Original research publications

Although a significant proportion of postpartum women use medication whilst breastfeeding, information regarding infant exposure to maternal medication via the breast milk is typically limited. In addition to growing pressures for the generation of clinical lactation data from regulators, interest in the use of alternative techniques, such as physiologically based pharmacokinetic (PBPK) modelling, to support clinical studies in this underserved population is increasing. This is consistent with the current interest in model-informed drug development. For lactation models to contribute to clinical decision making, the uncertainties underpinning these models must be understood and minimized where possible. This review therefore aimed to investigate the breast milk distribution models used to support PBPK modelling in the lactation context and to characterize the sources and extent of uncertainty associated with these models. Three models were identified throughout the literature, termed as the Phase Distribution, Log-Transformed Phase Distribution, and Semi-Mechanistic models. Model performance, as compared against observed data, was broadly consistent between each of the three models but significant limitations were identified. Specifically, there is a paucity of clinical lactation data in which breast milk constituents are adequately defined to allow validation of mechanistic models; in vitro data inconsistently support model assumptions; and limited data have been generated using samples from a range of women to offer an understanding of population variability. These gaps in available data are clearly addressable, and further work should be conducted to better support the use of modelling and help address the inequities in safe access to medicine currently faced by women who breastfeed their infants.

Effective targeting of cancer cells has great therapeutic prospects for treating cancer. However, the effects of FTO/MKL-1/SLC7A11 on ferroptosis in breast cancer cells (MDA-MB-231 and MDA-MB-468 cell line) have not been reported so far. Therefore, we investigated how FTO deficiency triggers ferroptosis and modulates the MKL-1/SLC7A11 pathway in cancer cells. Ferroptosis-associated events, including cell viability, GSH/GSSG ratio, and the levels of ROS and Fe 2+ , were detected in cancer cells with FTO overexpression or knockdown. The regulatory mechanism of FTO in the transduction of the MKL-1/SLC7A11 pathway in breast cancer cells was explored. FTO expression was downregulated in cancer cells treated with ferroptosis inducers. FTO overexpression downregulated RSL-3-induced ferroptosis, whereas FTO deletion enhanced ferroptosis by decreasing cell viability and GSH/GSSG ratio and increasing the relative levels of ROS and Fe 2+ . Epitranscriptomic profiling of m6A in the breast cancer tissue of FTO knockdown (KD) and FTO overexpression (OE) mice identified MKL-1 as a target of FTO. Both MKL-1 and SLC7A11 overexpression reversed FTO deficiency-induced ferroptosis. Luciferase assay and ChIP indicated that MKL-1 targets the SLC7A11 promoter. Paclitaxel can trigger ferroptosis in MDA-MB-231 and MDA-MB-468 cell line by repressing the FTO/MKL-1/SLC7A11 axis. These findings indicate that the FTO/MKL-1/SLC7A11 axis is a new regulatory signaling pathway for breast cancer, providing new insights into potential therapeutic targets for breast cancer.

Combination therapy has attracted widespread attention in the field of cancer treatment. However, the complexity of the tumor microenvironment makes it difficult to achieve precise targeting and controlled drug release at the tumor site. Therefore, this study developed a multifunctional delivery system (LEVs-Gel@DOX/Ce6) that integrates combination therapy with smart controlled release: Lemon extracellular vesicles (LEVs) were used as the carrier scaffold to load doxorubicin (DOX) and dihydropyrrole e6 (Ce6) into nanoparticles, which were then dispersed in a smart hydrogel (Gel) composed of oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCs). Following intratumoral injection combined with 660 nm laser irradiation (Laser, +L), the system utilizes the hydrogel's local reservoir function to achieve prolonged drug retention while enabling precise, pH-responsive drug release. Through the synergistic effects of chemotherapy, photodynamic therapy, and immunotherapy, this system directly kills tumor cells by activating apoptosis and ferrocytosis pathways, induces immunogenic cell death (ICD) to stimulate an antitumor immune response, and simultaneously inhibits autophagolysosomal degradation and tumor cell proliferation. In vivo tumor suppression experiments showed that the system achieved a 92.32% inhibition rate against 4T1 breast cancer, delivering highly effective and low-toxicity therapeutic outcomes and providing a novel strategy for the precision treatment of breast cancer.

Highly effective CFTR modulator therapy, such as elexacaftor/tezacaftor/ivacaftor (ETI), has significantly increased pregnancy rates in women with cystic fibrosis (wwCF). Data on health-related quality of life (HRQoL) during pregnancy and the early postpartum period under ETI remain limited. This retrospective observational study evaluated 18 wwCF receiving ETI during pregnancy. Maternal outcomes (lung function, BMI, gestational weight gain, pulmonary exacerbations) and HRQoL using the Cystic Fibrosis Questionnaire-Revised (CFQ-R) were assessed at baseline, during pregnancy, and postpartum. Maternal lung function remained stable across pregnancy and the postpartum period, while pulmonary exacerbations occurred in 50% of pregnancies. Gestational weight gain (GWG) deviated in 16 of 17 women (94%) from Institute of Medicine (IOM) recommendations: 8/17 (47%) had insufficient and 8/17 (47%) excessive GWG, while only 1/17 (6%) achieved adequate GWG. All women with insufficient GWG had a baseline BMI of 18.5-24.9 kg/m 2 , whereas excessive GWG occurred across all baseline body mass index (BMI) categories. In exploratory CFQ-R analyses, the largest changes were observed in the physical, respiratory, and social domains, with lower physical and social scores observed postpartum compared with baseline. Pregnancy in wwCF receiving ETI was associated with preserved maternal pulmonary stability. The high rate of GWG outside recommended ranges and exploratory changes in selected HRQoL identify nutritional and patient-reported outcomes that warrant further prospective investigation.

Tamoxifen and Aromatase Inhibitors are commonly used as adjuvant treatment for estrogen receptor positive (ER+) breast cancer. Our objective was to evaluate the gynecological referral of breast cancer patients treated with tamoxifen or aromatase inhibitors. We conducted a retrospective cohort study of 153 breast cancer patients treated at the McGill University Health Centre (MUHC) between 2015 and 2025. Variables assessed included age, body mass index (BMI), parity, menopausal status, symptoms at presentation (particularly abnormal uterine bleeding [AUB]), type of adjuvant therapy (tamoxifen and/or Aromatase Inhibitor), and findings from pelvic ultrasound, hysteroscopy, endometrial biopsy, and histopathology. Most patients (n = 143, 93.5%) were premenopausal. Tamoxifen alone was used in 50 patients (34.5%), Aromatase Inhibitors in 34 (24%), and sequential tamoxifen and Aromatase Inhibitors were used in 15 (10.5%). Among the 99 patients treated with tamoxifen and/or Aromatase Inhibitors, 7 (7.1%) experienced AUB, compared to none in the untreated group. Endometrial thickness during treatment was greater in those with AUB (median 11.0 mm, IQR 7.2-16.8) than in those without AUB (median 3.9 mm, IQR 1.5-6.8). Of 153 patients, 19 (12.4%) were referred to gynaecology for AUB and/or thickened endometrium. Only a small proportion of patients with breast cancer treated with tamoxifen or Aromatase Inhibitors are referred for gynaecological evaluation with AUB and/or a thickened endometrium as the main referral indications. Gynaecologic referrals at our institution align with current guidelines, with specialized assessment reserved primarily for symptomatic patients rather than for routine surveillance of asymptomatic patients receiving endocrine therapy.Résumé OBJECTIFS: Le tamoxifène et les inhibiteurs de l'aromatase sont couramment utilisés comme traitement adjuvant dans le cancer du sein à récepteurs d'œstrogènes positifs (ER+). Notre objectif était d'évaluer l'orientation en gynécologie de patientes atteintes d'un cancer du sein et traitées par le tamoxifène ou un inhibiteur de l'aromatase. MéTHODOLOGIE: Nous avons mené une étude de cohorte rétrospective auprès de 153 patientes atteintes d'un cancer du sein et traitées au Centre universitaire de santé McGill (CUSM) entre 2015 et 2025. Les variables évaluées comprenaient l'âge, l'indice de masse corporelle (IMC), la parité, l'état ménopausique, les symptômes initiaux (notamment les saignements utérins anormaux [SUA]), le type de traitement adjuvant (tamoxifène et/ou inhibiteur de l'aromatase), ainsi que les résultats de l'échographie pelvienne, de l'hystéroscopie, de la biopsie de l'endomètre et de l'analyse histopathologique.; Résultats : La plupart des patientes (n = 143, 93,5 %) étaient non ménopausées. Le tamoxifène seul a été utilisé chez 50 patientes (34,5 %), un inhibiteur de l'aromatase chez 34 (24 %), et le tamoxifène suivi d'un inhibiteur de l'aromatase chez 15 (10,5 %). Parmi les 99 patientes traitées par le tamoxifène et/ou par un inhibiteur de l'aromatase, 7 (7,1 %) ont présenté des SUA, comparativement à aucune dans le groupe non traité. L'épaisseur endométriale pendant le traitement était plus importante chez les patientes ayant présenté des SUA (médiane : 11,0 mm; IIQ : 7,2-16,8) que chez celles sans SUA (médiane : 3,9 mm; IIQ : 1,5-6,8). Sur les 153 patientes, 19 (12,4 %) ont été orientées en gynécologie en raison de SUA ou d'un épaississement de l'endomètre. Seule une faible proportion des patientes atteintes d'un cancer du sein et traitées par le tamoxifène ou un inhibiteur de l'aromatase sont orientées vers un examen gynécologique, principalement en raison de SUA ou d'un épaississement de l'endomètre. Dans notre établissement, l'orientation en gynécologie est conforme aux lignes directrices actuelles, l'évaluation spécialisée étant principalement réservée aux patientes symptomatiques, et non utilisée à des fins de surveillance systématique chez des patientes asymptomatiques sous endocrinothérapie.

Physical Activity during pregnancy has been a controversial field for years, despite its widely proven benefits in general population. The benefits of PA in both mother and the fetus should be highlighted to provide new insights. Examine the association of PA in Greek pregnant women with pregnancy outcomes. This is a multicenter, prospective, observational study. The participants completed the Greek PPAQ and pregnancy outcomes were collected after birth. The level of PA and consistency with the international PA recommendations was evaluated with the use of METs. All pregnant women speaking greek fluently were eligible. The study was approved by the Ethical Committee of the University Hospital of Ioannina. Statistical analysis was conducted with the R program version 4.3.1. A regression analysis was also conducted for all pregnancy outcomes adjusted to potential cofounders. A total of 915 pregnant women filled the PPAQ Greek version and were contacted postnatally for the outcomes. Neonates of active pregnant women had a lower median birthweight (3100 g vs 3170g, OR: 1.12, 95% CI:0.54- 2.11), lower incidence of admission to NICU (6.2% vs. 8.2%, OR: 0.76, 95% CI:0.33- 1.54) or neonatal complications (4.7% vs. 7.1%, OR: 0.64, 95% CI:0.24- 1.40). Moreover, pregnancy related hypertensive disorders and gestational diabetes mellitus were lower in the active group (0.01% vs. 3.8% OR: 0.20, 95% CI:0- 1.21 and 11.6% vs. 13.5%, OR: 0.85, 95% CI:0.46- 1.47 respectively). Vaginal delivery was more common in the active group (43% vs. 37.5% OR: 0.81, 95% CI:0.56- 1.19), as well as the incidence of PTB< 37 weeks (6.2% vs. 7.4%, OR: 0.84, 95% CI:0.36- 1.72). After adjusting for confounders, only birthweight differences were statistically significant (p = 0.036; 95% CI: -153, -5.5). This study demonstrates that PA during pregnancy is safe and beneficial for maternal-fetal health in several aspects of pregnancy outcomes. Clinicians should encourage incorporating PA in prenatal care in the absence of complications, while further studies using objective measures are needed to strengthen these findings.

