Local treatment with electrochemotherapy of superficial angiosarcomas: Efficacy and safety results from a multi-institutional retrospective study

Background: Angiosarcoma is an aggressive vascular neoplasm with a high propensity for local recurrence. Electrochemotherapy is an emerging skin-directed therapy, exerting prominent cytotoxic activity, and antivascular effects. Its efficacy in angiosarcoma has not been investigated. Methods: This multicenter retrospective analysis reviewed patients who underwent electrochemotherapy from 2007 to 2014 for superficial advanced angiosarcomas. Bleomycin was administered intravenously and delivered within tumors by means of percutaneously applied electric pulses, according to the European Standard Operating Procedures for Electrochemotherapy. Tumor assessment was performed using RECIST (version 1.1). Toxicity (CTCAE, v4.0) and local progression-free survival (LPFS) were also evaluated. Results: Nineteen patients (13 with locally advanced and 6 with metastatic angiosarcomas) were treated. Tumor sites were: scalp (n¼5), breast(n¼8), other skin sites (n¼3), and soft tissue (n¼3). Target lesions (n¼54) ranged in size from 1.5 to 2.5 cm (median, 2 cm). Treatment was well tolerated. After 2 months, an objective response was observed in 12/19 (63%) patients, complete in 8 (42%). One-year LPFS within treatment field was 68%. Local symptom improvement included palliation of bleeding (5/19 patients) and pain relief (6/19 patients). Conclusions: Electrochemotherapy may represent a new locoregional treatment for selected patients with superficial angiosarcomas

Electrochemotherapy: a Valid Treatment for Gorlin Goltz syndrome

Gorlin-Goltz syndrome is a rare disorder, characterized by systemic manifestations included multiple basal cell carcinomas, palmar or plantar pits, odontogenic keratocysts and ectopic calcifications of the falx cerebri. The therapy of the clinical manifestations of Gorlin-Goltz syndrome is not simple treatment. We performed  electrochemotherapy in a patient affected by Gorlin-Goltz syndrome with an extensive and  unresectable basal cell carcinoma on the scalp, obtaining excellent results.</p

Sensitization and Interoception as Key Neurological Concepts in Osteopathy and Other Manual Medicines

Historically, approaches used in manual medicine to explain patient reported symptoms have been focused on the so-called exteroceptive paradigm. Arguably, this mindset lacks an appropriate "reading system" able to interpret musculoskeletal disorders from a different perspective, where the properties of the nervous system are embraced into a more holistic and functional-related context. Interestingly, if the underpinning mechanisms of a given treatment scenario/effect are taking into account, the majority of research outcomes focuses on a proprioceptive/exteroceptive explanation, leaving ting aside the additional or even central role of interoception. Currently, to date, the application of theoretical knowledge acquired on the relatively recent neuroscientific concepts and evidence concerning of interoception, sensitization, touch, autonomic functions, inflammation, and pain into a clinical/research manual medicine scenario is lacking, even if theoretically, the impact on the possible etiological mechanisms and treatment effects seems to be important. Here, we propose the conceptual foundations for a new way of interpreting and reading patients' clinical reported outcomes scenario based on interoception and sensitization. We argue that this will provide a foundation to create the ground for future research focusing on the hypotheses that manual therapies, specifically osteopathy, can intercede with sensitization states, at all levels, using interoceptive pathways

Loss of FGFR4 promotes the malignant phenotype of PDAC

Transcriptomic analyses of pancreatic ductal adenocarcinoma (PDAC) have identified two major epithelial subtypes with distinct biology and clinical behaviours. Here, we aimed to clarify the role of FGFR1 and FGFR4 in the definition of aggressive PDAC phenotypes. We found that the expression of FGFR4 is exclusively detected in epithelial cells, significantly elevated in the classical PDAC subtype, and associates with better outcomes. In highly aggressive basal-like/squamous PDAC, reduced FGFR4 expression aligns with hypermethylation of the gene and lower levels of histone marks associated with active transcription in its regulatory regions. Conversely, FGFR1 has more promiscuous expression in both normal and malignant pancreatic tissues and is strongly associated with the EMT phenotype but not with the basal-like cell lineage. Regardless of the genetic background, the increased proliferation of FGFR4-depleted PDAC cells correlates with hyperactivation of the mTORC1 pathway both in vitro and in vivo. Downregulation of FGFR4 in classical cell lines invariably leads to the enrichment of basal-like/squamous gene programs and is associated with either partial or full switch of phenotype. In sum, we show that endogenous levels of FGFR4 limit the malignant phenotype of PDAC cells. Finally, we propose FGFR4 as a valuable marker for the stratification of PDAC patients

Towards a muon collider

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements