AB0462 BEHCET'S DISEASE: CLINICAL FEATURES AND OFF-LABEL BIOLOGIC TREATMENT STRATEGIES

Background:The treatment of Behçet's disease (BD) is still mainly based on the evidence derived from case reports, case series, retrospective analyses, and few clinical trials suggesting the safety and potential efficacy of off-label use of biologic agents in refractory cases.1Objectives:To describe clinical manifestations and their management, with particular focus on treatment indications, outcomes and safety of biologic therapy, in a cohort of patients with BD.Methods:Patients with a diagnosis of BD who visited our outpatient clinic until December 2019 were included in the study. Clinical data were recorded since diagnosis until the latest follow-up visit, analyzing clinical features, flares and therapeutic strategies adopted.Results:A total of 95 patients were included in the study with a medium follow-up of 108.54 ± 169.59 months. 20 of them (21. 05%) were treated with biologic agents. Patients treated with biologic therapy compared to those on conventional non-biologic therapies had a higher proportion of musculoskeletal (80% vs 46.67%, p = 0.008), neurological (30% vs 10.67%, p = 0.031), intestinal involvement (40% vs 12%, p = 0.004), and they were treated with a higher dose of glucocorticoids at diagnosis (16.84 mg ±14.01 vs 8.89 mg ± 11.76, p = 0.012). The most frequent indications for biologic step-up therapy were musculoskeletal involvement (40%), eye involvement (25%), neurological involvement (15%) and intestinal involvement (10%). Most patients initiated a biologic treatment within the first year of follow-up. TNF-inhibitor (TNFi) were more frequently prescribed (95%) and one patient was treated with 8 therapeutic cycles of Rituximab (500 mg/weekly for 4 infusions to be repeated after at least 6 months) because of recurrent pancytopenia. All patients experienced non-biologic therapy before starting a TNFi. The preferred first-line TNFi was infliximab (50%), followed by adalimumab (40%) and etanercept (5%). As second line treatment were also prescribed certolizumab (10%) and golimumab (5%). 10 patients switched to a second line treatment because of inefficacy of the first biologic agent, mainly because of refractory arthritis, intestinal and mucocutaneous involvement. One patient switched from infliximab to certolizumab during pregnancy with subsequent worsening of arthritis.85% of patients treated with biologic agents reached a clinical remission by the time of the latest follow up visit without any safety or tolerability issues.Conclusion:A relevant proportion of patients in our BD cohort were treated with biologic therapy, because of severe or refractory manifestations. The most frequent indications were musculoskeletal, neurological or intestinal involvement. Biologic agents were a generally effective and safe therapeutic approach.References:[1]F. Alibaz-Oner, M. H. Sawalha, H. Direskeneli. Management of Behçet disease, Curr. Opin. Rheumatol, 2018Table 1.General characteristics and disease involvement at diagnosisBiologic therapyNo biologic therapyp value20 (21.05%)75 (78.95%)General characteristicsMediaSDMediaSDAge at disease onset(years ± SD)34.5± 10.4938.64± 13.18p = 0.1976Diagnostic delay(months ± SD)45.28± 67.4828.09± 48.42p = 0.1996Glucocorticoids at diagnosis (mg prednisone ± SD)16.84± 14.018.89± 11.76p = 0.0115Glucocorticoids at latest follow up visit (mg prednisone ± SD)6.38± 7.763.83± 4.81p = 0.0707N%N%F / M12 / 860 / 4054 / 4172 / 28p = 0.3030Disease involvement at diagnosisOral ulcers2010075100Genital ulcers11553749,33p = 0.6540Cutaneous lesions15755066,67p = 0.4787Eye involvement6302736p = 0.6184Musculoskeletal involvement16803546,67p = 0.0082Neurological involvement630810,67p = 0.0311Intestinal involvement840912p = 0.0039Thrombosis2101824p = 0.1747Disclosure of Interests:None declare

CFD analysis of the fuel-air mixture formation process in passive prechambers for use in a high-pressure direct injection (HPDI) Two-stroke engine

The research on two-stroke engines has been focused lately on the development of direct injection systems for reducing the emissions of hydrocarbons by minimizing the fuel shortcircuiting. Low temperature combustion (LTC) may be the next step to further improve emissions and fuel consumption; however, LTC requires unconventional ignition systems. Jet ignition, i.e., the use of prechambers to accelerate the combustion process, turned out to be an effective way to perform LTC. The present work aims at proving the feasibility of adopting passive prechambers in a high-pressure, direct injection, two-stroke engine through non-reactive computational fluid dynamics analyses. The goal of the analysis is the evaluation of the prechamber performance in terms of both scavenging efficiency of burnt gases and fuel/air mixture formation inside the prechamber volume itself, in order to guarantee the mixture ignitability. Two prechamber geometries, featuring different aspect ratios and orifice numbers, were investigated. The analyses were replicated for two different locations of the injection and for three operating conditions of the engine in terms of revolution speed and load. Upon examination of the results, the effectiveness of both prechambers was found to be strongly dependent on the injection setup

Cytokine release syndrome after CAR infusion in pediatric patients with refractory/relapsed B-ALL: is there a role for diclofenac?

BACKGROUND: Cytokine release syndrome (CRS) is a major complication after chimeric-antigen receptor T-cell treatment, characterized by an uncontrolled systemic inflammatory reaction. We investigated the potential role of diclofenac in the management of CRS in five pediatric patients treated for relapsed/refractory B-lineage acute lymphoblastic leukemia. METHODS: In case of persistent fever with fever-free intervals shorter than 3 hours, diclofenac continuous infusion was initiated, at the starting dose of 0.5 mg/Kg/day, the lowest effective pediatric dose in our experience, possibly escalated up to 1 mg/Kg/day, as per institutional guidelines. RESULTS: CRS occurred at a median of 20 hours (range 8–27) after tisagenlecleucel infusion. Diclofenac was started at a median of 20 hours (range 13–33) after fever onset. A mean of 3.07 febrile peaks without diclofenac and 0.95 with diclofenac were reported (p = 0.02). Clinical benefit was achieved by hampering the progression of tachypnea and tachycardia. Despite fever control, CRS progressed in four of the five patients, and hypotension requiring vasopressors and fluid retention, as well as hypoxia, occurred. Vasopressors were followed by 1–2 doses of tocilizumab (one in patient 2 and two in patients 3, 4, and 5), plus steroids in patients 4 and 5. CONCLUSION: Based on a limited number of patients, diclofenac leads to better fever control, which translates into symptom relief and improvement of tachycardia, but could not prevent the progression of CRS

Urticaria in an infant with SARS-CoV-2 positivity

Last months have been marked by the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 19 (COVID-19) pandemic

A review of the literature of surgical and nonsurgical treatments of invasive squamous cells carcinoma

Cutaneous squamous cell carcinoma (cSCC) is an increasing public health problem. It is a primary malignant skin tumor with Malpighian differentiation and together with basal cell carcinoma is classified among nonmelanoma skin cancers (NMSCs). cSCC usually occurs on photoexposed areas, such as the head, the neck, and the extremities, and its incidence increases with age. Invasive forms of this skin tumor tend to be more aggressive showing a higher metastatic potential, usually regarding regional lymph nodes. Treatment options for invasive cSCCs include both surgical and nonsurgical options. The therapeutic choice depends on several factors, such as anatomic location, risk factors for tumor recurrence, age, and health status of the patient. This review aims to provide an overview of the current evidence on therapeutic surgical and nonsurgical management of invasive cSCC

Predictive Role Of Body Composition Parameters In Operable Breast Cancer Patients Treated With Neoadjuvant Chemotherapy.

BACKGROUND: Fat tissue is strongly involved in BC tumorigenesis inducing insulin resistance, chronic inflammation and hormonal changes. Computed tomography (CT) imaging instead of body mass index (BMI) gives a reliable measure of skeletal muscle mass and body fat distribution. The impact of body composition parameters (BCPs) on chemosensitivity is still debated. We examined the associations between BCPs and tumor response to neoadjuvant chemotherapy (NC) in patients treated for operable breast cancer (BC). METHODS: A retrospective review of BC patients treated with NC in Modena Cancer Center between 2005 and 2017 was performed. BCPs, such as subcutaneous fat area (SFA), visceral fat area (VFA), lumbar skeletal muscle index (LSMI) and liver-to-spleen (L/S) ratio were calculated by Advance workstation (General Electric), software ADW server 3.2 or 4.7. BMI and BCPs were correlated with pathological complete response (pCR) and survival outcomes. RESULTS: 407 patients were included in the study: 55% with BMI < 25 and 45% with BMI 65 25. 137 of them had pre-treatment CT scan imagines. Overweight was significantly associated with postmenopausal status and older age. Hormonal receptor positive BC was more frequent in overweight patients (p<0.05). Postmenopausal women had higher VFA, fatty liver disease and obesity compared to premenopausal patients. No association between BMI classes and tumor response was detected. High VFA and liver steatosis were negative predictive factors for pCR (pCR rate: 36% normal VFA vs 20% high VFA, p= 0.048; no steatosis 32% vs steatosis 13%, p=0.056). Neither BMI classes nor BCPs significantly influenced overall survival and relapse-free survival. CONCLUSION: Visceral adiposity as well as steatosis were closely involved in chemosensitivity in BC patients treated with NC. Their measures from clinically acquired CT scans provide significant predictive information that outperform BMI value. More research is required to evaluate the relationship among adiposity site and survival outcomes

IL-17 and its role in inflammatory, autoimmune, and oncological skin diseases. State of art

Recent data support the theory of the involvement of IL-17 in the pathogenesis of several chronic inflammatory skin diseases (psoriasis, atopic dermatitis, acne, hidradenitis suppurativa) and autoimmune skin diseases (alopecia areata, vitiligo, bullous diseases). Even if the role of IL-17 in inflammatory and autoimmune diseases has been reported extensively, its role in tumor is still controversial. Some reports show that Th17 cells eradicate tumors, while others reveal that they promote the initiation and early growth of tumors. Herein, we review the role of IL-17 in the involvement of some common dermatologic diseases: psoriasis, atopic dermatitis, hidradenitis suppurativa, acne, vitiligo, melanoma, and nonmelanoma skin cancers

Therapeutic options for the treatment of actinic keratosis with scalp and face localization

Actinic keratosis (AK) is a common skin disease related to ultraviolet chronic exposure, that is now considered a squamous cell carcinoma in situ. Primary skin cancer prevention strategies should be recommended for high risk patients. There is a wide spectrum of treatment options available for AKs, and several variables should be taken into account regarding the best therapeutic choice for each patient. The purpose of this article is to review the current treatment strategies for AKs localized on the face and scalp, with a focus on the practical point of view that could be useful for choosing the best therapeutic option. The two main therapeutic approaches will be distinguished first: lesion-directed and field-directed. Afterwards, the treatment based on clinical type and patient comorbidity will be discusse