Exposure to per- and polyfluoroalkyl substances (PFAS), including emerging substitutes, is associated with several adverse pregnancy outcomes. However, the evidence on intrauterine exposure to PFAS during human early pregnancy was limited. This study measured the concentrations of 31 (18 legacy and 13 emerging) PFAS chemicals in 402 maternal serum and 221 placental villi tissues collected during the first trimester. The associations of individual and combined PFAS exposures with early pregnancy loss (EPL) were estimated using multivariable generalized additive models, logistic regression models, quantile g-computation, subgroup stratified, and interaction analyses. Six PFAS chemicals detected simultaneously in the serum and villi with detection rates exceeding 80% showed strong correlations between the two matrices, with correlation coefficients ranging from 0.78 to 0.93, and with 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (9Cl-PF3ONS) exhibiting the highest correlation. Odds ratios (95% confidence intervals) of EPL were 1.72 (1.04, 2.83), 2.18 (1.02, 4.69), 1.99 (1.04, 3.79), 2.66 (1.35, 5.22), and 5.17 (2.30, 11.63) associated with per ten-fold increase in the concentrations of serum 9Cl-PF3ONS, serum perfluorohexane sulfonate (PFHxS), serum perfluorooctane sulfonate (PFOS), villi 9Cl-PF3ONS, and villi perfluorooctanoic acid (PFOA), respectively. However, the associations of serum 9Cl-PF3ONS, PFHxS, and PFOS with EPL were no longer statistically significant after false discovery rate correction. The joint association between PFAS mixture in villi and EPL was positive, with 9Cl-PF3ONS having the largest positive weights. Subgroups with age ≤ 30 years, body mass index ≥ 24 kg/m 2 , or tobacco exposure showed higher odds ratios of EPL associated with specific PFAS chemicals. In conclusion, emerging substitute 9Cl-PF3ONS could arrive at early placenta. Maternal and placental exposure to PFAS including 9Cl-PF3ONS showed positive associations with EPL; however, the findings in serum should be interpreted cautiously.

Pathological complete response (pCR) after neoadjuvant therapy is associated with favorable outcomes in breast cancer, yet differences in response cannot be explained by immune-cell abundance alone. This review examines pCR and residual disease from a spatial perspective. An effective antitumor response requires coordinated immune recruitment, local activation and renewal, movement across tissue boundaries, contact with malignant cells, and maintenance of effector function. Disruption at any stage may preserve resistant tumor regions despite substantial overall immune infiltration. Current evidence indicates that immune-cell positioning, multicellular organization, and the spatial distribution of stromal, vascular, and metabolic constraints can provide information beyond conventional cell-density measurements. However, the strength and clinical meaning of these associations vary according to breast cancer subtype, treatment regimen, sampling time point, and analytical platform. Pretreatment tissue, early on-treatment samples, and surgical residual disease address distinct baseline response-associated, pharmacodynamic, and prognostic questions and should therefore be interpreted separately. Residual disease represents a treatment-selected ecosystem rather than simply a smaller version of the untreated tumor. We integrate available evidence into a time-resolved framework linking baseline spatial architecture, treatment-related remodeling, residual disease organization, and subsequent clinical outcome. Translation into clinical practice will require standardized spatial definitions and measurements, reproducible assessment of organized immune structures, subtype- and regimen-specific validation, and demonstration of added value beyond established pathological indicators. Spatially resolved analysis may improve understanding of heterogeneous neoadjuvant responses and support more precise post-treatment risk assessment.

Electronic health record-based oncology studies depend on computable case definitions, but different operational definitions may identify different patient populations and change downstream estimates. This retrospective benchmarking cohort study evaluated three definitions of incident invasive breast cancer in the TriNetX Global Collaborative Network: at least one malignant breast cancer diagnosis code (Dx1), a repeated diagnosis-code definition within 90 days (Dx2), and a diagnosis code plus breast cancer-directed treatment evidence (DxTx). Female patients aged 20 years or older were identified after a 12-month washout period and exclusion of patients with carcinoma in situ only. Pairwise one-to-one propensity-score matching was performed using 13 baseline covariates. Outcomes were all-cause mortality and time to the first emergency department visits, assessed from day 180 after the index date to 1, 3, and 5 years after the original index date. Appendicitis and femoral neck fracture were included as negative-control outcomes. Dx1, Dx2, and DxTx identified 1,450,233, 678,739, and 578,576 patients, respectively. After matching, more restrictive definitions were consistently associated with higher hazards of mortality and emergency department visits. For mortality, hazard ratios ranged from 1.26 to 1.32 for DxTx versus Dx1, 1.13 to 1.14 for Dx2 versus Dx1, and 1.13 to 1.17 for DxTx versus Dx2 across assessment windows. Emergency department visit estimates showed a similar but attenuating pattern. These associations should be interpreted as differences between phenotype-defined populations arising from selection and ascertainment mechanisms rather than as treatment effects. Negative-control outcomes were generally close to the null; small appendicitis associations observed in comparisons involving Dx1 did not remain statistically significant after correction for multiple testing. These findings indicate that plausible electronic health record-based breast cancer definitions are not analytically interchangeable. Phenotype specification should therefore be treated as a core analytic decision and evaluated through transparent reporting and sensitivity analyses.

Pregnancy in women with type 1 diabetes (T1D) complicated by overt diabetic nephropathy (DN) remains a major clinical challenge, with limited data on maternal-foetal outcomes. This study describes the clinical course and outcomes of pregnancies in women with overt DN followed in a dedicated nephrology-obstetric care setting. We conducted a retrospective analysis including 15 pregnancies, 13 of which had complete baseline and delivery data, in women with T1D and overt DN followed at Policlinico Umberto I (Rome-Italy), between 2010 and 2022. Maternal characteristics, renal and obstetric complications, and perinatal outcomes were analysed from baseline to six months postpartum. Thirteen pregnancies were analysed. Median baseline estimated glomerular filtration rate (eGFR) was 67.6 (42.9-95.8) ml/min/1.73m2, median proteinuria 0.8 (0.5-1.6) g/day; 69% had chronic hypertension and 84% diabetic retinopathy. Proteinuria increased during pregnancy in 9/13 cases. Two patients developed acute kidney injury, one of whom required haemodialysis during pregnancy and remained dialysis-dependent thereafter. Superimposed preeclampsia occurred in five cases and was associated with lower baseline eGFR. Preterm delivery was common; all the patients delivered by caesarean section. A decline ≥10 mL/min/1.73 m2 in eGFR or dialysis initiation was observed in 4 patients at 6-month follow-up; in the remaining patients, no significant changes were observed, although the follow-up was limited to 6 months. Pregnancy in women with overt DN continues to entail substantial maternal and foetal risk. Early nephrology referral, strict metabolic and blood pressure control, and systematic preconception counselling are crucial to optimising outcomes and preventing irreversible renal decline.

