The Combination of Mechanically Isolated Stromal Vascular Fraction and Fibrin Hydrogel: A Processing Protocol.

The regenerative potential of adipose-derived stromal cells (ASCs) has gained significant attention in regenerative and translational research. In the past, the extraction of these cells from adipose tissue required a multistep enzyme-based process, resulting in a heterogenous cell mix consisting of ACSs and other cells, which are jointly termed the stromal vascular fraction (SVF). More recently introduced mechanical SVF (mSVF) isolation protocols are less time-consuming and bypass regulatory concerns. We recently proposed a protocol that generates mSVF rich in stromal cells based on a combination of emulsification and centrifugation. One current issue in mSVF application for wound therapy application is the lack of a scaffold providing protection from mechanical manipulation and desiccation. Fibrin hydrogels have been shown to be a useful adjunct in cell transfer for wound healing purposes in the past. In the work herein, we delineate the preparation steps of an mSVF-fibrin hydrogel construct as a novel approach for translational research and clinical application.

Impact of a High-Fat Diet at a Young Age on Wound Healing in Mice.

As the prevalence of juvenile-onset obesity rises globally, the multitude of related health consequences gain significant importance. In this context, obesity is associated with impaired cutaneous wound healing. In experimental settings, mice are the most frequently used model for investigating the effect of high-fat diet (HFD) chow on wound healing in wild-type or genetically manipulated animals, e.g., diabetic ob/ob and db/db mice. However, these studies have mainly been performed on adult animals. Thus, in the present study, we introduced a mouse model for a juvenile onset of obesity. We exposed 4-week-old mice to an investigational feeding period of 9 weeks with an HFD compared to a regular diet (RD). At a mouse age of 13 weeks, we performed excisional and incisional wounding and measured the healing rate. Wound healing was examined by serial photographs with daily wound size measurements of the excisional wounds. Histology from incisional wounds was performed to quantify granulation tissue (thickness, quality) and angiogenesis (number of blood vessels per mm2). The expression of extracellular matrix proteins (collagen types I/III/IV, fibronectin 1, elastin), inflammatory cytokines (MIF, MIF-2, IL-6, TNF-α), myofibroblast differentiation (α-SMA) and macrophage polarization (CD11c, CD301b) in the incisional wounds were evaluated by RT-qPCR and by immunohistochemistry. There was a marked delay of wound closure in the HFD group with a decrease in granulation tissue quality and thickness. Additionally, inflammatory cytokines (MIF, IL-6, TNF-α) were significantly up-regulated in HFD- when compared to RD-fed mice measured at day 3. By contrast, MIF-2 and blood vessel expression were significantly reduced in the HFD animals, starting at day 1. No significant changes were observed in macrophage polarization, collagen expression, and levels of TGF-ß1 and PDGF-A. Our findings support that an early exposition to HFD resulted in juvenile obesity in mice with impaired wound repair mechanisms, which may be used as a murine model for obesity-related studies in the future.

Involvement of the Macrophage Migration Inhibitory Factor (MIF) in Lipedema.

Lipedema is a chronic disorder that mainly affects women. It is often misdiagnosed, and its etiology remains unknown. Recent research indicates an accumulation of macrophages and a shift in macrophage polarization in lipedema. One known protein superfamily that contributes to macrophage accumulation and polarization is the macrophage migration inhibitory factor (MIF) family. MIF-1 and MIF-2 are ubiquitously expressed and also regulate inflammatory processes in adipose tissue. In this study, the expression of MIF-1, MIF-2 and CD74-a common receptor for both cytokines-was analyzed in tissue samples of 11 lipedema and 11 BMI-matched, age-matched and anatomically matched control patients using qPCR and immunohistochemistry (IHC). The mRNA expression of MIF-1 (mean 1.256; SD 0.303; p = 0.0485) and CD74 (mean 1.514; SD 0.397; p = 0.0097) were significantly elevated in lipedema patients, while MIF-2 expression was unaffected (mean 1.004; SD 0.358; p = 0.9718). The IHC analysis corroborated the results for CD74 expression on a cellular level. In conclusion, our results provide first evidence for a potential involvement of the MIF family, presumably via the MIF-1-CD74 axis, in lipedema.

