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Gene Jun 2024This study aimed to investigate placental microblood flow perfusion in fetal growth restriction (FGR) both pre- and post-delivery, and explore the influence of LINC00473...
This study aimed to investigate placental microblood flow perfusion in fetal growth restriction (FGR) both pre- and post-delivery, and explore the influence of LINC00473 and its downstream targets on FGR progression in trophoblast cells. Placental vascular distribution, placental vascular index (VI), CD34 expression, and histological changes were compared between control and FGR groups. FGR-related differentially expressed genes (DEGs) were analyzed and validated by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in placentae. In vitro experiments examined the regulatory relationships among LINC00473, miR-5189-5p, and StAR, followed by investigations into their impacts on cell proliferation and apoptosis. FGR placentae exhibited irregular shapes, uneven parenchymal echo, stromal dysplasia, ischemic infarction, and variable degrees of thickening in some cases. FGR samples showed less prominent mother vessel lakes, significantly lower VI, and decreased CD34 expression. Hematoxylin & eosin (H&E) staining revealed placental fibrosis, fibrin adhesion, infarction, and interstitial dysplasia in FGR. LINC00473, miR-5189-5p, and StAR were identified as DEG, with qPCR demonstrating a significant increase in LINC00473 and a decrease in miR-5189-5p in FGR, while both qPCR and IHC indicated a significant increase in StAR expression. LINC00473 served as an endogenous sponge against miR-5189-5p in human HTR-8/SV neo cells, and StAR expression was regulated by both LINC00473 and miR-5189-5p. Dysregulation of these genes affected cell proliferation and apoptosis. Pathological changes in the placenta are significant contributors to FGR, with placental microblood flow potentially serving as an indicator for monitoring its progression. LINC00473 and its downstream targets may modulate trophoblasts proliferation and apoptosis, thus influencing the onset of FGR, suggesting novel avenues for diagnosis and treatment.
PubMed: 38942180
DOI: 10.1016/j.gene.2024.148727 -
American Journal of Obstetrics &... Jun 2024
PubMed: 38942172
DOI: 10.1016/j.ajogmf.2024.101416 -
Preventive Medicine Jun 2024Pregnant persons with opioid use disorder (OUD) face a multitude of comorbid conditions that may increase the risk of adverse drug and health outcomes. This study...
INTRODUCTION
Pregnant persons with opioid use disorder (OUD) face a multitude of comorbid conditions that may increase the risk of adverse drug and health outcomes. This study characterizes typologies of comorbidities among pregnant persons with OUD and assesses the associations of these typologies with hospitalizations in the first year postpartum.
METHODS
A cohort of pregnant persons with OUD at delivery in 2018 were identified in a Pennsylvania statewide hospital dataset (n = 2055). Latent class analysis assessed 12 comorbid conditions including substance use disorders (SUDs), mental health conditions, and infections. Multivariable logistic regressions examined the association between comorbidity classes and hospitalizations (all-cause, OUD-specific, SUD-related, mental health-related) during early (0-42 days) and late (43-365 days) postpartum.
RESULTS
A three-class model best fit the data. Classes included low comorbidities (56.9% of sample; low prevalence of co-occurring conditions), moderate polysubstance/depression (18.4%; some SUDs, all with depression), and high polysubstance/bipolar disorder (24.7%; highest probabilities of SUDs and bipolar disorder). Overall, 14% had at least one postpartum hospitalization. From 0 to 42 days postpartum, the moderate polysubstance/depression and high polysubstance/bipolar disorder classes had higher odds of all-cause and mental health-related hospitalization, compared to the low comorbidities class. From 43 to 365 days postpartum, the high polysubstance/bipolar disorder class had higher odds of all-cause hospitalizations, while both the high polysubstance/depression and moderate polysubstance/bipolar disorder classes had higher odds of SUD-related and mental health-related hospitalizations compared to the low comorbidities class.
CONCLUSIONS
Findings highlight the need for long-term, multidisciplinary healthcare delivery interventions to address comorbidities and prevent adverse postpartum outcomes.
PubMed: 38942123
DOI: 10.1016/j.ypmed.2024.108057 -
The American Journal of Clinical... Jun 2024The current Institute of Medicine pregnancy weight gain guidelines were developed using the best available evidence, but were limited by substantial knowledge gaps. Some...