The prognostic relevance of angiogenesis in breast cancer remains unclear when modeled as a coordinated gene program rather than individual gene effects. This study aimed to characterize the multidimensional structure of angiogenesis and assess the prognostic relevance of its latent components for overall survival in breast cancer. Using RNA sequencing data from 1,096 patients with The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) from the United States, we summarized 36 angiogenesis-related genes via principal component analysis (PCA) applied to standardized log-counts per million values. The first three components ([Formula: see text]), retained based on variance explained, scree plot inspection, and interpretable gene loading patterns, were evaluated for association with overall survival using Kaplan-Meier and Cox proportional hazards models adjusted for age and molecular subtype. The first three components captured a multi-dimensional structure of angiogenesis activity. None was significantly associated with overall survival in multivariable Cox models (Z1: HR = 1.016, 95% CI: 0.957-1.078, p = 0.603; Z2: HR = 1.049, 95% CI: 0.954-1.153, p = 0.319; Z3: HR = 1.007, 95% CI: 0.918-1.105, p = 0.878), and Kaplan-Meier analyses showed no significant survival differences across median-based groups. Functional enrichment analyses indicated that the retained components represented distinct biological dimensions of angiogenesis. Subtype-specific analyses showed no statistically significant associations within individual subtypes and no strong evidence of effect modification. However, marked differences in latent component distributions across molecular subtypes revealed substantial subtype-specific heterogeneity. Collectively, these findings indicate limited independent prognostic relevance for overall survival despite substantial biological heterogeneity and subtype-specific variation. Angiogenesis is a multi-dimensional and biologically heterogeneous process. No latent angiogenesis component demonstrated independent prognostic value for overall survival, indicating that angiogenesis is insufficient as a standalone prognostic biomarker. Nevertheless, subtype-specific variation across latent dimensions highlights its relevance for understanding biological heterogeneity in breast cancer.

This cross-sectional study examined the associations of policy support and social support with postpartum depressive symptoms and quality of life among 528 postpartum women in China. Data were collected from June to December 2024. Higher policy support was associated with greater social support and fewer postpartum depressive symptoms. Greater social support was also associated with fewer postpartum depressive symptoms and better quality of life. Serial mediation analysis identified statistically significant indirect associations linking policy support with quality of life through social support and postpartum depressive symptoms. These findings were consistent with an associative serial mediation model but should not be interpreted as evidence of temporal or causal relationships.

Substance use disorders (SUDs) are common in pregnancy and the postpartum year (the perinatal period), yet research, guidance, and reimbursement have concentrated on opioid use disorder (OUD).Meanwhile, alcohol, cannabis, tobacco, and stimulant use disorders are similarly prevalent and often co-occur. This review examines medication options for these five SUDs in the perinatal period, together with the behavioral treatments that accompany or preempt them. This narrative review synthesizes literature published from January 2020 to September 2026 (PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov), plus foundational studies, on medications and principal behavioral treatments for tobacco, alcohol, cannabis, opioid, and stimulant use disorders in pregnancy and the first 12 months postpartum. Evidence is graded from pregnancy-specific trials to extrapolation from nonpregnant populations. The focus on OUD has left alcohol, cannabis, and stimulant use disorders comparatively orphaned in the perinatal period, and emerging medications need pregnancy-specific evaluation rather than extrapolation or blanket avoidance. For any SUD, a shared, dyadic decision-making framework that weighs the risks of untreated illness against those of treatment can guide care.

To voice surgeons' experiences with pregnancy loss during training and identify current gaps in support structures within training programs. Previous literature emphasizes the prevalence of pregnancy loss among female surgeons, frequently reporting a rate of more than double that of the general population. Despite this, little has been done to voice the personal experiences behind this data and to identify solutions to support trainees through these events. Semistructured focus groups and individual interviews were conducted between June and August of 2025. Surgeons within 5 years of general surgery residency graduation and current surgical fellows and general surgery trainees who identify as female and as having had a pregnancy loss during surgical training were recruited through targeted social media platforms. Transcripts were individually coded, and emerging codes were iteratively refined into themes related to the pregnancy loss experience and gaps in support resources. Participants described the multidimensional impact of pregnancy loss during general surgery training. Mental health, physical, and professional impacts were pervasive. Five barriers to seeking support were identified: burden to colleagues, privacy concerns, reputation concerns, guilt and isolation, and rigidity of training. Facilitators to seeking support, though fewer, were greatly beneficial. These thematic categories informed critical gaps in general surgery program support structures and important components of a pregnancy loss policy designed to reduce stigma, promote trainee well-being, and mitigate attrition from the field. This study highlights the pregnancy loss experience among current and former general surgery trainees and uses these experiences to propose necessary support structures to be implemented within training programs.

To examine age-specific breast cancer incidence trends. Breast cancer case counts were obtained from the National Cancer Incidence Reporting System (1984-1991) and the Canadian Cancer Registry (1992-2023) both housed at Statistics Canada. Trends in age-specific and age standardized incidence rates (ASIR), and associated annual percent changes (APC), were determined using JoinPoint. The most recent breast cancer age-specific trends were observed to be increasing for all age groups under age 55, especially 45-49 since 2018 (APC = 2.4, P < .001); were stable for 55-59, and decreasing for age groups within 60-74, though not significantly for 70-74 (APC = -0.4, P = .076). An increasing breast cancer ASIR trend was observed throughout the study period except for 1999-2004. Between 1984-1986 and 2021-2023 incidence rates increased in each age group <85; however, they decreased among women 90+ by 23.5%. Apart from the 55-59 age group, relative increases of 20% or more combined with absolute increases of 50 per 100 000 or more between these two periods were observed for each age group between 50-54 and 70-74. The largest absolute increase occurred among women 65-69 (76.1 per 100 000). The age group corresponding to the peak incidence rate has become younger over time from 90+ (1984-1986) to 70-74 (since 2011-2013). Highlighted by increasing rates among younger women, especially those 45-49, recent trends in age-specific breast cancer incidence rates are diverging with important implications for screening and clinical care. Over several decades, the shape of the age-specific breast cancer incidence rate curve has changed with peak incidence occurring at a younger age.

