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ID PMID Title PublicationDate abstract
30069226 Evaluation on Analgesic and Anti-Inflammatory Activities of Total Flavonoids from Juniperu 2018 The leaves of Juniperus sabina (Cupressaceae) are used in traditional Uygur medicine for the treatment of rheumatism and arthritic pain. This study aimed to investigate the analgesic and anti-inflammatory effects of total flavonoids from leaves of Juniperus sabina (JSTF) on rodents. The anti-inflammatory activity was investigated using the carrageenan, egg albumin, or histamine-induced rat paw edema as well as xylene-induced ear edema, capillary permeability, and cotton pellet granuloma while the antinociceptive activity was evaluated using the mouse writhing, formalin, and hot-plate tests. JSTF (125, 250, 500 mg/kg) significantly inhibited xylene-induced ear edema in mice (inhibition ratio as 16.22%, 40.67%, and 51.78%, respectively) and also significantly ameliorated acetic acid increased vascular permeability in mice (inhibition ratio as 11.63%, 32.56%, and 53.49%, respectively). JSTF (250 and 500 mg/kg) gave significant reduction of carrageenin-induced paw oedema at the interval of 1 h and 5 h. Administration of JSTF (500 mg/kg) caused a significant anti-inflammatory effect against oedema induced by egg albumin or histamine at the interval of 0.5 h and 4 h, and both which induced the paw oedema were also inhibited by JSTF (250 mg/kg) at a point in 1, 2, or 3 h after the inflammation. Furthermore, JSTF (125, 250, and 500 mg/kg) produced time-course increase in pain threshold in hot-plate test also. JSTF produced concentration-dependent inhibition on cyclooxygenase-2 (COX-2) or 5-lipoxygenase (5-LO) activities in vitro, and their IC(50) values were 31.92 and 129.26 μg/mL, respectively. Moreover, JSTF significantly caused a significant dose-dependent inhibition on acetic acid induced writhing response in mice (inhibition ratio as 23.27%, 36.91%, and 50.76%, respectively). JSTF also significantly ameliorated formalin-induced pain in mice in the late phase on dose-dependent way. These results confirms the clinical use of J. sabina for treatment of rheumatoid arthritis in ethnomedicine, and its effective mechanism will be further studied in the future.
30056876 Kidney Transplant Recipients With Rheumatic Diseases: Epidemiological Data From the Polish 2018 Jul Chronic kidney disease (CKD) is a common complication of rheumatic disorders. We analyzed the incidence of different rheumatic conditions as a primary diagnosis of end-stage renal disease (ESRD) in kidney transplant recipients in Poland. Data were received from the national waiting list for organ transplantation (Poltransplant) registries. Primary diagnosis leading to ESRD were analyzed in 15,984 patients who received kidney transplants between 1998 and 2015. There was no information about primary diagnosis in 4981 cases (31%) and in 1482 cases (9%) the diagnosis was described as unknown. Rheumatic diseases were specified in 566 (5.14%) kidney transplant recipients: lupus erythematosus, (systemic lupus erythematous nephritis) in 211 (1.92%), vasculitis in 176 (1.60%), amyloidosis AA in 82 (0.75%), hemolytic uremic syndrome in 59 (0.54%), secondary glomerulonephritis in 24 (0.22%), scleroderma in 9 (0.08%), rheumatoid arthritis in 4 (0.04%) and Sjögren syndrome in 1 (0.01%). Graft survival at 1 and 5 years were significantly better in the nonrheumatic versus rheumatic group (90 vs 87% and 76 vs 72% respectively, P = .04). Recipient survival at 5 years was significantly better in the nonrheumatic versus the rheumatic group (88 vs 84%, P = .02). Our study showed that systemic lupus erythematosus and systemic vasculitides are the major rheumatic causes of ESRD in the Polish population. Long-term graft and recipient survival were significantly better in the nonrheumatic versus the rheumatic group in the Poltransplant cohort.
