Local recurrence of soft tissue sarcoma: A radiomic analysis

Background To perform a radiomics analysis in local recurrence (LR) surveillance of limb soft tissue sarcoma (STS) Patients and methods This is a sub-study of a prospective multicenter study with Institutional Review Board approval supported by ESSR (European Society of Musculoskeletal Radiology). radiomics analysis was done on fast spin echo axial T1w, T2w fat saturated and post-contrast T1w (T1wGd) 1.5T MRI images of consecutively recruited patients between March 2016 and September 2018. Results N = 11 adult patients (6 men and 5 women; mean age 57.8 \ub1 17.8) underwent MRI to exclude STS LR: a total of 33 follow-up events were evaluated. A total of 198 data-sets per patients of both pathological and normal tissue were analyzed. Four radiomics features were significantly correlated to tumor size (p < 0.02) and four radiomics features were correlated with grading (p < 0.05). ROC analysis showed an AUC between 0.71 (95%CI: 0.55-0.87) for T1w and 0.96 (95%CI: 0.87-1.00) for post-contrast T1w. Conclusions radiomics features allow to differentiate normal tissue from pathological tissue in MRI surveillance of local recurrence of STS. radiomics in STS evaluation is useful not only for detection purposes but also for lesion characterization

A critical appraisal of the quality of adult dual-energy X-ray absorptiometry guidelines in osteoporosis using the AGREE II tool: An EuroAIM initiative

Objectives: Dual energy X-ray absorptiometry (DXA) is the most widely used technique to measure bone mineral density (BMD). Appropriate and accurate use of DXA is of great importance, and several guidelines have been developed in the last years. Our aim was to evaluate the quality of published guidelines on DXA for adults. Methods: Between June and July 2016 we conducted an online search for DXA guidelines, which were evaluated by four independent readers blinded to each other using the AGREE II instrument. A fifth independent reviewer calculated scores per each domain and agreement between reviewers\u2019 scores. Results: Four out of 59 guidelines met inclusion criteria and were included. They were published between 2005 and 2014. Three out of four guidelines reached a high level of quality, having at least five domain scores higher than 60%. Domain 1 (Scope and Purpose) achieved the highest result (total score = 86.8 \ub1 3.7%). Domain 6 (Editorial Independence) had the lowest score (total score = 54.7 \ub1 12.5%). Interobserver agreement ranged from fair (0.230) to good (0.702). Conclusions: Overall, the quality of DXA guidelines is satisfactory when evaluated using the AGREE II instrument. The Editorial Independence domain was the most critical, thus deserving more attention when developing future guidelines. Main messages: \u2022 Three of four guidelines on DXA had a high quality level (>60%). \u2022 Scope/purpose had the highest score (86.8 \ub1 3.7%). \u2022 Editorial Independence had the lowest score (54.7 \ub1 12.5%). \u2022 Interobserver agreement ranged from fair (0.230) to good (0.702)

Induction of tumor-specific cytotoxicity in tumor infiltrating lymphocytes by HPV16 and HPV18 E7-pulsed autologous dendritic cells in patients with cancer of the uterine cervix.

OBJECTIVE: To evaluate the potential of autologous dendritic cells (DC) pulsed with HPV16 and HPV18 E7 oncoprotein in restoring tumor-specific cytotoxicity in populations of tumor infiltrating lymphocytes (TIL) for adoptive immunotherapy of cervical cancer patients. METHODS: Full-length E7-pulsed DC-stimulated CD8(+) T cells derived from peripheral blood (PBL) and from tumor tissues (TIL) were tested and compared for their ability to induce a HLA class-I-restricted cytotoxic T lymphocyte (CTL) response against autologous tumor cells. In addition, in order to correlate cytotoxic activity by CTL with a particular lymphoid subset, analysis of surface antigens and intracellular CD3 zeta chain and two-color flow cytometric analysis of intracellular cytokine expression (IFN-gamma vs IL-4) at the single cell level were performed. RESULTS: DC stimulation induced powerful cytotoxicity against autologous tumor target cells by TIL-derived CD8(+) T cells from all three cervical cancer patients, while autologous Epstein-Barr virus-transformed lymphoblastoid cell lines were not lysed. Killing of autologous tumor cells was higher by CD8(+) T cells from TIL compared to PBL (P > 0.01) and was more strongly inhibited by anti-HLA class I MAb (P > 0.05). Phenotypically, all CTL populations were CD3(+)/CD8(+), with higher levels of CD56 expression by TIL-derived CTL. Finally, although a marked Type 1 cytokine bias (i.e., IFN-gamma(high)/IL-4(low)) was observable in both PBL- and TIL-derived DC-stimulated CD8(+) T cell populations, TIL-derived CD8(+) T cells showed a higher percentage of IFN-gamma-positive cells compared to PBL. CONCLUSIONS: Full-length E7-pulsed DC can consistently restore strong CD8(+) CTL responses against autologous HPV16- and HPV18-infected cervical cancer cells. DC-stimulated TIL may represent a superior source of tumor-specific CTL compared to PBL for adoptive T cell immunotherapy of patients harboring metastatic or recurrent cervical cancer refractory to standard treatment modalities

Restoration of tumor specific human leukocyte antigens class I-restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer

Despite the large number of potentially cytotoxic tumor-infiltrating (TIL) and tumor-associated (TAL) lymphocytes accumulated in the peritoneal cavity ascitic fluid and tumor tissue, advanced ovarian cancer is a progressive disease, suggesting that TIL and TAL populations eventually become functionally suppressed in vivo. Dendritic cells (DC) are the most powerful professional antigen presenting cells known in humans and recently, ovarian tumor antigen pulsed DC have been shown to elicit tumor specific human leukocyte antigens (HLA)-class I-restricted cytotoxicity from the peripheral blood of advanced ovarian cancer patients. In this study, we have evaluated the potential of tumor antigen-pulsed fully mature DC stimulation in restoring tumor-specific cytotoxicity in anergic TIL populations from advanced ovarian cancer patients. In addition, we have compared tumor-specific T-cell responses induced by tumor antigen-loaded DC in TIL to those induced in TAL and peripheral blood lymphocytes (PBL). DC stimulation induced powerful cytotoxicity against autologous tumor target cells in TIL-derived CD8+ T-cells from all patients tested, while autologous Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) were not lysed. Killing of autologous tumor cells was higher by CD8+ T-cells from TIL compared to PBL and TAL (P < 0.01) and was more strongly inhibited by anti-HLA class I MAb (P < 0.05 compared to PBL and TAL). Phenotypically, all cytotoxic T lymphocyte (CTL) populations were CD3+/CD8+, with variable levels of CD56 expression. Finally, although a marked Type 1 cytokine bias [ie, interferon-gamma/interleukin-4 (IFN-gammahigh/IL-4low)] was observable in all DC-stimulated CD8+ T-cell populations, TIL derived CD8+ T-cells showed a higher percentage of IFN-gamma positive cells compared to TAL and PBL. Taken together, these data show that tumor lysate-pulsed DC can consistently restore strong CD8+ CTL responses from TIL against autologous ovarian cancer cells. DC-stimulated TIL may represent a superior source of tumor-specific CTL for adoptive T-cell immunotherapy for advanced ovarian cancer

Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer

<p>Abstract</p> <p>Background</p> <p>The absence of highly sensitive and specific serum biomarkers makes mass screening for ovarian cancer impossible. The claudin proteins are frequently overexpressed in ovarian cancers, but their potential as prognostic, diagnostic, or detection markers remains unclear. Here, we have explored the possible use of these proteins as screening biomarkers for ovarian cancer detection.</p> <p>Methods</p> <p>Claudin protein shedding from cells was examined by immunoblotting of conditioned culture media. The presence of claudins in exosomes released from ovarian cancer cells was demonstrated by sucrose gradient separation and immunogold electron microscopy experiments. Claudin-4-containing exosomes in the plasma of ovarian cancer patients were evaluated in a pilot panel of 63 ovarian cancer patients and 50 healthy volunteers. The CA125 marker was also assessed in these samples and compared with claudin-4 positivity.</p> <p>Results</p> <p>We show that full-length claudins can be shed from ovarian cancer cells in culture and found in the media as part of small lipid vesicles known as exosomes. Moreover, 32 of 63 plasma samples from ovarian cancer patients exhibited the presence of claudin-4-containing exosomes. In contrast, only one of 50 samples from individuals without cancer exhibited claudin-4-positive exosomes. In our small panel, at a specificity of 98%, the claudin-4 and CA125 tests had sensitivities of 51% and 71%, respectively. The two tests did not appear to be independent and were strongly correlated.</p> <p>Conclusion</p> <p>Our work shows for the first time that claudin-4 can be released from ovarian cancer cells and can be detected in the peripheral circulation of ovarian cancer patients. The development of sensitive assays for the detection of claudin-4 in blood will be crucial in determining whether this approach can be useful, alone or in combination with other screening methods, for the detection of ovarian cancer.</p

Rapidly Rising Transients in the Supernova - Superluminous Supernova Gap

The American Astronomical Society. All rights reserved..We present observations of four rapidly rising (trise ≈ 10 days) transients with peak luminosities between those of supernovae (SNe) and superluminous SNe (Mpeak ap; -20) - one discovered and followed by the Palomar Transient Factory (PTF) and three by the Supernova Legacy Survey. The light curves resemble those of SN 2011kl, recently shown to be associated with an ultra-long-duration gamma-ray burst (GRB), though no GRB was seen to accompany our SNe. The rapid rise to a luminous peak places these events in a unique part of SN phase space, challenging standard SN emission mechanisms. Spectra of the PTF event formally classify it as an SN II due to broad Hα emission, but an unusual absorption feature, which can be interpreted as either high velocity Hα (though deeper than in previously known cases) or Si ii (as seen in SNe Ia), is also observed. We find that existing models of white dwarf detonations, CSM interaction, shock breakout in a wind (or steeper CSM), and magnetar spin down cannot readily explain the observations. We consider the possibility that a "Type 1.5 SN" scenario could be the origin of our events. More detailed models for these kinds of transients and more constraining observations of future such events should help to better determine their nature. © 2016

Elbow US: Anatomy, variants, and scanning technique

As with other musculoskeletal joints, elbow ultrasonography (US) depends on the examination technique. Deep knowledge of the relevant anatomy, such as the bone surface anatomy, tendon orientation, nerves, and vessels, is crucial for diagnosis. It is important to be aware of the primary imaging pitfalls related to US technique (anisotropy) in the evaluation of deep tendons such as the distal biceps and peripheral nerves. In this article, US scanning technique for the elbow as well as the related anatomy, primary variants, and scanning pitfalls are described. In addition, an online video tutorial of elbow US describes a possible approach to elbow evaluation

Update on Ultrasound-Guided Interventional Procedures on Peripheral Nerves

This article is a practical review update on ultrasound (US)-guided interventional procedures on peripheral nerves. Technical considerations, biopsy techniques, and some examples of injections are described. US is considered a safe imaging guidance for interventional procedures, due to its high spatial resolution and the possibility to image the needle and inject drugs in real time. US-guided injections could be considered a diagnostic and therapeutic option in the most common neuropathy, before or as an alternative to surgery. US-guided injection techniques in patients with carpal tunnel syndrome, cubital tunnel syndrome, meralgia paresthetica, and Morton neuroma are reviewed. US-guided injections of the iliohypogastric, ilioinguinal, genitofemoral, and pudendal nerve are also illustrated. Knowledge of anatomy is crucial; therefore a brief description of the courses of anatomical nerves and clinical notes are also reported. Treatment of stump neuromas treatment was excluded