Severe anemia may be life-threatening and is associated with adverse maternal outcomes; however, there is a paucity of literature on socio-cultural practices that may influence anemia in pregnancy. Women in many African societies value cultural practices in the perinatal period. These practices are known to influence the prevention, detection, and management of anemia in pregnancy. To explore the socio-cultural practices and beliefs that influence anemia in pregnancy among women in Cape Coast, Ghana. A qualitative descriptive exploratory study design was used, consisting of semi-structured face-to-face interviews with 32 puerperal women. Interviews were audio-recorded and transcribed verbatim. A hybrid thematic analysis was undertaken, incorporating a deductive, theoretical (top-down) process and an inductive, data-driven (bottom-up) approach. The theoretical domains framework was used to develop the interview questions and to guide the deductive analysis. Women believed certain traditional medicines would influence pregnancy outcomes; however, they perceived that they had limited autonomy concerning their antenatal attendance, food choices, and preferences. Partners were reported to make decisions about the location and timing of the initial antenatal visit and to manage the money for transportation and out-of-pocket healthcare-related expenses. Family members were reported to prohibit women from consuming foods believed to impact pregnancy adversely. Family support played a crucial role, while practical community support was generally lacking. Socio-cultural factors may influence anemia in pregnancy management. This study highlights the need for empowerment of women, and for education of partners and other family members about anemia in pregnancy. There is also a need to understand women's socio-cultural backgrounds and familial power dynamics when providing care.

Twin pregnancies occur in ~12 per 1,000 pregnancies worldwide and are associated with substantially increased maternal, fetal and neonatal morbidity and mortality compared with singleton pregnancies. Although zygosity describes whether twins arise from one fertilized egg (monozygotic) or two fertilized ova (dizygotic), clinical risk is primarily determined by chorionicity (whether twins share a placenta) and amnionicity (whether twins share an amniotic sac). Accurate early determination of chorionicity and amnionicity is therefore fundamental to counselling, risk stratification, surveillance and management, and should be established and documented consistently throughout pregnancy. Monochorionic twins are uniquely susceptible to complications arising from shared placental vascular anastomoses, including twin-twin transfusion syndrome and twin anaemia-polycythaemia sequence or unequal placental sharing in the form of selective fetal growth restriction. Preterm birth remains the leading cause of perinatal morbidity and mortality in twin pregnancies, with the risk of extreme preterm birth markedly higher than in singleton gestations. Contemporary surveillance strategies aim to identify evolving complications sufficiently early to enable timely intervention and optimize outcomes.

Metastatic HER2-positive breast cancer is frequently associated with secondary spread to the central nervous system. Although the blood-brain barrier can limit drug exposure, intracranial activity is not determined by molecular size alone and has now been demonstrated with both tyrosine kinase inhibitors (TKIs) and trastuzumab deruxtecan (T-DXd). Among anti-HER2 TKIs, tucatinib combined with trastuzumab and capecitabine has the strongest randomized evidence in patients with active brain metastases, based on HER2CLIMB. Lapatinib retains a European marketing authorisation but now has only a marginal role in French practice. Neratinib has no metastatic indication in the European Union and is not reimbursed in France in its sole European indication, extended adjuvant therapy. Recent DESTINY-Breast12 data confirm substantial intracranial activity with T-DXd, while DESTINY-Breast09 and HER2CLIMB-05 are reshaping the first-line landscape. Community pharmacists play an important role in safe dispensing, interaction screening, toxicity management and adherence support for oral therapies.

Pregnancy-associated triple-negative breast cancer (PA-TNBC) is a highly aggressive, hard-to-treat malignancy, with increased risk linked to post-lactational mammary gland involution. To understand this, we used GeoMx Digital Spatial Profiler to analyze the transcriptional landscape of 46 treatment-naïve PA-TNBC tissues from 33 women (10 pre-involution/PRE; 23 post-involution/POST, diagnosed within 3 years of delivery), focusing on epithelial and microenvironmental changes. Our findings reveal that the most significant transcriptional differences between PRE and POST exist in non-invasive epithelia and during the transition to invasion. POST non-invasive epithelia showed distinct activation of inflammatory and developmental pathways, while transitioning to TNBC involved elevated chromatin remodeling and migration. Notably, the tumor microenvironment (TME) surrounding POST invasive epithelia featured the greatest immune cell infiltration yet also increased immune exhaustion. Pseudotime analysis highlighted the 1-2 year postpartum window as having the strongest inflammatory signaling. These results underline the need for early molecular detection in normal-appearing post-involution tissues and suggest that targeting the TME is a viable strategy for treating POST PA-TNBC.

