A Multistep Approach to Deal With Advanced Heart Failure: A Case Report on the Positive Effect of Cardiac Contractility Modulation Therapy on Pulmonary Pressure Measured by CardioMEMS

During the last years, the management of heart failure (HF) made substantial progress, focusing on device-based therapies to meet the demands of this complex syndrome. In this case report, we present a multistep approach to deal with HF. Specifically, we report the first patient subjected to the implantation of both Optimizer Smart(R) (Impulse Dynamics Inc., Marlton, NJ, USA) and CardioMEMS devices. A 72-year-old male patient with HF and reduced ejection fraction (HFrEF) was admitted to our cardiology department in January 2021, following a progressive shortening of the time between hospitalizations for levosimendan infusions. Specifically, the patient was monitored daily by CardioMEMS, and a strategy of levosimendan infusions guided by the device had been adopted. He was also a carrier of MitraClips and cardiac resynchronization therapy defibrillator (CRT-D) and had optimized HF medical therapy. In January 2021, the patient implanted Optimizer Smart(R) device for cardiac contractility modulation (CCM) therapy because of poor response to therapy and elevated pulmonary artery pressure (PAP). CCM significantly reduced PAP values following discharge (systolic PAP 33.67 & PLUSMN; 2.92 vs. 40.6 & PLUSMN; 3.37 mmHg, diastolic PAP 14.5 & PLUSMN; 2.01 vs. 22.5 & PLUSMN; 2.53 mmHg, mean PAP 22.87 & PLUSMN; 2.20 vs. 30.9 & PLUSMN; 2.99 mmHg, HR 60.93 & PLUSMN; 1.53 vs. 80.83 & PLUSMN; 3.66 bpm; p < 0.0001), with persisting effect at 9 months. The usefulness of CCM is objectively demonstrated for the first time by continuous invasive monitoring of PAP by CardioMEMS, which can suggest the correct timing for CCM implantation

Automatic generation of co-seismic displacement maps by using Sentinel-1 interferometric SAR data

Abstract We present a tool for the automatic generation of co-seismic Differential Synthetic Aperture Radar Interferometry (DInSAR) products by using space-borne SAR data. In particular, the implemented tool relies on the large availability of Sentinel-1 SAR data and on-line earthquake catalogues (e.g. USGS, INGV) to generate co-seismic Line Of Sight (LOS) interferograms and displacement maps. The processing is triggered by the occurrence of a main seismic event, according to the accessible earthquake catalogues. The tool automatically retrieves all the needed SAR acquisitions that cover a defined area across the epicentre and generates the DInSAR products that will be then openly available through the European Plate Observing System (EPOS) portal. Moreover, the possibility to implement the presented tool into the upcoming Copernicus Data and Information Access Services (DIAS) will significantly reduce the product processing time, thus implying a faster product generation and delivery. Accordingly, such a tool not only will contribute to expand the use of DInSAR products in the geoscience field, but also will play a key role on the support of the Civil Protection authorities during the management of seismic crisis

Formation of Ferroelectrically Defined Ag Nanoarray Patterns

In order to produce the most effective Ag nanoarrays for plasmon enhanced fluorescence and Raman scattering made using ferroelectric substrates, the optimum conditions for the creation of arrays must be identified. We study here Ag nanopattern arrays formed using ferroelectric lithography based on periodically proton exchanged (PPE) template methods. We examine different conditions in regard to deposition of Ag nanoparticles and analyze the plasmon enhanced signal from the resulting nanoarray. We apply FLIM (fluorescence lifetime imaging) to assess different Ag nanoarray preparation conditions on fluorescence emission from selected fluorphores. In addition, we apply Raman and luminescence spectroscopy with AFM (atomic force microscopy) to study the plasmon enhancement of luminescence and Raman from the Ag nanoarrays

Interface modulated currents in periodically proton exchanged Mg doped lithium niobate

Conductivity in Mg doped lithium niobate (Mg:LN) plays a key role in the reduction of photorefraction and is therefore widely exploited in optical devices. However, charge transport through Mg:LN and across interfaces such as electrodes also yields potential electronic applications in devices with switchable conductivity states. Furthermore, the introduction of proton exchanged (PE) phases in Mg:LN enhances ionic conductivity, thus providing tailorability of conduction mechanisms and functionality dependent on sample composition. To facilitate the construction and design of such multifunctional electronic devices based on periodically PE Mg:LN or similar ferroelectric semiconductors, fundamental understanding of charge transport in these materials, as well as the impact of internal and external interfaces, is essential. In order to gain insight into polarization and interface dependent conductivity due to band bending, UV illumination, and chemical reactivity, wedge shaped samples consisting of polar oriented Mg:LN and PE phases were investigated using conductive atomic force microscopy. In Mg:LN, three conductivity states (on/off/transient) were observed under UV illumination, controllable by the polarity of the sample and the externally applied electric field. Measurements of currents originating from electrochemical reactions at the metal electrode-PE phase interfaces demonstrate a memresistive and rectifying capability of the PE phase. Furthermore, internal interfaces such as domain walls and Mg:LN-PE phase boundaries were found to play a major role in the accumulation of charge carriers due to polarization gradients, which can lead to increased currents. The insight gained from these findings yield the potential for multifunctional applications such as switchable UV sensitive micro-and nanoelectronic devices and bistable memristors. (C) 2016 AIP Publishing LLC

Interface and thickness dependent domain switching and stability in Mg doped lithium niobate

Controlling ferroelectric switching in Mg doped lithium niobate (Mg: LN) is of fundamental importance for optical device and domain wall electronics applications that require precise domain patterns. Stable ferroelectric switching has been previously observed in undoped LN layers above proton exchanged (PE) phases that exhibit reduced polarization, whereas PE layers have been found to inhibit lateral domain growth. Here, Mg doping, which is known to significantly alter ferroelectric switching properties including coercive field and switching currents, is shown to inhibit domain nucleation and stability in Mg: LN above buried PE phases that allow for precise ferroelectric patterning via domain growth control. Furthermore, piezoresponse force microscopy (PFM) and switching spectroscopy PFM reveal that the voltage at which polarization switches from the \"up\" to the \"down\" state increases with increasing thickness in pure Mg: LN, whereas the voltage required for stable back switching to the original \"up\" state does not exhibit this thickness dependence. This behavior is consistent with the presence of an internal frozen defect field. The inhibition of domain nucleation above PE interfaces, observed in this study, is a phenomenon that occurs in Mg: LN but not in undoped samples and is mainly ascribed to a remaining frozen polarization in the PE phase that opposes polarization reversal. This reduced frozen depolarization field in the PE phase also influences the depolarization field of the Mg: LN layer above due to the presence of uncompensated polarization charge at the PE-Mg: LN boundary. These alterations in internal electric fields within the sample cause long-range lattice distortions in Mg: LN via electromechanical coupling, which were corroborated with complimentary Raman measurements. (C) 2015 AIP Publishing LLC

Ectopic Lymphoid Structures Support Ongoing Production of Class-Switched Autoantibodies in Rheumatoid Synovium

Costantino Pitzalis and colleagues show that lymphoid structures in synovial tissue of patients with rheumatoid arthritis support production of anti-citrullinated peptide antibodies, which continues following transplantation into SCID mice

Thickness, humidity, and polarization dependent ferroelectric switching and conductivity in Mg doped lithium niobate

Mg doped lithium niobate (Mg:LN) exhibits several advantages over undoped LN such as resistance to photorefraction, lower coercive fields, and p-type conductivity that is particularly pronounced at domain walls and opens up a range of applications, e.g., in domain wall electronics. Engineering of precise domain patterns necessitates well founded knowledge of switching kinetics, which can differ significantly from that of undoped LN. In this work, the role of humidity and sample composition in polarization reversal has been investigated under application of the same voltage waveform. Control over domain sizes has been achieved by varying the sample thickness and initial polarization as well as atmospheric conditions. In addition, local introduction of proton exchanged phases allows for inhibition of domain nucleation or destabilization, which can be utilized to modify domain patterns. Polarization dependent current flow, attributed to charged domain walls and band bending, demonstrates the rectifying ability of Mg: LN in combination with suitable metal electrodes that allow for further tailoring of conductivity. (C) 2015 AIP Publishing LLC

Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis

Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. Through evaluation of synovial tissues from rheumatoid arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression corresponds with an increased incidence of ELS and gene signatures associated with their development and activity. The presence of synovial ELS was also noted in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory arthritis. Here, pathology was associated with increased synovial expression of pro-inflammatory cytokines, homeostatic chemokines, and transcriptional regulators linked with lymphoid neogenesis. In both clinical and experimental RA, synovial ELS coincided with the heightened local expression of cytokines and transcription factors of the Th17 and T follicular helper (Tfh) cell lineages, and included podoplanin-expressing T cells within lymphoid aggregates. IL-27 inhibited the differentiation of podoplanin-expressing Th17 cells, and an increased number of these cells were observed in IL-27R–deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector T cells. These studies open new opportunities for patient stratification and treatment

Guidelines on the diagnosis, treatment and management of visceral and renal arteries aneurysms: a joint assessment by the Italian Societies of Vascular and Endovascular Surgery (SICVE) and Medical and Interventional Radiology (SIRM)

: The objective of these Guidelines is to provide recommendations for the classification, indication, treatment and management of patients suffering from aneurysmal pathology of the visceral and renal arteries. The methodology applied was the GRADE-SIGN version, and followed the instructions of the AGREE quality of reporting checklist. Clinical questions, structured according to the PICO (Population, Intervention, Comparator, Outcome) model, were formulated, and systematic literature reviews were carried out according to them. Selected articles were evaluated through specific methodological checklists. Considered Judgments were compiled for each clinical question in which the characteristics of the body of available evidence were evaluated in order to establish recommendations. Overall, 79 clinical practice recommendations were proposed. Indications for treatment and therapeutic options were discussed for each arterial district, as well as follow-up and medical management, in both candidate patients for conservative therapy and patients who underwent treatment. The recommendations provided by these guidelines simplify and improve decision-making processes and diagnostic-therapeutic pathways of patients with visceral and renal arteries aneurysms. Their widespread use is recommended

Consolidative thoracic radiation therapy for extensive-stage small cell lung cancer in the era of first-line chemoimmunotherapy: preclinical data and a retrospective study in Southern Italy

BackgroundConsolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented.MethodsA total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy.ResultsPreclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027).ConclusionMulti-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation