Study of lncRNAs expression profile in the response to biological drugs in Psoriatic Arthritis: MEG3 could be a potential genomic biomarker of therapy efficacy.

We aimed to identify an expression profile of lncRNAs potentially related to treatment response in Psoriatic arthritis (PsA) patients, to be used as potential genomic biomarkers predictors of drug treatment effectiveness. In addition, we evaluated a possible association between lncRNAs genetic variants and the response to therapy using the clinical parameter of Disease Activity Index. For the expression study, we collected 48 treated PsA patients, monitoring the treatment response for 12 months. We initially used PCR Array and, then, we validated the results with qRT-PCR. We also retrospectively genotyped 163 treated PsA patients. Firstly, we observed a significant difference in the expression level between Responder and non-Responder patients, of 4 lncRNAs in the group of PsA patients treated with TNFi and of 3 lncRNAs in the group of patients treated with IL17i. Then, we confirmed a significant decrease of MEG3 expression in non-Responder patients compared to Responders, also considering separately the single groups of patients treated with TNFi and IL17i. In addition, our results seem to highlight a potential dose-dependent effect of rs941576 (MEG3) variant allele on Disease Activity Index. Our study suggests a possible role of the lncRNA MEG3 in the treatment response to biological drugs.

The steroid-sparing effect of JAK inhibitors across multiple patient populations.

Introduction: JAK-inhibitors (JAK-i) represent an effective treatment in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA). Oral glucocorticoids (OGC) are commonly used in combination with JAK-i to reach therapeutic target. We aimed to assess, in a real-life setting, the reduction of OGC dose during JAK-i treatment in active RA and PsA patients. Methods: We prospectively enrolled 103 patients (88 RA, 15 PsA) treated with JAK-i: 24% bio-naïve (b-naïve), 76% bDMARD-insufficient responders (bDMARD-IR) and 40% difficult to treat (D2T), defined as failure of ≥2 bDMARDs with different mechanism of action. Disease activity (DAS28 and DAPSA, VAS-pain, GH) and OGC dose was collected at baseline and after 3, 6 and 12 months (T3, T6, T12) of treatment. Results: In all the cohort and in b-naïve patients we reported a reduction of OGC dose at all time-points; bDMARD-IR patients were able to reduce OGC dose at T3 and T12; D2T ones only at T3. We reported an improvement of disease activity and withdrawal of OGC as early as three months of therapy, at all time-points, regardless of line of bDMARD treatment. Conclusion: Chronic OGC may cause detrimental bone, metabolic, cardiovascular side effects and infections; therefore JAK-i steroid-sparing effect may be beneficial for patients in long-term treatment.

Risankizumab Efficacy in Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) Remission: A Case Report on Rheumatologic and Dermatologic Disease Manifestations with Literature Review.

SAPHO syndrome is a complex disease that encompasses both inflammatory arthritis and/or osteitis and dermatologic manifestations. It is considered a rare disease, in fact, no clinical trials have been conducted on its therapy and management. Therefore, therapeutic approach is based on small case studies. Here, we described the case of a 63-year-old woman affected by SAPHO syndrome, treated with the selective IL-23p19 antagonist, Risankizumab, after unsuccessful therapies with Methotrexate, Infliximab, Adalimumab, and an allergic reaction to Secukinumab. At the beginning of therapy, in November 2022, the patient presented with arthritis in both knees associated with palmar pustulosis and guttate psoriasis on the trunk. DAPSA score was 24, PtGA 80 mm, PASI score 11.1, and BSA 40%. Thereafter, Risankizumab was started at the standard dosage of 150 mg. At week 24 patient achieved clinical remission, DAPSA score was 8, PtGA was 30 mm, PASI was 1, and BSA 2.5. Patient maintained clinical remission state at the subsequent week 52 evaluation. At the same time, the patient did not report any adverse effects. Health-related quality of life was also assessed at the same time points aforementioned, showing significant improvement. In conclusion, this case report wants to point out the efficacy and safety of Risankizumab in SAPHO syndrome, reporting a sustained disease remission through a 12 months long follow-up period. We can consider IL-23p19 targeted therapy as a novel treatment option for SAPHO-with a high efficacy potential-especially on patients that have already been treated with other biologics.