Breast cancer is a leading cause of morbidity and mortality in Low- and Middle-Income Countries (LMICs). Hematological and inflammatory markers offer accessible, low-cost tools for patient assessment; hence, this study synthesized evidence on hematological parameters and serum cytokine levels in breast cancer patients from LMICs. Following PRISMA guidelines, we searched PubMed, Scopus, and Google Scholar for studies published between January 2013 and December 2025 comparing hematological parameters or serum cytokine levels between breast cancer patients and controls in LMICs, the protocol was registered on PROSPERO (CRD420261543115). Of 25 eligible studies identified, 22 were included in the meta-analysis. Data on complete blood count indices and inflammatory cytokines were extracted and pooled using random-effects models. Pooled effect sizes were calculated as standardized mean differences (SMD) with 95% confidence intervals. Subgroup analyses were performed by treatment status, and heterogeneity, sensitivity, and publication bias were assessed. All statistical analyses were performed using R software (version 4.5.0). Erythrocyte parameters were consistently lower, including red blood cell count (SMD = -1.83; 95% CI: -3.32 to -0.33), packed cell volume (SMD = -4.04; 95% CI: -8.08 to -0.00), mean corpuscular volume (SMD = -1.15; 95% CI: -2.64 to -0.34), and mean corpuscular hemoglobin (SMD = -0.99; 95% CI: -2.19 to -0.20). Platelet-related parameters were elevated, including pretreatment platelet count (SMD = 0.44; 95% CI: 0.17-0.70) and mean platelet volume (SMD = 0.44; 95% CI: 0.07-0.81). Leukocyte profiles showed decreased lymphocytes (SMD = -1.07; 95% CI: -1.82 to -0.83) and eosinophils (SMD = -2.33; 95% CI: -5.90 to -1.25), with increased monocytes (SMD = 0.79; 95% CI: 0.29- 1.29). One study reported markedly elevated inflammatory cytokines in patients versus controls: IL-6 (20.6 vs. 4.4 pg/mL), IL-10 (8.8 vs. 2.8 pg/mL), and TNF-α (26.0 vs. 4.7 pg/mL); all p = 0.001. These findings support the integration of routine complete blood count parameters as accessible, low-cost tools for monitoring disease burden and systemic inflammation in resource-limited settings. Further research is needed to characterize cytokine profiles and establish normative reference data for LMIC populations.

Age-based mammography screening fails to account for individual breast cancer risk variation, particularly in Asian populations where prospective evidence is absent. The BREAst Screening Tailored for HEr (BREATHE) study is a multicentre prospective cohort of 4,513 women aged 35-59 years recruited across six Singapore clinical sites (2021-2023). Risk-stratified screening recommendations were assigned using a five-year absolute risk threshold of 0.9% (equivalent to the population-average risk of an average 50-year-old Singaporean woman) to initiate screening based on polygenic risk score (PRS) and Gail model, as well as mammographic density, family history, abnormal prior screening. Two independent breast cancer case cohorts provided comparative analyses: Singapore Breast Cancer Cohort (SGBCC, n = 2,782) and Malaysian Breast Cancer Genetic Study (MyBrCa, n = 2,466); combined n = 9,761. Among 2,003 healthy women aged 40-49 years currently recommended annual mammography, risk stratification downgraded 776 (38.7%) to no screening and 960 (47.9%) to biennial as they were not in the top 2.5th percentile of PRS and Gail risk and did not have any additional risk indicators. Of 41 breast cancers diagnosed after BREATHE enrolment, 35 (85.4%) occurred in women assigned to screening-eligible categories at baseline. Risk stratification combining PRS and Gail model captured 68-69% of cases aged 40-49 in SGBCC (n = 1,184) and MyBrCa (n = 1,122), versus ~ 54% by PRS alone. Relative to cases meeting screening criteria for both PRS and Gail model, PRS-missed cases were enriched for progesterone receptor negativity (OR 1.24; 95% CI 1.01-1.52), tumour size ≥ 50 mm (OR 1.43; 95% CI 1.02-2.00), and germline protein-truncating variants (PTVs) in breast cancer predisposition genes (OR 1.53; 95% CI 1.03-2.29). Risk stratification combining PRS with classical risk factors reshapes mammography recommendations in Asian women. However, due to the limited number of events in BREATHE, this finding requires evaluation in larger prospective studies. PRS-missed cancers exhibit a biologically aggressive profile, defining the current limits of common-variant prediction and identifying the biology that future precision screening tools must address.

Breast cancer is the most common cancer among women globally, accounting for one in four cancer cases and one in six cancer deaths. Timely initiation of treatment after diagnosis is critical to improving survival outcomes. However, delays in treatment initiation remain widespread, influenced by health system constraints, socio-demographic factors, and the COVID-19 pandemic. Despite growing recognition of this issue, no prior study has comprehensively quantified global evidence on diagnosis-to-treatment delays in breast cancer. Our objective was to systematically review and synthesize global evidence on time to treatment initiation (TTI) among patients with breast cancer, and to estimate pooled mean delays and the proportion of patients experiencing delays at predefined cutoffs (30, 60, and 90 days). This systematic review and meta-analysis was conducted following PRISMA 2020 guidelines. Four databases (PubMed, Scopus, Web of Science, and Embase) were searched from inception to October 15, 2025. Eligible observational studies reported TTI as mean/median days or as proportions of patients with delayed initiation. Data were pooled using DerSimonian-Laird random-effects models. Subgroup analyses were performed by publication period, WHO region, study setting, and World Bank income group. A sensitivity analysis excluded United States datasets. Risk of delay was compared by stage at diagnosis. Risk of bias was assessed with the Joanna Briggs Institute checklist. Sixty studies (analyzed as 62 datasets) involving 3644,548 breast cancer patients from 21 countries were included. The pooled mean TTI was 51.7 days (95% CI: 46.5-56.9; I² = 99.9%). At the 30-day cutoff, 37% (95% CI: 25-49%) of patients experienced delays; at 60 days, 17% (95% CI: 11-22%); and at 90 days, 4% (95% CI: 3-5%). The United States contributed 32 datasets and 70.1% of participants. Excluding these datasets raised the pooled mean TTI to 75.0 days (95% CI: 44.5-105.5). Mean TTI was 39.8 days in high-income countries and 79.7 days in low- and middle-income countries (p = 0.07). Delays beyond 90 days affected 2.6% and 26.5% of patients, respectively (p < 0.001). Stage at diagnosis was not associated with delay. Delays between diagnosis and treatment initiation are common, with more than one-third of patients waiting over 30 days. The pooled estimate reflects mainly high-income settings. Delays are longer, and very long delays more frequent, in low- and middle-income countries, where evidence remains sparse. Agreed TTI benchmarks, stronger oncology services, and more primary studies from low- and middle-income countries are priorities to close the cancer care gap.

