Infectious aetiology of marginal zone lymphoma and role of anti-infective therapy

Marginal zone lymphomas have been associated with several infectious agents covering both viral and bacterial pathogens and in some cases a clear aetiological role has been established. Pathogenetic mechanisms are currently not completely understood. However, the role of chronic stimulation of the host immune response with persistent lymphocyte activation represents the most convincing explanation for lymphoproliferation. Gastric MALT lymphoma is strictly associated with Helicobacter pylori infection and various eradicating protocols, developed due to increasing antibiotic resistance, represent the first line therapy for gastric MALT. The response rate to eradication is good with 80% of response at 1 year; this finding is also noteworthy because it recapitulates cancer cured only by the antibacterial approach and it satisfies the Koch postulates of causation, establishing a causative relationship between Hp and gastric MALT lymphoma. Patients with chronic HCV infection have 5 times higher risk to develop MZL, in particular, an association with splenic and nodal MZL has been shown in several studies. Moreover, there is evidence of lymphoma regression after antiviral therapy with interferon+ribavirin, thus raising hope that newly available drugs, extremely efficient against HCV replication, could improve outcome also in HCV-driven lymphomas. Another case-study are represented by those rare cases of MZL localized to orbital fat and eye conjunctivas that have been associated with Chlamydophila psittaci infection carried by birds. Efficacy of antibacterial therapy against C. psittaci are conflicting and generally poorer than gastric MALT. Finally, some case reports will cover the relationship between primary cutaneous B-cell Lymphomas and Borrelia Burgdorferi

The Non Uniform Adaptive Angular Spectrum Method and its Application to Neural Network Assisted Coherent Beam Combining

Increasing the number of laser beams that can be coherently combined requires accurate and fast algorithms for compensating phase and alignment errors. The paper proposes to use a Fully Connected Artificial Neural Network (FCANN) to correct the beam positioning perturbations by evaluating the beam shifts and tilts from two images taken at slightly different locations. Then, since it is practically impossible to have a large enough experimental dataset to train the neural network, this approach required developing an accurate and fast simulation method to evaluate the beam propagation in arbitrary directions, overcoming the limitations occurring when the computation must be repeated a large number of times. The numerical approach is a variant of the Angular Spectrum (AS) method, called Non Uniform ADaptive Angular Spectrum (NUADAS) method, which relies on the combination of non-uniform and adaptive Fourier transform algorithms to allow the computation of an arbitrary field distribution in a plane that is shifted and tilted with respect to the source. The parallel implementation of the NUADAS method is discussed and the numerical and experimental validations are presented. Then, an FCANN is trained using the synthetic dataset generated with the NUADAS method and the results are discussed, demonstrating the viability of the proposed approach not only for coherent beam combing, but also in other beam alignment applications

Development of a Flexible Lead-Free Piezoelectric Transducer for Health Monitoring in the Space Environment

In this work we report on the fabrication process for the development of a flexible piezopolymeric transducer for health monitoring applications, based on lead-free, piezoelectric zinc oxide (ZnO) thin films. All the selected materials are compatible with the space environment and were deposited by the RF magnetron sputtering technique at room temperature, in view of preserving the total flexibility of the structures, which is an important requirement to guarantee coupling with cylindrical fuel tanks whose integrity we want to monitor. The overall transducer architecture was made of a c-axis-oriented ZnO thin film coupled to a pair of flexible Polyimide foils coated with gold (Au) electrodes. The fabrication process started with the deposition of the bottom electrode on Polyimide foils. The ZnO thin film and the top electrode were then deposited onto the Au/Polyimide substrates. Both the electrodes and ZnO layer were properly patterned by wet-chemical etching and optical lithography. The assembly of the final structure was then obtained by gluing the upper and lower Polyimide foils with an epoxy resin capable of guaranteeing low outgassing levels, as well as adequate thermal and electrical insulation of the transducers. The piezoelectric behavior of the prototypes was confirmed and evaluated by measuring the mechanical displacement induced from the application of an external voltage

Geological and geophysical characterization of the Brindisi di Montagna Scalo landslide (Basilicata, Southern Italy)

The Brindisi di Montagna Scalo Landslide in Southern Italy is an active complex mass movement, which affects the left slope of the Basento River. In the last few decades, this landslide has been continuously monitored, as it directly threatened some of the most important communication routes in the Basilicata Region. Nevertheless, little progresses have been made to prevent further landslide advancement, and continuous maintenance is required. With the aims of better understanding, the main factors controlling the evolution of this landslide, and suggesting the most appropriate countermeasures, a multidisciplinary study, based on the integration of direct and indirect techniques, was carried out. Direct techniques included multi-temporal geomorphological analysis of the slope, alongside geological and structural field observations. Indirect techniques consisted of electrical resistivity tomography acquisition. The combined analyses of the geological and geophysical data showed that Quaternary tectonic processes played a fundamental role as a predisposing factor, whereas seasonal rainfall, and the perpetual undercutting by erosional processes caused by the Basento River at the toe of the landslide are the main triggering mechanisms. The Brindisi di Montagna Scalo Landslide represents an outstanding case-study, concerning the interaction between a flow-like complex landslide and essential linear infrastructure, such as motorways and railways