The rs11568820 Variant in the Promoter Region of Vitamin D Receptor Gene Is Associated with Clinical Remission in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors.

The vitamin D receptor (VDR), binding to the active form of the vitamin, promotes the transcription of numerous genes involved in the proliferation of immune cells, cytokine production and lymphocyte activation. It is known that vitamin D deficiency can influence the risk of developing rheumatoid arthritis (RA) or modulate its disease activity. The aim of this study was to investigate a possible association between the rs11568820 (C > T) polymorphism in the promoter region of VDR gene and the response to therapy with anti-TNF drugs in patients with RA. A total of 178 consecutive Italian patients with RA treated with anti-TNF, naïve for biological therapy, were recruited. Disease activity data were evaluated using specific indices such as DAS28, CDAI and SDAI, measured at the start of therapy and subsequently at 22, 52, 104 and 240 weeks. A statistically significant association emerged between the rs11568820 variant allele of VDR gene and failure to remission assessed by CDAI and SDAI at 52 weeks, and by DAS28, CDAI and SDAI at 104 weeks of follow-up. Furthermore, the variant allele of this polymorphism was observed more frequently in patients who did not undergo sustained remission calculated by CDAI and SDAI. The variant T allele of rs11568820 in VDR gene is associated with a reduced remission rate with anti-TNFα drugs. These data suggest the role of VDR genetic variability in the response to therapy and in the achievement of remission.

Clinical and imaging findings in enteropathic spondyloarthritis with special emphasize in diagnostic delay: a cross-sectional study.

Background: Enteropathic spondyloarthritides (eSpAs) are chronic inflammatory joint diseases associated with inflammatory bowel disease (IBD). Limited data are available on the prevalence since arthritis in IBD patients may be underestimated because medications may hide disease activity with a possible diagnostic delay. Objectives: We aimed to evaluate diagnostic delay in eSpA and explore associated demographic, clinical, and radiographic characteristics. Design: Single-centre cross-sectional study conducted on consecutive out-patients referred to the combined Gi-Rhe clinic (November 2018-October 2019). Methods: We analysed eSpA patients for diagnostic delay, disease activity, inflammatory markers, conventional radiography (CR) and magnetic resonance images (MRI) of sacroiliac joints/spine. Results: A total of 190 eSpA patients [118 peripheral SpA, 72 axial (Ax) SpA including 44 non-radiographic (nr)-axSpA] were enrolled. axSpA patients had a higher prevalence of men sex, HLA-B27 positivity, uveitis and pancolitis compared with peripheral eSpA. Median diagnostic delay in eSpA was 48 months (IQR 6-77) with no difference between axial and peripheral patients. Radiographic-axial SpA (r-axSpA) patients displayed a higher diagnostic delay compared with nr-axSpA (median/IQR 36/17-129 versus 31/10-57 months, p = 0.03) and were older, with longer disease duration, low education status and high rate of employment than patients with nr-axSpA. r-axSpA patients with sclerosis, syndesmophytes and bridge at CR had higher diagnostic delay than those without lesions. Men showed higher prevalence of spine damage lesions than women as sclerosis, squaring, syndesmophytes and bridges. Longer disease duration was detected in patients with radiographic damage as bridge and sacroiliitis grade 3. On MRI, sacroiliac bone oedema was associated with reduced diagnostic delay, whereas bone erosions were associated with higher diagnostic delay compared with that in patients without these lesions. Patients with psoriasis displayed a higher diagnostic delay compared to those without skin involvement. Conclusion: Diagnostic delay was higher in r-axSpA compared with nr-axSpA despite the same treatment. Demographic, clinical features and radiological lesions were associated with diagnostic delay.