Basic Principles in the Management of Acute Burn Injuries in Adults.

INTRODUCTION: This review outlines an overview of up-to-date, stage-appropriate treatment methods for burn injuries as practiced at the National Burn Center of the University Hospital Zurich. It intends to provide practitioners with recommendations for the management of acute minor to severe burn injuries based on scientific evidence as well as the long-term experience of the Burn Center. The focus is on a practical guideline and various options including novel, innovative conceptual approaches.

Methacrylated Gelatin as a Scaffold for Mechanically Isolated Stromal Vascular Fraction for Cutaneous Wound Repair.

Mechanically processed stromal vascular fraction (mSVF) is a highly interesting cell source for regenerative purposes, including wound healing, and a practical alternative to enzymatically isolated SVF. In the clinical context, SVF benefits from scaffolds that facilitate viability and other cellular properties. In the present work, the feasibility of methacrylated gelatin (GelMA), a stiffness-tunable, light-inducible hydrogel with high biocompatibility is investigated as a scaffold for SVF in an in vitro setting. Lipoaspirates from elective surgical procedures were collected and processed to mSVF and mixed with GelMA precursor solutions. Non-encapsulated mSVF served as a control. Viability was measured over 21 days. Secreted basic fibroblast growth factor (bFGF) levels were measured on days 1, 7 and 21 by ELISA. IHC was performed to detect VEGF-A, perilipin-2, and CD73 expression on days 7 and 21. The impact of GelMA-mSVF on human dermal fibroblasts was measured in a co-culture assay by the same viability assay. The viability of cultured GelMA-mSVF was significantly higher after 21 days (p < 0.01) when compared to mSVF alone. Also, GelMA-mSVF secreted stable levels of bFGF over 21 days. While VEGF-A was primarily expressed on day 21, perilipin-2 and CD73-positive cells were observed on days 7 and 21. Finally, GelMA-mSVF significantly improved fibroblast viability as compared with GelMA alone (p < 0.01). GelMA may be a promising scaffold for mSVF as it maintains cell viability and proliferation with the release of growth factors while facilitating adipogenic differentiation, stromal cell marker expression and fibroblast proliferation.

Upscaled Skeletal Muscle Engineered Tissue with In Vivo Vascularization and Innervation Potential.

Engineering functional tissues of clinically relevant size (in mm-scale) in vitro is still a challenge in tissue engineering due to low oxygen diffusion and lack of vascularization. To address these limitations, a perfusion bioreactor was used to generate contractile engineered muscles of a 3 mm-thickness and a 8 mm-diameter. This study aimed to upscale the process to 50 mm in diameter by combining murine skeletal myoblasts (SkMbs) with human adipose-derived stromal vascular fraction (SVF) cells, providing high neuro-vascular potential in vivo. SkMbs were cultured on a type-I-collagen scaffold with (co-culture) or without (monoculture) SVF. Large-scale muscle-like tissue showed an increase in the maturation index over time (49.18 ± 1.63% and 76.63 ± 1.22%, at 9 and 11 days, respectively) and a similar force of contraction in mono- (43.4 ± 2.28 µN) or co-cultured (47.6 ± 4.7 µN) tissues. Four weeks after implantation in subcutaneous pockets of nude rats, the vessel length density within the constructs was significantly higher in SVF co-cultured tissues (5.03 ± 0.29 mm/mm2) compared to monocultured tissues (3.68 ± 0.32 mm/mm2) (p < 0.005). Although no mature neuromuscular junctions were present, nerve-like structures were predominantly observed in the engineered tissues co-cultured with SVF cells. This study demonstrates that SVF cells can support both in vivo vascularization and innervation of contractile muscle-like tissues, making significant progress towards clinical translation.

