Ultrasound Contrast Agents (UCAs) consisting of gas-filled-coated Microbubbles (MBs) with diameters between 1 and 10 µm have been used for a number of decades in diagnostic imaging. In recent years, ...submicron contrast agents have proven to be a viable alternative to MBs for ultrasound (US)-based applications for their capability to extravasate and accumulate in the tumor tissue via the enhanced permeability and retention effect. After a short overview of the more recent approaches to ultrasound-mediated imaging and therapeutics at the nanoscale, phase-change contrast agents (PCCAs), which can be phase-transitioned into highly echogenic MBs by means of US, are here presented. The phenomenon of acoustic droplet vaporization (ADV) to produce bubbles is widely investigated for both imaging and therapeutic applications to develop promising theranostic platforms.
Purpose
Triple-negative breast cancer (TNBC) patients have usually poor outcome after chemotherapy and early prediction of therapeutic response would be helpful.
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FF-FDG-PET/CT acquisitions are ...often carried out to monitor variation in metabolic activity associated with response to the therapy, despite moderate accuracy and radiation exposure limit its application. The glucoCEST technique relies on the use of unlabelled D-glucose to assess glucose uptake with conventional MRI scanners and is currently under active investigations at clinical level. This work aims at validating the potential of MRI-glucoCEST in monitoring the therapeutic responses in a TNBC tumor murine model.
Procedures
Breast tumor (4T1)–bearing mice were treated with doxorubicin or dichloroacetate for 1 week. PET/CT with
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FF-FDG and MRI-glucoCEST were performed at baseline and after 3 cycles of treatment. Metabolic changes measured with
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FF-FDG-PET and glucoCEST were compared and evaluated with changes in tumor volumes.
Results
Doxorubicin-treated mice showed a significant decrease in tumor growth when compared to the control group. GlucoCEST imaging provided metabolic response after three cycles of treatment. Conversely, no variations were detected in
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FF-FDG uptake. Dichloroacetate-treated mice did not show any decrease either in tumor volume or in tumor metabolic activity as assessed by both glucoCEST and
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FF-FDG-PET.
Conclusions
Metabolic changes during doxorubicin treatment can be predicted by glucoCEST imaging that appears more sensitive than
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FF-FDG-PET in reporting on therapeutic response. These findings support the view that glucoCEST may be a sensitive technique for monitoring metabolic response, but future studies are needed to explore the accuracy of this approach in other tumor types and treatments.
Purpose
Pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have a higher risk of hospitalization, admission to intensive care unit (ICU) and invasive ...ventilation, and of acute respiratory distress syndrome (ARDS). In case of ARDS and critical severe coronavirus disease 2019 (COVID-19), the use of extracorporeal membrane oxygenation (ECMO) is recommended when other respiratory support strategies (oxygen insufflation, non-invasive ventilation NIV, invasive ventilation through an endotracheal tube) are insufficient. However, available data on ECMO in pregnant and postpartum women with critical COVID-19 are very limited.
Methods
A case series of three critically ill pregnant women who required ECMO support for COVID-19 in pregnancy and/or in the postpartum period.
Results
The first patient tested positive for COVID-19 during the second trimester, she developed ARDS and required ECMO for 38 days. She was discharged in good general conditions and a cesarean-section CS at term was performed for obstetric indication. The second patient developed COVID-19-related ARDS at 28 weeks of gestation. During ECMO, she experienced a precipitous vaginal delivery at 31 weeks and 6 days of gestation. She was discharged 1 month later in good general conditions. The third patient, an obese 43-year-old woman, tested positive at 38 weeks and 2 days of gestation. Because of the worsening of clinical condition, a CS was performed, and she underwent ECMO. 143 days after the CS, she died because of sepsis and multiple organ failure (MOF). Thrombosis, hemorrhage and infections were the main complications among our patients. Neonatal outcomes have been positive.
Conclusion
ECMO should be considered a life-saving therapy for pregnant women with severe COVID-19.
