Anti-inflammatory Treatment In Patients Research Articles

Synthesis and evaluation of TSPO-targeting radioligand [18F]F-TFQC for PET neuroimaging in epileptic rats

The translocator protein (TSPO) positron emission tomography (PET) can noninvasively detect neuroinflammation associated with epileptogenesis and epilepsy. This study explored the role of the TSPO-targeting radioligand [18F]F-TFQC, an m-trifluoromethyl ER176 analog, in the PET neuroimaging of epileptic rats. Initially, [18F]F-TFQC was synthesized with a radiochemical yield of 8%–10% (EOS), a radiochemical purity of over 99%, and a specific activity of 38.21 ± 1.73 MBq/nmol (EOS). After determining that [18F]F-TFQC exhibited good biochemical properties, [18F]F-TFQC PET neuroimaging was performed in epileptic rats at multiple time points in various stages of disease progression. PET imaging showed specific [18F]F-TFQC uptake in the right hippocampus (KA-injected site, i.e., epileptogenic zone), which was most pronounced at 1 week (T/NT 1.63 ± 0.21) and 1 month (T/NT 1.66 ± 0.20). The PET results were further validated using autoradiography and pathological analysis. Thus, [18F]F-TFQC can reflect the TSPO levels and localize the epileptogenic zone, thereby offering the potential for monitoring neuroinflammation and guiding anti-inflammatory treatment in patients with epilepsy.

Cartilaginous glycoprotein‑39 as laboratory marker of dynamics of course and effectiveness of treatment in patients with osteoarthritis

Backgrounds. Osteoarthritis (OA) occupies the first rank among diseases of the musculoskeletal system and accounts for 18.4% of the structure of this pathology. Currently, OA is considered as a disease in which there is a violation of the processes of remodeling (degradation and synthesis) of cartilage tissues, subchondral bone, joint capsule, tendon-ligamentous and muscular apparatus. An increased concentration of cartilage glycoprotein-39 (CGP-39) in the circulation is associated with inflammatory diseases and the processes of active tissue restructuring. To date, CGP-39 is a marker of chondrocyte activation and a sign of progressive OA, which determines its clinical significance. Along with this, the role of this biomarker in evaluating the effectiveness of anti-inflammatory therapy is relevant.The purpose. Comparative assessment of the quantitative content of CGP-39 in patients with knee joint OA, depending on the severity of inflammatory changes in the joints, the dynamics of the disease and the effectiveness of therapy.Methods. The study included 36 patients with OA and 30 practically healthy volunteers, identical in gender and age to the examined patients. The mean age of patients was 64 years, the average duration of the disease was 6 years. The diagnosis was determined according to the diagnostic criteria of the American College of Rheumatology (ACR, 1991). Along with the generally accepted clinical, laboratory and instrumental diagnosis of OA, in all patients and in control persons the levels of circulating CGP-39 were measured by enzyme immunoassay (ELISA). All examined patients received Ambene® Bio for 20 days, followed by repeated determination of the level of CGP-39. For statistical processing of the obtained data, we have used the programs Microsoft Excel 2007 and Statistica 10.0. Using the application program KRelRisk 1.1, the relative risk indicator for the studied factor was determined.Results. In the blood of patients with OA, a significant increase in the levels of CGP-39 has been found in comparison with the group of healthy individuals, which indicates increased degradation of articular cartilage in OA. As the severity of knee OA increased, the concentration of CGP-39 in the blood serum significantly raised, including in comparison with the control group. Reliable direct correlations were found between CGP-39 and clinical indices of knee OA severity. The content of CGP-39 in serum in patients with stage III radiological OA was significantly higher than in patients with stage I–II. The highest level of CGP-39 in patients with OA is associated with the presence of synovitis. TThe level of CGP-39 significantly decreased in patients with knee OA after a course of Ambene® Bio therapy, which confirms the participation of CGP-39 in inflammation on the one hand and the possibility of its use as an indicator of the effectiveness of anti-inflammatory therapy on the other hand.Conclusions. CGP-39 as a marker of inflammation and degradation of articular cartilage reflects the severity of the course of OA. The investigation of this biomarker is useful not only for diagnostic purposes, but also to assess the response to anti-inflammatory treatment in patients with knee OA.

Study of the clinical complex efficacy of natural cytokines and antimicrobial peptides in the treatment of patients with inflammatory periodontal diseases

The aim of the work was to determine the anti-inflammatory effectiveness of the use of a complex of natural cytokines and antimicrobial peptides (Superlimf) in the treatment of patients with mild chronic generalized periodontitis.
 Materials and methods: 60 patients were randomized into 2 equal groups. Patients of both groups were removed dental deposits using the Piezon-Master-400 ultrasound machine and the surfaces of the roots of the teeth were polished using periodontal bores (SRP — Scaling, Root Planning), taught the rules of oral hygiene with subsequent three-time control. Resorbable plates of the Superlimf preparation were additionally applied to the gum in the patients of the main group. To assess the intensity of inflammation in periodontal tissues, the clinical indices of Muhlemann and PMA were used.
 Results: The dynamics of the clinical indices of Mulleman and PMA before treatment, 7 days later and 21 days after treatment showed a statistically significant more pronounced anti-inflammatory effect in patients in the main group who were treated with Superlimf in addition to SPR.
 Conclusions: Local use of the drug Superlimf in combination with SRP increases the effect of anti-inflammatory treatment of patients with mild chronic generalized periodontitis.

The Impact of Aspiration and Corticosteroid Injection after ACL Injury on Post-Reconstruction Infection Rate (161)

Objectives:Knee injections of bioactive substances, including corticosteroids, hyaluronic acid, and platelet-rich-plasma, are very common in orthopaedic practice. Recently, injecting a corticosteroid into the knee after an anterior cruciate ligament (ACL) injury has been shown in a pilot randomized controlled trial to mitigate articular cartilage damage from the pro-inflammatory effects of the hemearthrosis.1 It is imperative to know if injecting a corticosteroid after ACL tear increases the risk of infection after ACL reconstruction (ACLR). The objective of this study is to report the infection rate in a retrospective cohort of primary bone-tendon-bone (BTB) ACLR patients of one fellowship-trained sports medicine orthopaedic surgeon’s practice where post-injury aspiration and corticosteroid injection occurred prior to ACLR. 1. Lattermann, C. et al. A Multicenter Study of Early Anti-inflammatory Treatment in Patients With Acute Anterior Cruciate Ligament Tear. The American Journal of Sports Medicine 45, 325–333 (2017).Methods:All patients from the ages of 10-65 who underwent primary BTB autograft ACLR by one fellowship-trained sports medicine orthopaedic surgeon between 1/1/2011 and 3/1/2019 at two institutions were reviewed. The variables reviewed were if there was a postoperative infection (as defined by undergoing an intra-articular irrigation and debridement reoperation), if there were any positive cultures, and the medications of the post-injury intra-articular injection (corticosteroid).The time between the following events was also recorded: initial injury and initial presentation, initial injury and corticosteroid injection, injection and ACLR, and ACLR and last date of follow-up. Statistical analysis determined the upper 95% confidence bound for infection probability for the three main groups of the study: the entire cohort, the cohort who underwent post-injury preoperative aspiration and injection, and the cohort who did not undergo aspiration and injection. This statistical approach was taken to determine with 95% confidence the upper limit of what the infection risk would likely be in each group.Results:There were 518 primary BTB ACLR performed with follow-up on 79% (410/518). 174 were found to have undergone a post-injury aspiration and injection, leaving 236 who did not. There were no infections (washout reoperations or positive cultures) in the entire 410 case group. The upper 95% confidence bound for the probability of a postoperative infection is shown in three left columns in table 1 was 0.7% for the whole cohort (n= 410), 1.7% for the cohort who underwent aspiration and injection (n=174), and 1.3% for the cohort that did not (n= 236). Table 1 compares our study to the ACLR infection rate from MOON ADDIN ZOTERO_ITEM CSL_CITATION{"citationID":"XkJTnLOw","properties":{"formattedCitation":"\\\\super2\\\ osupersub{}","plainCitation":"2","noteIndex":0},"citationItems":[{"id":2186,"uris":["http://zotero.org/users/2554704/items/N87NRZ9H"],"uri":["http://zotero.org/users/2554704/items/N87NRZ9H"],"itemData":{"id":2186,"type":"article-journal","container-title":"TheJournal of Bone and Joint Surgery","DOI":"10.2106/JBJS.N.00694","ISSN":"0021-9355","issue":"6","language":"en","page":"450-454","source":"Crossref","title":"FactorsAssociated with Infection Following Anterior Cruciate LigamentReconstruction:","title-short":"Factors Associated withInfection Following Anterior Cruciate Ligament Reconstruction","volume":"97","author":[{"family":"Brophy","given":"RobertH."},{"family":"Wright","given":"RickW."},{"family":"Huston","given":"LauraJ."},{"family":"Nwosu","given":"SamuelK."},{"family":"Spindler","given":"KurtP."},{"family":"Kaeding","given":"ChristopherC."},{"family":"Parker","given":"RichardD."},{"family":"Andrish","given":"JackT."},{"family":"Marx","given":"RobertG."},{"family":"Amendola","given":"Annunziato"},{"family":"Wolf","given":"BrianR."},{"family":"McCarty","given":"EricC."},{"family":"Dunn","given":"WarrenR."}],"issued":{"date-parts":[["2015",3]]}}}],"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}2 . The infection rate for the entire MOON cohort is 0.8% (allograft and autograft), the BTB autograft is 0.3%, and the hamstring autograft is1.3%. In our injection group, the mean time between injury and aspiration and injection was 7.6 days. The mean time elapsed between the date of aspiration and injection and the surgical date was 48.9 days. 2. Brophy, R. H. et al. Factors Associated with Infection Following Anterior Cruciate Ligament Reconstruction: The Journal of Bone and Joint Surgery 97, 450–454 (2015).Conclusions:Our data show that aspiration and injection with corticosteroids following ACL injury does not greatly increase post-operative infection risk. This can be observed when comparing the MOON BTB published rate of 0.3% to the upper limit of infection in our entire cohort, which is 0.7% (see Table 1). The difference in upper 95% confidence limits among our three groups is the result of sample size for each cohort. Even in the worst-case scenario for the preoperative injection group, which has the smallest sample size of 174, the upper 95% CI is 1.7%. This is only 1% higher than the confidence bound calculated for the entire MOON cohort (0.7%). When comparing this finding with the MOON autograft hamstring graft infection rate (1.3%) compared to the BTB infection rate (0.3%), the known 1% difference does not alter practice. The results of this study support a very minimal risk of postoperative infection after ACLR with or without a post-injury aspiration and corticosteroid injection, at most potentially 1%.