30039255 A novel technique of cervical pedicle screw placement with a pilot screw under the guidanc 2018 Nov PURPOSE: The cervical pedicle screw (CPS) requires careful and accurate placement because of the critical risk for neurovascular injury. This study aimed to introduce and evaluate the safety and efficacy of a new CPS placement technique using intraoperative C-arm cone-beam CT (CBCT) and a pilot screw without navigation system. METHODS: This was a case-control study to compare the accuracy and safety of intraoperative C-arm CBCT-guided CPS placement with freehand CPS placement under lateral fluoroscopy using control data from a previous multicenter study. A total of 166 CPSs were inserted under intraoperative C-arm CBCT guidance in 48 consecutive patients (20 rheumatoid arthritis, 16 degenerative spinal disorders, 6 spinal tumor, 2 congenital deformity, 2 ossification of posterior longitudinal ligament, and 2 fracture dislocation). Accuracy and safety of CPS placement were assessed. RESULTS: The overall malposition rate was 2.4% (4 screws in grade 1: malposition by less than half-screw diameter, 0 in grade 2: malposition by more than half-screw diameter), which was significantly lower than the reported malposition rate of 14.8% in lateral fluoroscopy-guided freehand placement. There were no complications directly related to CPS insertion. The average estimated effective radiation dose per surgery was 14.7 mSv. CONCLUSIONS: The novel technique enables intraoperative adjustment of the trajectory of the CPS as well as confirmation of the CPS path before penetrating the isthmus of the pedicle, resulting in accurate and safe CPS placement, which outweighs the demerits of radiation exposure. These slides can be retrieved under Electronic Supplementary Material.
29774953 Dermoscopic patterns of filiform papillae of the tongue in patients with and without conne 2018 Aug BACKGROUND: Connective tissue autoimmune diseases (CTADs) constitute a group of conditions, including rheumatoid arthritis; systemic lupus erythematosus; mixed connective tissue disease; calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome; scleroderma; dermatomyositis; and Sjögren syndrome. There are few studies on the alterations in filiform papillae in CTAD. Thus, the objective of this work was to determine whether there are changes in the macroscopic and dermoscopic patterns of filiform papillae. METHODS: This case-control study included patients who were diagnosed with CTAD. The dependent variable was the dermoscopic pattern of filiform papillae of the tongue, and the independent variables were age, gender, time of evolution, and current treatment. A photograph of the back of the tongue was taken, and subsequently, the same site was examined by dermatoscopy. The microscopic and dermoscopic patterns of filiform papillae were classified (Maeda). RESULTS: We included 50 cases and 50 controls, 94% of whom were female. The mean age was 43.96 ± 14.65 years. Of the cases with CTAD, 25% presented with a normal macroscopic pattern, versus 36% (18) with pattern II, 12% (6) with pattern III, and 20% (10) with pattern IV. The dermoscopic pattern was type I in 23 cases (46%), type II in 16 (32%), type III in 10 (20%), and type IV in one patient (2%). CONCLUSIONS: We have noted alterations in filiform papillae in CTADs, which emphasizes the importance of a detailed intraoral exploration and the macroscopic and dermoscopic evaluation of the dorsum of the tongue, specifically the filiform papillae.
29607151 Lung cancer in connective tissue disease-associated interstitial lung disease: clinical fe 2018 Feb BACKGROUNDS: Lung cancer (LC) adversely impacts survival in patients with idiopathic pulmonary fibrosis. However, little is known about LC in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The aim of this study was to evaluate the prevalence of and risk factors for LC in CTD-ILD, and the clinical characteristics and survival of CTD-ILD patients with LC. METHODS: We conducted a single-center, retrospective review of patients with CTD-ILD from 2003 to 2016. Patients with pathologically diagnosed LC were identified. The prevalence, risk factors, and clinical features of LC and the impact of LC on CTD-ILD patient outcomes were observed. RESULTS: Of 266 patients with CTD-ILD, 24 (9.0%) had LC. CTD-ILD with LC was more likely in patients who were older, male, and smokers; had rheumatoid arthritis, a usual interstitial pneumonia pattern, emphysema on chest computed tomography scan, and lower diffusing capacity of the lung carbon monoxide (DLco)% predicted; and were not receiving immunosuppressive therapy. Multivariate analysis indicated that the presence of emphysema [odds ratio (OR), 8.473; 95% confidence interval (CI), 2.241-32.033] and nonuse of immunosuppressive therapy (OR, 8.111; 95% CI, 2.457-26.775) were independent risk factors for LC. CTD-ILD patients with LC had significantly worse survival than patients without LC (10-year survival rate: 28.5% vs. 81.8%, P<0.001). CONCLUSIONS: LC is associated with the presence of emphysema and nonuse of immunosuppressive therapy, and contributes to increased mortality in patients with CTD-ILD.
