The success of Eso-SPONGE® therapy in the treatment of anastomotic dehiscence after Ivor-Lewis subtotal esophagectomy: A case report

Introduction Eso-SPONGE® has proved to be an excellent method for the treatment of persistent dehiscence of the intrathoracic esophagogastric anastomosis during the operation of subtotal esophagectomy sec. Ivor Lewis. Clinical case presentation The case presented is of a 72-year-old patient with esophageal adenocarcinoma (ADK) who underwent sub-total esophagectomy and esophagoplasty sec. Ivor Lewis complicated by an esophageal leak. The Eso-SPONGE® therapy has been successful halving the index of inflammation after the first two sessions and generation of a neowall after seven sessions. Discussion Eso-SPONGE® therapy has proven to be a valuable resource as a treatment for esophageal anastomotic dehiscences because it is easily repeatable in suburban centers, provided that they have a digestive endoscopy specialized in the positioning process. Conclusions Eso-SPONGE® is a minimally invasive method that delivers excellent results in the treatment of fragile patients, such as those who have post-esophageal anastomotic dehiscence

Evaluation of tsunamigenic hazard through numerical modeling from seismic and non-seismic sources in the Crotone offshore (Calabria, Southern Italy)

Tsunamis in the Mediterranean Sea can be considered among the major sources of hazard, both for the extension of the area that can be involved by the water impact and for the closeness of potential sources to the coast, which reduces dramatically the alert and evacuation time. Moreover, landslides, as other non-seismic tsunami sources, are often characterized by a lack of precursors (such as seismic shaking), a reason for which the ensuing waves are sometimes called “surprise tsunamis”

Real-world Outcomes of Relapsed/Refractory Diffuse Large B-cell Lymphoma Treated With Polatuzumab Vedotin-based Therapy.

After FDA and EMA approval of the regimen containing polatuzumab vedotin plus rituximab and bendamustine (PolaBR), eligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients in Italy were granted early access through a Named Patient Program. A multicentric observational retrospective study was conducted focusing on the effectiveness and safety of PolaBR in everyday clinical practice. Fifty-five patients were enrolled. There were 26 females (47.3%), 32 patients were primary refractory and 45 (81.8%) resulted refractory to their last therapy. The decision to add or not bendamustine was at physician's discretion. Thirty-six patients underwent PolaBR, and 19 PolaR. The 2 groups did not differ in most of baseline characteristics. The final overall response rate was 32.7% (18.2% complete response rate), with a best response rate of 49.1%. Median disease-free survival was reached at 12 months, median progression-free survival at 4.9 months and median overall survival at 9 months, respectively. Overall, 88 adverse events (AEs) were registered during treatment in 31 patients, 22 of grade ≥3. Eight cases of neuropathy occurred, all of grades 1-2 and all related to polatuzumab. The two groups of treatment did not differ for effectiveness endpoints but presented statistically significant difference in AEs occurrence, especially in hematological AEs, in AEs of grade equal or greater than 3 and in incidence of neuropathy. Our data add useful information on the effectiveness of Pola(B)R in the setting of heavily pretreated DLBCL and may also suggest a better tolerability in absence of bendamustine without compromise of efficacy

Treatment with Idelalisib in Patients with Relapsed or Refractory Follicular Lymphoma: The Observational Italian Multicenter FolIdela Study

Follicular lymphoma (FL) is an indolent hematological disease, often responsive to the first line of treatment, but characterized by repeated relapses. The therapeutic algorithm for relapsed/refractory FL patients comprises phosphatidylinositol 3-kinase inhibitors. Idelalisib showed anticancer activity, while inducing a significant rate of toxicities. Since the evidence in the literature on its use in normal clinical practice is scarce, a retrospective multicenter study was conducted to evaluate effectiveness and tolerability in a real-life context. Seventy-two patients with a median age at diagnosis of 57.2 years—mostly with an advanced stage (88.9%) and relapsed to the most recent therapy (79.1%)—were enrolled. The median number of prior therapies was three (20.8% refractory to the last therapy before idelalisib). With a median number of 4 months of treatment, the overall response rate was 41.7% (20.8% complete responses). Median disease-free survival and overall survival were achieved at 8.4 months and at 4 years, respectively. Forty-four percent of patients experienced at least one drug-related toxicity: 6.9% hematological ones and 43% non-hematological. The study confirmed that idelalisib has anticancer effectiveness and an acceptable safety profile in relapsed/refractory FL with unfavorable prognostic characteristics, even in the context of normal clinical practice

The Calabrian Arc subduction complex in the Ionian Sea: Regional architecture, active deformation, and seismic hazard