Комплексное лечение увеита с макулярным отеком, ассоциированного с системными заболеваниями, с использованием аутологичной плазмы, обогащенной тромбоцитами

In patients with uveitis associated with systemic diseases, a common cause of low vision is macular edema, which develops at any localization of the inflammatory process in 38–84% of cases. Autologous platelet-rich plasma is widely used in various branches of medicine, however, in the treatment of uveitis accompanied by macular edema, the clinical efficacy of its use has not been sufficiently studied. Purpose. To conduct a clinical and laboratory assessment of the effectiveness of complex treatment of uveitis with macular edema associated with systemic diseases using autologous platelet-rich plasma. Material and methods. The study included 120 people (120 eyes) from 18 to 50 years old with uveitis and macular edema associated with systemic diseases: 51 men, 69 women. Patients were divided into 2 groups: the main group consisted of patients who received anti-inflammatory treatment and administration of autologous plasma platelet-rich; comparison group – patients who received anti-inflammatory treatment. All patients underwent a comprehensive ophthalmological examination. Results. It has been established that the administration of autologous platelet-rich plasma against the background of anti-inflammatory treatment in patients with uveitis associated with systemic diseases accompanied by macular edema improves the maximally corrected visual acuity, a statistically significant decrease in the thickness of the retina in the fovea and an increase in the light sensitivity of the retina, relative to the data obtained in the comparison group. Conclusion. The use of autologous platelet-rich plasma in combination with anti-inflammatory treatment leads to a decrease in the incidence of recurrence of uveitis associated with systemic diseases, helps to reduce macular edema and improve functional parameters. Key words: uveitis, macular edema, anti-inflammatory treatment, autologous platelet-rich plasma.

P411 Baseline Hypertrophy of the Submucosa at intestinal ultrasound predicts Failure of Treatment in patients with ulcerative colitis

Abstract Background Submucosal fibrosis in ulcerative colitis (UC) has been associated with disease severity in colectomy specimens. As intestinal ultrasound (IUS) visualizes all individual wall layers, we aimed to evaluate baseline IUS features to determine endoscopic response and investigate changes in wall layers during anti-inflammatory treatment in patients with UC Methods Moderate-severe UC patients (endoscopic Mayo score (EMS)≥2) extending beyond the rectum starting treatment were included. Simple Clinical Colitis Activity Index (SCCAI), fecal calprotectin (FCP), IUS and endoscopy were performed at baseline and at follow-up between week 8 and 26. BWT, individual wall layer thickness (WT) (mucosa (MC), submucosa (SM) and muscularis propria (MP)) and ratios among layers, Colour Doppler Signal, loss of haustrations, loss of stratification and hyperechogenicity of the submucosa (HoS) (Figure 1) were scored for the sigmoid colon (SC). EMS was assessed for the SC: endoscopic remission (ER) was defined as EMS=0 and endoscopic improvement (EI) as EMS≤1. For statistical analysis a paired t-test and X2-test were used. Results 49 patients were included of whom 61% failed ≥1 biological. 59% started tofacitinib and 41% started a biological. At follow-up, 30% and 49% reached ER and EI, respectively. BWT decreased significantly when ER (2.32 ± 1.63 mm vs 1.00 ± 1.98 mm, p=0.034) or EI (2.53 ± 1.66 mm vs 0.30 ± 1.58 mm, p<0.0001) was reached. In patients with ER and EI, the SM thickness showed significantly more pronounced decrease compared to the other wall layers (Table 1 and Figure 2). Baseline presence of HoS (29% of patients) predicted failure of treatment (ER: OR: 0.10, 95% CI: 0.01-0.87, p=0.014, EI: OR: 0.16, 95% CI: 0.04-0.65, p=0.008,). Furthermore, when HoS was present, SCCAI (7.33 ± 3.62 vs 9.75 ± 3.23, p=0.023) and FCP (1249 ± 903 µg/g vs 2494 ± 2277 µg/g, p=0.008) were significantly lower at baseline. Also, patients with HoS more frequently failed one (OR: 4.44, 95% CI: 1.08-18.32, p=0.03) or multiple biologicals (OR: 5.63, 95% CI: 1.54-20.52, p=0.009). However, disease duration (p=0.950) or age at onset (p=0.853) did not differ between groups. Conclusion This is the first study showing that HoS on IUS is a predictor of endoscopic non-response to biologicals and tofacitinib in patients with UC. Additionally, changes in SM layer thickness is the most important component of the total bowel wall when evaluating mucosal healing on IUS.

