Person: Adoamnei, Evdochia
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Immune checkpoint inhibitors‑associated thrombosis in patients with head and neck cancer: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group
Purpose Both venous and arterial thrombotic events (VTE/AT) can be associated with Immune Checkpoint Inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice.Methods /Patients. This retrospective, multicenter study was promoted by the Thrombosis and Cancer Section of the Spanish Society of Medi cal Oncology (SEOM). Individuals with head and neck cancer who initiated ICI between 01/01/2015 and 31/12/2021 were recruited. Minimum follow-up was months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT, with secondary objectives including the analysis of their impact on survival and the identifcation of variables predictive of VTE/AT. Results A total of 143 patients with head and neck cancer were enrolled. The incidence of VTE/AT during follow-up (median 8.6 months) was 2.8%. Survival analysis showed no signifcant diferences (p=0.644) between the group that developed VTE/AT (median 7.13 months, 95% CI 0–22.9) and the group that did not (median 9.86 months, 95% CI 6.3–13.4). The presence of liver metastases was predictive of VTE/AT (p<0.05). Conclusions: Thromboembolic disease associated with immunotherapy in patients with head and neck neoplasia does not signifcantly impact survival. The presence of liver metastases can predict these events.
Thrombosis in breast cancer patients on cyclin-dependent kinase inhibitors: Survival impact and predictive factors - A study by the cancer and thrombosis group of the spanish society of medical oncology (SEOM)
Thrombosis may be included in the profile of side effects associated with CDK4/6 inhibitors. Its significance might be greater than reported in randomized clinical trials. To investigate this, a retrospective, multicenter study was conducted. The primary objective was to calculate the incidence of thrombosis associated with CDK4/6 inhibitors. Secondary objectives included examining the impact of thrombosis on survival and identifying predictor variables for the development of venous thromboembolism (VTE) or arterial thrombosis (AT). A total of 986 patients were recruited. The incidence of VTE/AT associated with CDK4/6 inhibitor treatment during the follow-up period was 5.48 %. Survival analysis did not indicate that the development of VTE/AT during CDK4/6 inhibitor treatment significantly impacted patient survival (p = 0.133). In our analysis, two variables were found to be statistically significant (p < 0.05) as predictors of VTE/AT in breast cancer patients receiving CDK4/6 inhibitor therapy. These variables were the presence of central nervous system (CNS) metastasis with an odds ratio (OR) of 3.68 (95 % CI 1.18 - 11.49) and the use of abemaciclib with an OR of 2.3 (95 % CI 1.16 - 4.57).
Maternal non-compliance with recommended folic acid supplement use alters global DNA methylation in cord blood of newborns: a cohort study
Background & aims: Prenatal folate exposure may alter epigenetic marks in the offspring. We aimed to evaluate associations between prenatal exposure to folic acid (FA) in preconception and in utero with cord blood DNA methylation in long interspersed nuclear element 1 (LINE-1) and Alu short interspersed nuclear elements (SINEs) as markers of global DNA methylation levels. Methods: Data come from 325 motherechild pairs participating in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015e2018). Pregnant women were asked about supplement use, including brand name and dose, one month before pregnancy (preconception) and through the trimesters of pregnancy. Maternal dietary folate intake was assessed using a validated food frequency questionnaire with additional questions for FA supplement use. Folate serum levels were measured in mothers at 24 weeks of gestation and in cord blood of newborns. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 5 LINE-1 and 3 Alu different elements. Associations were estimated using multivariable linear regression models. Results: A reduction in methylation levels of LINE-1 in newborns was associated with the use of FA supplements below the recommended doses (<400 ug/day) during preconception ( 0.50; 95% CI: 0.91, 0.09; P ¼ 0.016), and from preconception up to 12 weeks of gestation ( 0.48; 95% CI: 0.88, 0.08; P ¼ 0.018). Maternal use of FA supplements above the tolerable upper intake level of 1000 ug/day from preconception until 12 weeks of gestation was also related to lower methylation in LINE-1 at birth ( 0.77; 95% CI: 1.52, 0.02; P ¼ 0.044). Neither FA supplement use after 12 weeks of gestation nor maternal total folate intake (diet plus supplements) were associated with global DNA methylation levels at birth.