Diagnostic delay in patients affected by enteropathic spondyloarthritis Enteropathic Spondyloarthritides (eSpA) are chronic inflammatory joint diseases associated with inflammatory bowel disease (IBD). Limited data are available on the prevalence since arthritis in IBD patients may be underestimated because medications may hide disease activity with a possible diagnostic delay. We aimed to evaluate diagnostic delay in eSpA and explore associated demographic, clinical and radiographic characteristics. We analysed eSpA patients for diagnostic delay, disease activity, inflammatory markers, conventional radiography and magnetic resonance images of sacroiliac joints/spine. 190 eSpA patients (118 peripheral SpA, 72 axial (Ax) SpA including 44 non-radiographic (nr)-axSpA)) were enrolled. Median diagnostic delay in eSpA was 48 months with no difference between axial and peripheral patients. Radiographic-axial SpA (r-axSpA) patients displayed a higher diagnostic delay compared with nr-axSpA and were older, with longer disease duration, low education status and high rate of employment than patients with nr-axSpA. Patients with psoriasis displayed a higher diagnostic delay compared to those without skin involvement. Diagnostic delay was higher in r-axSpA compared with nr-axSpA despite the same treatment. Demographic, clinical features and radiological lesions were associated with diagnostic delay.

Impact of biological therapy in reducing the risk of arthritis development in inflammatory bowel diseases.

OBJECTIVE: Evaluate spondyloarthritis (SpA) incidence in inflammatory bowel diseases (IBD) between patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) and conventional DMARDs (cDMARDs) and define risk factors associated with SpA development. METHODS: Retrospective cohort study was conducted on patients with Crohn's disease (CD) or ulcerative colitis (UC) and divided into two cohorts: cDMARDs or bDMARDs/targeted synthetic (ts) DMARDs treated patients. Rheumatological assessment was performed in patients presenting musculoskeletal symptoms. Multivariate analysis and Kaplan-Meier curves were used to evaluate the adjusted SpA risk development. RESULTS: 507 patients were included in the study. 176 patients with CD received bDMARDs, 112 cDMARDs and 106 new SpA diagnosies were formulated. Females (OR 1.7 (95% CI 1.1 to 3), adjusted p=0.04), non-stricturing/non-penetrating phenotype (OR 2 (95% CI 1.1 to 3.4), adjusted p=0.01), psoriasis (OR 2.1 (95% CI 1 to 4.6), adjusted p=0.04) and non-infectious uveitis (OR 6.8 (95% CI 1.4 to 33.4), adjusted p=0.01) were associated with increased SpA risk development, while bDMARDs usage was protective (OR 0.4 (95% CI 0.2 to 0.8), adjusted p=0.01), statistically higher than cDMARDs throughout the entire follow-up (effect size 0.47). 98 patients with UC received b-tsDMARDs, 121 cDMARDs and 56 new SpA diagnoses were formulated. Females (OR 2.1 (95% CI 1 to 4.3), adjusted p=0.02) and psoriasis (OR 2.7 (95% CI 1 to 6.8), adjusted p=0.03) were associated with increased SpA risk development, while bDMARDs were protective for SpA development for up to 12 months of treatment compared with cDMARDs (p=0.03). CONCLUSIONS: bDMARDs treatment had an impact in reducing SpA development and clinical associated risk factors to transition from IBD to IBD-SpA emerged.

Relationship between retinal microvascular impairment and subclinical atherosclerosis in SLE.