Application of Magnetic Resonance Imaging in the Evaluation of Disease Activity in Graves’ Ophthalmopathy

ObjectiveTo evaluate magnetic resonance imaging parameters, T2 signal intensity ratios (SIRs), and normalized apparent diffusion coefficients (n-ADC) of the extraocular muscles (EOMs) in the identification of different stages of Graves’ ophthalmopathy (GO) and to find out the correlation of T2-SIRs and n-ADC values with disease changes after anti-inflammatory treatment. MethodsAltogether, 43 patients (86 orbits) were enrolled and classified into “active” or “inactive” stages by clinical activity score (CAS). Twenty-three (53.5%) patients received anti-inflammatory treatment and underwent a follow-up evaluation. Fifteen age- and gender-matched control participants (30 orbits) were included. T2-SIRs and n-ADC values of EOMs were calculated among GO and healthy controls and were correlated with CAS. Changes in these parameters were also evaluated before and after anti-inflammatory treatment. ResultsMean T2-SIRs and n-ADC values were both significantly higher in GO patients than in controls and higher in active GO than in inactive GO. In the inactive stage, n-ADC values of inferior rectus muscles were still higher than those in healthy controls. Both T2-SIRs and n-ADC values decreased after intravenous steroid pulse therapy. The cutoff value of pretreatment n-ADC was 1.780 to detect stages with specificity of 93.7% and sensitivity of 48.3% (P = .035). ConclusionT2-SIRs and n-ADC values are valuable magnetic resonance imaging indicators of the inflammatory activity in GO by detecting involvement of EOMs. They are also ideal tools to monitor the efficacy of anti-inflammatory treatment in patients with active stage GO. n-ADC values, when combined with CAS, can be promising predictive factors in the detection of stages of diseases.

Conjunctival microvascular responses to anti-inflammatory treatment in patients with dry eye

PurposeThis study characterized conjunctival microvascular morphological and haemodynamic responses after anti-inflammatory treatment in dry eye (DE). Materials and methodsTwenty-five patients with moderate DE (17 females and 8 males aged 48 ± 16 years) who underwent anti-inflammatory therapy (0.1% fluorometholone) and 25 healthy subjects (20 females and 5 males aged 48 ± 17 years) recruited as controls were enrolled. The conjunctival blood flow rate (BFR), blood flow velocity (BFV) and vessel diameter were measured by functional slit-lamp biomicroscopy (FSLB). DE symptoms and signs were assessed. All measurements were performed at baseline and at 30 and 60 days after commencement of treatment. ResultsAt baseline, the conjunctival BFR, BFV, and vessel diameter were higher in the DE group than in the control group (p < 0.05). The BFR, BFV and corneal fluorescein staining (CFS) scores decreased at 60 days after therapy compared to at baseline and 30 days (all pcorrected < 0.05); Ocular surface diseases index (OSDI), the hyperaemia index (HI) and vessel diameters only showed significant decreases at 30 days. Moreover, significant increases in the noninvasive tear film break-up time (NI-BUT) and Schirmer I test score (ST) were observed. The CFS score correlated positively with BFV (r = 0.46), BFR (r = 0.58) and vessel diameter (r = 0.47). ConclusionThis study characterized conjunctival microvascular responses to anti-inflammatory treatment in DE patients. The results suggest that conjunctival BFV and BFR can be used as dynamic markers for treatment efficacy in DE.

