Objectives:To investigate the effect of Mediterranean diet (MedDiet) or mindfulness-based stress reduction (MBSR) in high-risk pregnancies on placental histopathological lesions. Methods: In a randomized clinical trial with parallel-group conducted at a University Hospital in Barcelona, Spain (2017-2020, 1221 pregnant women at high-risk for SGA were randomly allocated at 19-23 weeks of gestation into three groups: a MedDiet intervention, a MBSR program or non-intervention. Participants in the MedDiet group (n = 407) received monthly individual and group educational sessions, and free provision of extra-virgin olive oil and walnuts. Women in the MBSR group (n = 407) underwent an 8-week MBSR program adapted for pregnancy. While the primary outcome was the prevalence of SGA, placental histopathological lesions were considered as a secondary outcome, classified into vascular (maternal/fetal), immune-inflammatory and other lesions according to according to the 2014 Amsterdam Placental Workshop Group Consensus Statement. Results: Among 1182 participants considered for the intention-to-treat-analysis, 741 placentas were collected and studied (n = 257 non-intervention, n = 252 MedDiet, n = 253 MBSR). No differences were observed between the study groups in placental weight, placental dimensions, fetoplacental ratio or any of the placental lesions' categories. Likewise, no differences were detected between pregnancies with an SGA newborn from the three study groups (n = 59 non-intervention, n = 39 MedDiet, n = 37 MBSR). However, in pregnancies complicated by pre-eclampsia (n = 25 non-intervention, n = 17 MedDiet, n = 14 MBSR), we observed a tendency towards less maternal vascular lesions in MedDiet (35.3%, p = 0.19) and MBSR (21.4%, p = 0.05) compared to non-intervention (56%). Conclusions: Structured interventions during pregnancy based onMedDiet or MBSR may reduce maternal vascular placental lesions in pregnancies that develop pre-eclampsia. These results must be considered with caution since the trial was not designed for this specific outcome.

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Background: NSCLC Patients with common sensitive EGFR mutations (deletion in exon 19 or L858R mutation in exon 21) benefit remarkably from first-generation EGFR-TKIs (gefitinib and erlotinib). In this meta-analysis, we aim to investigate their treatment efficacy in patients with uncommon EGFR mutations (S768I, L861Q, G719X, R705K, etc.) by comparing with that in patients with common mutations. Methods: We searched PubMed for eligible studies from the date of inception to 31th December, 2015. Overall objective response rate (ORR) and 6-month progression free survival (PFS) rates were estimated by fix-effect model and relative effects were presented using odds ratio (OR). Mutations within the same exons were grouped in the subgroup analyses.Results: Of 6404 patients from 13 included studies, 466 (7.3%) patients were diagnosed as EGFR uncommon mutations and chose gefitinib and erlotinib as any line of treatment. In single-arm synthesis, the overall ORR in uncommon and common mutations was 34.0% (95% CI 22.5 to 45.5) and 71% (66.7 to 75.3), respectively. Direct comparison indicated significantly less response in uncommon-mutation patients (OR = 0.30, 95% CI 0.23 to 0.41, P < 0.001). Patients with uncommon mutations, compared with common ones, were associated with an inferior 6-month PFS rate (OR = 0.44, 95% CI 0.32 to 0.59; P < 0.001). In exploratory analyses, ORR was 30.7% (16.3 to 45.0), 33.3% (N.A.), 32.1% (13.2 to 51.0) and 38.5% (19.5 to 57.6) in patients with rare mutations in EGFR exon 18, 19, 20 and 21 exons, respectively. In patients with complex mutations (two or more uncommon mutant sites), the ORR was 64.2 % (49.9 to 78.5). Conclusions: Compared with those in sensitive mutations, first-generation EGFR-TKIs presented less clinical benefits in uncommon mutations; but the responses are still considerable, historically compared with that of chemotherapy, especially in complex mutations. First-generation EGFR-TKIs remained an option for uncommon mutations but decision-making should be cautious. Exact efficacy in each specific mutation site merits future studies with larger sample size.Legal entity responsible for the study: N/A Funding: The first affiliated hospital of Guangzhou medical university Disclosure: All authors have declared no conflicts of interest.