40 research outputs found

    Successful remission of extensive liver metastases in a breast cancer patient with acute liver failure using a combined chemotherapy regimen with mitomycin, folinate, and 5-fluorouracil (Mi/Fo/FU)

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    Liver failure due to disseminated hepatic secondaries represents a therapeutic dilemma in patients with metastatic breast cancer (MBC). Reduced liver function and non-assessable toxicity are limiting factors in the selection of chemotherapeutic agents. Currently, there is no standard treatment after failure of anthracycline-and taxane-based first-line therapies, although there is a variety of well evaluated drugs such as capecitabine

    Postponed pregnancies and risks of very advanced maternal age

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    QUESTIONS UNDER STUDY To evaluate pregnancy outcome in pregnant women aged ≥45 years, termed very advanced maternal age (VAMA). METHODS We retrospectively compared the outcome of pregnancies in VAMA patients with controls aged 30 years at time of delivery. Subgroups of singleton and multiple pregnancies were also analysed. Incidences of maternal and fetal adverse outcomes were measured. Statistical significance was set at p 7 days (37.8% vs 15.1%; OR 3.42) was found. Infant complications such as prematurity (44.9% vs 16.2%; OR 4.2) and low birthweight <5th percentile (11.0% vs 5.6%; OR 2.1) were also increased. CONCLUSION Pregnant women of very advanced maternal age (≥45 years) have significantly increased maternal and fetal risks. Women postponing pregnancy or planning a pregnancy in very advanced age should be informed about these risks, in particular before artificial reproductive technologies are applied or "social freezing"

    Position at birth as an important factor for the occurrence of anal sphincter tears: a retrospective cohort study

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    Objective: This work aimed to analyze the association between maternal position at birth in spontaneous deliveries and the occurrence of anal sphincter tears (AST) given the lack of evidence related to the least traumatic birth position. Study design: A total of 7832 vaginal deliveries were included. Vaginal-operative deliveries and deliveries with fundal pressure were excluded. Birth positions on bed, in water, kneeling, and in a squatting position on a low stool were compared. Birth position on bed was considered as the reference group, and a logistic regression analysis adjusting for important fetomaternal parameters was performed. Results: The overall incidence of AST was 1.1%. AST rate was significantly increased in squatting (2.9%) and kneeling (2.1%) positions compared with birth position on bed (1.0%) or in water (0.9%). Logistic regression analysis revealed a significantly higher risk for ASTs in squatting (OR 2.92, CI 95% 1.04-8.18) and in kneeling positions (OR 2.14, CI 95% 1.05-4.37) compared with the reference group on bed. When adjusting for risk factors, birth in a kneeling position remained significantly associated with ASTs (adj. OR 2.21, CI 95% 1.07-4.54). Conclusions: Birth in squatting or in kneeling position is associated with an elevated risk for ASTs. Birth in water is not associated with an increased risk for AST. Based on the results, women should be informed about the association of certain birth positions with the occurrence of AST

    Prevalence of RT-qPCR-detected SARS-CoV-2 infection at schools: First results from the Austrian School-SARS-CoV-2 prospective cohort study.

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    BACKGROUND: The role of schools in the SARS-CoV-2 pandemic is much debated. We aimed to quantify reliably the prevalence of SARS-CoV-2 infections at schools detected with reverse-transcription quantitative polymerase-chain-reaction (RT-qPCR). METHODS: This nationwide prospective cohort study monitors a representative sample of pupils (grade 1-8) and teachers at Austrian schools throughout the school year 2020/2021. We repeatedly test participants for SARS-CoV-2 infection using a gargling solution and RT-qPCR. We herein report on the first two rounds of examinations. We used mixed-effects logistic regression to estimate odds ratios and robust 95% confidence intervals (95% CI). FINDINGS: We analysed data on 10,734 participants from 245 schools (9465 pupils, 1269 teachers). Prevalence of SARS-CoV-2 infection increased from 0·39% at round 1 (95% CI 028-0·55%, 28 September-22 October 2020) to 1·39% at round 2 (95% CI 1·04-1·85%, 10-16 November). Odds ratios for SARS-CoV-2 infection were 2·26 (95% CI 1·25-4·12, P = 0·007) in regions with >500 vs. ≤500 inhabitants/km2, 1·67 (95% CI 1·42-1·97, P<0·001) per two-fold higher regional 7-day community incidence, and 2·78 (95% CI 1·73-4·48, P<0·001) in pupils at schools with high/very high vs. low/moderate social deprivation. Associations of regional community incidence and social deprivation persisted in a multivariable adjusted model. Prevalence did not differ by average number of pupils per class nor between age groups, sexes, pupils vs. teachers, or primary (grade 1-4) vs. secondary schools (grade 5-8). INTERPRETATION: This monitoring study in Austrian schools revealed SARS-CoV-2 infection in 0·39%-1·39% of participants and identified associations of regional community incidence and social deprivation with higher prevalence. FUNDING: BMBWF Austria