An Open-label Study With Pirfenidone on Chronic Hypersensitivity Pneumonitis

BackgroundChronic hypersensitivity pneumonitis (cHP) represents a severe lung disease often evolving to fibrosis with the subsequent destruction of the lung parenchyma. There are no approved therapies with confirmed efficacy to deal with this disease. MethodsWe performed an open-label, proof of concept study, to evaluate the efficacy and safety of pirfenidone added to immunosuppressive drugs on the treatment of cHP. We included 22 patients assigned to two groups: Group 1, nine patients that received prednisone plus azathioprine and Group 2, thirteen patients, received prednisone plus azathioprine and pirfenidone (ClinicalTrials.gov identifier NCT02496182). There were no significant imbalances in clinically relevant baseline characteristics between two study groups. ResultsAfter 1 year of treatment, inclusion of pirfenidone was not associated with improved forced vital capacity (primary end-point). A not significant tendency to show higher improvement of diffusion capacity of the lung for carbon monoxide (DLCO) was observed in the group receiving pirfenidone (p=0.06). Likewise, a significant improvement in the total score on the SGRQ was found in the group 2 (p=0.02) without differences in other two questionnaires related to quality of life (ATAQ-IPF and EQ-5D-3L). HRCT showed a decrease of the ground glass attenuation without changes in the fibrotic lesions and without differences between both groups. ConclusionsThese findings suggest that the addition of pirfenidone to the anti-inflammatory treatment in patients with chronic HP may improve the outcome with acceptable safety profile. However, prospective randomized double-blind, placebo-controlled trials in largest cohorts are needed to validate its efficacy.

An Open-label Study With Pirfenidone on Chronic Hypersensitivity Pneumonitis

BackgroundChronic hypersensitivity pneumonitis (cHP) represents a severe lung disease often evolving to fibrosis with the subsequent destruction of the lung parenchyma. There are no approved therapies with confirmed efficacy to deal with this disease. MethodsWe performed an open-label, proof of concept study, to evaluate the efficacy and safety of pirfenidone added to immunosuppressive drugs on the treatment of cHP. We included 22 patients assigned to two groups: Group 1, nine patients that received prednisone plus azathioprine and Group 2, thirteen patients, received prednisone plus azathioprine and pirfenidone (ClinicalTrials.gov identifier NCT02496182). There were no significant imbalances in clinically relevant baseline characteristics between two study groups. ResultsAfter 1 year of treatment, inclusion of pirfenidone was not associated with improved forced vital capacity (primary end-point). A not significant tendency to show higher improvement of diffusion capacity of the lung for carbon monoxide (DLCO) was observed in the group receiving pirfenidone (p=0.06). Likewise, a significant improvement in the total score on the SGRQ was found in the group 2 (p=0.02) without differences in other two questionnaires related to quality of life (ATAQ-IPF and EQ-5D-3L). HRCT showed a decrease of the ground glass attenuation without changes in the fibrotic lesions and without differences between both groups. ConclusionsThese findings suggest that the addition of pirfenidone to the anti-inflammatory treatment in patients with chronic HP may improve the outcome with acceptable safety profile. However, prospective randomized double-blind, placebo-controlled trials in largest cohorts are needed to validate its efficacy.

Microglial cell activation and senescence are characteristic of the pathology FXTAS.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with premutation alleles of the FMR1 gene. Expansions of more than 200 CGG repeats give rise to fragile X syndrome, the most common inherited form of cognitive impairment. Fragile X-associated tremor/ataxia syndrome is characterized by cerebellar tremor and ataxia, and the presence of ubiquitin-positive inclusions in neurons and astrocytes. It has been previously suggested that fragile X-associated tremor/ataxia syndrome is associated with an inflammatory state based on signs of oxidative stress-mediated damage and iron deposition. Determine whether the pathology of fragile X-associated tremor/ataxia syndrome involves microglial activation and an inflammatory state. Using ionized calcium binding adaptor molecule 1 and cluster differentiation 68 antibodies to label microglia, we examined the number and state of activation of microglial cells in the putamen of 13 fragile X-associated tremor/ataxia syndrome and 9 control postmortem cases. Nearly half of fragile X-associated tremor/ataxia syndrome cases (6 of 13) presented with dystrophic senescent microglial cells. In the remaining fragile X-associated tremor/ataxia syndrome cases (7 of 13), the number of microglial cells and their activation state were increased compared to controls. The presence of senescent microglial cells in half of fragile X-associated tremor/ataxia syndrome cases suggests that this indicator could be used, together with the presence of intranuclear inclusions and the presence of iron deposits, as a biomarker to aid in the postmortem diagnosis of fragile X-associated tremor/ataxia syndrome. An increased number and activation indicate that microglial cells play a role in the inflammatory state present in the fragile X-associated tremor/ataxia syndrome brain. Anti-inflammatory treatment of patients with fragile X-associated tremor/ataxia syndrome may be indicated to slow neurodegeneration. © 2018 International Parkinson and Movement Disorder Society.

Clinical activity is an independent risk factor of ischemic heart and cerebrovascular arterial disease in patients with inflammatory bowel disease.

