MRI of placenta accreta: diagnostic accuracy and impact of interventional radiology on foetal-maternal delivery outcomes in high-risk women

To assess accuracy and reproducibility of MRI diagnosis of invasive placentation (IP) in high-risk patients and to evaluate reliability of MRI features. Secondary aim was to evaluate impact of interventional radiology (IR) on delivery outcomes in patients with IP at MRI

Heterotypic paracrine signaling drives fibroblast senescence and tumor progression of large cell carcinoma of the lung

Senescence in cancer cells acts as a tumor suppressor, whereas in fibroblasts enhances tumor growth. Senescence has been reported in tumor associated fibroblasts (TAFs) from a growing list of cancer subtypes. However, the presence of senescent TAFs in lung cancer remains undefined. We examined senescence in TAFs from primary lung cancer and paired control fibroblasts from unaffected tissue in three major histologic subtypes: adenocarcinoma (ADC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC). Three independent senescence markers (senescence-associated beta-galactosidase, permanent growth arrest and spreading) were consistently observed in cultured LCC-TAFs only, revealing a selective premature senescence. Intriguingly, SCC-TAFs exhibited a poor growth response in the absence of senescence markers, indicating a dysfunctional phenotype rather than senescence. Co-culturing normal fibroblasts with LCC (but not ADC or SCC) cancer cells was sufficient to render fibroblasts senescent through oxidative stress, indicating that senescence in LCC-TAFs is driven by heterotypic signaling. In addition, senescent fibroblasts provided selective growth and invasive advantages to LCC cells in culture compared to normal fibroblasts. Likewise, senescent fibroblasts enhanced tumor growth and lung dissemination of tumor cells when co-injected with LCC cells in nude mice beyond the effects induced by control fibroblasts. These results define the subtype-specific aberrant phenotypes of lung TAFs, thereby challenging the common assumption that lung TAFs are a heterogeneous myofibroblast-like cell population regardless of their subtype. Importantly, because LCC often distinguishes itself in the clinic by its aggressive nature, we argue that senescent TAFs may contribute to the selective aggressive behavior of LCC tumors

Diagnostic role of circulating extracellular matrix-related proteins in non-small cell lung cancer.

BACKGROUND: Interactions between cancer cells and the surrounding microenvironment are crucial determinants of cancer progression. During this process, bi-directional communication among tumor cells and cancer associated fibroblasts (CAF) regulate extracellular matrix (ECM) deposition and remodeling. As a result of this dynamic process, soluble ECM proteins can be released into the bloodstream and may represent novel circulating biomarkers useful for cancer diagnosis. The aim of the present study was to measure the levels of three circulating ECM related proteins (COL11A1, COL10A1 and SPARC) in plasma samples of lung cancer patients and in healthy heavy-smokers controls and test whether such measurements have diagnostic or prognostic value. METHODS: Gene expression profiling of lung fibroblasts isolated from paired normal and cancer tissue of NSCLC patients was performed by gene expression microarrays. The prioritization of the candidates for the study of circulating proteins in plasma was based on the most differentially expressed genes in cancer associated fibroblasts. Soluble ECM proteins were assessed by western blot in the conditioned medium of lung fibroblasts and by ELISA assays in plasma samples. RESULTS: Plasma samples from lung cancer patients and healthy heavy-smokers controls were tested for levels of COL11A1 and COL10A1 (n = 57 each) and SPARC (n = 90 each). Higher plasma levels of COL10A1 were detected in patients (p ≤ 0.001), a difference that was driven specifically by females (p < 0.001). No difference in COL11A1 levels between patients and controls was found. SPARC levels were also higher in plasma patients than controls (p < 0.001) with good performance in discriminating the two groups (AUC = 0.744). No significant association was observed between plasma proteins levels and clinicopathological features or survival. CONCLUSION: Soluble factors related to proficient tumor-stroma cross-talk are detectable in plasma of primary lung cancer patients and may represent a valuable complementary diagnostic tool to discriminate lung cancer patients from healthy heavy-smokers individuals as shown for the SPARC protein

Rapid and well tolerated action of idarucizumab for antagonizing dabigatran in a patient needing urgent thrombolysis: a case report

Dabigatran is a direct oral anticoagulant drug exhibiting clinical benefits over vitamin K antagonists. A procedure for reversing the anticoagulant effect of direct oral anticoagulants may be needed in emergency clinical settings, and is traditionally accomplished by using plasma products or hemostatic physical interventions. Idarucizumab, a specific antidote for dabigatran, has recently become available. This compound can be rapidly administered by intravenous injection and is effective in reversing anticoagulation in few minutes. We describe here the case of a 78-year-old woman taking dabigatran for atrial fibrillation, who was admitted to the emergency department with a diagnosis of acute cerebral ischemia. Dabigatran plasma levels on admission (74\u200ang/ml) were measured with diluted thrombin time. Idarucizumab was immediately administered and dabigatran plasma concentration suddenly decreased to less than 2\u200ang/ml. Successful systemic thrombolysis could hence be performed with full recovery