The Significance of Exposure to Pregestational Type 2 Diabetes in Utero on Fetal Renal Size and Subcutaneous Fat Thickness.

Objectives: To determine the relationship between exposure to pregestational type 2 diabetes (T2D) and renal size and subcutaneous fat thickness in fetuses during routine obstetrical ultrasound. Methods: This was a case-control study (January 1, 2019 to December 31, 2019). Routine obstetrical ultrasounds performed between 18 and 22 weeks' gestation at a tertiary-care fetal assessment unit were reviewed. "Cases" comprised ultrasounds of fetuses exposed to pregestational T2D in utero. The control group was assembled from ultrasounds of healthy controls. Postprocessing measurements of fetal renal size and abdominal wall thickness from stored images were performed by two independent observers, and findings were compared between groups. Results: There were 54 cases and 428 ultrasounds of healthy controls. The mean maternal age of cases was 32.1 years (SD 6.2) compared to 33.2 years (SD 5.3) for healthy controls, and the majority of ultrasounds were performed in multiparous patients (83%). At the 18 to 22 week ultrasound, there was a significant reduction in renal size amongst fetuses exposed to maternal T2D in utero compared to controls; among cases, the mean renal width was 8.0 mm (95% CI 7.8-8.1) compared to 11.4 mm (95% CI 10.6-12.7) in controls (p < 0.0001); the mean renal thickness among cases was 8.1 mm (95% CI 7.9-8.2) compared to 11.5 mm (95% CI 10.7-12.9) in controls (p=0.001). There was no obvious difference in estimated fetal weight between groups, yet fetuses exposed to maternal T2D had increased subcutaneous abdominal wall fat thickness at this early gestational age (p=0.008). Conclusions: Fetal renal size in cases exposed to pregestational T2D is significantly smaller compared to controls, and subcutaneous abdominal wall fat is significantly thicker. Given emerging evidence about the developmental origins of disease, further study is needed to correlate the association between fetal renal size and fat distribution in the fetus and the long-term risk of chronic renal disease and diabetes in these offspring.

Bizonal cardiac engineered tissues with differential maturation features in a mid-throughput multimodal bioreactor.

Functional three-dimensional (3D) engineered cardiac tissue (ECT) models are essential for effective drug screening and biological studies. Application of physiological cues mimicking those typical of the native myocardium is known to promote the cardiac maturation and functionality in vitro. Commercially available bioreactors can apply one physical force type at a time and often in a restricted loading range. To overcome these limitations, a millimetric-scale microscope-integrated bioreactor was developed to deliver multiple biophysical stimuli to ECTs. In this study, we showed that the single application of auxotonic loading (passive) generated a bizonal ECT with a unique cardiac maturation pattern. Throughout the statically cultured constructs and in the ECT region exposed to high passive loading, cardiomyocytes predominantly displayed a round morphology and poor contractility ability. The ECT region with a low passive mechanical stimulation instead showed both rat- and human-origin cardiac cell maturation and organization, as well as increased ECT functionality.

Modified frozen elephant trunk procedure as standard approach in acute type A aortic dissection: A propensity-weighted analysis.