To develop and evaluate the efficacy of a self-management intervention program based on Health Empowerment Theory for breast cancer patients with totally implantable venous access ports (TIVAP). This study adopted a prospective, parallel-group, randomized controlled trial design. Breast cancer patients with TIVAP were recruited from tertiary hospitals and underwent longitudinal quantitative outcome assessments at four follow-up time points. This randomized controlled trial was retrospectively registered with the Chinese Clinical Trial Registry (ChiCTR) on February 2, 2026 (registration number: ChiCTR2600118117). The intervention program was developed through literature review and expert consultation. A total of 54 participants were randomly assigned to the intervention group (n=27) and the control group (n=27). Three patients were lost to follow-up during the 12-week study, and 51 patients (intervention group, n=26; control group, n=25) were included in the final complete-case analysis. The primary outcome was patients' TIVAP self-management ability measured by the C-SUPPH. Secondary outcomes included health empowerment (CEQ), quality of life (EORTC QLQ-BR42), and TIVAP-related complications, which were assessed at baseline (T0), 4 weeks (T1), 8 weeks (T2), and 12 weeks (T3). Repeated-measures ANOVA was used to analyze longitudinal continuous outcomes, and the chi-square test was applied for categorical complication data. For key continuous outcomes, between-group mean differences with 95% confidence intervals were reported to quantify intervention effects and improve result interpretability, rather than relying solely on P-values. All statistical analyses were performed using SPSS 27.0, with P＜0.05 indicating statistical significance. The dropout rate was 5.56%. No significant between-group differences were observed at baseline (P>0.05). From T2 onward, CEQ and C-SUPPH scores were significantly higher in the intervention group than in the control group (P<0.05). Between-group differences in the QLQ-BR42 symptom domain emerged at T2, while differences in the functional domain emerged at T3. At T3, the complication rate was significantly lower in the intervention group (8%, 2/25) than in the control group (30.77%, 8/26; χ²=4.192, P<0.05). The intervention effectively reduced TIVAP-related complications and improved health empowerment, self-management efficacy, and quality of life among breast cancer patients, providing a targeted clinical nursing strategy.

Preeclampsia (PE) is a severe pregnancy-specific disorder and a leading cause of maternal and perinatal morbidity and mortality. Although the traditional two-stage model links abnormal placentation to maternal endothelial dysfunction, it does not fully explain how placental stress is converted into persistent systemic inflammation. This review reframes the mitochondria-immune axis as a hierarchical and self-amplifying network in PE. In this model, placental hypoxia-reoxygenation, endoplasmic reticulum stress and anti-angiogenic stress act as initiating events that destabilize mitochondrial homeostasis in trophoblasts, endothelial cells and immune cells. Damaged mitochondria then release reactive oxygen species (ROS), mitochondrial DNA (mtDNA) and other danger signals, which activate innate immune sensors, including the NLRP3 inflammasome, cGAS-STING, TLR9 and NF-kB pathways. These pathways induce IL-1β, TNF-α, type I interferon signaling, complement activation, neutrophil extracellular traps and macrophage/T-cell imbalance, which in turn aggravate mitochondrial injury and sustain a pathogenic feedback loop. We further distinguish the likely contribution of this axis across PE subtypes, including early-onset, late-onset, maternal, canonical and immunological PE. The review critically evaluates circulating mtDNA and mitochondria-related genes as biomarkers, emphasizing the effects of sample processing, vesicle-bound mtDNA, cellular contamination, gestational timing and assay choice. Therapeutic opportunities are discussed according to translational maturity, from clinically relevant supportive approaches and PE-tested preclinical interventions to extrapolated mitochondrial and immunopharmacological strategies. Overall, the mitochondria-immune axis provides a structured framework for subtype-aware biomarker development and mechanism-guided intervention in PE, while highlighting the need for standardized longitudinal cohorts and pregnancy-specific safety validation.

Women who have had certain pregnancy complications have an increased risk of future cardiovascular disease. The first year postpartum is an ideal window of opportunity for cardiovascular risk screening, management, and cardiovascular disease prevention. Recognizing that access to postpartum care can be challenging, particularly for those who live in rural or remote areas, it is the role of the obstetrical care providers to identify the women who are at risk and to initiate discussions about the importance of postpartum blood pressure monitoring and cardiovascular risk screening and to identify who is responsible for both the short-term and longer-term medical follow-up.

Chronic stress is associated with increased risk of breast cancer metastasis and poor clinical outcomes; however, the underlying mechanisms remain incompletely understood. Here, we demonstrated that chronic stress elevates lactate levels in the tumor microenvironment, thereby promoting lactylation of metastasis associated 1 family member 2 (MTA2) at lysine 460. Mechanistically, chronic stress not only enhances lactate metabolism within the tumor microenvironment, providing sufficient substrate for lactylation, but also activates the β2-adrenergic receptor (β2-AR)/PKA signaling axis, leading to P300 phosphorylation and cooperatively facilitating MTA2 lactylation. This modification weakens the interaction between MTA2 and RBBP7, resulting in destabilization of the nucleosome remodelling and histone deacetylase (NuRD) complex and impaired transcriptional repression. This is accompanied by increased H3K9 acetylation and upregulation of genes associated with both tumor progression and metastasis, including MMP16, NRP1, and VCAM1. Importantly, a cell-penetrating peptide specifically targeting MTA2 lactylation effectively inhibits breast tumor growth and reduces lung metastatic burden in chronic stress models. Together, our findings identify protein lactylation, especially that of MTA2, as a key regulatory event in chronic stress-induced tumor progression, providing new insights into the link between tumor epigenetics and chronic stress, and suggesting a potential biomarker and therapeutic target for prognostic assessment and clinical intervention in breast cancer patients under chronic stress.