We analyzed the structure and evolution of the external Calabrian Arc (CA) subduction complex through an integrated geophysical approach involving multichannel and single‐channel seismic data at different scales. Pre‐stack depth migrated crustal‐scale seismic profiles have been used to reconstruct the overall geometry of the subduction complex, i.e., depth of the basal detachment, geometry and structural style of different tectonic domains, and location and geometry of major faults. High‐resolution multichannel seismic (MCS) and sub‐bottom CHIRP profiles acquired in key areas during a recent cruise, as well as multibeam data, integrate deep data and constrain the fine structure of the accretionary wedge as well as the activity of individual fault strands. We identified four main morpho‐structural domains in the subduction complex: 1) the post‐Messinian accretionary wedge; 2) a slope terrace; 3) the pre‐Messinian accretionary wedge and 4) the inner plateau. Variation of structural style and seafloor morphology in these domains are related to different tectonic processes, such as frontal accretion, out‐of-sequence thrusting, underplating and complex faulting. The CA subduction complex is segmented longitudinally into two different lobes characterized by different structural style, deformation rates and basal detachment depths. They are delimited by a NW/SE deformation zone that accommodates differential movements of the Calabrian and the Peloritan portions of CA and represent a recent phase of plate re‐organization in the central Mediterranean. Although shallow thrust‐type seismicity along the CA is lacking, we identified active deformation of the shallowest sedimentary units at the wedge front and in the inner portions of the subduction complex. This implies that subduction could be active but aseismic or with a locked fault plane. On the other hand, if underthrusting of the African plate has stopped recently, active shortening may be accommodated through more distributed deformation. Our findings have consequences on seismic hazard, since we identified tectonic structures likely to have caused large earthquakes in the past and to be the source regions for future events

Tsunami hazards in the Catalan Coast, a low-intensity seismic activity area

The final publication is available at Springer via http://dx.doi.org/10.1007/s11069-017-2918-zThe potential impacts of tsunamis along the Catalan Coast (NW Mediterranean) are analysed using numerical modelling. The region is characterized by moderate to low seismic activity and by moderate- to low-magnitude earthquakes. However, the occurrence of historical strong earthquakes and the location of several active offshore faults in front of the coast suggest that the possibility of an earthquake-triggered tsunami is not negligible although of low probability. Up to five faults have been identified to generate tsunamis, being the highest associated possible seismic magnitudes of up to 7.6. Coastal flooding and port agitation are characterized using the Worst-case Credible Tsunami Scenario Analysis approach. The results show a multiple fault source contribution to tsunami hazard. The shelf dimensions and the existence of submerged canyons control the tsunami propagation. In wide shelves, waves travelling offshore may become trapped by refraction causing the wave energy to reach the coastline at some distance from the origin. The free surface water elevation increases at the head of the canyons due to the sharp depth gradients. The effects of potential tsunamis would be very harmful in low-lying coastal stretches, such as deltas, with a high population concentration, assets and infrastructures. The Ebro delta appears to be the most exposed coast, and about the 20% of the delta surface is prone to flooding due to its extremely low-lying nature. The activity at Barcelona port will be severely affected by inflow backflow current at the entrance of up to 2 m/s.Peer ReviewedPostprint (author's final draft

APP Processing Induced by Herpes Simplex Virus Type 1 (HSV-1) Yields Several APP Fragments in Human and Rat Neuronal Cells

Lifelong latent infections of the trigeminal ganglion by the neurotropic herpes simplex virus type 1 (HSV-1) are characterized by periodic reactivation. During these episodes, newly produced virions may also reach the central nervous system (CNS), causing productive but generally asymptomatic infections. Epidemiological and experimental findings suggest that HSV-1 might contribute to the pathogenesis of Alzheimer's disease (AD). This multifactorial neurodegenerative disorder is related to an overproduction of amyloid beta (Aβ) and other neurotoxic peptides, which occurs during amyloidogenic endoproteolytic processing of the transmembrane amyloid precursor protein (APP). The aim of our study was to identify the effects of productive HSV-1 infection on APP processing in neuronal cells. We found that infection of SH-SY5Y human neuroblastoma cells and rat cortical neurons is followed by multiple cleavages of APP, which result in the intra- and/or extra-cellular accumulation of various neurotoxic species. These include: i) APP fragments (APP-Fs) of 35 and 45 kDa (APP-F35 and APP-F45) that comprise portions of Aβ; ii) N-terminal APP-Fs that are secreted; iii) intracellular C-terminal APP-Fs; and iv) Aβ1-40 and Aβ1-42. Western blot analysis of infected-cell lysates treated with formic acid suggests that APP-F35 may be an Aβ oligomer. The multiple cleavages of APP that occur in infected cells are produced in part by known components of the amyloidogenic APP processing pathway, i.e., host-cell β-secretase, γ-secretase, and caspase-3-like enzymes. These findings demonstrate that HSV-1 infection of neuronal cells can generate multiple APP fragments with well-documented neurotoxic potentials. It is tempting to speculate that intra- and extracellular accumulation of these species in the CNS resulting from repeated HSV-1 reactivation could, in the presence of other risk factors, play a co-factorial role in the development of AD