Tag: pubmed

JAMA Netw Open. 2022 Oct 3;5(10):e2236609. doi: 10.1001/jamanetworkopen.2022.36609.

ABSTRACT

IMPORTANCE: There is a lack of information regarding the need to postpone conception after COVID-19 vaccination.

OBJECTIVE: To investigate the time interval between the first dose of inactivated COVID-19 vaccine and in vitro fertilization (IVF) treatment as well as the rate of pregnancy after a fresh embryo transfer.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted at a single public IVF center in China. Female patients aged 20 to 47 years and undergoing IVF treatment were consecutively registered from May 1 to December 22, 2021, with follow-up until March 31, 2022. Patients with SARS-CoV-2 infection before or during IVF treatment and those who underwent 2 or more IVF treatments, received the noninactivated or unknown COVID-19 vaccine, or did not have a fresh embryo transfer were excluded from this study.

EXPOSURES: The vaccinated group (subdivided into 4 subgroups of time interval from first vaccination to fertilization treatment: ≤30 days, 31-60 days, 61-90 days, and ≥91 days) and nonvaccinated group.

MAIN OUTCOMES AND MEASURES: Risk ratios (RRs) for the association between the time interval and ongoing pregnancy (pregnancy continued at least 12 weeks).

RESULTS: A total of 3052 female patients (mean [SD] age, 31.45 [3.96] years) undergoing IVF treatment were analyzed in this study. There were 667 vaccinated patients receiving IVF (35 were vaccinated ≤30 days, 58 were vaccinated 31-60 days, 105 were vaccinated 61-90 days, and 469 were vaccinated ≥91 days before fertilization treatment), and 2385 unvaccinated patients receiving treatment. The ovarian stimulation and laboratory parameters were similar among all groups. Ongoing pregnancy was significantly lower in the 30 days or less subgroup (34.3% [12 of 35]; adjusted RR [aRR], 0.61; 95% CI, 0.33-0.91) and the 31 to 60 days’ subgroup (36.2% [21 of 58]; aRR, 0.63; 95% CI, 0.42-0.85). A slightly but not statistically lower rate was found in the 61 to 90 days’ subgroup, and no reduced risk for ongoing pregnancy in the 91 days or more subgroup was observed (56.3% [264 of 469]; aRR, 0.96; 95% CI, 0.88-1.04) compared with the unvaccinated group (60.3% [1439 of 2385], as reference).

CONCLUSIONS AND RELEVANCE: Findings of this study suggest that receipt of the first inactivated COVID-19 vaccine dose 60 days or less before fertilization treatment is associated with a reduced rate of pregnancy. In patients undergoing IVF treatment with a fresh embryo transfer, the procedure may need to be delayed until at least 61 days after COVID-19 vaccination.

PMID:36239937 | DOI:10.1001/jamanetworkopen.2022.36609

JAMA Netw Open. 2022 Oct 3;5(10):e2236763. doi: 10.1001/jamanetworkopen.2022.36763.

ABSTRACT

IMPORTANCE: Breast cancer diagnosed within 5 to 10 years after childbirth, called postpartum breast cancer (PPBC), is associated with increased risk for metastasis and death. Whether a postpartum diagnosis is an independent risk factor or a surrogate marker of cancer features associated with poor outcomes remains understudied.

OBJECTIVE: To determine whether diagnostic temporal proximity to childbirth is associated with features of breast cancer associated with poor outcomes, including tumor stage, estrogen receptor (ER) status, and risk for distant metastasis and breast cancer-specific mortality, using a population database from the state of Utah.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study using the Utah Population Database (UPDB) included individuals with stage I to III breast cancer diagnosed at age 45 years or younger between 1996 and 2017, followed-up until February 2020. Participant data were analyzed from November 2019 to August 2022.

EXPOSURE: The primary exposures were no prior childbirth or time between most recent childbirth and breast cancer diagnosis. Patients were grouped by diagnoses within less than 5 years, 5 to less than 10 years, or 10 years or more since recent childbirth.