OBJECTIVES: To evaluate whether the modified frozen elephant trunk (mFET) procedure provides comparable outcome compared with the standard approach for DeBakey type I aortic dissection. METHODS: From November 2008 to December 2018, 262 (mean age 62.7 ± 12.4 years) patients with acute DeBakey type I aortic dissection were included. mFET was performed in 100 (38.2%) patients and isolated ascending aorta and hemiarch replacement (iAoA) were performed in 162 (61.8%). Outcome analyses included in-hospital mortality, stroke rate, incidence of composite cardiovascular events, survival, freedom from aorta-related intervention, as well as freedom from neurologic event. Inverse probability of treatment weighting was applied. RESULTS: After inverse probability of treatment weighting, in-hospital mortality was greater in the iAoA group. The incidence of cardiac cause of death, new postoperative renal failure, as well as stroke rate were similar in both groups. The survival at 1 year, 3 years, and 4 years was 84%, 81%, and 77%, respectively, in the iAoA group and 91%, 86%, and 86%, P = .025, respectively, in the mFET group. Cause-specific HR for aortic reoperation 1.03 (confidence interval [CI], 0.43-2.48, P = .95) and neurovascular event 2.72 (CI, 0.62-11.93, P = .19) was similar in 2 groups. Subhazard ratio (sHR) for mortality as competing outcome for aorta-related reintervention sHR of 0.52 (CI, 0.32-0.86, P = .011) and neurologic event sHR of 0.45 (95% CI, 0.26-0.76, P = .003) was significantly lower in mFET. CONCLUSIONS: The mFET procedure as surgical treatment modality for DeBakey type I acute aortic dissection may be considered as viable alternative with beneficial mid-term outcome.

Outcome of right ventricular assist device implantation following left ventricular assist device implantation: Systematic review and meta-analysis.

OBJECTIVES: The main aim was a systematic evaluation of the current evidence on outcomes for patients undergoing right ventricular assist device (RVAD) implantation following left ventricular assist device (LVAD) implantation. METHODS: This systematic review was registered on PROSPERO (CRD42019130131). Reports evaluating in-hospital as well as follow-up outcome in LVAD and LVAD/RVAD implantation were identified through Ovid Medline, Web of Science and EMBASE. The primary endpoint was mortality at the hospital stay and at follow-up. Pooled incidence of defined endpoints was calculated by using random effects models. RESULTS: A total of 35 retrospective studies that included 3260 patients were analyzed. 30 days mortality was in favour of isolated LVAD implantation 6.74% (1.98-11.5%) versus 31.9% (19.78-44.02%) p = 0.001 in LVAD with temporary need for RVAD. During the hospital stay the incidence of major bleeding was 18.7% (18.2-19.4%) versus 40.0% (36.3-48.8%) and stroke rate was 5.6% (5.4-5.8%) versus 20.9% (16.8-28.3%) and was in favour of isolated LVAD implantation. Mortality reported at short-term as well at long-term was 19.66% (CI 15.73-23.59%) and 33.90% (CI 8.84-59.96%) in LVAD respectively versus 45.35% (CI 35.31-55.4%) p ⩽ 0.001 and 48.23% (CI 16.01-80.45%) p = 0.686 in LVAD/RVAD group respectively. CONCLUSION: Implantation of a temporary RVAD is allied with a worse outcome during the primary hospitalization and at follow-up. Compared to isolated LVAD support, biventricular mechanical circulatory support leads to an elevated mortality and higher incidence of adverse events such as bleeding and stroke.

Planning of graft size and 3D reconstruction using virtual reality technique in aortic valve reimplantation.

Objectives: To evaluate applicability and feasibility of the virtual imaging technology for diagnosis and planning of the aortic valve sparing procedure. Methods: Pre-operative electrocardiography-gated computed tomography images of 12 adult patients with aortic root pathology were used for 3D reconstruction of the aortic root geometry. The structural analysis was conducted with focusing on spatial architecture of key aortic root structures such as the three commissures, intervalvular triangles (IVT), as well as on morphology of the aortic root base (AoB) and of the sinotubular junction (STJ). Results: In all included patients, the 3D mapping of aortic root (AoR) morphology was successfully performed. The pre-operative diameter of the AoB was 30.6 ± 2.6 mm and of the STJ 46.5 ± 7.5 mm (p < 0.001). Based on measured AoB diameter, the mean size of prosthesis used was 28.3 ± 1.37 mm. The planar arrangement of the three commissures was similar to an equilateral triangle where the three commissures were at similar distance for each individual sinus with 39.8 ± 6.64 mm for right, 37.5 ± 7.10 mm for left, and 39.2 ± 7.52 mm for non-coronary sinus (p = 0.72) subsequently. The similar height of the three IVT's with 32.6 ± 5.87 mm for right, 33.6 ± 6.14 mm for anterior, and 31.7 ± 5.83 mm for left IVT (p = 0.73) was suggestive for all three commissures being positioned in the same plane. Consequently at reimplantation, the orientation of the three commissures followed the pattern of an equilateral triangle. Conclusion: The reconstructed images revealed a detailed 3D anatomy of the aortic root, with the spatial arrangement of the intervalvular triangles, planimetric orientation of the commissures, as well as determination of the AoB and STJ diameters. Obtained information was successfully applied to pre-operative surgical planning. The reimplantation technique, the height of the reimplanted intervalvular triangles, as well as their orientation are crucial for achieving adequate aortic valve function.

