Novel Diagnostic and Prognostic Approaches to Systemic Vasculitides

Background. The management of giant cell arteritis (GCA) has gone through a number of paradigmatic changes in the last few years, including novel diagnostic approaches and treatment options. Objectives. We aimed at investigating and improving the management of GCA by: (i) assessing the impact of the fast track ultrasonographic clinic (FTA) of the Rheumatology Department, IRCCS Policlinico S. Matteo, University of Pavia on the risk of permanent visual loss and future relapse; (ii) evaluating the role of quantitative ultrasound assessment in terms of diagnostic and prognostic outcomes in GCA in an International study in collaboration with the University of Oxford; (iii) contributing to the update of the European recommendations on the management of large vessel vasculitis (LVV) by leading on the systematic literature review and participating in the recommendations development process. Methods. Patients referred for suspected GCA to the FTA were recruited if a diagnosis of GCA was confirmed. The role of quantitative ultrasound findings data was assessed, in collaboration with the University of Oxford, from the data of a large cohort study (TABUL Study) with the FTA cohort from the University of Pavia as an independent cohort. Quantitative ultrasound data [number of sites with halos, intima-media thickness (IMT), presence of bilateral halos] at the level of the temporal arteries (TA) and axillary arteries (AX) were assessed. Two systematic literature reviews (SLR) were performed by searching MEDLINE, EMBASE and Cochrane CENTRAL library to inform the European League Against Rheumatism (EULAR) update of the recommendations on the management of LVV. Results. The GCA cohort included 160 patients [female 120 (75%), mean age 72.4±8.2 years]. Sixty-three (39.4%) evaluated with FTA, 97 (60.6%) with conventional approach. Since the introduction of FTA the need for TAB reduced by 93%. Median follow-up duration was shorter in the FTA group compared to the conventional one (0.9 vs. 5.0 years; p<0.001). Permanent visual loss (PVL) occurred in 8 (12.7%) FTA patients and 26 (26.8%) conventional ones (p=0.03). During COVID-19 there was a significant increase in the occurrence of PVL (40%) including bilateral blindness despite a regularly operating FTA clinic. Cumulative incidence of relapses and time to first relapse did not change after FTA introduction. Quantitative ultrasound data were evaluated on 135 GCA patients from TABUL [female 92 (68%), age 73±8 years] and 72 patients from the independent cohort [female 33 (46%), age 75±7 years]. The best-fitting CDS model for TAB used maximum IMT and bilaterality of TA and AX halos. The best-fitting clinical model included raised inflammatory markers, polymyalgia rheumatica, headache and ischaemic symptoms. By combining CDS and clinical models a score to calculate the probability of having a positive TAB, given the ultrasonographic and clinical information, was derived. No significant association was found for prediction of clinical outcome at 6 months. The SLRs confirmed the need to urgently refer the patient to a specialised team, including FTA clinics. The main treatment for LVV remain high-dose GC, however, more evidence has been retrieved to support the use of adjunctive immunosuppressants, including novel biologic treatments for GCA. Conclusion. With our studies we have contributed to clarify the role of novel diagnostic approaches to the disease as part of fast track clinics and supported the role of ultrasound as a reliable diagnostic tool and to significantly reduce the risk of permanent blindness. A quantitative ultrasound analysis (extention and degree of vascular involvement) supported by clinical findings is useful to identify patients with a positive biopsy. Relapse rate and LV-complications did not change upon FTA introduction, highlighting the need for better disease activity monitoring and therapeutic strategies.Background. The management of giant cell arteritis (GCA) has gone through a number of paradigmatic changes in the last few years, including novel diagnostic approaches and treatment options. Objectives. We aimed at investigating and improving the management of GCA by: (i) assessing the impact of the fast track ultrasonographic clinic (FTA) of the Rheumatology Department, IRCCS Policlinico S. Matteo, University of Pavia on the risk of permanent visual loss and future relapse; (ii) evaluating the role of quantitative ultrasound assessment in terms of diagnostic and prognostic outcomes in GCA in an International study in collaboration with the University of Oxford; (iii) contributing to the update of the European recommendations on the management of large vessel vasculitis (LVV) by leading on the systematic literature review and participating in the recommendations development process. Methods. Patients referred for suspected GCA to the FTA were recruited if a diagnosis of GCA was confirmed. The role of quantitative ultrasound findings data was assessed, in collaboration with the University of Oxford, from the data of a large cohort study (TABUL Study) with the FTA cohort from the University of Pavia as an independent cohort. Quantitative ultrasound data [number of sites with halos, intima-media thickness (IMT), presence of bilateral halos] at the level of the temporal arteries (TA) and axillary arteries (AX) were assessed. Two systematic literature reviews (SLR) were performed by searching MEDLINE, EMBASE and Cochrane CENTRAL library to inform the European League Against Rheumatism (EULAR) update of the recommendations on the management of LVV. Results. The GCA cohort included 160 patients [female 120 (75%), mean age 72.4±8.2 years]. Sixty-three (39.4%) evaluated with FTA, 97 (60.6%) with conventional approach. Since the introduction of FTA the need for TAB reduced by 93%. Median follow-up duration was shorter in the FTA group compared to the conventional one (0.9 vs. 5.0 years; p<0.001). Permanent visual loss (PVL) occurred in 8 (12.7%) FTA patients and 26 (26.8%) conventional ones (p=0.03). During COVID-19 there was a significant increase in the occurrence of PVL (40%) including bilateral blindness despite a regularly operating FTA clinic. Cumulative incidence of relapses and time to first relapse did not change after FTA introduction. Quantitative ultrasound data were evaluated on 135 GCA patients from TABUL [female 92 (68%), age 73±8 years] and 72 patients from the independent cohort [female 33 (46%), age 75±7 years]. The best-fitting CDS model for TAB used maximum IMT and bilaterality of TA and AX halos. The best-fitting clinical model included raised inflammatory markers, polymyalgia rheumatica, headache and ischaemic symptoms. By combining CDS and clinical models a score to calculate the probability of having a positive TAB, given the ultrasonographic and clinical information, was derived. No significant association was found for prediction of clinical outcome at 6 months. The SLRs confirmed the need to urgently refer the patient to a specialised team, including FTA clinics. The main treatment for LVV remain high-dose GC, however, more evidence has been retrieved to support the use of adjunctive immunosuppressants, including novel biologic treatments for GCA. Conclusion. With our studies we have contributed to clarify the role of novel diagnostic approaches to the disease as part of fast track clinics and supported the role of ultrasound as a reliable diagnostic tool and to significantly reduce the risk of permanent blindness. A quantitative ultrasound analysis (extention and degree of vascular involvement) supported by clinical findings is useful to identify patients with a positive biopsy. Relapse rate and LV-complications did not change upon FTA introduction, highlighting the need for better disease activity monitoring and therapeutic strategies