MAIN OUTCOMES AND MEASURES: The 2 primary outcomes were distant metastasis-free survival and breast cancer-specific death. Cox proportional hazard models were used to investigate associations between exposures and outcomes adjusting for diagnosis year, patient age, tumor stage, and estrogen receptor (ER) status.

RESULTS: Of 2970 individuals with breast cancer diagnosed at age 45 years or younger (mean [SD] age, 39.3 [5.0] years; 12 Black individuals [0.4%], 2679 White individuals [90.2%]), breast cancer diagnosis within 5 years of recent childbirth was independently associated with approximately 1.5-fold elevated risk for metastasis (hazard ratio [HR], 1.5; 95% CI, 1.2-2.0) and breast cancer-specific death (HR, 1.5; 95% CI, 1.1-2.1) compared with nulliparous individuals. For cancers classically considered to have tumor features associated with good outcomes (ie, stage I or II and ER-positive), a postpartum diagnosis was a dominant feature associated with increased risk for metastasis and death (eg, for individuals with ER-positive disease diagnosed within <5 years of childbirth: age-adjusted metastasis HR, 1.5; 95% CI, 1.1-2.1; P = .01; age-adjusted death HR, 1.5; 95% CI, 1.0-2.1; P = .04) compared with nulliparous individuals. Furthermore, liver metastases were specifically increased in the group with diagnosis within 5 years postpartum and with positive ER expression (38 of 83 patients [45.8%]) compared with the nulliparous (28 of 77 patients [36.4%]), although the difference was not statistically significant. Overall, these data implicate parity-associated breast and liver biology in the observed poor outcomes of PPBC.

CONCLUSIONS AND RELEVANCE: In this cohort study of individuals with breast cancer diagnosed at age 45 years or younger, a postpartum breast cancer diagnosis was a risk factor associated with poor outcomes. Irrespective of ER status, clinical consideration of time between most recent childbirth and breast cancer diagnosis could increase accuracy of prognosis in patients with young-onset breast cancer.

PMID:36239933 | DOI:10.1001/jamanetworkopen.2022.36763

J Racial Ethn Health Disparities. 2022 Oct 14. doi: 10.1007/s40615-022-01429-w. Online ahead of print.

ABSTRACT

A spatially disadvantaged census tract is one that is surrounded by disadvantaged tracts. More spatially disadvantaged neighborhoods may experience more violence, independent of their own level of disadvantage, and majority Black middle-class neighborhoods are more likely to be spatially disadvantaged than majority white neighborhoods. The purpose of this paper is to study how much of the racial difference in gun homicide rates between majority Black and majority white middle-class neighborhoods can be explained by differences in spatial disadvantage. To study this, comparable majority Black and majority white tracts were matched to understand how gun homicide rates differ in neighborhoods with similar levels of disadvantage. Further matching on spatial disadvantage reduced the disparity in gun homicides between majority Black and majority white middle-class neighborhoods, suggesting that spatial disadvantage accounts for some but not all of the disparity.

PMID:36239904 | DOI:10.1007/s40615-022-01429-w

Environ Sci Pollut Res Int. 2022 Oct 14. doi: 10.1007/s11356-022-23548-x. Online ahead of print.

ABSTRACT

Traditional Production-Based Accounting (PBA) principle does not consider the embodied carbon emissions in export and import trade. A multiregional input-output (MRIO) model is constructed to estimate the embodied carbon dioxide emissions of 41 countries and regions worldwide, based on the PBA and shared responsibility approach in this paper. The results indicate that the embodied carbon emissions in 2018 in China’s export trade were 1326 million tons higher than that of import trade. China, India, and the USA have a different carbon coefficient in the 35 sectors, but electricity, gas, and water supply sectors are the largest coefficient for them. A reduction in carbon emission coefficient would contribute to a decrease in imports and exports. Through the empirical analysis of the embodied carbon emissions in China’s import and export trade, it can be seen that China is a major producer of carbon emissions, not a consumer country, and has taken more carbon emissions responsibility for the world. The developed countries should take more shared carbon emission responsibility than the PBA. And it is more reasonable and impartial to assign developed and developing countries carbon emissions responsibility in the light of the shared responsibility method.