29526633 Association between allelic variants of the human glucocorticoid receptor gene and autoimm 2018 May INTRODUCTION: The human glucocorticoid receptor gene (NR3C1) is considered to play a role in the differences and sensitivities of the glucocorticoid response in individuals with autoimmune diseases. The objective of this study was to examine by means of a systematic review previous findings regarding allelic variants of NR3C1 in relation to the risk of developing systemic autoimmune diseases. METHODS: Studies that analysed the genotype distribution of NR3C1 allelic variants among patients with systemic autoimmune diseases were retrieved. A meta-analysis was conducted with a random effects model. Odds ratios (ORs) and their confidence intervals (CIs) were calculated. In addition, sub-analysis by ethnicity, sensitivity analysis and tests for heterogeneity of the results were performed. RESULTS: Eleven studies met the inclusion criteria for meta-analysis. We found no evidence that the analysed NR3C1 polymorphisms, rs6198, rs56149945, and rs6189/rs6190, modulate the risk of developing a systemic autoimmune disease. Nonetheless, a protective role for the minor allele of rs41423247 was found among Caucasians (OR=0.78; 95% CI: 0.65, 0.92; P=0.004). A subgroup analysis according to underlying diseases revealed no significant association either for Behçet's disease or rheumatoid arthritis, while correlations between NR3C1 polymorphisms and disease activity or response to glucocorticoids could not be evaluated due to insufficient data. CONCLUSIONS: There is no clear evidence that the analysed NR3C1 allelic variants confer a risk for developing systemic autoimmune diseases although the minor G allele of rs41423247 may be protective among Caucasians.
29086909 Acid-sensing ion channel 1a mediates acid-induced inhibition of matrix metabolism of rat a 2018 Jun The acid-sensing ion channel 1a (ASIC1a), which is activated by extracellular acid, contributes to the pathogenesis of rheumatoid arthritis. However, it remains unclear whether ASIC1a mediates acid-induced matrix metabolism in rat articular chondrocytes via activation of the MAPK signaling pathway. In the current study, we found that extracellular acidification (pH 6.0) inhibited proliferation and induced apoptosis of articular chondrocytes in a dose-dependent manner, while the expression of phosphorylated ERK1/2 and P38 MAPK increased, but, this effect was blocked by the Ca(2+) chelator BAPTA-AM and the ASIC1a-specific blocker PcTx-1. In addition, extracellular acidification increased the expression of c-fos, GAG, HYP, and TIM1/2. These effects were inhibited by the Ca(2+) chelator BAPTA-AM, ERK1/2 inhibitor PD98059, and ASIC1a-specific blocker PcTx-1, but not the P38 MAPK inhibitor SB203580. Finally, extracellular acidification increased the expression of c-jun and MMP-2/9, and these effects were blocked by the Ca(2+) chelator BAPTA-AM, P38 MAPK inhibitor SB203580, and ASIC1a-specific blocker PcTx-1, but not the ERK1/2 inhibitor PD98059. In conclusion, ASIC1a inhibits the expression of MMP-2/9, GAG, HYP, and TIMP-1/2 by the Ca(2+)-dependent P38 MAPK/c-jun and ERK/c-fos signaling pathways.
29770511 Liver enzyme abnormalities of inpatients with rheumatic diseases: A 10-year retrospective 2018 Sep Herbal medicines have been used as a treatment option for rheumatic disease (RD), but they often produce liver enzyme abnormality. This study examines the incidence of herb-induced liver injury (HILI) and the relationship between risk factors and liver enzyme abnormality (LEA) in inpatients with RD. HILI was analyzed using the Roussel Uclaf causality assessment method liver injury criteria and causality assessment. Multivariable analysis was performed to assess the relationship between patient characteristics and LEA in RD. The features of LEA were also examined in each RD. Among 352 patients included in this study, 105 patients showed LEA on admission, of which 6 had fulfilled the Roussel Uclaf causality assessment method criteria. The incidence risks of LEA and HILI were 12.55% and 0.58%, respectively. Multivariable analysis showed that LEA on admission and occasional use of alcohol could be risk factors for LEA on follow-up. In an additional analysis with each RD, all rheumatoid arthritis patients with LEA were taking nonsteroidal anti-inflammatory drugs, steroids, and disease-modifying antirheumatic drugs, and 4 out of 5 gout patients with LEA were taking steroids. The use of herbal medicine in RD is relatively safe. However, regular monitoring of liver enzyme tests and examination of alcohol consumption are required.