BACKGROUND
The current Institute of Medicine pregnancy weight gain guidelines were developed using the best available evidence, but were limited by substantial knowledge gaps. Some have raised concern that the guidelines for individuals affected by overweight or obesity are too high and contribute to short- and long-term complications for the mother and child.
OBJECTIVE
To determine the association between pregnancy weight gain below the lower limit of the current Institute of Medicine (IOM) recommendations and risk of 10 adverse maternal and child health outcomes among individuals with overweight and obesity.
METHODS
We used data from a prospective cohort study of US nulliparae with prepregnancy overweight (n=955) or obesity (n=897) followed from the first trimester to 2-7 years postpartum. We used multivariable Poisson regression to relate pregnancy weight gain z-scores with a severity-weighted composite outcome consisting of ≥1 of 10 adverse outcomes (gestational diabetes, preeclampsia, unplanned cesarean delivery, maternal postpartum weight increase >10kg, maternal postpartum metabolic syndrome, infant death, stillbirth, preterm birth, small-for-gestational age birth, and childhood obesity).
RESULTS
Pregnancy weight gain z-scores below, within, and above the IOM-recommended ranges occurred in 5%, 13%, and 80% of pregnancies with overweight and 17%, 13%, and 70% of pregnancies with obesity. There was a positive association between pregnancy weight gain z-scores and all adverse maternal outcomes, childhood obesity, and the composite outcome. Pregnancy weight gain z-scores below the lower limit of the recommended ranges (<6.8 kg for overweight, <5 kg for obesity) were not associated with the severity-weighted composite outcome. For example, compared with the lower limit, adjusted rate ratios (95% confidence interval) for z-scores of -2 standard deviations in pregnancies with overweight (equivalent to 3.6kg at 40 weeks) and obesity (-2.8kg at 40 weeks) were 0.99 (0.91, 1.06) and 0.97 (0.87, 1.07).
CONCLUSIONS
These findings support arguments to decrease the lower limit of recommended weight gain ranges in these prepregnancy BMI groups.
PubMed: 38942117
DOI: 10.1016/j.ajcnut.2024.06.011 -
Modern Pathology : An Official Journal... Jun 2024PLAG1 gene fusions were recently identified in a subset of uterine myxoid leiomyosarcomas (M-LMS). However, we have encountered cases of PLAG1-rearranged uterine...
PLAG1 gene fusions were recently identified in a subset of uterine myxoid leiomyosarcomas (M-LMS). However, we have encountered cases of PLAG1-rearranged uterine sarcomas (PLAG1-US) lacking M-LMS-like morphology and/or any expression of smooth muscle markers. To better characterize their clinicopathological features, we performed a multi-institutional search which yielded 11 cases. The patients ranged in age from 34-72 years (mean: 57). All tumors arose in the uterine corpus, ranging in size from 6.5-32 cm (mean: 15). The most common stage at presentation was pT1b (n=6), three cases had stage pT1 (unspecified) and one case each presented in stage pT2a and pT3b. Most were treated only by hysterectomy with adnexectomy. The follow-up (range: 7-71 months; median: 39 months) was available for 7 patients. Three cases (7-21 months of follow-up) had no evidence of disease. Three out of 4 remaining patients died of disease within 55-71 months, while the last developed peritoneal spread and was transferred for palliative care at 39 months. Morphologically, the tumors showed a high inter- and intratumoral heterogeneity. M-LMS-like and epithelioid LMS-like morphology was present in 3 and 5 primary tumors, respectively, the rest mostly presented as non-descript ovoid/spindle cell sarcomas. Unusual morphological findings included prominently hyalinized stroma (n=3), adipocytic differentiation with areas mimicking myxoid liposarcoma (n=2), osteosarcomatous differentiation (n=1) and undifferentiated pleomorphic sarcoma-like areas (n=1). The mitotic activity ranged from 3-24 mitoses/10 high-power fields (mean: 9), 3/10 cases showed necrosis. In 3/11 cases, no expression of SMA, h-caldesmon or desmin was noted, whereas 5/5 cases expressed PLAG1. By RNA-sequencing, the following fusion partners were identified: PUM1, CHCHD7 (each n=2), C15orf29, CD44, MYOCD, FRMD6, PTK2 and TRPS1 (each n=1). One case only showed PLAG1 gene break by FISH. Our study documents a much broader morphological spectrum of PLAG1-US than previously reported, encompassing but not limited to M-LMS-like morphology with occasional heterologous (particularly adipocytic) differentiation. Since it is currently difficult to precisely define their line of differentiation, for the time being, we suggest using a descriptive name PLAG1-rearranged uterine sarcoma.