OBJECTIVES: Patients with SLE have higher cardiovascular (CV) risk compared with healthy controls (HC) and are characterised by accelerated atherosclerosis; intima media thickness (IMT), marker of subclinical atherosclerosis, is higher in patients with SLE than in HCs. Retinal microvascular impairment detected through optical coherence tomography angiography (OCTA) was investigated as a marker of systemic vascular involvement in SLE.The aim of the study was to evaluate the relationship between retinal vascular impairment and IMT in SLE. METHODS: Cross-sectional study recruiting patients with SLE and HCs. Data of the study population were collected. CV risk was evaluated through the American College of Cardiology/American Heart Association (ACC/AHA) guidelines, Framingham and QRESEARCH risk estimator V.3 (QRISK3) scores. Both groups underwent OCTA and carotid ultrasound with IMT assessment.Statistical analysis was accomplished using Pearson/Spearman, t-test/Mann-Whitney or χ2 test. Variables statistically significant at univariate regression analysis were tested in an age-corrected and sex-corrected multivariate regression model. RESULTS: 43 patients with SLE and 34 HCs were recruited. Patients with SLE showed higher triglycerides (p=0.019), Triglycerides-Glucose (TyG) Index (p=0.035), ACC/AHA guidelines (p=0.001), Framingham Risk Scores (p=0.008) and a reduced superficial (p<0.001) and deep (p=0.005) whole retinal vessel density (VD) compared with HCs.In SLE univariate analysis, deep whole VD showed a negative correlation with IMT (p=0.027), age (p=0.001), systolic blood pressure (p=0.011), QRISK3 Score (p<0.001), Systemic Lupus International Collaborating Clinics Damage Index (p=0.006) and apolipoprotein B (p=0.021), while a positive correlation was found with female sex (p=0.029). Age-adjusted and sex-adjusted multivariate analysis confirmed QRISK3 Score (p=0.049) and IMT (p=0.039) to be independent risk factors for reduced retinal VD. CONCLUSIONS: Patients with SLE showed lower retinal VD and higher CV risk indicators compared with HCs. Among patients with SLE, QRISK3 Score and IMT were found to be independent risk factors for retinal vascular impairment, suggesting a role of OCTA in evaluating preclinical CV involvement in SLE. Moreover, TyG Index could represent a biomarker of CV risk in patients with SLE compared with HCs.

Rheumatologist's Perspective on Non-Infectious Uveitis: Patterns from Tertiary Referral Rheumatologic Clinics in Italy.

Non-infectious uveitis (NIU) can be an early or even the first extra-articular manifestation of systemic rheumatic diseases, or the first one; thus, rheumatologists are often involved in the diagnostic and therapeutic assessment of NIU. We evaluated 130 patients with a diagnosis of NIU who were admitted to two Italian rheumatologic clinics (Tor Vergata University Hospital in Rome, and Federico II University in Naples) from January 2018 to December 2021. Anterior uveitis (AU) occurred in 75.4% of patients, followed by posterior uveitis (PU, 21.5%); acute (54.6%) and recurrent (35.4%) NIU were more documented than chronic NIU (10%), and a bilateral involvement was observed in 38.7% of cases. Half of NIU cases were associated with spondyloarthritis (SpA); the remaining were affected by Behçet disease (BD)-related uveitis (13.9%) and idiopathic NIU (9.2%). HLA-B27+ patients (34.8%) had a higher prevalence of anterior and unilateral NIU (p = 0.005) with acute course (p = 0.04) than HLA-B27- patients. On the contrary, HLA-B51+ patients (19.6%) had mostly PU and bilateral NIU (p < 0.0001) and recurrent course (p = 0.04) than HLA-B51- patients. At the first rheumatologic referral, 117 patients (90%) received systemic treatments. Findings from this study demonstrate that rheumatologic referral has a pivotal role in the diagnostic work-up of NIU and may dramatically influence NIU-treatment strategies.

Failure and multiple failure for disease modifying antirheumatic drugs in rheumatoid arthritis: Real-life evidence from a tertiary referral center in Italy.