29164284 Uncommon observation of bifocal giant subchondral cysts in the hip: diagnostic role of CT 2018 Apr Subchondral cysts (or geodes) are common in osteoarthritis (OA), usually in association with other typical signs, i.e., joint space narrowing, subchondral bone sclerosis, and osteophytosis. However, large lesions without the typical signs of OA or lesions located outside the weight-bearing areas are unusual and may be confused for other conditions, in particular, those of tumoral origin. We report the findings in a 48-year-old man who had been complaining of left buttock pain for 3 years, getting worse over the last year, and an evolutive limited range of motion of the hip. The pain was increased by weight-bearing and was not relieved by nonsteroidal anti-inflammatory drugs. Radiographs and CT showed a large multilocular lytic lesion within the femoral head and a large lytic lesion in the left ilio-ischiatic ramus, raising the question of bifocal tumoral involvement. On MRI, the lesions had low signal intensity on T1- and high signal intensity on T2-weighted MR images, with subtle peripheral enhancement on post-contrast T1-weighted images. CT arthrography, by demonstrating a communication between the femoral head and ischiatic cysts and the joint space allowed us to definitively rule out malignant conditions and to make the diagnosis of subchondral bone cysts. Total hip arthroplasty was performed. Pathological analysis of the resected femoral head and of material obtained at curettage of the ischiatic lesion confirmed the diagnosis of degenerative geodes. This case illustrates an atypical bifocal location of giant subchondral cysts in the hip joint mimicking lytic tumors, in the absence of osteoarthritis or rheumatoid arthritis, and highlights the role of CT arthrography in identifying this condition.
29063666 Dimethyl fumarate inhibits osteoclasts via attenuation of reactive oxygen species signalli 2018 Feb Bone destructive diseases are common worldwide and are caused by dysregulation of osteoclast formation and activation. During osteoclastogenesis, reactive oxygen species (ROS) play a role in the intracellular signalling triggered by receptor activator of nuclear factor-κB ligand (RANKL) stimulation. Previously, we demonstrated that induction of antioxidant enzymes by Nrf2 activation using Nrf2-gene transfer, an ETGE-peptide or polyphenols, successfully ameliorated RANKL-dependent osteoclastogenesis. Dimethyl fumarate (DMF) has been shown to activate Nrf2 signalling and has been lately used in clinical trials for neurodegenerative diseases. In this study, we hypothesized that Nrf2 activation by DMF would inhibit osteoclastogenesis and bone destruction via attenuation of intracellular ROS signalling through antioxidant mechanisms. RAW 264.7 cells were used as osteoclast progenitor cells. We found that DMF induced Nrf2 translocation to the nucleus, augmented Nrf2 promoter-luciferase reporter activity and increased antioxidant enzyme expression. Using flow cytometry, we found that DMF attenuated RANKL-mediated intracellular ROS generation, which resulted in the inhibition of RANKL-mediated osteoclastogenesis. Local DMF injection into the calvaria of male BALB/c mice resulted in attenuated bone destruction in lipopolysaccharide-treated mice. In conclusion, we demonstrated in a preclinical setting that DMF inhibited RANKL-mediated osteoclastogenesis and bone destruction via induction of Nrf2-mediated transcription of antioxidant genes and consequent decrease in intracellular ROS levels. Our results suggest that DMF may be a promising inhibitor of bone destruction in diseases like periodontitis, rheumatoid arthritis and osteoporosis.