Undifferentiated connective tissue disease (UCTD) is characterized by signs and symptoms suggestive of a connective tissue disease (CTD), but not fulfilling criteria for a specific CTD. Although UCTD ...is probably the most common rheumatic disease diagnosed in pregnant women, data about disease course during pregnancy and perinatal outcomes are very limited. Compared to other CTDs, UCTD seems to have milder clinical manifestations in pregnancy. Its natural history is related to disease activity at conception. In fact, if the disease is in a state of remission or minimal activity at conception, pregnancy outcomes are generally good. On the contrary, patients who become pregnant in a moment of high disease activity and/or who have multiple antibodies positivity show an increased risk of disease flares, evolution to a definite CTD and obstetric complications, such as fetal growth restriction, preeclampsia and preterm birth. Therefore, a preconception assessment is essential in women with UCTD to evaluate maternal and fetal risks, to initiate interventions to optimize disease activity, and to adjust medications to those that are least harmful to the fetus. The aim of the present study was to review the available literature about pregnancy course, maternal and fetal outcomes and therapeutic approaches of pregnant women with UCTD.
Background: The purpose of this study was to describe the placental lesions in pregnancies complicated by hypertensive disorders (HDP) and/or fetal growth restriction (FGR) and in uneventful control ...pregnancies. Methods: This is a case control study that included singleton pregnancies with HDP and normally grown fetus (HDP-AGA fetus), with HDP and FGR, early FGR, late FGR, and uneventful pregnancies. Feto-placental Doppler velocimetry and sFlt-1/PlGF ratio were performed. Placental histology was evaluated blinded according to the Amsterdam Consensus criteria. Results: Placental lesions with maternal vascular malperfusion (MVM) were significantly more frequent in HDP-FGR and early FGR (92% and 83%). MVM were significantly associated with abnormal feto-placental Doppler parameters, especially in early FGR. Delayed villous maturation (DVM) was associated with late FGR (83%). HDP-AGA fetus cases presented a heterogeneous pattern of placental lesions, including 60% of cases with MVM, but were not associated with abnormal Doppler feto-placental velocimetry. Conclusions: We found a prevalence of placental maternal vascular malperfusion in HDP-FGR and early FGR groups. These lesions were also associated with abnormal, anti-, and angiogenic markers. Conversely HDP-AGA fetus and late FGR presented more heterogeneous placental lesions not severe enough to cause feto-placental Doppler anomalies. These conditions are likely associated with different etiologies, such as maternal pre-pregnancy risk factors for metabolic syndrome. These findings suggest a possible preventive nutritional approach in addition to low-dose aspirin in pregnant women with predisposing factors for HDP-AGA fetuses and late FGR.
Tumor oxygenation is a critical issue for enhancing radiotherapy (RT) effectiveness. Alternating RT with hyperthermia improves tumor radiosensitivity by inducing a massive vasodilation of the ...neoangiogenic vasculature provided the whole tumor is properly heated. The aim of this work was to develop superparamagnetic oxygen-loaded nanobubbles (MOLNBs) as innovative theranostic hyperthermic agents to potentiate tumor oxygenation by direct intracellular oxygen administration. Magnetic oxygen-loaded nanobubbles were obtained by functionalizing dextran-shelled and perfluoropentane-cored nanobubbles with superparamagnetic iron oxide nanoparticles. Magnetic oxygen-loaded nanobubbles with sizes of about 380 nm were manufactured, and they were able to store oxygen and
in vitro
release it with prolonged kinetics.
In vitro
investigation showed that MOLNBs can increase tissue temperature when exposed to radiofrequency magnetic fields. Moreover, they are easily internalized by tumor cells, herein releasing oxygen with a sustained kinetics. In conclusion, MOLNBs can be considered a multimodal theranostic platform since, beyond their nature of contrast agent for magnetic resonance imaging due to magnetic characteristics, they showed echogenic properties and can be visualized using medical ultrasound.
To verify whether the use of the temporal criterion of 32 weeks' gestation is effective in identifying maternal hemodynamic differences between early- and late-onset fetal growth restriction (FGR), ...and to test the statistical performance of a classificatory algorithm for FGR.
