Spontaneous splenic rupture in Waldenstrom's macroglobulinemia: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report the case of a patient with Waldenstrom's macroglobulinemia complicated by spontaneous splenic rupture.</p> <p>Case presentation</p> <p>A 49-year-old Caucasian woman was referred to our emergency department by her general practitioner following a three-week history of malaise, night sweats, six kilograms of weight loss, intermittent nausea and vomiting, progressive upper abdominal pain and easy bruising. On the fourth day following her admission, she had a rapid clinical deterioration, with subsequent radiological investigations revealing a splenic rupture. Her morphology, biochemistry, flow cytometry and histology were strongly suggestive of Waldenstrom's macroglobulinemia.</p> <p>Conclusions</p> <p>Spontaneous splenic rupture is not an expected complication of low-grade lymphoplasmacytic lymphomas, such as Waldenstrom's macroglobulinemia. To the best of our knowledge, this is the only reported case of early spontaneous splenic rupture due to Waldenstrom's macroglobulinemia. Our case highlights that despite the typical disease course of low-grade hematological malignancies, signs and symptoms of imminent splenic rupture should be considered when formulating a clinical assessment.</p

Vegetation dynamics within afforested coastal areas: regeneration by native species or invasion by alien species?

During the last century, massive reforestation projects along the dunes of the southern Sicily have been carried out. Such interventions, far from being in line with the current trends of close-to-nature silviculture, are, however, particularly interesting to assess the vegetation dynamics in afforestation areas. Furthermore, these kind of interventions may determine two opposite effects, that is renaturalization by native woody species or invasion by alien species. Acacia spp. are among the most widespread and prominent invaders within Mediterranean-climate areas, where they have already shown the capability to deeply change the characters and the functioning of native ecosystems. For instance, Acacia longifolia (Andrews) Willd. may successfully invade the understory of pine forests, causing the alteration of the water balance and carbon storage of the whole forest ecosystem. In Sicily, especially in the last decades, Acacia saligna started to abundantly regenerate in many natural and semi-natural areas, with a stark preference for dune and coastal afforested sites. The nature reserve \u201cFoce del Fiume Platani\u201d represents an excellent case study in this respect

Evidence that regulation of intramembrane proteolysis is mediated by substrate gating during sporulation in Bacillus subtilis

© 2018 Ramírez-Guadiana et al. http://creativecommons.org/licenses/by/4.0/. During the morphological process of sporulation in Bacillus subtilis two adjacent daughter cells (called the mother cell and forespore) follow different programs of gene expression that are linked to each other by signal transduction pathways. At a late stage in development, a signaling pathway emanating from the forespore triggers the proteolytic activation of the mother cell transcription factor σK. Cleavage of pro-σK to its mature and active form is catalyzed by the intramembrane cleaving metalloprotease SpoIVFB (B), a Site-2 Protease (S2P) family member. B is held inactive by two mother-cell membrane proteins SpoIVFA (A) and BofA. Activation of pro-σK processing requires a site-1 signaling protease SpoIVB (IVB) that is secreted from the forespore into the space between the two cells. IVB cleaves the extracellular domain of A but how this cleavage activates intramembrane proteolysis has remained unclear. Structural studies of the Methanocaldococcus jannaschii S2P homolog identified closed (substrate-occluded) and open (substrate-accessible) conformations of the protease, but the biological relevance of these conformations has not been established. Here, using co-immunoprecipitation and fluorescence microscopy, we show that stable association between the membrane-embedded protease and its substrate requires IVB signaling. We further show that the cytoplasmic cystathionine-β-synthase (CBS) domain of the B protease is not critical for this interaction or for pro-σK processing, suggesting the IVB-dependent interaction site is in the membrane protease domain. Finally, we provide evidence that the B protease domain adopts both open and closed conformations in vivo. Collectively, our data support a substrate-gating model in which IVB-dependent cleavage of A on one side of the membrane triggers a conformational change in the membrane-embedded protease from a closed to an open state allowing pro-σK access to the caged interior of the protease

A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens

The objective of this study was to determine the objective response rate in patients with platinum-sensitive and platinum-resistant recurrent ovarian cancer to treatment with trabectedin (Yondelis®) administered as a 3-h infusion weekly for 3 weeks of a 4-week cycle. We carried out a multicentre Phase II trial of trabectedin in patients with advanced recurrent ovarian cancer. Trabectedin (0.58 mg m−2) was administered via a central line, after premedication with dexamethasone, to 147 patients as a 3-h infusion weekly for 3 weeks followed by 1-week rest. Major eligibility criteria included measurable relapsed advanced ovarian cancer and not more than two prior platinum-containing regimens. Patients were stratified according to the treatment-free interval (TFI) between having either platinum-sensitive (⩾6 months TFI) or platinum-resistant disease (<6 months TFI)/platinum-refractory disease (progression during first line therapy). In the platinum-sensitive cohort, 62 evaluable patients with measurable disease had an overall response rate (ORR) of 29.0% (95% CI: 18.2–41.9%) and median progression-free survival (PFS) was 5.1 months (95% CI: 2.8–6.2). Four patients with measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) criteria had no follow-up scans at the end of treatment. In the platinum-resistant/refractory cohort, 79 patients were evaluable with an ORR of 6.3% (95% CI: 2.1–14.2%). Median PFS was 2.0 months (95% CI: 1.7–3.5 months). Two patients with measurable disease per RECIST criteria had no follow-up scans at the end of treatment. The most frequent (⩾2% of patients) drug-related treatment-emergent grade 3/4 adverse events were reversible liver alanine transferase elevation (10%), neutropaenia (8%), nausea, vomiting, and fatigue (5% each). Trabectedin is an active treatment, with documented responses in patients with platinum sensitive advanced relapsed ovarian cancer, and has a manageable toxicity profile

imPlatelet classifier: image-converted RNA biomarker profiles enable blood-based cancer diagnostics

Liquid biopsies offer a minimally invasive sample collection, outperforming traditional biopsies employed for cancer evaluation. The widely used material is blood, which is the source of tumor-educated platelets. Here, we developed the imPlatelet classifier, which converts RNA-sequenced platelet data into images in which each pixel corresponds to the expression level of a certain gene. Biological knowledge from the Kyoto Encyclopedia of Genes and Genomes was also implemented to improve accuracy. Images obtained from samples can then be compared against standard images for specific cancers to determine a diagnosis. We tested imPlatelet on a cohort of 401 non-small cell lung cancer patients, 62 sarcoma patients, and 28 ovarian cancer patients. imPlatelet provided excellent discrimination between lung cancer cases and healthy controls, with accuracy equal to 1 in the independent dataset. When discriminating between noncancer cases and sarcoma or ovarian cancer patients, accuracy equaled 0.91 or 0.95, respectively, in the independent datasets. According to our knowledge, this is the first study implementing an image-based deep-learning approach combined with biological knowledge to classify human samples. The performance of imPlatelet considerably exceeds previously published methods and our own alternative attempts of sample discrimination. We show that the deep-learning image-based classifier accurately identifies cancer, even when a limited number of samples are available.publishedVersio