28589388 [Efficacy and safety analysis of off-label treatment with biologics in autoinflammatory di 2018 Feb OBJECTIVE: To evaluate the safety and efficacy of therapy with biologics in patients with autoinflammatory diseases (AIF) or macrophage activating syndrome (MAS) in a real-life setting in Germany. METHODS: The German Register of Autoimmune Diseases 2 (GRAID2) is a retrospective, non-interventional, multicenter registry collecting data from all patients with inflammatory rheumatic diseases refractory to conventional therapy and treated with initial off-label biologics between August 2006 and December 2013. Patients with MAS could be included without prior treatment with a biologic agent. RESULTS: Data from 26 patients with AIF and 5 with MAS were collected. Of the AIF patients 13 (50%) were diagnosed with adult onset Still's disease (AOSD), 6 (23%) with familial Mediterranean fever (FMF), 4 (15.4%) with tumor necrosis factor-associated periodic syndrome (TRAPS), 1 (3.8%) patient with cryopyrin-associated periodic syndrome (CAPS) and 2 (8%) with undifferentiated fever syndromes. The 5 MAS patients suffered from rheumatoid arthritis (RA) with chronic myeloid leukemia, systemic lupus erythematosus and in 2 cases AOSD. In 1 patient a chronic neurological disease was documented without further differentiaton. All patients with TRAPS were primarily treated with etanercept and all CAPS patients with canakinumab. The AOSD and FMF patients were treated with anakinra as the first line off-label biologic in 6 out of 13 and 5 out of 6 cases, respectively. The MAS patients responded very well or well to therapy in 40% and 60% had a moderate response. There were no non-responders. Within the group of AIF patients the physicians documented a very effective or effective treatment in 38.5%, a moderate response in 30.8% and no response in 30.7%. The tolerance was very good in 5 out of 5 of the MAS and in 92% of the AIF patients. CONCLUSION: The data of this retrospective register provide indications for an effective and safe treatment with off-label biologic medication in patients with AIF and MAS in daily practice.
31367290 The cost-effective, but forgotten, medical endometriosis therapy: a prospective, quasi-ran 2018 Dec Endometriosis represents nowadays a real burden for the patients as well as for the physicians, as it requires surgical and/or medical treatment, often long - termed and repeated. Moreover, the high costs necessary to diagnose and treat endometriosis represent a real economic burden, being comparable to other chronic diseases like diabetes or rheumatoid arthritis. Therefore, the physicians dealing with this disease should take into account not only the efficacy of the treatment, but also the economic aspects and patients compliance. The present paper analyses the efficiency of progestins (lynestrenol and medrogestone) in endometriosis as a cost - effective, but forgotten medical therapy of the disease. Our study underlines the good tolerability of progestins, as they have limited side effects, the compliance of patients being high. They are also low-cost medications, which could represent an effective alternative method in the endometriosis treatment, especially in less - developed countries that cannot afford the higher therapeutic costs.
30312932 Anti-inflammatory abietanes diterpenoids isolated from Tripterygium hypoglaucum. 2018 Dec Tripterygium hypoglaucum (H. Lév.) Hutch. has been used to remedy rheumatoid arthritis, however, it shows frequent toxicity to the body. In this study, liquid chromatograph-mass spectrometer (LC-MS) was guided to characterize abietanes diterpenoids with anti-inflammatory activity from the stem of T. hypoglaucum. Thirteen undescribed abietanes diterpenoids were isolated and purified, and their chemical structure was identified using various spectroscopic methods. These compounds belonged to abietanes with splitting C ring, abietanes with benzenoid rings, diterpene quinoids, diterpene quinoids with lactone rings, and abietanes with benzenoid and lactone rings, respectively. Lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages was used to evaluate anti-inflammatory activity of the compounds. The results indicated that hypoglicin B-G and hypoglicin J-M exhibited inhibitory activity of NO production with the IC(50) values of 6.01, 25.21, 8.29, 3.63, 0.72, 0.89, 36.91, 0.82, 2.85, 11.92 μM, respectively. Among these compounds, compound hypoglicin L showed high anti-inflammatory activity and low toxicity (SI = 5.02 × 10(4)). Further QPCR analysis revealed that hypoglicin D and hypoglicin L can inhibit the mRNA expression of iNOS in LPS-stimulated RAW264.7 cells at doses of 12.5 and 3.13 μM, respectively. Taken together, ten anti-inflammatory diterpenoids were found from T. hypoglaucum in this study.