Background and aimsIn inflammatory bowel disease (IBD), the impact of established cardiovascular risk factors and disease-related factors on the risk of acute arterial events is still unclear. We aimed to identify risk factors of acute arterial events in patients with IBD.MethodsAll consecutive patients followed at Saint-Antoine Hospital between 1996 and 2015 with subsequent occurrence of acute arterial events (acute coronary syndrome or ischemic stroke) were identified. Traditional cardiovascular risk factors, treatment exposure, systemic inflammation (mean serum CRP level greater than or equal to 5 mg/L) and IBD clinical activity were assessed. A nested case-control study was performed including cases and controls without arterial ischemic event, matched on age, gender, and disease extent.ResultsA total of 30 patients (median age at acute vascular event occurrence: 42 years (interquartile range: 25–59)) developed acute coronary syndrome (n = 22) or ischemic stroke (n = 8). In univariate analysis, clinical disease activity and the persistence of systemic inflammation, diabetes, dyslipidemia and hypertension were significantly associated with an increased risk of acute arterial events. Neither protective nor aggravating effects associated with treatment exposure were identified. In multivariate analysis, the presence of diabetes (Odds ratio (OR): 14.5, 95% confidence interval (CI): 1.1–184.7) and clinical disease activity (OR: 10.4, 95% CI: 2.1–49.9) remained significantly associated with the risk of acute arterial event.ConclusionDisease activity may have an independent impact on the risk of acute arterial events in patients with IBD. These findings may highlight new potential benefits of optimizing anti-inflammatory treatment in patients with persisting clinical activity.

Diffusion-weighted magnetic resonance enterography for prediction of response to tumor necrosis factor inhibitors in stricturing Crohn's disease.

Distinguishing between fibrotic and inflammatory strictures in Crohn's disease (CD) is still challenging. The capacity of diffusion-weighted (DWI) magnetic resonance (MRE) to identify intestinal fibrosis was recently demonstrated; however, the therapeutic implications of this association have never been evaluated. The aim of the current study was to identify imaging features, including DWI, which can predict response to anti-inflammatory treatment in patients with stricturing CD. Consecutive CD patients with intestinal strictures that initiated treatment with anti-tumor necrosis alpha (anti-TNF) between June 2012 and April 2017 with MRE adjacent to treatment onset were retrospectively collected. The primary outcome was treatment failure, defined as drug discontinuation, CD-related surgery, or endoscopic dilatation of the stricture. Clinical, demographic, and imaging data were compared between patients who did and did not develop treatment failure within 12 months of anti-TNF treatment initiation. A total of 21 patients were included in the study; 9/21 (42.8%) developed treatment failure. None of the clinical/demographic parameters were associated with the risk of treatment failure. Among imaging parameters, only ADC value (< 1 × 10-3mm2/s) was significantly associated with the risk of treatment failure (AUC = 0.81, 66% vs. 0%, p = 0.015). Our results suggest that ADC value on DWI MRE may predict the risk of treatment failure in stricturing CD. If replicated in larger studies, these results may guide therapeutic decisions and suggest avoiding anti-TNF treatment.

P189 Diffusion-weighted magnetic resonance enterography for prediction of response to tumour necrosis factor inhibitors in stricturing Crohn’s disease

Patients with Crohn’s disease (CD) frequently develop intestinal strictures that are a major cause of surgical and endoscopic interventions. Predominantly fibrotic strictures are less likely to respond to anti-inflammatory therapy. None of the currently available diagnostic modalities can reliably distinguish between fibrotic and inflammatory strictures. The capacity of diffusion-weighted (DWI) magnetic resonance (MRE) to identify intestinal fibrosis was recently demonstrated; however the therapeutic implications of this association have never been evaluated. The aim of the current study was to identify the imaging factors associated with response to anti-inflammatory treatment in patients with stricturing CD. Consecutive CD patients with intestinal strictures that initiated treatment with anti-tumour necrosis alpha (anti-TNF) between June 2012 and April 2017 with MRE adjacent to treatment ONSET were retrospectively collected. Patients with previous intestinal surgery or active penetrating complications on index MRE were excluded. The primary outcome was treatment failure, defined as drug discontinuation, CD-related surgery or endoscopic dilatation of the stricture. Clinical, demographic and imaging parameters including stricture length, prestenotic dilatation diameter, presence of ulcers, apparent diffusion coefficient (ADC), relative contrast enhancement (RCE), magnetic resonance index of activity (MaRIA) and Clermont score were compared between patients who did and did not develop treatment failure within 12 months of anti-TNF treatment. A total of 21 patients were included in the study; 9/21 (42.8) developed treatment failure. None of the clinical and demographic variables were associated with the likelihood of treatment failure. Among imaging parameters, only ADC (<1 x 10–3 mm2/s) was significantly associated with the risk of treatment failure (66% vs. 0%, p = 0.015, OR-30.1 (95% CI −1.2–785, AUC = 0.81). Our results suggest that ADC value on DWI MRE can predict the risk of treatment failure in stricturing CD. If replicated in larger studies, these results may guide therapeutic decisions and suggest avoiding anti-TNF treatment in patients with intestinal strictures with ADC <1 × 10–3 mm2/s.