Inguino-abdominal combined approach for laterally extended pelvic resection: a step by step procedure

This video article demonstrates an inguino-abdominal combined approach for laterally extended pelvic resection, a major surgical procedure for locally advanced primary or recurrent gynecological cancer infiltrating the pelvic sidewall, for which palliative therapy is the only alternative.1 After local institutional review board approval (protocol No CICOG 02/03/62), we made a step by step surgical video of an inguino-abdominal combined approach for laterally extended pelvic resection , defined as an en bloc resection of a pelvic tumor with pelvic sidewall structures, including the iliopsoas and/or obturator internus muscles.2 3 The patient, a 48-year-old woman, diagnosed with single pelvic platinum resistant recurrence after five lines of chemotherapy for serous ovarian cancer G3, International Federation of Gynecology and Obstetrics (FIGO) stage IIIC, BRCA wild type. The preoperative positron emission tomography/computed tomography scan detected uptake on the right side at the level of the external iliac region and obturator fossa: the tumor surrounded the right external iliac vessels by more than 50% of their circumferences, with possible involvement of the vascular wall and venous vascular compression (Tinelli's score=4).4 The tumor extended towards the obturator fossa, with possible involvement of the inguinal canal. Due to an uncertain pathological response, the size of the recurrence, and its close contiguity with the ureter and bowel, we decided to avoid radiation therapy as it could result in a ureteral or intestinal fistula. We performed a laterally extended pelvic resection, as shown step by step in the video.The procedure was conducted until complete removal of recurrence (R0). Estimated blood loss was 1000 mL and total operative time was 240 min. The patient was discharged after 15 days; we reported a urinary infection, a likely postoperative complication. The pathology report described a lymphnodal relapse of ovarian cancer (diameter=6 cm) with infiltration of surrounding tissue and in the sano margins. Six months after surgery, the patient is alive without evidence of relapse.The borders of pelvic surgical anatomy are continually extending, requiring surgeons to use a personalized approach and to continually update their anatomic knowledge. In this context, laterally extended pelvic resection could be a feasible surgical procedure, representing a salvage treatment in recurrent or persistent primary gynecological malignancies infiltrating the pelvic sidewall, when other approaches have failed. However, additional clinical trials are needed to confirm these results.

Pharmacoutilization of epoetins in na\uc3\uafve patients with hematological malignancies in an unselected italian population under clinical practice setting: A comparative analysis between originator and biosimilars

Aim: The purpose of this study was to assess the prescription of epoetins and consumption of health care resources (in terms of drug treatments) in na\uc3\uafve patients with hematological malignancies in a real-world setting; in particular, we compared the results between reference product and biosimilar products. Methods: An observational retrospective study based on administrative and laboratory databases of three local health units was conducted. All adults diagnosed with hematological malignancies and who had received at least one epoetin (either reference product or biosimilars) prescription for the first time between 1 January 2010 and 30 April 2012 (enrollment period) were included. The date of the first prescription of epoetin within the enrollment period was defined as index date (ID). Patients were followed up for 4 weeks after ID (follow-up period) and were investigated for the 1-year period before the ID. The difference between the last hemoglobin (Hb) measurement after ID and the one prior to ID (\uce\u94Hb) was evaluated. The drug cost analysis was conducted from the perspective of the Italian National Health System. Results: Overall, 69 patients were included in the study; 48 of them received reference epoetin product and 21 received biosimilars as first prescription. Among reference product users, the mean \uc2\ub1 standard deviation (SD) age was 62.5\uc2\ub114.7 years; this cohort of patients was slightly significantly younger than the biosimilar users (71.8\uc2\ub111.8 years). The mean \uc2\ub1SD overall Hb level prior to treatment was lower among patients who started with biosimilar products (9.6\uc2\ub11.1 g/dL) compared to those who started with a reference product (10.1\uc2\ub12.1 g/dL). No significant differences in \uce\u94Hb were observed between biosimilar and originator groups during the followup period. The mean \uef\u82\u81\uef\u81\ubd\uef\u80 SD cost per patient was \ue2\u82\uac667.98\uc2\ub1573.93 and \ue2\u82\uac340.85\uc2\ub1235.73 for the reference product and biosimilar users, respectively (p=0.065). Conclusion: Our study showed that the use of biosimilar products might contribute to controlling health care costs (in terms of drug treatments) for patients with hematological malignancies being maintained by high-quality anemia therapy. Our findings also showed some discordances regarding the most appropriate therapeutic approach in daily clinical practice