30172209 Using plasma circRNA_002453 as a novel biomarker in the diagnosis of lupus nephritis. 2018 Sep This study aimed to determine the expression of circRNAs in plasma from lupus nephritis (LN) patients to identify novel biomarkers for LN screening. We initially performed microarray screening of circRNA changes in plasma from 5 L N patients, 5 systemic lupus erythematosus (SLE) patients without LN, and 5 healthy controls. We then confirmed the selected circRNA changes in plasma from 59 SLE patients (30 with LN and 29 without LN), 26 rheumatoid arthritis (RA) patients, and 27 age- and sex-matched controls using real-time quantitative reverse transcription-polymerase chain reaction. Spearman's correlation test was performed to assess the correlation of circRNAs and clinical variables. The receiver operating characteristic (ROC) curve was created to evaluate the diagnostic value. We confirmed that plasma circRNA_002453 was significantly elevated in LN patients when compared with SLE patients without LN, RA patients, and healthy controls. Plasma circRNA_002453 was also found to be upregulated in SLE patients when compared with RA patients and healthy controls. Among these LN patients, we detected no significant correlation between plasma circRNA_002453 and disease activity, including complement 3 (C3), complement 4 (C4), and SLE disease activity index 2000 (SLEDAI-2 K) score. However, its expression level was significantly and positively correlated with 24-hour proteinuria (r = 0.571, p = 0.001) and renal SLEDAI score (r = 0.640, p < 0.001). ROC analysis showed that plasma circRNA_002453 had an area under the curve of 0.906 (95% CI 0.838-0.974, p < 0.001) to discriminate LN patients from controls (SLE patients without LN, RA patients, and healthy controls) with sensitivity of 0.900 and specificity of 0.841. The highest Youden index was 0.741 and the corresponding optimal cut-off value was 0.001. This study suggests that upregulated plasma circRNA_002453 level in LN patients is associated with the severity of renal involvement and may also serve as a potential biomarker for LN patient diagnosis.
30146381 Increased risk of symptomatic progression of instability following decompression for lumba 2019 Jan BACKGROUND: Lumbar decompression surgery is a commonly used treatment for degenerative lumbar spinal stenosis; however, some patients develop symptomatic spinal instability following decompression surgery. The objective of this study was to reveal risk factors for delayed instability following decompression surgery for lumbar spinal stenosis. METHODS: One hundred ten patients who underwent single-level lumbar decompression between 2008 and 2014 were retrospectively reviewed. Surgical indication for decompression surgery was symptomatic lumbar canal stenosis without spondylolisthesis or with minimum spondylolisthesis (less than 4 mm translation). Patients with gross segmental motion (>10° in disc angle, >2 mm translation) on flexion-extension lumbar radiographs were excluded. Age, sex, body mass index, smoking history, diabetes mellitus, autoimmune connective tissue diseases including rheumatoid arthritis, and the use of glucocorticoids were investigated. Radiographic measurements included disc angle, disc height, slippage, facet angle, segmental motion (flexion-extension), lumbar alignment, facet effusion, and disc degeneration. Data were analyzed using multivariate forward selection stepwise logistic regression, chi-square tests, and Student t-test. RESULTS: Six of 110 patients (5.5%) developed symptomatic spinal instability at the operative level and underwent spinal fusion surgery at an average of 2.1 years postoperatively. Autoimmune connective tissue disorders and chronic use of glucocorticoids were associated with the occurrence of symptomatic spinal instability requiring spine fusion surgery, while there was no significant difference in radiographic parameters and demographic factors excluding autoimmune connective tissue diseases between reoperation and non-reoperation groups. CONCLUSIONS: Patients with autoimmune connective tissue disorders receiving chronic glucocorticoid therapy are more likely to develop symptomatic spinal instability following decompression surgery for lumbar canal stenosis without or with minimal spondylolisthesis.
