534 SIX-MONTH EFFICACY OF INTRA-ARTICULAR HYALURONIC ACID FOR CARPOMETACARPAL JOINT OSTEOARTHRITIS

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Long-term evaluation of infliximab in the treatment of persistently active juvenile idiopathic arthritis refractory to conventional therapy

Objectives: To evaluate, in long-term open label prospective study, infliximab as therapeutic choice for Juvenile Idiopathic Arthritis (JIA) non responsive to conventional therapy. Methods: We enrolled to treat with infliximab 78 JIA patients (66 females, 12 males): the mean age was 20.7±7.1 years (median 20.9, range 5.4-34.9); mean JIA duration was 13.6±7.6 years (median 13.5, range 0.4-31.4). Infliximab, at dose of 3-10 mg/kg/infusion added to weekly subcutaneous Methotrexate or other previous DMARDs, was administered by intravenous infusions at weeks 0, 2, 6 and every 8 weeks thereafter. Chest X-ray, Mantoux's test, electrocardiogram were performed at baseline; laboratory tests and clinical evaluation were performed at each infusion. Response was evaluated according to ACR improvement criteria. Results: Mean treatment period was 21.6 months±18.8 (median 14.7, range 1.4-72.4). Just after first infusion most of patients reported significant improvement in pain, fatigue, morning stiffness. Infliximab is still successfully administered to 23 patients (29.5%); 55 (70.5%) patients suspended because of: inefficacy (7), infusion reactions (17), adverse events (9), disease flare-up after a period of effectiveness on synovitis, pain, and morning stiffness (19), remission (2), lack of compliance to treatment (1). Infusion reactions, like dyspnea, flushing, chills, headache, hypotension, anxiety, throat oedema, were observed in 29 patients (34.5%). Anti-DNA antibodies were present in 7 patients (none developed Systemic Lupus Eritematous). Conclusions: Infliximab showed impressive effectiveness treating refractory JIA, although most of patients had to discontinue treatment because of disease flare-up or adverse events. Infliximab may represent a good therapeutic choice in patients non-responders to Methotrexate

Side effects of anti-TNFa therapy in juvenile idiopathic arthritis

Aim of the study: To report adverse events registered in our population affected by JIA and treated with anti-TNFαblockers. Methods: Ninety-five patients were enrolled to be treated with Etanercept, median age 14 years (range 4-34); median duration of therapy 12 months (range 1-40). 19 patients were als treated with MTX (median dose 12.5 mg/week).Fifty-six patients were enrolled to be treated with Infliximab associated with MTX (median dose of MTX 8.8mg/week),median age 23.2 years (range 7.8-34.9); median duration of therapy 20.1 months (range 1.4-60.4). All adverse events were divided in definitely, probably and possibly related to the biologic agent. Results: Side effects definitely related to Infliximab were the reactions to infusions and the Anti-dsDNA positivity. Side effects definitely related to Etanercept were severe headache and thrombocytopenia. Side effects probably correlated to both the biological agents were behavioural modifications and pain amplification syndrome. Probably correlated to the treatment with Etanercept was the onset of Crohn’s disease in 3 patients. Possibly correlated to the biological agents were the new onset or flare-up of Chronic Iridocyclitis and single cases of thyroideal cancer, hypoglossal nerve paralysis and a severe Cytomegalovirus pulmonary infection. No case of tuberculosis infection was registered during this study. Conclusions: Treatment with a TNFαantagonist seems to be associated with various adverse events. Some of them,like onset of Crohn’s disease, behavioural modifications are unusual and others, like pain amplification syndrome were never described before. Children and young adults affected by JIA should be monitored very carefully so as to limit as much as possible the risk of serious side effects on anti-TNFα therapy

Paroxysmal Nocturnal Hemoglobinuria (Pnh) : Brain Mri Ischemic Lesions in Neurologically Asymtomatic Patients

This study investigated for the first time brain ischemic involvement in 19 consecutive neurologically asymptomatic PNH patients by non-enhanced cerebral MRI, and by intracranial arterial and venous angio-MRI. Eleven cases (58%, 7 aged 5 mm, and 5 cases a score >4 by the age-related white matter changes (ARWMC) scale. Compared with age and sex-matched controls (1:2 ratio), patients showed an increased frequency of periventricular WM vascular degeneration (32% versus 5.2%, p = 0.04) and of severe lesions (ARWMC scale score >4) (26% versus 2.6%, p = 0.05), and a higher overall ARWMC scale score (3.5 \uc2\ub1 1.07 versus 2.0 \uc2\ub1 0.8, mean \uc2\ub1 SD, p < 0.0001). Notably, vascular abnormalities suspected for prior partial venous thrombosis, were observed in PNH cases only. MRI lesions were not related to blood counts, hemolytic markers, clone size, disease duration, and therapy with eculizumab. Neurological examination was unremarkable in all patients but one (Parkinson disease). Psychiatric assessment revealed a case of generalized anxiety disorder, 1 bipolar disorder type 2, and 1 adjustment disorder. In conclusion, brain MRI may be useful at diagnosis and during the course of the disease to explore subclinical neurological involvement

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Simultaneous ultrasonography and arthroscopy for the study of the joint environment: indications and limits

Arthroscopy is a mini-invasive technique that allows the direct observation of the joint cavity and the execution of diagnostic and therapeutic procedures; arthroscopy needs a very long learning-time curve as well as dedicated spaces and instruments. Ultrasonography is an imaging technique that enables to perform an immediate extension of the standard physical examination. The opportunity to visualize soft tissues, to obtain multiplanar and dynamic images in real time makes this practice easy repeatable at low costs. Ultrasonography allows to detect a variety of changes during inflammatory processes. The wide experience in arthroscopy of rheumatic patients acquired through the years by our team at the G. Pini Institute led us to study in vivo, during arthroscopy, the correspondence between arthroscopic and ultrasonographic images. Up to now three knee arthroscopies have been conducted with the double equipment (ultrasonographic and arthroscopic devices) in operating room. In our experience, the combination of the two methods in operating room may improve the validation of ultrasonography with arthroscopy as gold standard, helps to train the ultrasonographer to give immediate answers in order to clear the doubts aroused by ultrasonographic images; it also allows the arthroscopist to visualize the deeper layers of the synovial membrane making double guided targeted biopsies possible. Limits are the complexity of the procedure (instruments, operators, spaces, training of the doctors), the loose of power-doppler signal with the blood tourniquet and the always difficult evaluation of cartilage

Levels of chemerin and interleukin 8 in the synovial fluid of patients with inflammatory arthritides and osteoarthritis.

OBJECTIVES: Chemerin and interleukin (IL)-8 are pro-inflammatory mediators whose role in joint inflammation and cartilage degradation has been demonstrated in in-vitro findings. Studies on their presence in synovial fluid (SF) samples may offer further information on their pathogenic role. The aim of this study was to investigate SF chemerin and IL-8 levels in patients with different joint diseases. METHODS: 37 patients were enrolled: 18 with rheumatoid arthritis (RA), 8 with psoriatic arthritis (PsA) and 11 with osteoarthritis (OA). 41 SF samples were obtained by arthrocentesis in case of knee synovitis. Serum samples were obtained from 13 patients (4 with RA, 6 with PsA and 3 with OA) at the time of arthrocentesis. Chemerin, IL-8, TNF-α and IL-6 levels were measured using commercially available ELISA kits. Immunohistochemical analysis of synovial RA specimens was also performed. RESULTS: No difference in chemerin SF levels emerged between patients with immune-mediated inflammatory arthritides and those with OA (p=0.0656), while subjects with inflammatory arthritis displayed significantly higher levels of SF IL-8 compared to OA (p=0.0020). No significant difference emerged across the three conditions in the serum levels of both chemerin and IL-8. IL-8 strongly correlated with inflammatory markers as ESR, CRP, IL-6 and TNF-α. CONCLUSIONS: We observed similar chemerin SF and serum levels in the three conditions. Although flawed by some limitations, our findings support the emerging concept of OA as an inflammatory disorder. However the increased IL-8 levels we described in patients with inflammatory arthritis suggest a selective involvement of this pro-inflammatory and angiogenic cytokine in these conditions