Predictive markers and prenatal management of isolated fetal complete atrioventricular block: A retrospective review at a single institution.

The study was conducted to determine an effective method for identifying patients at high risk of developing isolated complete atrioventricular block (CAVB) and to review the efficacy of prenatal anti-inflammatory treatment. Fourteen CAVB cases and 76 anti-Ro-positive cases without CAVB were included in the study. Anti-Ro/La titers by double immunodiffusion and the prevalence of anti-52 kDa/60 kDa-Ro/48 kDa-La by Western blotting were compared between anti-Ro-positive women with and without CAVB. Outcomes of anti-Ro-positive CAVB cases were compared based on active prenatal anti-inflammatory treatment (plasma exchange or transplacental betamethasone). We evaluated the outcomes of five pregnancies from three women who had an affected child and underwent prophylactic plasma exchange (PEX) during subsequent pregnancy. Ten out of 14 patients with CAVB were positive for anti-Ro. Anti-Ro titers were significantly higher in patients with CAVB (CAVB median 64; without CAVB median 16; P < 0.01). All cases with CAVB showed high titers of anti-Ro (≥ 32×), whereas only 42% of cases without CAVB showed high titers (≥ 32×) (P < 0.001). The survival rate at one year was 80% in anti-Ro-positive CAVB cases with active prenatal anti-inflammatory treatment, but only 40% in cases that did not receive treatment. Recurrence was not observed in cases treated with prophylactic PEX. An anti-Ro level of 32× could be the threshold value for CAVB development. Prenatal anti-inflammatory treatment in patients with CAVB and prophylactic PEX in patients who had an affected child may have the potential to improve pregnancy outcomes.

Anti-inflammatory treatment improves high-density lipoprotein function in rheumatoid arthritis

ObjectivePatients with rheumatoid arthritis (RA) are at increased cardiovascular risk. Recent studies suggest that high-density lipoprotein (HDL) may lose its protective vascular phenotype in inflammatory conditions. However, the effects of...

A Multicenter Study of Early Anti-inflammatory Treatment in Patients With Acute Anterior Cruciate Ligament Tear

Background: It is increasingly recognized that biochemical abnormalities of the joint precede radiographic abnormalities of posttraumatic osteoarthritis (PTOA) by as much as decades. A growing body of evidence strongly suggests that the progression from anterior cruciate ligament (ACL) injury to PTOA is multifactorial, involving the interplay between biomechanical disturbances and biochemical homeostasis of articular cartilage. Purpose: The purposes of this randomized study using an acute ACL injury model were to (1) evaluate the natural progression of inflammatory and chondrodegenerative biomarkers, (2) evaluate the relationship between subjective reports of pain and inflammatory and chondrodegenerative biomarkers, and (3) determine if postinjury arthrocentesis and corticosteroid injection offer the ability to alter this biochemical cascade. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 49 patients were randomized to 4 groups: group 1 (corticosteroid at 4 days after ACL injury, placebo injection of saline at 2 weeks), group 2 (placebo at 4 days after ACL injury, corticosteroid at 2 weeks), group 3 (corticosteroid at both time intervals), or a placebo group (saline injections at both time intervals). Patient-reported outcome measures and synovial biomarkers were collected at approximately 4 days, 11 days, and 5 weeks after injury. The change between the time points was assessed for all variables using Wilcoxon tests, and the relationship between changes in outcome scores and biomarkers were assessed by calculating Spearman ρ. Outcomes and biomarkers were also compared between the 4 groups using Kruskal-Wallis tests. Results: No adverse events or infections were observed in any study patients. With the exception of matrix metalloproteinase 1 (MMP-1) and tumor necrosis factor–inducible gene 6 (TSG-6), chondrodegenerative markers worsened over the first 5 weeks while all patient-reported outcomes improved during this time, regardless of treatment group. Patient-reported outcomes did not differ between patients receiving corticosteroid injections and the placebo group. However, increases in C-telopeptide of type II collagen (CTX-II), associated with collagen type II breakdown, were significantly greater in the placebo group (1.32 ± 1.10 ng/mL) than in either of the groups that received the corticosteroid injection within the first several days after injury (group 1: 0.23 ± 0.27 ng/mL [P = .01]; group 3: 0.19 ± 0.34 ng/mL [P = .01]). Conclusion: PTOA begins at the time of injury and results early on in dramatic matrix changes in the knee. However, it is encouraging that early intervention with an anti-inflammatory agent was able to affect biomarkers of chondral degeneration. Should early intervention lead to meaningful changes in either the onset or severity of symptomatic PTOA, the current treatment paradigm for patients with ACL injury may have to be restructured to include early aspiration and intra-articular intervention. Trial Registration: ClinicalTrials.gov identifier: NCT01692756.