a novel mutation with mild clinical presentation

Background A highly variable phenotype characterized by thyroid, respiratory and neurological defects has been reported in an already established group of disorders namely NKX2.1-related disorders. We describe here the case of an infant with a novel mutation of the NKX2.1 gene characterized by mild clinical presentation. Aim of the study was to elucidate the genotype-phenotype correlation in our patient. Methods We performed genetic analysis of the NKX2.1 gene in an infant with no neonatal respiratory distress and near-normal results at neonatal screening test for congenital hypothyroidism, choreoathetosis, ataxia and delayed independent walking. Results A novel mutation of the NKX2.1 gene has been identified, that is responsible for a mild framework of congenital hypothyroidism and neurological symptoms. Conclusions The frequency of congenital hypothyroidism cases associated with NKX2.1 mutations is expected to be higher in a subgroup of patients, selected according to the neurological presentation. In these patients the analysis of NKX2.1 mutational status is recommended

NKX2.1-Related Disorders: a novel mutation with mild clinical presentation.

Background: A highly variable phenotype characterized by thyroid, respiratory and neurological defects has been reported in an already established group of disorders namely NKX2.1-related disorders. We describe here the case of an infant with a novel mutation of the NKX2.1 gene characterized by mild clinical presentation. Aim of the study was to elucidate the genotype-phenotype correlation in our patient. Methods: We performed genetic analysis of the NKX2.1 gene in an infant with no neonatal respiratory distress and near-normal results at neonatal screening test for congenital hypothyroidism, choreoathetosis, ataxia and delayed independent walking. Results: A novel mutation of the NKX2.1 gene has been identified, that is responsible for a mild framework of congenital hypothyroidism and neurological symptoms. Conclusions: The frequency of congenital hypothyroidism cases associated with NKX2.1 mutations is expected to be higher in a subgroup of patients, selected according to the neurological presentation. In these patients the analysis of NKX2.1 mutational status is recommended

Spatial and temporal trends in the ecological risk posed by polycyclic aromatic hydrocarbons in Mediterranean Sea sediments using large-scale monitoring data

Abstract Benthic organisms play an important role in aquatic ecosystems and are often used as indicators of toxic environments. In this study, we reconstructed the spatial and temporal trend of risk to benthic communities living in sediments of the Mediterranean Sea posed by the presence of 16 polycyclic aromatic hydrocarbons (PAHs). Moreover, the origins of PAH contamination in the sea were also investigated. The analysis included multiple steps, starting with an in-depth review of available studies (from the early 1980s to 2019) reporting PAH concentrations in sediments of the Mediterranean Sea. Subsequently, the collected data were spatialised and clustered according to the four basins of the Mediterranean as defined by the Mediterranean Strategy on Sustainable Development and the United Nations Environment Programme Mediterranean Action Plan. We employed additive models, a flexible and versatile tool for coping with non-linear trends by means of smooth functions, to estimate temporal trends in PAH concentrations. Finally, the primary origins of contamination and temporal trends in ecological risk were determined using a combination of approaches. The results indicated that PAHs in Mediterranean sediments originate primarily from biomass burning, with a contribution from combustion of coal and liquid fossil fuels, the latter being representative of sites near urban centres or harbours. A significant positive correlation between annual growth rates of PAH concentration in sediment and wildfires was found. The estimated non-linear trends of concentrations and risk showed different temporal patterns across basins. In recent years, especially in the Western Mediterranean, the estimated trends suggest PAH concentrations are posing an increasing risk. These results indicate the need for stronger efforts to achieve the objectives of the Marine Strategy Framework Directive