PubMed: 38942115
DOI: 10.1016/j.modpat.2024.100552 -
Cell Host & Microbe Jun 2024Gut microbiota influence anti-tumor immunity, often by producing immune-modulating metabolites. However, microbes consume a variety of metabolites that may also impact...
Gut microbiota influence anti-tumor immunity, often by producing immune-modulating metabolites. However, microbes consume a variety of metabolites that may also impact host immune responses. We show that tumors grow unchecked in the omenta of microbe-replete mice due to immunosuppressive Tregs. By contrast, omental tumors in germ-free, neomycin-treated mice or mice colonized with altered Schaedler's flora (ASF) are spontaneously eliminated by CD8 T cells. These mice lack Proteobacteria capable of arginine catabolism, causing increases in serum arginine that activate the mammalian target of the rapamycin (mTOR) pathway in Tregs to reduce their suppressive capacity. Transfer of the Proteobacteria, Escherichia coli (E. coli), but not a mutant unable to catabolize arginine, to ASF mice reduces arginine levels, restores Treg suppression, and prevents tumor clearance. Supplementary arginine similarly decreases Treg suppressive capacity, increases CD8 T cell effectiveness, and reduces tumor burden. Thus, microbial consumption of arginine alters anti-tumor immunity, offering potential therapeutic strategies for tumors in visceral adipose tissue.
PubMed: 38942027
DOI: 10.1016/j.chom.2024.06.003 -
Gynecologic Oncology Jun 2024To report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol...
OBJECTIVE
To report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs.
METHODS
Eligible were patients with stages T1a1/LVSI+ to T1b2 (<4 cm, ≤2 cm for fertility sparing), common tumor types, no suspicious lymph nodes on imaging, and bilateral SLN detection. SLNs were examined intraoperatively and processed by an intensive protocol for ultrastaging (paraffin blocks sectioned completely in 150-μm intervals/levels). SLNs from each site were submitted for central quality control.
RESULTS
In the SENTIX SLN study, 647 out of 733 enrolled patients underwent SLN ultrastaging, identifying 12.5% (81/647) with node positive, N1 cases. Intraoperative detection revealed metastases in 56.8% (46/81) of these cases, categorized into macrometastases (83.7%), micrometastases (26.3%), and isolated tumor cells (9.1%). Ultrastaging identified additional metastatic involvement in 43.2% (35/81) of patients, with detailed sectioning revealing metastases (MAC/MIC) at first level in 20 cases (24.7%), at levels 2-4 in 9 cases (11.1%), and at level ≥5 in 6 cases (7.4%).
CONCLUSION
SLN ultrastaging detects additional 43% of N1 (MAC/MIC) in patients with negative LNs by imaging and intraoperative pathological assessment. The detection rate of positive SLN correlates with the intensity (number of levels) of ultrastaging. Examination of four levels from paraffin blocks, which detects >90% of patients with N1, is a reasonable compromise for an international standard for ultrastaging.
STUDY REGISTRATION
NCT02494063 (ClinicalTrials.gov).
PubMed: 38941963
DOI: 10.1016/j.ygyno.2024.06.015 -
European Journal of Surgical Oncology :... Jun 2024In 2023, the International Federation of Gynecology and Obstetrics (FIGO) updated the endometrial cancer staging system (FIGO2023). Our study aimed to validate the...
BACKGROUND
In 2023, the International Federation of Gynecology and Obstetrics (FIGO) updated the endometrial cancer staging system (FIGO2023). Our study aimed to validate the prognostic value of FIGO2023 in patients with early-stage EC (Stage I and Stage II).
METHODS
After screening eligible EC patients from the Surveillance, Epidemiology and End Results (SEER) database, Kaplan-Meier cancer-specific survival (CSS) curves were used to evaluate the prognosis of patients with different stages. In addition, AUC, C-index, Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), and Decision curve analysis (DCA) were used to comprehensively compare the efficacy of the new and the old staging system in predicting prognosis.
RESULTS
A total of 33,156 patients were enrolled. The introduction of FIGO2023 significantly increased the proportion of stage II patients from 5.53 % to 24.76 %. The FIGO2023 defines different substages for patients, which show significant differences in CSS. Compared with FIGO2009, FIGO2023 performed better in discrimination, goodness of fit and clinical decision making.
CONCLUSION
Compared with FIGO2009, FIGO2023 had a higher accuracy in predicting CSS in patients with early-stage EC in the SEER database.
PubMed: 38941954
DOI: 10.1016/j.ejso.2024.108480 -
Journal of Reproductive Immunology Jun 2024The roles of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 genes in the potential correlation between polycystic ovary syndrome (PCOS), inflammation, and cancer remain...
Comparison of serum levels of IL-10 and IL-11 and mRNA expression of IL-10, IL-11, COX-2, BCL6, and ZEB Family in peripheral blood mononuclear cells (PBMC) of women with polycystic ovary syndrome and healthy individuals.
BACKGROUND
The roles of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 genes in the potential correlation between polycystic ovary syndrome (PCOS), inflammation, and cancer remain controversial.
AIMS
This study aimed to compare serum levels of IL-10 and IL-11 and gene expression of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 in PBMCs of women with PCOS and healthy controls.
METHODS
A case-control study included 40 women with PCOS as the case group and 40 healthy women as controls. Group matching for age and BMI was performed. Serum levels of IL-10 and IL-11 were assessed using ELISA, while gene expression was measured using real-time PCR. Parameters were compared between groups, and correlations among gene expression and serum levels were explored.
RESULTS
In comparison to healthy women, women with PCOS exhibited a significant decrease in the expression of COX-2 and IL-10 genes (p<0.001), alongside a significant increase in ZEB2 gene expression (p<0.001). There were no significant differences observed in the expression of IL-11, BCL6, and ZEB1 genes. Furthermore, the serum level of IL-10 was significantly lower in women with PCOS compared to the control group (p<0.001), while no significant difference was found in IL-11 levels. Additionally, no significant correlations were identified between gene expression and serum levels.
CONCLUSION
In women with PCOS, reduced IL-10 gene expression may indicate inflammation and serve as a diagnostic biomarker. However, conflicting findings on COX-2 expression complicate understanding. Elevated ZEB2 expression in PCOS women may lead to infertility, epithelial-mesenchymal transition, and aggressive phenotypes.
PubMed: 38941927
DOI: 10.1016/j.jri.2024.104281 -
Journal of Reproductive Immunology Jun 2024Chronic Intervillositis of Unknown Etiology (CIUE) is a rare idiopathic inflammatory disorder of the placenta. The evidence suggests an increased risk for poor... (Review)
Review
Chronic Intervillositis of Unknown Etiology (CIUE) is a rare idiopathic inflammatory disorder of the placenta. The evidence suggests an increased risk for poor obstetrical outcomes and a risk of recurrence as high as 100 %. This meta-analysis examined CIUE prevalence, recurrence, association with autoimmune disorders, reproductive outcomes, pregnancy complications, and the benefits of medical treatments. A systematic review, following PRISMA guidelines, involved a thorough search across multiple databases including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Evidence Based Medical Reviews, and Scopus. Out of 590 initially identified studies, 19 studies were included for both qualitative synthesis and meta-analysis after full-text review. Risk of bias was assessed using appropriate tools: The Risk Of Bias In Non-randomized Studies of Interventions tool was applied to twelve studies, while the Joanna Briggs Institute case series critical appraisal tool was used for seven studies. Our findings confirm that CIUE is a rare condition (0.7 %). CIUE is associated with decreased live birth rates (53 %), increased recurrent pregnancy loss (23 %), fetal loss beyond 22 weeks gestation (25 %), a higher prevalence of autoimmune diseases (14 %), and a recurrence rate of 30 % in subsequent pregnancies. Moreover, individuals with CIUE had higher rates of pregnancy complications, including gestational hypertension (19 %), intrauterine growth restriction (45 %), and preterm births (43 %). No significant improvement in live birth rate was observed among treated CIUE patients; however, caution is warranted when interpreting these findings due to the limited sample size. Future research in CIUE is crucial given its rarity and complexity.
PubMed: 38941926
DOI: 10.1016/j.jri.2024.104285