BACKGROUND: Rheumatoid Arthritis (RA) is a chronic inflammatory disease with a heterogeneous treatments' clinical response. Goals of treatment are remission and low disease activity, which are not achieved in all patients despite the introduction of early treatment and the treat to target strategy. OBJECTIVE: To investigate the causes of disease-modifying antirheumatic drugs (DMARDs) discontinuation and treatment failure and multiple failure for inefficacy, and to identify possible failure predictors' according to RA patient characteristics in a real-world setting. METHODS: 718 RA patients were retrospectively evaluated. Conventional synthetic (cs) and biologic (b)DMARDs treatments line/s, effectiveness, and reasons of discontinuations were evaluated. Patients failing to at least two csDMARDs or bDMARDs' drug for inefficacy were defined "csDMARDs multifailure" and "bDMARDs multifailure", respectively. Discontinuation of at least two cs- and bDMARDs was termed "global multifailure". RESULTS: In total, 1422 csDMARDs and 714 bDMARDs treatment were analysed. Causes of csDMARDs discontinuation were intolerance (21.8%), inefficacy (20.2%), acute adverse reactions (5.3%) and severe infections (0.6%) while csDMARDs multifailure for inefficacy was observed in 5.7% of cases. Reasons of bDMARDs withdrawal were inefficacy (29%), intolerance (10.0%), acute adverse reaction (6.3%) and severe infections (1.5%). Altogether, 8.4% of patients were bDMARDs multifailure for inefficacy while 16.6% were global multifailure. Longstanding disease (≥ 12 months) and smoke habit, resulted as positive predictor of csDMARDs failure (OR 2.6 and OR 2.7, respectively). Thyreopathy was associated with both csDMARDs failure and global multifailure (OR 2.4 and OR 1.8, respectively). Higher prevalence of failure to at least one bDMARDs and global multifailure was detected in female than male (OR 2.3 and OR 2, respectively). CONCLUSIONS: Different causes of drug discontinuation were observed on DMARDs treatments. Demographic and clinical features were identified as possible predictors of both cs- and bDMARDs treatment failure and multiple failure, underlining the need of a more personalized therapeutic approach to achieve treatment targets.

How Has Molecular Biology Enhanced Our Undertaking of axSpA and Its Management.

PURPOSE: This review aims at investigating pathophysiological mechanisms in spondyloarthritis (SpA). Analysis of genetic factors, immunological pathways, and abnormalities of bone metabolism lay the foundations for a better understanding of development of the axial clinical manifestations in patients, allowing physician to choose the most appropriate therapeutic strategy in a more targeted manner. RECENT FINDINGS: In addition to the contribution of MHC system, findings emerged about the role of non-HLA genes (as ERAP1 and 2, whose inhibition could represent a new therapeutic approach) and of epigenetic mechanisms that regulate the expression of genes involved in SpA pathogenesis. Increasing evidence of bone metabolism abnormalities secondary to the activation of immunological pathways suggests the development of various bone anomalies that are present in axSpA patients. SpA are a group of inflammatory diseases with a multifactorial origin, whose pathogenesis is linked to the genetic predisposition, the action of environmental risk factors, and the activation of immune response. It is now well known how bone metabolism leads to long-term structural damage via increased bone turnover, bone loss and osteoporosis, osteitis, erosions, osteosclerosis, and osteoproliferation. These effects can exist in the same patient over time or even simultaneously. Evidence suggests a cross relationship among innate immunity, autoimmunity, and bone remodeling in SpA, making treatment approach a challenge for rheumatologists. Specifically, treatment targets are consistently increasing as new drugs are upcoming. Both biological and targeted synthetic drugs are promising in terms of their efficacy and safety profile in patients affected by SpA.

Assessment of microvascular involvement in lupus nephritis patients by retinal OCT-angiography and kidney biopsies.

OBJECTIVES: Ocular and renal microvascular damage in lupus nephritis (LN) share similar physiopathological pathways that have investigated using traditional fundus examination and high-resolution colour electroretinography. Optical coherence tomography angiography (OCTA) is a recent, non-invasive technique for imaging the microvasculature of retina and choroid. Aim of the study was to investigate through OCTA analysis the relationship between retinal microvascular alterations and renal functional and histologic features. METHODS: Systemic lupus erythematosus (SLE) patients with LN, SLE without renal involvement and healthy controls were recruited and accomplished an ophthalmological evaluation, including OCTA. SLE-LN patients underwent a rheumatological evaluation, including disease-related clinical and laboratory features collection and kidney biopsy examination. RESULTS: This cross-sectional study enrolled forty-six eyes of 23 LN patients, thirty-two eyes of 16 SLE patients and forty-two eyes of 21 controls. Thirteen SLE-LN patients (56.5%) displayed lupus retinopathy, 10 at moderate (77%) and 3 at severe stage (23%) by fundus oculi examination. Analysis of OCTA data showed with high/moderate accuracy a reduction of retinal capillary vessel density in both SLE and SLE-LN patients compared to controls in superficial and deep plexi. A reduction in fovea thickness and an increase in foveal avascular zone were also detected. OCTA data of LN patients correlated with LN duration, disease activity, kidney function and the presence of LN-vascular lesions at kidney biopsy. CONCLUSIONS: Our results suggest the role of OCTA in early detection of systemic vascular involvement in SLE-LN patients and related kidney functional-histological impairment.