PMID:36239886 | DOI:10.1007/s11356-022-23548-x

Target Oncol. 2022 Oct 14. doi: 10.1007/s11523-022-00916-8. Online ahead of print.

ABSTRACT

BACKGROUND: The combination of trifluridine-tipiracil and bevacizumab was compared with trifluridine-tipiracil monotherapy in a randomized, open-label, phase II trial, resulting in a statistically significant and clinically relevant improvement in progression-free survival (PFS), with tolerable toxicity in patients with refractory metastatic colorectal cancer (mCRC); however, evidence supporting the role of this combination in a real-world setting is limited.

OBJECTIVE: The aim of our work was to provide further evidence on the activity and safety of this combination in a real-world series of Western mCRC patients refractory or intolerant to previous therapies.

PATIENT AND METHODS: We conducted a retrospective, observational study of patients with mCRC refractory or intolerant to standard therapies. Patients were treated with trifluridine-tipiracil and bevacizumab. Previous therapy with fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab, aflibercept, regorafenib, and cetuximab or panitumumab (only RAS wild-type) was allowed, as was previous participation in clinical trials. Clinicopathological characteristics, overall response rate (ORR), disease control rate (DCR), overall survival (OS), PFS, and safety data were retrospectively collected and analyzed.

RESULTS: We recorded 31 patients treated between 1 December 2017 and 30 June 2022. Median age was 69 years (range 38-82 years), 39% were male, 100% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1, tumor location was left-sided in 77% of cases, 54% had synchronous presentation, 35% were RAS mutant, 3% were BRAF mutant, and 71% underwent primary tumor resection; 64% of patients had liver metastases, 55% had lung metastases, and 23% had peritoneal carcinomatosis. The median number of previous treatment lines was 2 (range 0-5), and 84% of patients received at least one previous anti-angiogenic agent. The ORR and DCR were 3% and 71%, respectively. With a median follow-up of 8 months (range 2-39), median PFS was 6 months (95% confidence interval [CI] 3.1-8.9 months) and median OS was 14 months (95% CI 10.1-17.8 months). Adverse events of any grade were reported in 58% of patients. The most common grade 3-4 toxicities were neutropenia (19%) and anemia (6%); 35% of patients required either dose delays or dose reductions due to toxicity. Granulocyte colony-stimulating factor (G-CSF) prophylaxis was administered either on first or subsequent cycles of treatment in 35% of patients. No treatment-related deaths occurred. Sixty percent of the patients who discontinued treatment eventually received one or more lines of subsequent therapy.

CONCLUSIONS: Our series provides further evidence on the activity and safety of the combination of trifluridine-tipiracil and bevacizumab in a real-world series of Western refractory mCRC patients.

PMID:36239883 | DOI:10.1007/s11523-022-00916-8

Cancer Causes Control. 2022 Oct 14. doi: 10.1007/s10552-022-01639-x. Online ahead of print.

ABSTRACT

PURPOSE: Prostate cancer (PCa) is the most commonly diagnosed cancer in men, resulting in a large cancer burden given a relatively higher 5-year survival rate of patients after cancer diagnosis. The underlying etiology of prostate cancer is not well understood. Chronic inflammation plays a significant role in carcinogenesis overall and may be involved in the development of PCa, but immune-related biomarker studies in prostate cancer are limited.

METHODS: The associations of serum concentrations of cytokines, systemic immune biomarkers, with risk of PCa were assessed in a randomly selected sub-cohort (n = 798, mean age = 73 years) of the Osteoporotic Fractures in Men (MrOS) study, a prospective cohort of older men. At baseline, we measured serum interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), soluble receptors (SR) of IL-6 (IL-6SR) and TNF (TNFαSR1 and TNFαSR2), and IL-10. The risk of PCa was calculated for higher tertile levels of measured individual cytokines relative to the lowest tertile using Cox proportional hazards regression models.

