated into maternity care in an effort to reduce cesarean birth rates for the low-risk population.  相似文献   
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