What's new and what's next for biological and targeted synthetic treatments in psoriatic arthritis?

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic arthritis typically associated with cutaneous psoriasis (PsO). Its pathogenesis is connected to an innate and acquired immune response, as well as genetic risk alleles. The extent of immunopathogenic mechanisms and the heterogenicity of clinical manifestation make the identification of patient-targeted therapies a critical issue, and the treatment decision challenging in patients' management. AREAS COVERED: This review includes a brief overview of biological and small-molecule therapies, focusing on evidence from clinical trials and real-world data that support their use in PsA. We summarize novel and future possible therapeutic strategies, the importance that comorbidities have on selection of therapy and discuss the adverse event of each drug. Relevant papers for up to 1 August 2022 (trials, real-life studies, and reviews) regarding biologics and/or small molecules were summarized. EXPERT OPINION: In recent years, the treatment of PsA has been revolutionized by new targeted therapies, which offer the opportunity to perform a tailored-tail management, considering risk factors, comorbidities, and the different PsA phenotypes. Growing experience with these new agents allows novel treatment approaches that may improve clinical outcomes for PsA patients, in terms of remission/low disease activity and quality of life.

A multilocus genetic study evidences the association of autoimmune-related genes with Psoriatic Arthritis in Italian patients.

Psoriatic Arthritis (PsA) is an immune-mediated rheumatic disease caused by the interaction between environmental factors and genetic predisposition. Many of the risk loci associated with PsA susceptibility are shared with other autoimmune diseases, suggesting an involvement of the same pathways in these diseases. We investigated the association between nine selected polymorphisms and PsA susceptibility and their possible role in the modulation of the disease activity. We analysed 163 patients with PsA and 298 age and sex-matched healthy subjects. Our results showed the associations of five polymorphisms with the disease development: rs33980500 (TRAF3IP2), rs6920220 (TNFAIP3), rs27524 (ERAP1), rs7574865 (STAT4) and rs1800872 (IL10). Patients carrying the variant allele of TRAF3IP2 polymorphism had a higher number of tender/swollen joints and a higher Disease Activity Index for PsA score. The multilocus genetic risk profile showed a higher probability to develop the disease in subjects with at least four risk alleles.

Effectiveness and safety of secukinumab in axial spondyloarthritis: a 24-month prospective, multicenter real-life study.

Objectives: To evaluate, in a multicentric Italian cohort of axial spondyloarthritis (axSpA) patients on Secukinumab (SEC) followed for 24 months: (1) the long-term effectiveness and safety of SEC; (2) the drug retention rate and low disease activity (LDA) measured as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 4/Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1 and very low disease activity (VLDA) measured as BASDAI < 2/ASDAS < 1.3; (3) any differences in outcomes according to line of biological treatment (naïve/non-naïve), gender (male/female), subtype of axSpA [radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)]. Methods: Consecutive axSpA patients treated with SEC were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical-values were recorded at baseline (T0), 6 (T6), 12 (T12), and 24 (T24) months. Effectiveness was evaluated over-time with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug discontinuation and LDA at T6. Infections and adverse events were recorded. Results: A total 249 patients (47.8% male; median age 51) were enrolled; 40.9% had HLA-B27; 53.8% had r-axSpA, and 46.2% nr-axSpA. SEC was prescribed in 28.9% naïve and in 71.1% non-naïve patients. SEC effectiveness was shown as an improvement in several outcomes, such as ASDAS [T0 = 3.5 (2.9-4.4) versus T24 = 1.9 (1.2-2.4); p = 0.02] and BASDAI [T0 = 6.5 (5.0-7.5) versus T24 = 2.8 (1.8-4.0); p = 0.03]. At T24, naïve patients showed better physical functioning and lower disease activity than non-naïve. After 24 months of treatment, 90.7% of naïve and 75.3% of non-naïve patients achieved LDA (BASDAI < 4). Treatment was discontinued in 24.5% patients, mainly due to primary/secondary loss of effectiveness, and in 6.8% due to adverse events. Retention rate at T24 was 75% in the whole population, with some difference depending on gender (p = 0.002). Conclusion: In a real-life clinical setting, SEC proved to be safe and effective in axSpA, mainly in naïve-patients, with a notable drug retention rate. No differences were observed between r-axSpA and nr-axSpA.