A dynamic microscale mid-throughput fibrosis model to investigate the effects of different ratios of cardiomyocytes and fibroblasts.

Cardiac fibrosis is a maladaptive remodeling of the myocardium hallmarked by contraction impairment and excessive extracellular matrix deposition (ECM). The disease progression, nevertheless, remains poorly understood and present treatments are not capable of controlling the scarring process. This is partly due to the absence of physiologically relevant, easily operable, and low-cost in vitro models, which are of the utmost importance to uncover pathological mechanisms and highlight possible targets for anti-fibrotic therapies. In classic models, fibrotic features are usually obtained using substrates with scar mimicking stiffness and/or supplementation of morphogens such as transforming growth factor ß1 (TGF-ß1). Qualities such as the interplay between activated fibroblasts (FBs) and cardiomyocytes (CMs), or the mechanically active, three-dimensional (3D) environment, are, however, neglected or obtained at the expense of the number of experimental replicates achievable. To overcome these shortcomings, we engineered a micro-physiological system (MPS) where multiple 3D cardiac micro-tissues can be subjected to cyclical stretching simultaneously. Up to six different biologically independent samples are incorporated in a single device, increasing the experimental throughput and paving the way for higher yielding drug screening campaigns. The newly developed MPS was used to co-culture different ratios of neonatal rat CMs and FBs, investigating the role of CMs in the modulation of fibrosis traits, without the addition of morphogens, and in soft substrates. The expression of contractile stress fibers and of degradative enzymes, as well as the deposition of fibronectin and type I collagen were superior in microtissues with a low amount of CMs. Moreover, high CM-based microconstructs simulating a ratio similar to that of healthy tissues, even if subjected to both cyclic stretch and TGF-ß1, did not show any of the investigated fibrotic signs, indicating a CM fibrosis modulating effect. Overall, this in vitro fibrosis model could help to uncover new pathological aspects studying, with mid-throughput and in a mechanically active, physiologically relevant environment, the crosstalk between the most abundant cell types involved in fibrosis.

Long-Term Severe In Vitro Hypoxia Exposure Enhances the Vascularization Potential of Human Adipose Tissue-Derived Stromal Vascular Fraction Cell Engineered Tissues.

The therapeutic potential of mesenchymal stromal/stem cells (MSC) for treating cardiac ischemia strongly depends on their paracrine-mediated effects and their engraftment capacity in a hostile environment such as the infarcted myocardium. Adipose tissue-derived stromal vascular fraction (SVF) cells are a mixed population composed mainly of MSC and vascular cells, well known for their high angiogenic potential. A previous study showed that the angiogenic potential of SVF cells was further increased following their in vitro organization in an engineered tissue (patch) after perfusion-based bioreactor culture. This study aimed to investigate the possible changes in the cellular SVF composition, in vivo angiogenic potential, as well as engraftment capability upon in vitro culture in harsh hypoxia conditions. This mimics the possible delayed vascularization of the patch upon implantation in a low perfused myocardium. To this purpose, human SVF cells were seeded on a collagen sponge, cultured for 5 days in a perfusion-based bioreactor under normoxia or hypoxia (21% and <1% of oxygen tension, respectively) and subcutaneously implanted in nude rats for 3 and 28 days. Compared to ambient condition culture, hypoxic tension did not alter the SVF composition in vitro, showing similar numbers of MSC as well as endothelial and mural cells. Nevertheless, in vitro hypoxic culture significantly increased the release of vascular endothelial growth factor (p < 0.001) and the number of proliferating cells (p < 0.00001). Moreover, compared to ambient oxygen culture, exposure to hypoxia significantly enhanced the vessel length density in the engineered tissues following 28 days of implantation. The number of human cells and human proliferating cells in hypoxia-cultured constructs was also significantly increased after 3 and 28 days in vivo, compared to normoxia. These findings show that a possible in vivo delay in oxygen supply might not impair the vascularization potential of SVF- patches, which qualifies them for evaluation in a myocardial ischemia model.

Simple endovascular thoracic aortic stenting rescues a wrongly deployed frozen elephant trunk during a modified procedure.

We report a bail out approach of endovascular thoracic aorta repair following incorrect deployment of a modified frozen elephant trunk stent graft into the false lumen. A 76-year-old patient was admitted to our Emergency Department. A computed tomography angiography scan showed type I DeBakey aortic dissection. An emergency modified frozen elephant trunk procedure was performed. Immediate postoperative computed tomography angiography showed that the distal segment of the stent was deployed in the false lumen, probably through a re-entry tear at the descending thoracic aorta. Emergency endovascular repair of the thoracic aorta, as well as angioplasty of the superior mesenteric artery and left iliac artery, were performed.

Next Stage Approach to Tissue Engineering Skeletal Muscle.

Large-scale muscle injury in humans initiates a complex regeneration process, as not only the muscular, but also the vascular and neuro-muscular compartments have to be repaired. Conventional therapeutic strategies often fall short of reaching the desired functional outcome, due to the inherent complexity of natural skeletal muscle. Tissue engineering offers a promising alternative treatment strategy, aiming to achieve an engineered tissue close to natural tissue composition and function, able to induce long-term, functional regeneration after in vivo implantation. This review aims to summarize the latest approaches of tissue engineering skeletal muscle, with specific attention toward fabrication, neuro-angiogenesis, multicellularity and the biochemical cues that adjuvate the regeneration process.

"Noninfective Endocarditis": A Case Report of Hereditary Coagulation Disorders in a 28-Year-Old Male.

We report a case of a young male who presented with acute limb ischemia after sport. With no prior history of disease, a non-infective endocarditis of the native aortic valve was diagnosed. After surgical valve replacement, the patient suffered from acute myocardial ischemia under phenprocoumon therapy. Anti-coagulant monitoring was subsequently changed to Factor II analysis after a rare Factor VII deficiency and prothrombin mutation (G20210A) was diagnosed.

Severe Rh alloimmunization and hemolytic disease of the fetus managed with plasmapheresis, intravenous immunoglobulin and intrauterine transfusion: A case report.

Rh alloimmunization remains a potentially devastating complication of pregnancy, with fetal anemia causing hydrops and intrauterine death. Intrauterine transfusion is the standard treatment, but is particularly dangerous before 20 weeks gestation. When the need for intrauterine transfusion is anticipated early in pregnancy, immune-modulating therapies such as plasmapheresis and IVIG have been used to delay transfusion to a later gestational age. We report a 35-year-old G5P1 Rh(D)-negative woman with severe Rh alloimmunization managed successfully with sequential plasmapheresis, intravenous immune globulin and intrauterine transfusion. The optimal plasmapheresis treatment protocol and incremental benefit of IVIG remains unknown.

Evaluating the safety of labour in women with a placental edge 11 to 20 mm from the internal cervical Os.