Archetyps of wisdom: intercultural communication competences training in multicultural students groups

This paper presents a new approach to the problem of system decoupling in a power-system state estimation problem. The complexity of power systems is growing, thus challenging the way measurements for state estimation are traditionally managed. Following a previous experience in defining a decentralized solution for state estimation, the authors here propose a decentralized dynamic state estimation method for a large-scale power system in combination with a procedure to automatically identify how and which state information to exchange for reconstructing the states starting from partial knowledge. In particular, the problem of selecting the variables that each observer has to estimate is partially solved within the framework of a stochastic approach, i.e., the so-called collocation method. An optimization algorithm based on dynamic programming is also developed to determine the optimal set of strongly coupled variables necessary for a sufficiently accurate estimation. The developed method is evaluated by applying to an IEEE test bus system

switching from intravenous to subcutaneous formulation of abatacept different results in a series of 21 patients

To the Editor: We read with interest the article by Reggia, et al 1, a monocentric study analyzing the efficacy and safety of switching from intravenous (IV) to subcutaneous (SC) formulation of abatacept (ABA) in patients with rheumatoid arthritis. The authors report a relatively high risk of disease relapse (27%) occurring in a mean of 11 weeks after switching to SC administration. The study did not find any significant predictive factor for a switch failure. The concern that patients with a higher body mass index could receive lower cumulative doses compared to weight-tiered monthly infusions, leading to a significant influence on treatment efficacy, was not confirmed by this study, or by previous dose-finding trials and … Address correspondence to Dr. S. Monti; E-mail: sara.saramonti{at}gmail.co

Influence of Topology on the Ultrafast Carrier Dynamics in MoTe2

Transport properties of Weyl semimetals are intimately connected to the underlying band structure. The signature of Weyl semimetals are linear dispersing bands that touch, forming Weyl points that result in high charge carrier mobilities. The layered transition metal dichalcogenide MoTe2, undergoes a temperature dependent phase transition that directly converts the trivial 1Tprime phase to the nontrivial Td phase, providing an opportunity to understand how the formation of a Weyl point manifests in the ultrafast carrier dynamics. In this study, we use resonant X-ray photoemission to monitor the element specific evolution of excited carriers 1Tprime-MoTe2 and in the vicinity of the Weyl point in Td-MoTe2. We find that the delocalization time of 1Tprime-MoTe2 is a factor 1.5 times faster than in Td-MoTe2. We argue that this is a result of the change in the density of states and screening length, to a higher carrier scattering rate in Td-MoTe2. Our study tracks the fate of carriers in MoTe2 on sub-fs time-scales and with atomic site specificity

Updates on the diagnosis and monitoring of giant cell arteritis

: This mini-review offers a critical appraisal of the currently employed imaging or histopathological tools to diagnose and monitor giant cell arteritis (GCA). An overview of the most updated evidence and current application of color duplex ultrasonography (US), temporal artery biopsy (TAB), 18-fluorodeoxyglucose [18F] FDG-PET/CT, magnetic resonance imaging, and computed tomography angiography is provided. The main limitations of each tool, and the most relevant research developments are discussed. The review highlights the complementary value of the available modalities to ensure a correct diagnosis of GCA, and to provide valuable prognostic information. Novel evidence is accumulating to support the role of imaging, and particularly US, as a monitoring tool for the disease, opening new perspectives for the future management of large vessel vasculitis

Porphyrin-Based Nanostructures for Sensing Applications

The construction of nanosized supramolecular hosts via self-assembly of molecular components is a fascinating field of research. Such intriguing class of architectures, beside their intrinsic intellectual stimuli, is of importance in many fields of chemistry and technology, such as material chemistry, catalysis, and sensor applications. Within this wide scenario, tailored solid films of porphyrin derivatives are structures of great potential for, among others, chemical sensor applications. The formation ofsupramoleculesrelays on noncovalent interactions (electrostatic, hydrogen bond, , or coordinative interactions) driven by the chemical information stored on the assembling molecules, such as shape and functional groups. This allows, for example, the formation of large well-defined porphyrin aggregates in solution that can be spontaneously transferred onto a solid surface, so achieving a solid system with tailored features. These films have been used, covering the bridge between nanostructures and microsystems, for the construction of solid-state sensors for volatiles and metal ion recognition and detection. Moreover, the variation of peripheral substituents of porphyrins, such as, for example, chiral appended functionalities, can result in the formation of porphyrin aggregates featuring high supramolecular chirality. This would allow the achievement of porphyrin layers characterised by different chiroptical and molecular recognition properties