Does the Foot and Ankle Alignment Impact the Patellofemoral Pain Syndrome? A Systematic Review and Meta-Analysis.

BACKGROUND: A convincing association between the foot and ankle alignment (FAA) and patellofemoral pain syndrome (PFPS) remains debatable in the literature. Therefore, all studies investigating the role of FAA in patients with PFPS were systematically reviewed. METHODS: A systematic literature search was performed on the databases PubMed, Embase, Cochrane Library, and Web of Science. Inclusion criteria were all studies investigating static and/or dynamic FAA factors and PFPS. Studies with less than 20 patients or with patellofemoral osteoarthritis were excluded. The quality assessment was based on Cochrane study criteria, and the maximum score was set at eight. RESULTS: Of 2246 articles, only 13 case-control studies were eligible. Considering static FAA factors, two studies found an association with rearfoot eversion and one with rearfoot inversion. While examining dynamic FAA characteristics, one study found an association with rearfoot eversion range of motion and three with gait kinematics. No further associations were reported. The quality assessment mean score was 5.5 (SD = 0.97) corresponding to moderate quality. CONCLUSIONS: In contrast to our expectations, a limited number of studies were founded supporting an association between FAA and PFPS. At present, the quality of the literature is still poor and conflicting, thus the need for further studies to determine any association between FAA and PFPS.

Treatment of Zenker's Diverticulum With Endoscopic Stapled Esophago-divertisculostomy (ESD): Analysis of Long-term Outcome.

BACKGROUND: Endoscopic Zenker diverticulum (ZD) treatment has become quite common because of the low complication rates, reduced procedure time, and shorter hospital stay. Many endoscopic treatments are available including the endoscopic stapled esophago-diverticulostomy (ESD). Many data regarding ESD are available on the short-term outcomes, but few on the long-term ones. MATERIALS AND METHODS: From March 1998 to July 2016, 126 patients with ZD were candidate for ESD. Since 2009, 2 stay sutures were routinely positioned at the lateral edges of the septum using Medtronic Endostitch 10 mm suturing device. Demographic and perioperative data, symptoms, and surgical outcomes were recorded. Long-term ESD results were analyzed. An extra-analysis on the surgical outcome was performed comparing patients treated with or without stay sutures. RESULTS: In total, 117 patients successfully underwent ESD. The mean age was 69.9 years with a male predominance. Intraoperative complications occurred in 6.8% of cases. Only 2.6% of the patients reported postoperative complications. For the long-term analysis, we were able to contact 92 patients for a mean period follow-up of 65.3 months. At 6-month outpatient visit 77.68% of patients were completely asymptomatic. In total, 22.3% of the patients needed an extratreatment due to incomplete section of the septum, reaching a success rate of 95.5%. The long-term resolution rate remained high (91.3%). The use of stay sutures did not statistically influence the operative time (22.8 vs. 26.7 min, P=0.070), nor intraoperative and postoperative complication rate, but a statistically significant higher complete resolution rate of symptoms with a single session of ESD was observed respect those treated without (87.3% vs. 65.3%, respectively). CONCLUSIONS: ESD is a safe and effective treatment of ZD and it can control symptoms even in a long-term follow-up. In our experience, the use of stay sutures placed with Endostitch increases short and long-term results reducing the need for further treatments.

Inappropriateness of diagnostic imaging examinations in the inpatient setting: a case study research.