RESULTS: After an average 6 years of follow-up, 59 men developed incident PCa. Men in the middle or highest tertile of IL-10 had a statistically significant 50% lower risk of PCa compared to the lowest tertile (hazard ratio = 0.50, 95% confidence interval = 0.30-0.84). There was no significant association between any of the other cytokines measured and PCa risk.

CONCLUSION: IL-10, an anti-inflammatory cytokine, was associated with lower risk of PCa. Further research of IL-10 and inflammation in relation to PCa development is warranted.

PMID:36239865 | DOI:10.1007/s10552-022-01639-x

Metabolomics. 2022 Oct 14;18(10):78. doi: 10.1007/s11306-022-01941-4.

ABSTRACT

INTRODUCTION: Premature adrenarche (PA) for long time was considered a benign condition but later has been connected to various diseases in childhood and adulthood which remains controversial.

OBJECTIVE: To investigate the effect of premature adrenarche on the metabolic phenotype, and correlate the clinical and biochemical data with the metabolic profile of children with PA.

METHODS: Nuclear magnetic resonance (NMR)-based untargeted and targeted metabolomic approach in combination with multivariate and univariate statistical analysis applied to study the metabolic profiles of children with PA. Plasma, serum, and urine samples were collected from fifty-two children with Idiopathic PA and forty-eight age-matched controls from the division of Pediatric Endocrinology of the University Hospital of Patras were enrolled.

RESULTS: Metabolomic results showed that plasma and serum glucose, myo-inositol, amino acids, a population of unsaturated lipids, and esterified cholesterol were higher and significantly different in PA children. In the metabolic profiles of children with PA and age-matched control group a gradual increase of glucose and myo-inositol levels was observed in serum and plasma, which was positively correlated their body mass index standard deviation score (BMI SDS) values respectively. Urine ¹H NMR metabolic fingerprint of PA children showed positive correlation and a clustering-dependent relationship with their BMI and bone age (BA) respectively.

CONCLUSION: This study provides evidence that PA driven metabolic changes begin during the childhood and PA may has an inductive role in a BMI-driven increase of specific metabolites. Finally, urine may be considered as the best biofluid for identification of the PA metabolism as it reflects more clearly the PA metabolic fingerprint.

PMID:36239863 | DOI:10.1007/s11306-022-01941-4

Mol Cell Biochem. 2022 Oct 14. doi: 10.1007/s11010-022-04579-x. Online ahead of print.

ABSTRACT

Mutation or overexpression renders pan-RAS (rat sarcoma) proteins insensitive to inactivation. Activated pan-RAS communicates signal from the cell surface receptor to activate RAS-MAPK/ERK (RAS-mitogen-activated protein kinases/extracellular signal regulated kinases) signaling and orchestrates epithelial-to-mesenchymal transition-activating transcription factors (EMT-ATFs) reprogramming to induce EMT. Owing to limited studies available in bladder cancer, the present study is taken up to examine the expressions of the EMT-associated markers in pan-RAS-pERK1/2 (pan-RAS-phosphoERK1/2)-positive well-characterized cohort of forty-two non-muscle invasive bladder cancer (NMIBC) and forty-five muscle invasive bladder cancer (MIBC) patients. Immunohistochemical staining was performed on paraffin embedded tissue sections to determine the immunolevels and cellular localization of marker proteins. Semi-quantitative expressions of pan-RAS, pERK1/2, and EMT markers (E-cadherin, Vimentin, N-cadherin, Snail, Slug Twist, and Zeb1) were statistically examined with clinicohistopathological profile of the patients using SPSS, version 20.0 software. The study documents the diagnostic relevance of immunohistochemical expressions of pan-RAS-pERK1/2/EMT-associated markers in order to stratify NMIBC and MIBC patients. Follow-up studies supported the role of altered EMT phenotype in pan-RAS-pERK1/2-activated positive tumors with disease aggressiveness. To the best of our knowledge, our study is the first concluding the impact of altered EMT phenotype via pan-RAS-pERK1/2 axis on the short survival outcome [short overall survival (OS) (p = 0.04), short progression-free survival (PFS) (p = 0.02) and short cancer-specific survival (CSS) (p = 0.03)] of muscle invasive bladder cancer patients.