During pregnancy, placenta-derived proteins such as pregnancy-specific glycoprotein 1 (PSG1) enter the maternal circulation, providing a window into placental health and enabling liquid biopsy strategies for monitoring pregnancy disorders. PSG1, a highly glycosylated protein secreted by syncytiotrophoblast (STB) cells, reflects trophoblast differentiation status. Circulating PSG1 levels are reduced in early-onset preeclampsia (PE), but how PSG1 glycosylation is altered in this condition remains unclear. Here, we show by liquid chromatography-tandem mass spectrometry that native PSG1 purified from healthy and early-onset PE pregnancies carries an O-linked glycan in its N domain in addition to diverse N-linked glycans. In PE, PSG1 N-glycans displayed a shift toward increased oligomannose structures and reduced sialylation. Induction of endoplasmic reticulum (ER) stress in primary STBs altered the glycosylation enzyme machinery, and single-nucleus transcriptomic data indicated a reduced contribution of mature STB populations in PE, consistent with an immature STB-like glycoprotein signature. Altered N-glycosylation increased binding to mannose and asialoglycoprotein receptors and cellular uptake, suggesting enhanced hepatic clearance as a possible explanation for reduced circulating PSG1 levels in PE. Our data link ER stress during STB differentiation to altered glycoprotein maturation and identify PSG1 glycosylation as a readout of a stress-impaired STB in PE. Glycan features of circulating placental proteins could therefore provide information beyond protein levels alone and complement liquid biopsy approaches.

PHERGain was a randomized, non-comparative phase 2 trial evaluating a positron 18 F-fluorodeoxyglucose-positron emission tomography ( 18 F-FDG-PET)-guided, pathological complete response (pCR)-adapted strategy to omit chemotherapy in HER2-positive early breast cancer. Female patients with HER2-positive stages I-IIIA operable breast cancer (tumor size ≥ 1.5 cm) were randomized to receive chemotherapy plus trastuzumab and pertuzumab (HP; group A) or HP ± endocrine therapy (group B). In group B, treatment was adapted according to 18 F-FDG-PET response after two cycles and pCR, with chemotherapy administered to nonresponders or patients without pCR. We previously reported that this de-escalation approach revealed a 3-year invasive disease-free survival (iDFS) of 94.3% (95% confidence interval (CI): 90.9 to 96.8) in group B. Here we report the prespecified secondary endpoint, 5-year iDFS and exploratory circulating tumor DNA (ctDNA) findings. After a median follow-up of 5.6 years, the 5-year iDFS was 89.5% (95% CI: 85.7 to 93.4) in group B (n = 267) and 92.4% (95% CI: 86.7 to 98.5) among 18 F-FDG-PET responders achieving pCR without chemotherapy (n = 86), with one distant recurrence. The latter estimate describes a long-term outcome in a post-randomization subgroup defined by 18 F-FDG-PET response and pCR and should be interpreted as descriptive rather than as causal effects of omitting chemotherapy. Detectable ctDNA at baseline or during treatment was associated with inferior iDFS, whereas ctDNA clearance correlated with higher pCR rates and improved long-term outcomes. These findings continue to support the clinical validity of an 18 F-FDG-PET-guided, pCR-adapted approach and suggest a potential role for ctDNA in refining treatment individualization. ClinicalTrials.gov identifier: NCT03161353 .

Accumulating evidence suggests that combined prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) and phthalates (PAEs) may interfere with fetal development, yet relevant evidence based on fetal growth measures covering the transition phase from mid to late gestation remains limited. In this study, we enrolled 811 pregnant women from the Zunyi Birth Cohort and detected urinary metabolites of OH-PAHs and mPAEs in early pregnancy. Fetal growth measures including head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC), femur length (FL), and placental thickness (PT) were collected at 14 to 27 weeks of gestation. Linear regression and restricted cubic spline (RCS) models were used to explore linear and nonlinear relationships between exposure levels and fetal growth outcomes, and Bayesian kernel machine regression (BKMR) was further adopted to assess the combined effect of pollutant mixtures and screen core pollutants. RCS models revealed distinct linear and nonlinear exposure-response relationships for various pollutants. Supplementary RCS analyses using LOD-constrained truncated multiple imputation (truncated MI) indicated that overall exposure-outcome trends were largely consistent with the LOD/√2 substitution approach. Truncated MI was used to address measurement uncertainty within the low-exposure range. BKMR analyses found that the PAHs mixture was negatively associated with PT at the 75th percentile, with 1-OHPYR identified as the primary contributing component. For the combined PAH and PAE mixtures, MBP was positively associated with abdominal circumference z-scores (AC-z) at low concentrations, while MEP showed a negative association with AC-z at high concentrations.

The safety of intravenous thrombolytics for ischemic stroke in pregnancy is largely unknown. We performed a systematic review to identify published use of thrombolytics for stroke during pregnancy, with the aim of assessing maternal and fetal safety outcomes. To provide additional safety data, we included cases of thrombolysis for deep vein thrombosis, mechanical valve thrombosis, and pulmonary embolism in pregnancy. We used the PRISMA and MOOSE guidelines to conduct the review. We searched 3 databases (OVID Medline, EMBASE, Scopus) for studies published up to October 2025. We analyzed outcomes in a Bayesian aggregated case series to compare rates of adverse outcomes in our cohort with those in the general population. Elective termination and spontaneous abortion were grouped together, given that it was often difficult to determine whether complications of thrombolysis may have played a role in the decision for termination. We included 123 studies of 216 patients (median age 31 years) treated with thrombolytics during pregnancy, of whom 85 had ischemic stroke. Six of the 32 total fetal deaths were deemed likely to be causally related to thrombolytics (3 in stroke). The risk of miscarriage in our thrombolysis population was 12.4% higher (95% credible interval [CrI]: 2.6%, 23.2%) than published general pregnant population rates, and the risk of stillbirth was 5.9% higher (95% CrI: 1.6%, 12.7%). The proportion of pregnant patients with symptomatic intracerebral hemorrhage was similar between our pregnant cohort and young, nonpregnant patients receiving thrombolytics (risk difference -0.4%; 95% CrI: -0.8%, 2.7%). Thrombolytics were likely causally associated with a small minority of published cases of fetal death after thrombolysis in pregnancy. There was no signal of increased harm from thrombolysis to the mother, including similar rates of symptomatic intracerebral hemorrhage. In many cases, it was difficult to discern effects of thrombolytics on fetal outcomes from the effects of the disease itself; hence, our results should be interpreted with caution. Nonetheless, our findings broadly support the use of thrombolytics in otherwise-eligible pregnant patients but underscore the importance of the risk-benefit assessment in such patients. The study protocol was pre-registered on PROSPERO (registration number: CRD42024605043).