Transplantation during the COVID-19 pandemic. Nothing noble is accomplished without danger

The global health crisis due to the fast spread of coronavirus disease (COVID-19) has caused major disruption in all aspects of healthcare. Transplantation is one of the most affected sectors, as it relies on a variety of services that have been drastically occupied to treat patients affected by COVID-19. With this report from two transplant centers in Italy, we aim to reflect on resource organization, organ allocation, virus testing and transplant service provision during the course of the pandemic and to provide actionable information highlighting advantages and drawbacks.To what extent can we preserve the noble purpose of transplantation in times of increased danger? Strategies to minimize risk exposure to the transplant population and health- workers include systematic virus screening, protection devices, social distancing and reduction of patients visits to the transplant center. While resources for the transplant activity are inevitably reduced, new dilemmas arise to the transplant community: further optimization of time constraints during organ retrievals and implantation, less organs and blood products donated, limited space in the intensive care unit and the duty to maintain safety and outcomes

AB0563 DISCONTINUATION OF ANTI-TNFα IN PATIENTS WITH PSORIATIC ARTHRITIS: A SINGLE-CENTER EXPERIENCE

Background:TNF inhibitors have been largely demonstrated to be effective and reasonably safe for the treatment of psoriatic arthritis (PsA). Current EULAR guidelines recommend the use of an anti-TNF as first choice treatment in patients with PsA for whom a synthetic DMARD (usually methotrexate or leflunomide) is not efficacious or not well tolerated [1]. In a scenario where biologic treatments are easily available, and the treat to target strategy is widely accepted, a complete disease remission or at least a minimal disease activity are considered realistic goals to be achieved in a growing proportion of patients [2]. However, there remains very little research regarding anti-TNF discontinuation in patients who achieved a complete remission [3-5].Objectives:The primary aim of this study was to measure the disease-free interval after anti-TNF discontinuation, secondary it was investigated whether the use of Power Doppler Ultrasound (PDUS) and Contrast Enhanced Ultrasound (CEUS) could improve the diagnostic accuracy in the recognition of the relapse. Finally, we wanted to characterize the clinical features of the disease recurrence.Methods:From June 2018, 35 patients with PsA (27 males and 8 female) treated with anti-TNF, in stable remission were prospectively monitored for 1 year after treatment discontinuation. Remission was defined as documented absence of clinical and ultrasonographic signs of arthritis or enthesitis. Complete rheumatological and dermatological examinations were performed in all participants, at baseline and every 8-12 weeks: American College of Rheumatology (ACR) 66-68 joint count; Psoriasis Area Severity Index (PASI); patient pain visual analog score (VAS); patient global disease activity VAS; Health Assessment Questionnaire (HAQ); Leeds Enthesitis Index (LEI); Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); Bath Ankylosing Spondylitis Functional Index (BASFI); Power Doppler Ultrasound (PDUS) of the involved joints and entheses, Contrast Enhanced Ultrasound (CEUS) of a selected joint or enthesis and laboratory inflammation tests.Results:31 out of the 35 enrolled patients, experienced a disease recurrence with an average disease-free interval of 27.9±21.1 weeks (Figure 1). In 3 patients the treatment was restored for a relapse of the skin psoriasis, 8 patients reported only axial symptoms of disease relapse and 20 patients had both axial and peripheral joints involvement (average DAPSA score of 23.6±11.1; average BASDAI score of 4.7±2.6; average BASFI score 4.5±2.9). In all cases the disease flare was moderate and all patients promptly regained remission after restarting the treatment. Both PDUS and CEUS were safe and reliable showing a good percentage of accordance (95,4%) in detecting synovitis and enthesitis.Conclusion:The rate of disease relapse of PsA after anti-TNF discontinuation is relevant. However the disease-free interval was not short. Retreatment with the same anti-TNF was effective and safe.References:[1]Gossec L, Baraliakos X, Kerschbaumer A, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis. 2020 Jun;79(6):700-712.[2]Dures E, Shepperd S, Mukherjee S, et al. Treat-to-target in PsA: methods and necessity. RMD Open. 2020 Feb;6(1):e001083.[3]Stober C, Ye W, Guruparan T, et al. Prevalence and predictors of tumour necrosis factor inhibitor persistence in psoriatic arthritis. Rheumatology (Oxford). 2018 Jan 1;57(1):158-163.[4]Huynh DH, Boyd TA, Etzel CJ, et al. Persistence of low disease activity after tumour necrosis factor inhibitor (TNFi) discontinuation in patients with psoriatic arthritis. RMD Open. 2017 Jan 16;3(1):e000395.[5]Ye W, Tucker LJ, Coates LC. Tapering and Discontinuation of Biologics in Patients with Psoriatic Arthritis with Low Disease Activity. Drugs. 2018 Nov;78(16):1705-1715.Disclosure of Interests:None declared