OBJECTIVE: The purpose of our study was to audit the clinical appropriateness of the prescriptions of whole body CT (WB-CT), PET-CT and chest X-rays (CXRs) performed at Tor Vergata University Hospital in the inpatient setting. MATERIALS AND METHODS: WB-CT, PET-CT and CXRs examinations were retrospectively analysed in the period between January and December 2014. CXR examinations were divided into bedside CXRs and traditional CXRs. The appropriateness of the examinations was defined according the American College of Radiology Appropriateness Criteria. Inappropriate examinations were divided into six inappropriateness categories in accordance with the European Union Medical Imaging Guidelines. RESULTS: Appropriateness was suboptimal for all analysed techniques CXRs (A = 38%, I = 62%); bedside CXRs (A = 45%, I = 53%); WB-CT (A = 45%, I = 55%); PET-CT (A = 48%, I = 52%). With respect to WB-CT the highest rate of inappropriate imaging prescriptions came from the haematology clinical operative unit (OU) (44%) and emergency medicine (33%); with respect to PET-CT, the thoracic surgery OU (53%) and haematology OU (48%) showed the most inappropriate prescriptions. For CXRs, the percentage of inappropriateness was consistently distributed among all surgical OUs. For bedside CXRs, the largest inappropriate prescribers were the emergency medicine OU (48%), the cardiac surgery OU (58%), the intensive care OU (67%) and anaesthesia resuscitation OU (78%). The most represented classes of inappropriateness were 2, 3, 4 and 6. CONCLUSIONS: The elimination of inappropriate prescriptions would result in an annual savings of approximately 390,000 Euro. An implementation plan to increase prescription appropriateness is under development by our group.

Synovial fluid from patients with rheumatoid arthritis modulates monocyte cell-surface phenotype.

OBJECTIVES: To investigate the ability of synovial fluid from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) to modulate cell-surface phenotype, function and viability of monocytes. METHODS: Monocytes from healthy donors were incubated with synovial fluid from patients with RA or OA. These were then cultured with autologous healthy CD4+ T-cells. Immunoglobulin-like transcript 4 (ILT4) and CD86 were evaluated on stimulated monocytes and CD4+ T-cells via fluorescence activated cell sorting. RESULTS: Monocytes incubated with synovial fluid from patients with RA (SF-RA; n = 12) had significantly lower ILT4 and higher CD86 levels than those incubated with synovial fluid from patients with OA (SF-OA; n = 12) or medium alone. In patients with RA, there was a significant negative correlation between ILT4 and disease activity score (DAS; r = -0.699), and a positive correlation between CD86 and DAS (r = 0.626). T-cells costimulated with monocytes cultured with SF-RA produced significantly more interferon-γ and tumour necrosis factor-α than those costimulated with monocytes cultured with SF-OA or controls. CONCLUSIONS: Soluble mediators in SF-RA could contribute to modulating inflammation and local effectiveness of the immune response.

Expression of immunoglobulin-like transcript 4 as an inhibitory receptor in patients with psoriatic arthritis.

OBJECTIVES: To investigate the presence of immunoglobulin-like transcript (ILT)4 and costimulatory proteins (CD40, CD80 and CD86), as well as tumour necrosis factor (TNF)-α production in antigen-presenting cells (APCs) from patients with psoriatic arthritis, before and after treatment with the antitumour necrosis factor-α therapy, adalimumab. METHODS: Peripheral blood monocytes from patients with psoriatic arthritis and healthy controls were cultured with CD40 ligand (CD40L) to stimulate differentiation to APCs. Cell-surface phenotype was analysed via fluorescence-activated cell sorting. RESULTS: CD40L-stimulation resulted in significantly more ILT4+ monocytes in cultures from control subjects (n = 21) than those from patients (n = 20). ILT4-positivity on CD40L-stimulated monocytes was negatively correlated with disease activity in patients. Adalimumab treatment resulted in significant increases from baseline in ILT4-positivity, and in decreases in CD40, CD80 and CD86-positivity in monocytes from patients. CONCLUSION: The effect of adalimumab on monocyte surface phenotype may be due to modification of the inflammatory milieu associated with therapy-induced reduction of disease activity in psoriatic arthritis.