A retrospective pooled analysis of response patterns and risk factors in recurrent malignant glioma patients receiving a nitrosourea-based chemotherapy

Abstract Background At recurrence the use of nitrosoureas is widely-used as a therapeutic option for glioblastoma (GBM) patients. The efficacy of fotemustine (FTM) has been demonstrated in phase II clinical trials; however, these papers report a wide range of progression-free-survival (PFS-6 m) rates, ranging from 21% to 52%. We investigated whether FTM could have a different response pattern in respect to time to adjuvant temozolomide failure, or whether specific independent risk factors could be responsible for the wide range of response rates observed. Methods Recurrent GBM patients have been treated with fotemustine 75-100 mg/sqm at day 1, 8, 15 and after 4/5 weeks of rest with 100 mg/sqm every 21 days. Patients were stratified in 4 groups according to time to temozolomide failure: before starting (B0), during the first 6 months (B1), after more than 6 months of therapy (B2), and after a treatment-free interval (B3). Primary endpoint was PFS-6 m. A multivariable analysis was performed to identify whether gender, time after radiotherapy, second surgery and number of TMZ cycles could be independent predictors of the clinical benefit to FTM treatment. Results 163 recurrent GBM patients were included in the analysis. PFS-6 m rates for the B0, B1, B2 and B3 groups were 25%, 28%, 31.1% and 43.8%, respectively. The probability of disease control was higher in patients with a longer time after radiotherapy (p = 0.0161) and in those who had undergone a second surgery (p = 0.0306). Conclusions FTM is confirmed as a valuable therapeutic option for patients with recurrent GBM and was active in all study patient groups. Time after the completion of radiotherapy and second surgery are independent treatment-related risk factors that were predictive of clinical benefit.</p

From traumatic childhood to cocaine abuse: the critical function of the immune system

Background: Experiencing traumatic childhood is a risk factor for developing substance use disorder (SUD), but the mechanisms that underlie this relationship have not been determined. Adverse childhood experiences affect the immune system and the immune system mediates the effects of psychostimulants. However, whether this system is involved in the etiology of SUD in individuals who have experience early life stress is unknown. Methods:In this study, we performed a series of ex vivo and in vivo experiments in mice and humans to define the function of the immune system in the early-life stress-induced susceptibility to the neurobehavioral effects of cocaine. Results: We provide evidence that exposure to social-stress (S-S) at an early age permanently sensitizes the peripheral (splenocytes) and brain (microglia) immune responses to cocaine in mice. In the brain, microglial activation in the ventral tegmental area (VTA) of S-S mice was associated with functional alterations in dopaminergic neurotransmission, as measured by whole-cell voltage clamp recordings in dopamine (DA) neurons. Notably, preventing immune activation during the S-S exposure reverted the effects of DA in the VTA and the cocaine-induced behavioral phenotype to control levels. In humans, cocaine modulated Toll-like receptor 4-mediated innate immunity, an effect that was enhanced in cocaine addicts who had experienced a difficult childhood. Conclusions Collectively, our findings demonstrate that sensitization to cocaine in early-life-stressed individuals involves brain and peripheral immune responses and that this mechanism is shared between mice and humans

Novel Drugs and Radiotherapy in Relapsed Lymphomas. Abscopal Response and Beyond

Abstract: Combined modality has represented a mainstay of treatment across many lymphoma histologies, given their sensitivity to both multi-agent chemotherapy and intermediate-dose radiotherapy. More recently, several new agents, including immunotherapies, have reshaped the therapeutic panorama of some lymphomas. In parallel, radiotherapy techniques have witnessed substantial improvement, accompanied by a growing understanding that radiation itself comes with an immune-mediated effect. Six decades after a metastatic lesion regression outside the irradiated field was first described, there is increasing evidence that a combination of radiotherapy and immunotherapy could boost an abscopal effect. This review focuses on the mechanisms underlying this interaction in the setting of lymphomas, and on the results of pivotal prospective studies. Furthermore, the available evidence on the concomitant use of radiotherapy and small molecules (i.e., lenalidomide, venetoclax, and ibrutinib), as well as brentuximab vedotin, and chimeric antigen receptor (CAR) T-cell therapy, is summarized. Currently, combining radiotherapy with new agents in patients who are affected by lymphomas appears feasible, particularly as a bridge to anti-CD19 autologous CAR T-cell infusion. However, more studies are required to assess these combinations, and preliminary data suggest only a synergistic rather than a curative effec