Fusion proteins in lung cancer: addressing diagnostic problems for deciding therapy

Gene fusions are frequent chromosomal aberrations in solid tumors. In Lung cancer (LC) several druggable-fusions involving tyrosine kinase receptor genes have been described, including ALK, ROS1, RET and NTRK. In non-small cell lung cancer, testing for targetable fusions has become a part of routine clinical practice, greatly impacting therapeutic choice for patients with these aberrations. Although substantial technologies for gene fusion detection have been implemented over time including; cytogenetic, Fluorescence in situ hybridization (FISH), Immunohistochemistry (IHC), Retro-transcription Real-Time PCR (RT-qPCR), to Next Generation Sequencing (NGS), nCounter system (Nanostring technology), several critical issues remain. To date, only the companion diagnostic tests FISH and IHC for ALK-rearrangements and NGS for ROS1-rearrangments were approved. Other fusion approved tests are currently unavailable

Co-Ultramicronized Palmitoylethanolamide/Luteolin Restores Oligodendrocyte Homeostasis via Peroxisome Proliferator-Activated Receptor-&alpha; in an In Vitro Model of Alzheimer&rsquo;s Disease

Oligodendrocytes are cells fundamental for brain functions as they form the myelin sheath and feed axons. They perform these critical functions thanks to the cooperation with other glial cells, mainly astrocytes. The astrocyte/oligodendrocyte crosstalk needs numerous mediators and receptors, such as peroxisome proliferator-activated receptors (PPARs). PPAR agonists promote oligodendrocyte precursor cells (OPCs) maturation in myelinating oligodendrocytes. In the Alzheimer&rsquo;s disease brain, deposition of beta-amyloid (A&beta;) has been linked to several alterations, including astrogliosis and changes in OPCs maturation. However, very little is known about the molecular mechanisms. Here, we investigated for the first time the maturation of OPCs co-cultured with astrocytes in an in vitro model of A&beta;1&ndash;42 toxicity. We also tested the potential beneficial effect of the anti-inflammatory and neuroprotective composite palmitoylethanolamide and luteolin (co-ultra PEALut), which is known to engage the isoform alfa of the PPARs. Our results show that A&beta;1&ndash;42 triggers astrocyte reactivity and inflammation and reduces the levels of growth factors important for OPCs maturation. Oligodendrocytes indeed show low cell surface area and few arborizations. Co-ultra PEALut counteracts the A&beta;1&ndash;42-induced inflammation and astrocyte reactivity preserving the morphology of co-cultured oligodendrocytes through a mechanism that in some cases involves PPAR-&alpha;. This is the first evidence of the negative effects exerted by A&beta;1&ndash;42 on astrocyte/oligodendrocyte crosstalk and discloses a never-explored co-ultra PEALut ability in restoring oligodendrocyte homeostasis

Transvaginal ultrasound assessment of uterine scar after previous caesarean section: comparison with 3T-magnetic resonance diffusion tensor imaging

This study aimed to evaluate 3-T magnetic resonance imaging in the analysis of caesarean scars in women with prior caesarean section (pCS) and investigate the potential added value of diffusion tensor imaging (3T-MR-DTI) with fibre tracking reconstruction, compared with transvaginal ultrasound (TVUS). Thirty women who had previously undergone elective CS in a singleton pregnancy at term were examined (19 women with one pCS formed group 1 and 11 women with two pCS formed group 2). Patients underwent TVUS and 3T-MR-DTI within 2 days. Twelve women with prior vaginal delivery served as controls and underwent only 3T-MR. Uterine fibre architecture was depicted by MR-DTI with 3D tractography reconstruction providing quali-quantitative analysis of fibre, described as the reduction of number of longitudinal fibres that run through the uterine scar. Six subjects were excluded. According to 3T-MR morphology, scars were described as linear (n = 12) and retracting (n = 12); disagreement with TVUS was 54 %. The thickness of myometrium at the scar level was found to be significantly greater with 3T-MR compared to TVUS in linear scars (p = 0.01). No difference was found among retracting scars. In controls, according to 3T-MR-DTI, longitudinal myometrial fibres running in the anterior wall were similar to those in the posterior wall at same level -2 %; -27 % + 22 %). In groups 1 and 2 there was significant reduction in anterior fibres compared to posterior ones (-53 %; -77 % - 34 %; p = 0.0001). Among retracting scars, fibre reduction was significantly higher compared to linear scars, p &lt; 0.016. The added value of 3T-MR with DTI lies in the prompt evaluation of muscle fibre remaining at scar level