Multicenter Orthopaedic Outcome Network Early Anti-inflammatory Treatment in Patients with Acute ACL Tear” (MOON-AAA) Clinical Trial

Objectives:We present the early results from the “Multicenter Orthopaedic Outcome Network Early Anti-inflammatory Treatment in Patients with Acute ACL Tear and Painful Effusions” (MOON-AAA) clinical trial (figure 1). This trial allows for a well controlled prospective cohort of patients with isolated ACL injury at risk for OA. We compared the effect of a single versus a repeated dosage of Kenalog within the first two weeks after ACL injury and its effect on chondral degradation in the first 4 weeks prior to surgical reconstruction of the ACL.Methods:49 patients with isolated ACL tears were enrolled. Knee joints were aspirated and patients received an injection with 40 mg Kenalog either within 4 days, 10 days, both time points or not at all (saline injection control). Serum, synovial fluid and urine were collected at 3 time points. Permutated block randomization, triple blinding, independent monitoring and standardized x-ray was performed to comply with GCP standards. Patient reported outcomes were collected at 6 time points up to 6 months post-ACL reconstruction(IKDC, KOOS and Marx activity level). A standardized synovial fluid biomarker panel was analyzed according to OARSI guidelines. Statistical analysis were performed using SAS mixed models analysis.Results:Serum analysis shows significant change after injury. Chondrodegradatory markers such as CTX-II, MMP-1 and MMP-3 as well as COMP indicate a progressive destruction of chondral matrix and collagen breakdown . There is a dramatic (250%) increase of CTX-II in the first 4 weeks. Matrix proteins such as MMP-1 and 3 as well as COMP show an initial increase and then a steep decline (see figure 1). Inflammatory markers (IL-1 alpha, IL-1beta, IRAP) show a decline from the time of injury. IL-1 alpha, however shows a dramatic uptake after week 2. This longitudinal data confirms a dramatic onset of early osteoarthritic biomarker profiles immediately after ACL injury as measured in synovial fluid.The administration of 40 mg of Kenalog significantly changes this dynamic. CTX-II shows a dramatic reduction and stays close to baseline levels over the course of 4 weeks pre-operatively. COMP and MMP-1 show a significantly lesser decline.There is no significant difference in the effect of Kenalog if given within 4 days of injury or within 2 weeks. There is a statistical trend indicating that a repeated dose of Kenalog may be more efficient in normalizing the biomarker levels. No AE’s, infections were observed. Two of 49 patients suffered a retear at 6 months upon return to activities.Conclusion:Our data show that posttraumatic osteoarthritis begins at the time of injury and results early on in dramatic matrix changes in the knee joint. An early intervention with an antiinflammatory agent, such as Kenalog, maybe be able to prevent some of these changes observed.We do not currently know if the early intervention results in meaningful clinical differences in overall outcome. Further follow-up will answer this question. However, it is encouraging that a simple early intervention is able to affect early chondral degeneration. Should the early intervention with Kenalog lead to meaningful changes in outcome at 2 or 6 years the current treatment paradigm for ACL injured patients may have to be changed.

Use of mesenchymal stem cells in the combination therapy of ulcerative colitis

To compare results of treatment in patients with moderate and severe ulcerative colitis (UC), receiving standart anti-inflammatory therapy (second group) and its combination with bone marrow-derived mesenchymal stromal cells (MSC) (first group). Complex therapy of UC acute flare-up, including MSC did not influence on reccurence frequency, remission duration and mean value of clinical and endoscopic activity indices during 1 year of follow-up: in 1 group UC flare-up occurred in 2 (16.7%) patients, in 2 group--in 3 patients (30%). RR was 0.3 (95% CI 0/08--1.36; p=0.2; x2=1.47). After 2 years of follow-up risk of UC exacerbation in 1 group was 3 times lower than in the 2 group (p=0.03). Mean duration of remission in the 1 group was 22 months, in the 2 group--17 months (p=0.049). After 3 years of follow-up remission duration in the 1 and 2 groups were 22 and 22 months, respectively (p=0.66). Activity Index according to Rachmilevich in the 1 group was 4.75+/-1.13 points, in the 2--8.1+/-1.1 points (p=0.001). MSC application increases efficacy of anti-inflammatory treatment in patients with acute exacerbation of UC.

Repeat revascularisation outcomes after percutaneous coronary intervention in patients with rheumatoid arthritis

ObjectiveTo investigate repeat revascularisation outcomes in patients with rheumatoid arthritis(RA) after percutaneous coronary intervention (PCI).MethodsWe performed a single-centre, retrospective matched cohort study of patients with RA matched to non-RA patients...