Overview of the design of the ITER heating neutral beam injectors

The heating neutral beam injectors (HNBs) of ITER are designed to deliver 16.7MWof 1 MeVD0 or 0.87 MeVH0 to the ITER plasma for up to 3600 s. They will be the most powerful neutral beam\uf0a0(NB) injectors ever, delivering higher energy NBs to the plasma in a tokamak for longer than any previous systems have done. The design of the HNBs is based on the acceleration and neutralisation of negative ions as the efficiency of conversion of accelerated positive ions is so low at the required energy that a realistic design is not possible, whereas the neutralisation ofH 12 andD 12 remains acceptable ( 4856%). The design of a long pulse negative ion based injector is inherently more complicated than that of short pulse positive ion based injectors because: \u2022 negative ions are harder to create so that they can be extracted and accelerated from the ion source; \u2022 electrons can be co-extracted from the ion source along with the negative ions, and their acceleration must be minimised to maintain an acceptable overall accelerator efficiency; \u2022 negative ions are easily lost by collisions with the background gas in the accelerator; \u2022 electrons created in the extractor and accelerator can impinge on the extraction and acceleration grids, leading to high power loads on the grids; \u2022 positive ions are created in the accelerator by ionisation of the background gas by the accelerated negative ions and the positive ions are back-accelerated into the ion source creating a massive power load to the ion source; \u2022 electrons that are co-accelerated with the negative ions can exit the accelerator and deposit power on various downstream beamline components. The design of the ITER HNBs is further complicated because ITER is a nuclear installation which will generate very large fluxes of neutrons and gamma rays. Consequently all the injector components have to survive in that harsh environment. Additionally the beamline components and theNBcell, where the beams are housed, will be activated and all maintenance will have to be performed remotely. This paper describes the design of theHNBinjectors, but not the associated power supplies, cooling system, cryogenic system etc, or the high voltage bushingwhich separates the vacuum of the beamline fromthehighpressureSF6 of the high voltage (1MV) transmission line, through which the power, gas and coolingwater are supplied to the beam source. Also themagnetic field reduction system is not described

SARS-CoV2 and immunosuppression. A double-edged sword

Severe acute respiratory syndrome Coronavirus 2 (SARS-Cov2) outbreak has caused a pandemic rapidly impacting on the way of life of the entire world. This impact in the specific setting of transplantation and immunosuppression has been poorly explored to date. Discordant data exist on the impact of previous coronavirus outbreaks on immunosuppressed patients. Overall, only a very limited number of cases have been reported in literature, suggesting that transplanted patients not necessarily present an increased risk of severe SARS-Cov2-related disease compared to the general population. We conducted a literature review related to the impact of immunosuppression on coronavirus infections including case reports and series describing immunosuppression management in transplant recipients. The role of steroids, calcineurin inhibitors, and mycophenolic acid has been explored more in detail. A point-in-time snapshot of the yet released literature and some considerations in relation to the use of immunosuppression in SARS-Cov2 infected transplant recipients are provided here for the physicians dealing with immunocompromised patients

Evaluation of Clinical and Ultrasonographic Parameters in Psoriatic Arthritis Patients Treated with Adalimumab: A Retrospective Study

Objectives. The aim of this study was to evaluate clinical and US-PD parameters in PsA during adalimumab treatment. Methods. A retrospective study has been conducted in forty patients affected by moderate-to-severe peripheral PsA. Clinical, laboratory, and US-PD evaluations were performed at baseline, after 4, 12, and 24 weeks of treatment. They included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale (VAS), Health Assessment Questionnaire (HAQ) modified for Spondyloarthritis, Psoriasis Area Severity Index (PASI) score, the 28-joint Disease Activity Score (DAS 28), and US-PD assessment. US-PD findings were scored according to a semiquantitative scale (ranging 0–3) for synovial proliferation (SP), joint effusion (SE), bone erosions (BE), and PD. Results. Data obtained for clinical, laboratory findings and US-PD evaluation showed statistical significant improvement in all the measures performed except for BE. A significant parallel decrease in SE, SP, and PD values were demonstrated. Conclusion. This study demonstrated that US-PD is a valid technique in monitoring the response to adalimumab in moderate-to-severe PsA

Improving Diagnostic Performance for Thyroid Nodules Classified as Bethesda Category III or IV: How and by Whom Ultrasonography Should be Performed

Background: The purpose of this prospective study is to evaluate if the association of Bethesda system and a 3-categories Ultrasonography (US) risk stratification system proposed by the American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi improves the performance of cytology alone in III or IV categories and if further variables such as US provider (radiologist; endocrinologist, or endocrine surgeon both coming from a dedicated team) influence the accuracy of the diagnostic. Methods: 570 consecutive patients with complete clinical records, affected by Bethesda III or IV nodules, have been addressed to two public referral surgical centers of Western Sicily. Age, sex, autoimmunity, nodule size, and US provider were recorded. Fisher's exact test was used for the univariate analysis; Odd's ratios were calculated for the multivariate analysis. Results: 248 patients had malignancy at histology, 322 were benign. The mean age was 52 years for the malignancy group and 58 y for the benign group (P < 0.001). At univariate analysis, autoimmunity was correlated with benign group (P < 0.001), and US risk 2 and 3 were correlated with malignancy (nearly 10-folds, P < 0.001); In addition, no difference was found concerning nodule size. At multivariate analysis, US risk 2 and 3 were strong predictors of malignancy (P < 0.0001) especially if cytology was Bethesda IV; endocrinologist and surgeon were more accurate in predicting malignancy compared with the radiologist (P < 0.01). Conclusions: In the context of indeterminate nodules, the American College of Endocrinology/American Association of Clinical Endocrinologists/Associazione Medici Endocrinologi US risk stratification system strongly improves the results of Bethesda system especially when performed from dedicated endocrinologist or endocrine surgeon