Factors associated with neonatal brachial palsy in shoulder dystocia: a longitudinal study
Objectives: The main goal is to analyze factors related to brachial plexus injury (BPI) after shoulder dystocia (SD). Material and methods: Longitudinal prospective analysis of SD arose in a tertiary hospital from 1/1st/ 2019 to 12/31st//2020. A multivariable logistic regression for BPI after SD and a survival analysis for BPI recovery after SD were performed. Results: In this period 13,414 deliveries were attended, 10,676 of those were vaginal deliveries (79.6%) reporting 69 cases of SD, with an incidence of 0.65%. SD required 102.1 seconds (SD) 10.8) as an average for solving it. Internal maneuvers were needed in 42.0% of SD reported. Neonatal BPI was suspected in 23 newborns (33.3%) at birth. Neonatal BPI at 48 hours of life was statistically associated with maternal BMI above 30 kg/m2 (OR = 7.91; CI 95% 1.3–47.7; p = 0.024), > 120 seconds for solving SD (OR = 14.4; CI 95% 1.7–121.82; p = 0.014) and operative delivery (OR = 6.8; CI 95% 1.2–37.6; p = 0.028). The BPI recovery was statistically associated with clavicle fracture (HR = 0.31 CI 95% 0.10–0.96 p = 0.042) and specific rehabilitation treatment (HR = 9.2 CI 95% 1.87–45.23 p = 0.006). Conclusions: The following factors were associated with neonatal BPI at 48 hours of life: maternal BMI above 30 kg/m2, operative delivery, or shoulder dystocia that requires more than 120 seconds for solving it. The BPI recovery was associ ated with clavicle fracture and specific rehabilitation treatment.
Maternal urinary concentrations of bisphenol A during pregnancy are associated with global DNA methylation in cord blood of newborns in the “NELA” birth cohort
Endocrine disrupting chemicals (EDCs) set a public health risk through disruption of normal physiological processes. The toxicoepigenetic mechanisms of developmental exposure to common EDCs, such as bisphenol A (BPA), are poorly known. The present study aimed to evaluate associations between perinatal maternal urinary concentrations of BPA, bisphenol S (BPS) and bisphenol F (BPF) and LINE-1 (long interspersed nuclear elements) and Alu (short interspersed nuclear elements, SINEs) DNA methylation levels in newborns, as surrogate markers of global DNA methylation. Data come from 318 mother-child pairs of the `Nutrition in Early Life and Asthma´ (NELA) birth cohort. Urinary bisphenol concentration was measured by dispersive liquid–liquid microextraction and ultrahigh performance liquid chromatography with tandem mass spectrometry detection. DNA methylation was quantitatively assessed by bisulphite pyrosequencing on 3 LINEs and 5 SINEs. Unadjusted linear regression analyses showed that higher concentration of maternal urinary BPA in 24th week's pregnancy was associated with an increase in LINE-1 methylation in all newborns (p = 0.01) and, particularly, in male newborns (p = 0.03). These associations remained in full adjusted models [beta = 0.09 (95 % CI = 0.03; 0.14) for all newborns; and beta = 0.10 (95 % CI = 0.03; 0.17) for males], including a non-linear association for female newborns as well (p-trend = 0.003). No associations were found between maternal concentrations of bisphenol and Alu sequences. Our results suggest that exposure to environmental levels of BPA may be associated with a modest increase in LINE-1 methylation -as a relevant marker of epigenomic stability- during human fetal development. However, any effects on global DNA methylation are likely to be small, and of uncertain biological significance.
Fat intake pattern in women with polycystic ovary syndrome.
Research question: Do women with polycystic ovary syndrome (PCOS) have a different fat intake pattern to women without PCOS? Design: Case–control study of 276 women between 20 and 35 years old from the Murcia region of Spain. Cases (n = 121) attended the Department of Gynaecology and Obstetrics of the University Clinical Hospital and were diagnosed with PCOS using Rotterdam criteria. Controls (n = 155) were women without PCOS attending the gynaecological outpatient clinic for routine gynaecological examinations. Data from clinical, gynaecological and analytical examinations were collected, including a food frequency questionnaire. Associations between fat intake and presence of PCOS and its phenotypes were examined using multiple logistic regression, adjusting for potential confounding factors. Results: Although no association was found between fatty acid intake and PCOS, significant associations were observed for some PCOS phenotypes. The PCOS phenotype characterized by hyperandrogenism + oligo/amenorrhoea + polycystic ovarian morphology (‘H+O+POM’) was significantly associated with a higher intake of polyunsaturated fat (odds ratio [OR] 4.0; 95% confidence interval [CI] 1.1–14.2; fourth quartile of highest intake [Q4] versus lowest intake quartile as reference [Q1]) and omega-6 fatty acids (OR 3.5; 95% CI 1.01–12.4; Q3 versus Q1). The ‘H+O’ phenotype was positively associated with saturated fat intake (OR 6.9; 95% CI 1.1–41.6; Q4 versus Q1). Conclusion: This exploratory study suggests that higher intakes of specific fatty acids are related to some PCOS phenotypes although no association was found for PCOS on a global basis. It is recommended that studies with larger sample size be performed to further explore these associations, thus contributing to establishing recommendations about fat intake adapted to different PCOS phenotypes.
Is maternal use of Paracetamol during pregnancy associated with anogenital distance in male newborns? The results from the NELA Birth Cohort
Paracetamol is the one of the most commonly used medications during pregnancy. However, its potential antiandrogenic effect has been suggested. The objective of this study was to evaluate associations between maternal paracetamol use during pregnancy and anogenital distance (AGD) in male newborns from a Spanish birth cohort. The study included two hundred and seventy-seven mother-male child pairs with self-reported paracetamol use and frequency during each trimester of pregnancy. AGD measurements were taken employing standardized methods. The associations between maternal paracetamol use and AGD measures were evaluated using linear regression models, adjusting for potential confounders and covariates. Overall, 61.7% of pregnant women consumed paracetamol at any time of pregnancy with an average of 9.43 (SD = 15.33) days throughout pregnancy. No associations between the maternal use of paracetamol or its frequency and AGD measures among different trimesters or during the whole pregnancy were found in the adjusted final models. A non-differential misclassification error may have occurred—the recall of paracetamol intake independent of AGD measurements—introducing bias towards the null hypothesis. Nevertheless, the current evidence suggests that paracetamol might have a potential antiandrogenic effect especially in the early stages of fetal development. Thus, it would be highly recommendable to pursue further studies to elucidate the potential effects of paracetamol in human perinatal health and its use among pregnant women.
Urinary concentrations of bisphenol A, parabens and benzophenone-type ultra violet light filters in relation to sperm DNA fragmentation in young men: a chemical mixtures approach.
People are daily exposed to multiple endocrine disruptor compounds (EDCs) that may interfere with different molecular and cellular processes, promoting a potential estrogenic, androgenic, or anti-androgenic state. However, most epidemiological studies attempting to establish relationships between EDCs exposure and health effects are still considering individual compounds. A few studies have shown associations between exposure to individual non-persistent EDCs and sperm DNA fragmentation (SDF) in different male populations. Thus, the aim of this study was to investigate associations between combined exposure to non-persistent EDCs and SDF index in young men. A cross-sectional study was conducted with 158 healthy university students from Southeaster Spain. The participants provided spot urine and semen samples on the same day. The concentrations of urinary bisphenol A (BPA), benzophenones [2,4-dihydroxybenzophenone (BP-1); 2,2′,4,4′-tetrahydroxybenzophenone (BP-2), 2-hydroxy-4-methoxybenzophenone (BP-3), 2,2′-dihydroxy-4-methoxybenzophenone (BP-8), 4-hydroxybenzophenone (4OHBP)], and parabens (methylparaben, ethylparaben, propylparaben, butylparaben) were measured by dispersive liquid-liquid microextraction and ultrahigh-performance liquid chromatography with tandem mass spectrometry detection. SDF was analysed using a Sperm Chromatin Dispersion test. Statistical analyses were carried out using Bayesian Kernel Machine Regression models to evaluate associations between combined exposure to these compounds and SDF index while adjusting by relevant covariates. The increase in urinary concentration of 4OHBP was found to be the most important contributor to the negative association between urinary EDCs concentrations and SDF index, being of 5.5 % [95 % CI: 10.7, 0.3] for those in percentile 50, and 5.4 % [95 % CI: 10.8, 0.1] for those in percentile 75. No significant associations were observed between other EDCs and SDF index. Our findings show that urinary 4OHBP levels may be associated with a decrease in the SDF index. Nonetheless, the effects we observed were likely to be small and of uncertain clinical significance. Further research is needed to replicate our findings in other male populations.