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

Serum Anti-Thyroglobulin Autoantibodies Are Specific in Predicting the Presence of Papillary-like Nuclear Features and Lymphocytic Infiltrate in the Thyroid Gland

(1) Background: Previous studies have reported a correlation between serum anti-Thyroglobulin-antibodies (TgAb) and papillary thyroid carcinoma. The aim of our study was to evaluate whether serum TgAb and anti-thyroid-peroxidase antibody (TPO) positivity was also related to pre-neoplastic histological changes such as papillary-like nuclear features (PLNF) and with the presence of lymphocytic infiltrate (LI) in thyroid surgical specimens. (2) Methods: The study was retrospectively carried out on 70 consecutively recruited patients who underwent thyroidectomy for benign process and whose TgAb and TPOAb values were retrieved from clinical records. Histological sections of thyroid surgical samples were revised, looking for PLNF and lymphocytic infiltrate. HBME1 expression was assessed by immunohistochemistry. (3) Results: Our results showed a significant association between TgAb, PLNF, and lymphocytic infiltrate. The presence of TgAb was highly specific, but less sensitive, in predicting the presence of PLNF (sensitivity = 0.6, specificity = 0.9; positive predictive value (PPV) = 0.88; negative predictive value (NPV) = 0.63). TgAb positivity showed a good association with the presence of lymphocytic infiltrate (sensitivity = 0.62, specificity = 0.9; PPV = 0.88 and NPV = 0.68). HBME1 immunoreactivity was observed in the colloid of follicles showing PLNF and/or closely associated with LI. (4) Conclusions: The presence of PLNF and LI is associated with serum TgAb positivity. The presence of TgAb and of LI could be triggered by an altered thyroglobulin contained in the HBME1-positive colloid, and could be a first defense mechanism against PLNF that probably represent early dysplastic changes in thyrocytes

ANALYSIS OF THE TRADITIONAL PASSIVE SYSTEMS PERFORMANCE THROUGH THE APPLICATION OF CFD SOFTWARE

The need to reduce energy consumption is pushing the building design research to the evaluation of passive conditioning systems, since urban buildings are one of the major energy dissipater resulting in emission of CO2. This approach is not modern, but it is historically rooted in the architectural culture of the Mediterranean area and in the Middle East. The passive systems have ancient origins: they were developed to mitigate the summer heat and the winter cold. To understand the reasons that led to the development of passive systems, it should be remembered that about One-Fifth of the emerged planet surface and One-Third of the world's population live in conditions of warm-dry or hot-humid. In addition, most continental areas, even above high values of latitude (50\ub0), are characterized by climatic conditions with summer temperatures over the limit levels of comfort. Nowadays the scientific knowledge and the modern technologies allow to understand the working of passive systems in order to apply them on buildings to improve indoor comfort. This can be obtained through a new approach that involves the elaboration of design strategies based on the development of techniques and on computational and control tools. This work will show the results of a research that aims to verify the working of natural passive cooling systems employed in existing ancient buildings throughout CFD (Computational Fluid Dynamic) software application. Particularly we will define, through computational tools, models and study cases to compare and to set proposals able to actualize the original passive systems conceived and developed in an empirical way

Effects of the number of removed lymph nodes on survival outcome in patients with sentinel node-negative breast cancer

Background: Sentinel lymph node biopsy is the gold standard surgical technique for axillary staging in patients with clinically node-negative. However, it is still uncertain what is the optimal number of sentinel lymph nodes (SLNs) to be removed to reduce the false-negative rate. The aim of this study was to investigate whether patients with a single negative SLN have a worse prognosis than those with two or more negative SLNs. Methods: A retrospective review was conducted on a large series of SLN-negative breast cancer patients. Survival outcomes and regional recurrence rate were evaluated according to the number of removed SLNs. Secondly, the contribution of different adjuvant therapies on disease-free survival was explored. Statistical analysis included the chi-square, Wilcoxon–Mann–Whitney test, and Kaplan–Meier survival analysis. Results: A total of 1080 patients were included in the study. A first group consisted of 328 patients in whom a single SLN was retrieved, and a second group consisted of 752 patients in whom two or more SLNs were retrieved. There was no relevant difference in median DFS (64.9 vs 41.4) for SLN = 1 vs SLN > 1 groups (HR 0.76, CI 95% 0.39–1.46; p = 0.38). A statistically significant difference in mDFS was showed only for HT-treated patients who were SLN = 1 if compared to SLN > 1 (100.6 months versus 35.3 months). Conclusions: There is likely a relationship between the number of resected SNL and mDFS. Our results, however, showed no relevant difference in median DFS for SLN = 1 vs SLN > 1 group, except for a subset of the patients treated with hormone therapy