    Sensitivity and specificity of the antigen-based anterior nasal self-testing programme for detecting SARS-CoV-2 infection in schools, Austria, March 2021.

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    This study evaluates the performance of the antigen-based anterior nasal screening programme implemented in all Austrian schools to detect SARS-CoV-2 infections. We combined nationwide antigen-based screening data obtained in March 2021 from 5,370 schools (Grade 1-8) with an RT-qPCR-based prospective cohort study comprising a representative sample of 244 schools. Considering a range of assumptions, only a subset of infected individuals are detected with the programme (low to moderate sensitivity) and non-infected individuals mainly tested negative (very high specificity)

    Dietary Silicon Deficiency Does Not Exacerbate Diet-Induced Fatty Lesions in Female ApoE Knockout Mice.

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    BACKGROUND: Dietary silicon has been positively linked with vascular health and protection against atherosclerotic plaque formation, but the mechanism of action is unclear. OBJECTIVES: We investigated the effect of dietary silicon on 1) serum and aorta silicon concentrations, 2) the development of aortic lesions and serum lipid concentrations, and 3) the structural and biomechanic properties of the aorta. METHODS: Two studies, of the same design, were conducted to address the above objectives. Female mice, lacking the apolipoprotein E (apoE) gene, and therefore susceptible to atherosclerosis, were separated into 3 groups of 10-15 mice, each exposed to a high-fat diet (21% wt milk fat and 1.5% wt cholesterol) but with differing concentrations of dietary silicon, namely: silicon-deprived (-Si; <3-μg silicon/g feed), silicon-replete in feed (+Si-feed; 100-μg silicon/g feed), and silicon-replete in drinking water (+Si-water; 115-μg silicon/mL) for 15-19 wk. Silicon supplementation was in the form of sodium metasilicate (feed) or monomethylsilanetriol (drinking water). RESULTS: The serum silicon concentration in the -Si group was significantly lower than in the +Si-feed (by up to 78%; P < 0.003) and the +Si-water (by up to 84%; P < 0.006) groups. The aorta silicon concentration was also lower in the -Si group than in the +Si-feed group (by 65%; P = 0.025), but not compared with the +Si-water group. There were no differences in serum and aorta silicon concentrations between the silicon-replete groups. Body weights, tissue wet weights at necropsy, and structural, biomechanic, and morphologic properties of the aorta were not affected by dietary silicon; nor were the development of fatty lesions and serum lipid concentrations. CONCLUSIONS: These findings suggest that dietary silicon has no effect on atherosclerosis development and vascular health in the apoE mouse model of diet-induced atherosclerosis, contrary to the reported findings in the cholesterol-fed rabbit model

    STAT3 in acute myeloid leukemia facilitates natural killer cell-mediated surveillance

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    Acute myeloid leukemia (AML) is a heterogenous disease characterized by the clonal expansion of myeloid progenitor cells. Despite recent advancements in the treatment of AML, relapse still remains a significant challenge, necessitating the development of innovative therapies to eliminate minimal residual disease. One promising approach to address these unmet clinical needs is natural killer (NK) cell immunotherapy. To implement such treatments effectively, it is vital to comprehend how AML cells escape the NK-cell surveillance. Signal transducer and activator of transcription 3 (STAT3), a component of the Janus kinase (JAK)-STAT signaling pathway, is well-known for its role in driving immune evasion in various cancer types. Nevertheless, the specific function of STAT3 in AML cell escape from NK cells has not been deeply investigated. In this study, we unravel a novel role of STAT3 in sensitizing AML cells to NK-cell surveillance. We demonstrate that STAT3-deficient AML cell lines are inefficiently eliminated by NK cells. Mechanistically, AML cells lacking STAT3 fail to form an immune synapse as efficiently as their wild-type counterparts due to significantly reduced surface expression of intercellular adhesion molecule 1 (ICAM-1). The impaired killing of STAT3-deficient cells can be rescued by ICAM-1 overexpression proving its central role in the observed phenotype. Importantly, analysis of our AML patient cohort revealed a positive correlation between ICAM1 and STAT3 expression suggesting a predominant role of STAT3 in ICAM-1 regulation in this disease. In line, high ICAM1 expression correlates with better survival of AML patients underscoring the translational relevance of our findings. Taken together, our data unveil a novel role of STAT3 in preventing AML cells from escaping NK-cell surveillance and highlight the STAT3/ICAM-1 axis as a potential biomarker for NK-cell therapies in AML

    Position at birth as an important factor for the occurrence of anal sphincter tears: A retrospective cohort study

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    Objective: This work aimed to analyze the association between maternal position at birth in spontaneous deliveries and the occurrence of anal sphincter tears (AST) given the lack of evidence related to the least traumatic birth position. Study design: A total of 7832 vaginal deliveries were included. Vaginal-operative deliveries and deliveries with fundal pressure were excluded. Birth positions on bed, in water, kneeling, and in a squatting position on a low stool were compared. Birth position on bed was considered as the reference group, and a logistic regression analysis adjusting for important fetomaternal parameters was performed. Results: The overall incidence of AST was 1.1%. AST rate was significantly increased in squatting (2.9%) and kneeling (2.1%) positions compared with birth position on bed (1.0%) or in water (0.9%). Logistic regression analysis revealed a significantly higher risk for ASTs in squatting (OR 2.92, CI 95% 1.04-8.18) and in kneeling positions (OR 2.14, CI 95% 1.05-4.37) compared with the reference group on bed. When adjusting for risk factors, birth in a kneeling position remained significantly associated with ASTs (adj. OR 2.21, CI 95% 1.07-4.54). Conclusions: Birth in squatting or in kneeling position is associated with an elevated risk for ASTs. Birth in water is not associated with an increased risk for AST. Based on the results, women should be informed about the association of certain birth positions with the occurrence of AST

    Effect of dual tocolysis with fenoterol and atosiban in human myometrium

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    Objectives To measure the tocolytic effect of the combination of the oxytocin receptor antagonist atosiban with the β-mimetic agent fenoterol on human myometrium of pregnant women. Methods An in vitro study of contractility in human myometrium at the Laboratory of the Department of Obstetrics, University Hospital of Zürich, Switzerland, was performed. Thirty-six human myometrial biopsies were obtained during elective caesarean sections of singleton pregnancies at term. Tissue samples were exposed to atosiban, fenoterol and the combination of atosiban with fenoterol. Contractility was measured as area under the curve during 30 min of spontaneous contractions. The effect of treatment was expressed as the percentage of change from basal activity during 30 min of exposure. Differences were calculated using a paired Wilcoxon signed-rank test. An additive effect of dual tocolysis was assumed when no significant difference was detected between the observed and expected inhibition of dual tocolysis. When inhibition was greater or lower than expected, the dual combination was characterised as "synergistic" or "antagonistic", respectively. Results Atosiban and fenoterol alone suppressed contractions by a median of 43.2% and 29.8%, respectively. The combination of atosiban plus fenoterol was measured at a level of 67.3% inhibition. There was no significant difference in the expected (63.2%) and observed inhibition effect of dual tocolysis (P=0.945). Conclusions This study demonstrated an additive effect of dual tocolysis of atosiban and fenoterol on human myometrium in vitro, but no synergistic or antagonistic effect
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