30088677 Influence of age and renal impairment on the steady state pharmacokinetics of filgotinib, 2018 Dec AIMS: Filgotinib (GS-6034, formerly GLPG0634) is an oral, selective Janus kinase 1 (JAK1) inhibitor that showed early response and sustained efficacy in patients with rheumatoid arthritis and with Crohn's disease. The aim of the present study was to investigate the impact of age and renal impairment (RI) on the pharmacokinetics (PK) of filgotinib and its main metabolite. METHODS: The effect of age was assessed in two groups of 10 elderly healthy subjects (65-74 and ≥75 years of age) and a control group of 10 younger healthy subjects (40-50 years of age). The impact of RI was investigated in three groups of subjects with mild (n = 6), moderate (n = 6) and severe (n = 3) RI [estimated glomerular filtration rate (eGFR) 60-89, 30-59 and 15-29 ml min(-1) 1.73 m(-2) , respectively] and a control group (n = 9) with normal renal function (eGFR ≥90 ml min(-1) 1.73 m(-2) ). The PK of filgotinib and its metabolite were evaluated following filgotinib 100 mg once-daily doses for 10 days. RESULTS: At steady state, the exposure [area under the concentration-time curve over the dosing interval (AUC(0-24 h) )] of filgotinib and its metabolite was moderately higher (1.45- and 1.33-fold, respectively) in the elderly subjects (≥75 years) compared with younger subjects. Renal clearance for filgotinib and its metabolite decreased with the degree of RI, leading to a maximum increase in AUC(0-24 h) of 1.54-fold for filgotinib and 2.74-fold for the metabolite in subjects with severe RI. Filgotinib was generally safe and well tolerated. CONCLUSIONS: Age and mild to moderate impairment of renal function had limited impact on the PK of filgotinib. In subjects with severe RI, the exposure to the metabolite of filgotinib was elevated, consistent with its renal elimination pathway.
29924003 Predictability of severity of disc degeneration and disc protrusion using horizontal displ 2018 Jun The aim of this study is to investigate the usefulness of flexion-extension (dynamic) radiographs in evaluating the severity of disc degeneration and disc protrusion in cervical magnetic resonance image (MRI). Patients complaining of neck or arm pain with no prior surgical history and who had undergone both cervical MRI and dynamic radiographs were included in this study. The following patients were excluded: those who had any history of trauma, autoimmune disease such as rheumatoid arthritis or ankylosing spondylitis, prior cervical fracture or prior cervical spine surgery. Based on these criteria, 161 patients who visited our department for neck pain or upper extremity radicular symptoms were initially included retrospectively. Among them, 69 patients were excluded due to the lack of cervical MRI or dynamic radiographs. Therefore, a total of 92 patients were included for analysis in this study. The maximal diameter of disc protrusion in sagittal or axial MRI, the severity of cervical disc degeneration, and segmental horizontal displacement in dynamic cervical radiographs are the main outcome measurements. In the results of this study, the extension radiograph of C5/6 had the highest sensitivity (93.33%) and specificity (100%) in predicting cervical disc protrusion followed by C4/5 (sensitivity; 77.28%, specificity 92.86%) among the dynamic radiographs. Segmental horizontal displacement at the C3/4, C4/5, and C5/6 level in the neutral and extension radiographs had a significant correlation with the severity of cervical disc degeneration in MRI (P < .05). At the C6/7 level, however, only extension radiograph had a significant correlation with the severity of cervical disc degeneration in the MRI (P < .05). In conclusion, if MRI is not available in a primary clinical setting, dynamic cervical radiographs may be useful in predicting the severity of degenerative disc and disc protrusion in cervical MRI. Among the dynamic cervical radiographs, the extension radiograph was the most sensitive for predicting the severity of cervical disc degeneration and disc protrusion, especially at the C3/4, C4/5, C5/6, and C6/7 levels in MRI.