OBJECTIVE: The purpose of this study was to evaluate pregnancy outcomes in a cohort of women with a placental edge between 11 and 20 mm from the internal cervical os, and to determine the likelihood of a successful vaginal delivery when trial of labour is attempted in these women. METHODS: We carried out a prospective observational study of women with singleton pregnancies and a placental edge between 11 and 20 mm from the internal cervical os (identified by transvaginal sonography) who underwent a trial of labour. RESULTS: Fourteen women with the above characteristics underwent a trial of labour during the study period. The mean interval (± SD) from ultrasound to delivery was 17.2 ± 9.6 days. Thirteen women (92.9%) delivered vaginally with no complications, and only one woman (7.1%) required an emergency Caesarean section for intrapartum bleeding. The risks of antepartum and postpartum hemorrhage were 21.4% and 14.3%, respectively. CONCLUSION: Having a placental edge more than 10 mm from the internal os, measured by transvaginal sonography near term, justifies allowing a trial of labour and carries a low risk of subsequent obstetrical hemorrhage.

Objectif : Cette étude avait pour objectif d'évaluer les issues de grossesse au sein d'une cohorte de femmes qui présentaient un pourtour placentaire se situant à 11-20 mm d'écart par rapport à l'orifice cervical interne; elle cherchait également à déterminer la probabilité d'un accouchement vaginal réussi lorsqu'un essai de travail est tenté chez de telles femmes. Méthodes : Nous avons mené une étude observationnelle prospective portant sur des femmes qui connaissaient une grossesse monofœtale, qui présentaient un pourtour placentaire se situant à 11-20 mm d'écart par rapport à l'orifice cervical interne (identifié par échographie transvaginale) et qui ont tenté un essai de travail. Résultats : Quatorze femmes présentant les caractéristiques susmentionnées ont tenté un essai de travail au cours de la période d'étude. L'intervalle moyen (± σ) entre l'échographie et l'accouchement a été de 17,2 ± 9,6 jours. Treize femmes (92,9 %) ont connu un accouchement vaginal sans complications; une seule femme (7,1 %) a nécessité une césarienne d'urgence en raison de la présence de saignements pendant la période intrapartum. Les risques d'hémorragie antepartum et postpartum étaient de 21,4 % et de 14,3 %, respectivement. Conclusion : La constatation d'un pourtour placentaire se situant à plus de 10 mm d'écart par rapport à l'orifice cervical interne (mesuré par échographie transvaginale peu avant le terme) justifie la tenue d'un essai de travail et ne s'accompagne que d'un faible risque d'hémorragie obstétricale subséquente.

Effects of vaginal delivery, cesarean section and exposure to labor on endothelial function of pregnant women.

INTRODUCTION: This study was undertaken to assess the influence of labor and cesarean section on endothelial function. MATERIALS AND METHODS: Flow-mediated vasodilatation (FMD) was measured before and after delivery for an assessment of endothelial function in three groups: (1) the Vaginal delivery group (with spontaneous labor or induction of labor, n = 48), (2) the Elective C/S group (with a cesarean planned, n = 20), and (3) the C/S after FP group (scheduled for vaginal delivery but required to have an emergency cesarean section because of failure in progress, n = 11). RESULTS: There were statistically significant changes between the antepartum and postpartum FMD values in the Vaginal delivery group and the Elective C/S group but not in the C/S after FP group (P < 0.001, P = 0.023 and P = 0.22 respectively). CONCLUSIONS: These observations suggest that labor may enhance endothelial function and that cesarean section may impair endothelial function.

MG98, a second-generation DNMT1 inhibitor, in the treatment of advanced renal cell carcinoma.

BACKGROUND: In carcinogenesis, methylation of DNA promoter regions results in inactivation of tumor-suppressing genes. MG98 was designed to inhibit DNA methyltransferases enzyme 1 production. METHODS: This multicenter study explored two schedules of MG98 with Interferon-α-2ß to identify schedule and dose for patients with metastatic RCC. RESULTS: Doses of IFN 9 MIU/MG98 125 mg/m(2) for a continuous schedule and IFN 9 MIU/MG98 200 mg/m(2) for an intermittent schedule were considered the MTDs. Treatment resulted in one PR and eight SD. CONCLUSION: MG98 combined with IFN was safe and resulted in clinical activity.