Immunomorphological Patterns of Chaperone System Components in Rare Thyroid Tumors with Promise as Biomarkers for Differential Diagnosis and Providing Clues on Molecular Mechanisms of Carcinogenesis

Hurthle cell (HC), anaplastic (AC), and medullary (MC) carcinomas are low frequency thyroid tumors that pose several challenges for physicians and pathologists due to the scarcity of cases, information, and histopathological images, especially in the many areas around the world in which sophisticated molecular and genetic diagnostic facilities are unavailable. It is, therefore, cogent to provide tools for microscopists to achieve accurate diagnosis, such as histopathological images with reliable biomarkers, which can help them to reach a differential diagnosis. We are investigating whether components of the chaperone system (CS), such as the molecular chaperones, can be considered dependable biomarkers, whose levels and distribution inside and outside cells in the tumor tissue could present a distinctive histopathological pattern for each tumor type. Here, we report data on the chaperones Hsp27, Hsp60, and Hsp90. They presented quantitative levels and distribution patterns that were different for each tumor and differed from those of a benign thyroid pathology, goiter (BG). Therefore, the reported methodology can be beneficial when the microscopist must differentiate between HC, AC, MC, and BG

Quantitative immunomorphological analysis of heat shock proteins in thyroid follicular adenoma and carcinoma tissues reveals their potential for differential diagnosis and points to a role in carcinogenesis

Hsp27, Hsp60, Hsp70, and Hsp90 are chaperones that play a crucial role in cellular homeostasis and differentiation, but they may be implicated in carcinogenesis. Follicular neoplasms of the thyroid include follicular adenoma and follicular carcinoma. The former is a very frequent benign encapsulated nodule, whereas the other is a nodule that infiltrates the capsule, blood vessels and the adjacent parenchyma, with a tendency to metastasize. The main objective was to assess the potential of the Hsps in differential diagnosis and carcinogenesis. We quantified by immunohistochemistry Hsp27, Hsp60, Hsp70, and Hsp90 on thin sections of human thyroid tissue with follicular adenoma or follicular carcinoma, comparing the tumor with the adjacent peritumoral tissue. Hsp60, Hsp70, and Hsp90 were increased in follicular carcinoma compared to follicular adenoma, while Hsp27 showed no difference. Histochemical quantification of Hsp60, Hsp70, and Hsp90 allows diagnostic distinction between follicular adenoma and carcinoma, and between tumor and adjacent non-tumoral tissue. The quantitative variations of these chaperones in follicular carcinoma suggest their involvement in tumorigenesis, for instance in processes such as invasion of thyroid parenchyma and metastasization

Not all KIT 557/558 codons mutations have the same prognostic influence on recurrence-free survival: breaking the exon 11 mutations in gastrointestinal stromal tumors (GISTs)

Background: Although the gastrointestinal stromal tumor (GIST) genotype is not currently included in risk-stratification systems, a growing body of evidence shows that the pathogenic variant (PV) type and codon location hold a strong prognostic influence on recurrence-free survival (RFS). This information has particular relevance in the adjuvant setting, where an accurate prognostication could help to better identify high-risk tumors and guide clinical decision-making. Materials and Methods: Between January 2005 and December 2020, 96 patients with completely resected GISTs harboring a KIT proto-oncogene receptor tyrosine kinase (KIT) exon 11 PV were included in the study. We analyzed the type and codon location of the PV according to clinicopathological characteristics and clinical outcome; the metastatic sites in relapsed patients were also investigated. Results: Tumors harboring a KIT exon 11 deletion or deletion/insertion involving the 557 and/or 558 codons, showed a more aggressive clinical behavior compared with tumors carrying deletion/deletion/insertion in other codons, or tumors with duplication/insertion/single-nucleotide variant (SNV) (7-year RFS: 50% versus 73.1% versus 88.2%, respectively; p < 0.001). Notably, among 18 relapsed patients with 557 and/or 558 deletion or deletion/insertion, 14 patients (77.8%) harbored deletions simultaneously involving 557 and 558 codons, while only 4 patients (22.2%) harbored deletions involving only 1 of the 557/558 codons. Thus, when 557 or 558 deletions occurred separately, the tumor showed a prognostic behavior similar to the GIST carrying deletions outside the 557/558 position. Remarkably, patients with GISTs stratified as intermediate risk, but carrying the 557/558 deletion, showed a similar outcome to the high-risk patients with tumors harboring deletions in codons other than 557/558, or duplication/insertion/SNV. Conclusion: Our data support the inclusion of the PV type and codon location in routine risk prediction models, and suggest that intermediate-risk patients whose GISTs harbor 557/558 deletions may also need to be treated with adjuvant imatinib like the high-risk patients