PMID:36239855 | DOI:10.1007/s11010-022-04579-x

Cell Mol Neurobiol. 2022 Oct 14. doi: 10.1007/s10571-022-01292-7. Online ahead of print.

ABSTRACT

The dorsal hippocampus is involved in behavioral avoidance regulation. It is unclear how experiences such as the neonatal stress of maternal deprivation (MD) and post-weaning environmental enrichment (EE) affect avoidance behavior and the dorsal hippocampal parameters, including neuronal morphology, corticotrophin-releasing hormone (CRH) signaling, and oxytocin receptor (OTR) level. In male BALB/c mice, we found that MD impaired avoidance behavior in the step-on test compared to non-MD and EE rearing conditions could alleviate that partially. MD increased neuronal branches in the CA1 but decreased synaptic connection levels in the CA2, CA3, and DG. Meanwhile, MD increased the CA1’s OTR levels, which negatively correlated with nucleus densities. MD also increased the CA1’s and CA2’s CRH levels, which positively correlated with CRHR1 levels. However, MD statistically elevated the CA3’s CRH receptor 1 (CRHR1) levels, which negatively correlated with nucleus densities and, probably, synaptic connection levels in the CA3. The additive effects of MD and EE maintained similar CRH levels and CRHR1 levels as well as OTR levels in the hippocampal areas as the additive of non-MD and non-EE. However, the presence of MD and EE still decreased the CA1’s neuronal branches and the CA2’s and DG’s synaptic connection levels. The study illustrates how MD and EE affect avoidance behaviors, hippocampal neuron morphology, and CRH and OTR levels. The results indicate that the late-life environmental improvement partially restores the alterations in dorsal hippocampal areas induced by early life stress.

PMID:36239833 | DOI:10.1007/s10571-022-01292-7

Oral Maxillofac Surg. 2022 Oct 14. doi: 10.1007/s10006-022-01123-5. Online ahead of print.

ABSTRACT

PURPOSE: Three-dimensional surgical planning (3-DSP) is becoming commonplace in the management of benign and malignant disease for oral and maxillofacial surgery practice within the last decade. Surgeons utilize a virtual “wrap” to preoperatively delineate and define maxillofacial tumor resection margins. The investigators hypothesized that the use of a wrap is a predictable method to obtain negative bony margins.

METHODS: The investigators implemented a retrospective chart review. The sample was composed of patients over the age of 18 treated at John Peter Smith Health Network and Parkland/UT Southwestern Medical Center who obtained 3-DSP for the pathology of the head and neck, involving the bone, with a virtual wrap utilized for bony margins. The proportion of cases was calculated, descriptive statistics were reported, and binomial exact calculation was performed for confidence intervals. The primary variable analyzed was bony margin status on final histopathology, involved or uninvolved, based on the pathology report.

RESULTS: The sample was composed of 39 cases, one of which was excluded due to aborting the preplanned 3-DSP. Of the 38 included cases, one had involved bony margin on final histopathology (2.6%; 95% confidence limits, 0.1%, 13.8%). There were 16 malignant cases (42%) and 22 benign cases (58%). When stratified by pathology, 1 out of the 16 malignant cases (6.3%; 95% confidence interval, 0.2%, 30%) and 0 out of the 22 benign cases (95% confidence interval, 0%, 15.4%) had an involved bony margin on final histopathology.

CONCLUSION: The results of this preliminary study suggest three-dimensional surgical planning with wrap margins is a predictable method to obtain negative bony margins in benign and malignant disease of the maxillofacial complex. Further studies will focus on compiling prospective data to solidify the accuracy and predictability of using a wrap to obtain negative bony margins.

PMID:36239829 | DOI:10.1007/s10006-022-01123-5