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

Molecular chaperones and thyroid cancer

Thyroid cancers are the most common of the endocrine system malignancies and progress must be made in the areas of differential diagnosis and treatment to improve patient management. Advances in the understanding of carcinogenic mechanisms have occurred in various fronts, including studies of the chaperone system (CS). Components of the CS are found to be quantitatively increased or decreased, and some correlations have been established between the quantitative changes and tumor type, prognosis, and response to treatment. These correlations provide the basis for identi-fying distinctive patterns useful in differential diagnosis and for planning experiments aiming at elucidating the role of the CS in tumorigenesis. Here, we discuss studies of the CS components in various thyroid cancers (TC). The chaperones belonging to the families of the small heat-shock proteins Hsp70 and Hsp90 and the chaperonin of Group I, Hsp60, have been quantified mostly by immunohistochemistry and Western blot in tumor and normal control tissues and in extracellular vesicles. Distinctive differences were revealed between the various thyroid tumor types. The most frequent finding was an increase in the chaperones, which can be attributed to the augmented need for chaperones the tumor cells have because of their accelerated metabolism, growth, and division rate. Thus, chaperones help the tumor cell rather than protect the patient, exemplifying chaperonopathies by mistake or collaborationism. This highlights the need for research on chaperonotherapy, namely the development of means to eliminate/inhibit pathogenic chaperones

Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Background: The addition of PD-L1 inhibitors to platinum-based chemotherapy (CT) has newly received United States Food and Drug Administration (FDA) approval in extensive stage-small cell lung cancer (ES-SCLC). PD-1 agents similarly improved survival rates, even if not yet supported by international regulatory agencies. The current work aims to assess different efficacy and safety profiles among chemoimmunotherapy plus immuno-oncology (CT+IO) approaches according to different immune checkpoint inhibitor (ICI) subtypes. Material & Methods: We included in our meta-analysis six first-line randomised controlled trials (RCTs) comparing the association of single-agent ICI with CT versus CT alone in ES-SCLC. Pooled hazard ratios (HRs) and risk ratios (RRs) for progression-free survival (PFS), overall survival (OS), objective response rates (ORR), 12-month duration of response rate (DORR), disease control rate (DCR), treatment-related adverse events (TRAEs) and discontinuation rates (DRs) were obtained. Moreover, we performed indirect comparisons according to ICI subtypes, also among subgroups and landmark survival analyses. Results: Although no ORR benefit was observed, our results showed how CT+IO significantly improved DORR, resulting in improved PFS and OS with no differences in TRAEs; however, CT+IO led to a significant increase in DR. Interestingly, an Eastern Cooperative Oncology Group performance status (ECOG PS) of 1, the use of cisplatin, and the absence of brain metastases seem to be associated with a survival gain using CT+IO in ES-SCLC. Indirect comparisons suggested a slight advantage in favour of programmed cell death-1 (PD-1) and programmed death ligand 1 (PD-L1) over anti-CTLA-4 agents in terms of efficacy with no additional safety concerns. No further differences were observed between PD-1 and PD-L1 inhibitors among subgroups and landmark survival analyses with benefit trends towards anti-PD-1 in terms of DORR and DR. Conclusion: While confirming a survival advantage of CT+IO in selected patients, these results suggested the association of PD-1 inhibitors with CT as a viable option for novel therapeutic approaches in the frontline management of ES-SCLC. Further trials evaluating anti-CTLA-4 agents should be carefully studied in biomarker-selected patients

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

Potential Activity of Albino Grifola frondosa Mushroom Extract against Biofilm of Meticillin-Resistant Staphylococcus aureus

Mushroom extracts are a rich source of natural compounds with antimicrobial properties, which are able to prevent, to some extent, the growth of foodborne pathogens. The aim of this study was to investigate the potential of extracts from albino Grifola frondosa (GF), commonly known as maitake, to inhibit the growth of some bacteria and the biofilm production by Staphylococcus aureus. We obtained not only a significant reduction of OD score between biofilm and biofilm plus albino G. frondosa extract group, but also a reduction of category of biofilm. In addition, we observed a significant presence of isolates with strong category for the biofilm group and a significant presence of isolates with absent category for the biofilm plus albino G. frondosa extract group. These results confirm that the use of albino G. frondosa extract reduces in significant way the presence of biofilm. Our results suggest and confirm that albino G. frondosa extracts could be employed as functional food and could be used as a natural additive for food process control and food safety

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