A prospective multicenter study conducted at three centers over 17 months. Singleton pregnant women with a diagnosis of FGR based on the international Delphi survey consensus at ≥ 20 weeks of gestation were included. FGR was classified as early-onset if diagnosed <32 weeks' gestation and as late-onset if ≥32 weeks. Hemodynamic assessment was performed by USCOM-1A at the time of FGR diagnosis. Comparisons between early- and late-onset FGR among the entire study cohort, FGR associated with hypertensive disorders of pregnancy (HDP-FGR), and isolated FGR (i-FGR) were performed. In addition, HDP-FGR cases were compared to i-FGR, regardless of the temporal cut-off of 32 weeks' gestation. Finally, a classificatory analysis based on the Random Forest model was performed to identify significant variables with the ability to differentiate FGR phenotypes.
During the study period, 146 pregnant women fulfilled the inclusion criteria. In 44 cases, FGR was not confirmed at birth, thus limiting the final study population to 102 patients. In 49 (48.1%) women, FGR was associated to HDP. Fifty-nine (57.8%) cases were classified as early-onset. Comparison of the maternal hemodynamics between early- and late-onset FGR did not show any difference. Similarly, non-significant findings were observed in sensitivity analyses performed for HDP-FGR and for i-FGR. In turn, comparison between pregnant women with FGR and hypertension and women with i-FGR, independently of the gestational age at FGR diagnosis, revealed substantial differences, with the former showing higher vascular peripheral resistances and lower cardiac output, among other significant parameters. The classificatory analysis identified both phenotypic and hemodynamic variables as relevant in distinguishing HDP-FGR from i-FGR (p=0.009).
Our data show that HDP, rather than gestational age at FGR diagnosis, allows to appreciate specific maternal hemodynamic patterns and to accurately distinguish two different FGR phenotypes. In addition, maternal hemodynamics, alongside phenotypic characteristics, play a central role in classifying these high-risk pregnancies.
Gonadotrophins are mainly known to influence the body through the formation of gonadal steroids. However, receptors for luteinizing hormone (LH) and follicular-stimulating hormone (FSH) are present ...in a set of extra-gonadal tissues in humans and animals, but their functional relevance is uncertain. In this article, we present experimental evidence that, in T-47D breast cancer (BC) cells, FSH, and LH alter the expression of genes involved in adhesion, motility, and invasion through the activation of their receptors. Using miniarray technology we also found that LH influences the expression of a broad set of genes involved in cancer biology in T-47D cells. Interestingly, the regulatory actions of FSH and LH depend on the modality of exposure, with significant differences between pre-pubertal-like vs. post-menopausal-like amounts of gonadotrophins, but not after intermittent administration, representative of fertile life. We also studied the modulation of the circulating levels of gonadotrophins in an
rat model of BC progression and observed a direct correlation with the extent of cancer growth. These results support the hypothesis that gonadotrophins may have direct effects on extra-gonadal tissues. They also highlight that gonadotrophins could potentially contribute to BC progression, particularly in post-menopausal women who typically have higher gonadotrophin levels. This research may ultimately lead to testing the use of gonadotrophin-modulating drugs in BC patients.
Low molecular weight heparins (LMWH) have been largely studied for their use during pregnancy. The biology and the pharmacology of these molecules are well known and may be summarized in three main ...mechanisms of action: anti-coagulant, anti-inflammatory, and immunomodulant. The clinical implications of these drugs during pregnancy are mainly related to their action on the placenta, because of the presence of specific molecular and cellular targets, particularly at the trophoblast-endometrial interface. As well as for the prevention and treatment of thromboembolism, LMWH have been largely investigated for the improvement of embryo implantation and for the prevention of placenta-related complications such as preeclampsia, fetal growth restriction, and intrauterine fetal death. However, data on this topic are still unclear. The present review discusses the biological features, the mechanisms of action, and the possible contribution of LMWH to the success of placentation along pregnancy, pointing out the need for future basic science and clinical researches in this important field with the final aim to improve clinical practice in high-risk pregnancies.
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