30603535 Substance-P Ameliorates Dextran Sodium Sulfate-Induced Intestinal Damage by Preserving Tis 2018 Feb Intestinal inflammation alters immune responses in the mucosa and destroys colon architecture, leading to serious diseases such as inflammatory bowel disease. Thus, the modulation of intestinal integrity and immune responses in IBD can be the critical factor to be considered to reduce the severity of damages. Substance-P (SP), endogenous peptide to be involved in cell proliferation, migration and immune modulation, can exert the therapeutic effect on diverse diseases including cornea damage, rheumatoid arthritis and diabetic complications. SP was found to elevate expression of junctional molecule. Considering the function of SP reported previously, it was inferred that SP is capable of exert the beneficial effect of SP on intestinal diseases by controlling intestinal structure as well as immune responses. In this study, we explored the therapeutic effect of SP on dextran sodium sulfate-induced intestine damage by injecting SP. The effects of SP were evaluated by analyzing crypt structures, proliferating cell pool and infiltration of immune cells. DSS treatment provoked abnormal immune response and disruption of intestine epithelial barrier. However, co-treatment of SP obviously blocked the development of intestinal damages by declining inflammatory responses and sustaining intestinal structure more intact. The treatment of SP to chronic damages also promoted intestinal regeneration by preserving the integrity of colon tissue. Moreover, DSS-induced reduction of epithelial junctional molecule was obviously inhibited by SP treatment in vitro. Taken together, our data indicate that SP can reduce intestinal damages, possibly by modulating barrier structure and immune response. Our results propose SP as candidate therapeutics in intestinal damages.
30154855 Work Ability and Employment in Rheumatoid Arthritis: A Cross-Sectional Study on the Role o 2018 OBJECTIVE: The aim of the present study was to assess the association between muscle strength, lower extremity function, employment status, and work ability in RA patients. METHODS: One hundred seropositive RA outpatients of working age were included in this cross-sectional study. Employment status was assessed by interview and work ability by the Work Ability Index-Single Item Scale (WAS). Muscle strength was determined using dynamometer measurement of isometric hand grip and knee extensor strength. Lower extremity function was measured using the short physical performance battery (SPPB). Regression models estimate the association between unemployment, work ability and muscle strength, and lower extremity function, controlling for sociodemographic and disease-related factors. RESULTS: Forty-one percent of the RA patients were not gainfully employed, and their median work ability had a good WAS value (7.00 [4.00-7.00]). Patients with better knee extensor strength (OR=1.07, 95% CI [1.02-1.12) and better physical performance (OR=1.71, 95% CI [1.18-2.49]) had a significantly better chance of gainful employment. The odds for hand grip strength remained significant when adjusted for sociodemographic (OR=1.5, 95% CI [1.00-1.09]), but not for disease-specific variables. Better hand grip strength (β=0.25, p=0.039) and better knee extensor strength (β=0.45, p=0.001) as well as better lower extremity function (SPPB) (β=0.51, p<0.001) remained significantly associated with work ability following adjustment for sociodemographic and disease-specific variables. CONCLUSIONS: The association of employment status and work ability with parameters of physical fitness suggests that improvement in muscle strength and lower extremity function may positively influence work ability and employment in individuals with RA.
30412132 Prognostic significance and dynamic change of plasma macrophage migration inhibitory facto 2018 Oct Macrophage migration inhibitory factor (MIF) has been reported as an inflammatory cytokine in many inflammatory diseases, including rheumatoid arthritis and ischemic diseases. However, dynamic changes of MIF within the first 24 hours on admission and potential prognostic significance following ST-elevation myocardial infarction (STEMI) have been little known. In this study, we examined the dynamic change of MIF level and its potential diagnostic and prognostic value after the onset of STEMI. Plasma MIF levels were evaluated in symptomatic subjects who received coronary angiogram with a median 27 months follow-up for the development of major adverse cardiovascular events (MACEs).Of all 993 subjects, patients with STEMI showed a significantly higher MIF levels than in patients with non-ST elevation acute coronary syndrome, stable angina, and normal coronary artery, respectively (P < .01). Plasma MIF levels elevated as early as 12 hours post-onset of STEMI and peaked rapidly within 24 hours, and remained elevated from about day 5 till day 9 during hospitalization. In multivariate analysis, MIF was associated with a decreased risk of MACEs occurrence in STEMI patients after adjustment for traditional cardiovascular risk factors [hazard ratio 0.81, (0.72-0.90), P < .001]. The ROC curve for MACEs was 0.72 (95% CI 0.62-0.80, P < .001) and 0.85 (95% CI 0.80-0.90, P < .001) using Framingham risk factors only and combined with MIF, individually.Measurement of MIF adds potential information for the early diagnosis of acute STEMI and significantly improves risk prediction of MACEs when added to a prognostic model with traditional Framingham risk factors.