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ID PMID Title PublicationDate abstract
26449746 Activity profiling of aminopeptidases in cell lysates using a fluorogenic substrate librar 2016 Mar Aminopeptidases are exopeptidases that process peptide bonds at the N-terminus of protein substrates, and they are involved in controlling several metabolic pathways. Due to their involvement in diseases such as cancer or rheumatoid arthritis, their presence can also be used as a predictive biomarker. Here, we used a library of fluorogenic substrates containing natural and unnatural amino acids to reliably measure the aminopeptidase N (APN) activity in cell lysates obtained from human, pig and rat kidneys. We compared our results to the substrate specificity profile of isolated APN. Our data strongly support the observation that fluorogenic substrates can be successfully used to identify aminopeptidases and to measure their activity in cell lysates. Moreover, in contrast to assays using single substrates, which can result in overlapping specificity due to cleavage by several aminopeptidases, our library fingerprint can provide information about single enzymes.
26167771 [Indications and Borderline Indications for Medial Mobile Bearing Unicondylar Knee Replace 2015 Oct Beside the possibility of bicondylar knee replacement, patients with isolated anteromedial osteoarthritis also have the possibility of unicondylar knee replacement. Therefore some requirements are essential such as functionally intact cruciate and collateral ligaments, intact cartilage in the lateral compartment and an intraoperative flexion of more than 100°. An instability or contracture of the cruciate or collateral ligaments, a varus deformity more than 15°, a flexion deformity of more than 15°, an intraoperative flexion less than 100° as well as failed upper tibial osteotomy are seen as contraindications. In addition, a rheumatoid arthritis and a full thickness cartilage defect in the central part of the lateral compartment are seen as a contraindication because of the risk of a progression of the disease. With respect to these contraindications, excellent functional outcome and survival rates could be demonstrated in the long term. An expansion of these criteria, especially in patients with an insufficiency of the cruciate ligaments or after failed upper tibial osteotomy should only be done in certain cases after careful assessment of the benefits and risks. These patients should be informed about the lack of long-term results and the higher risk of complications. Quite commonly, the criteria of Kozinn and Scott are used for patient selection. These criteria were originally established for fixed-bearing prosthesis and have no relevance on mobile-bearing prosthesis. Criteria such as age, level of activity, weight, chondrocalcinosis and anterior knee pain have no effect on the clinical outcome or the long-term survival of a mobile-bearing prosthesis.
26062617 [New Indings in Methotrexate Pharmacology -  Diagnostic Possibilities and Impact on Clin 2015 Methotrexate is an anti-cancer drug used to treat several malignancies including pediatric acute lymphoblastic leukemia and choriocarcinoma. Despite recent advances in cancer chemotherapy, it remains a mainstay of therapy since its discovery in the early second half of the previous century. Moreover, low-dose methotrexate is a gold standard antirheumatic drug in the treatment of rheumatoid arthritis, psoriasis, systemic scleroderma and other autoimmune disorders. Side effects of methotrexate treatment are well known and described; however, their occurrence may often be unpredictable due to lack of specific biomarkers of toxicity. Methotrexate plasma levels are routinely monitored by therapeutic drug monitoring, nevertheless, occurrence and concentrations of its metabolites are not measured. During methotrexate treatment 7- hydroxymethotrexate and 2,4- diamino- N10- mehylpteroic acid appear in plasma. The latter can further be hydroxylated and glucuronidated resulting in five possible extracellular methotrexate metabolites. In addition, methotrexate is intracellularly converted to its active polyglutamylated forms. Therapeutic efficacy is dependent on formation of methotrexate polyglutamates as it keeps intracellular pool of the drug and enhances its affinity towards various target enzymes. In this study, we describe pharmacokinetic and pharmacodynamic characteristics of methotrexate metabolites. We also review methotrexate blood brain barrier transport to cerebrospinal fluid regarding its use in the prevention of leukemic central nervous system involvement and management of methotrexate toxicity with the use of carboxypeptidase- G2. Finally, we discuss laboratory methods for monitoring methotrexate metabolites and benefits of simultaneous determination of methotrexate and metabolites as possible biomarkers of therapeutic efficacy and clinical toxicity.
26039720 Biosimilars in inflammatory bowel disease: ready for prime time? 2015 Jul PURPOSE OF REVIEW: The goal is to review the most recent literature about biosimilars in inflammatory bowel disease (IBD), with emphasis on controversial regulatory issues. RECENT FINDINGS: Although biosimilars have been in use in Europe since 2005, the recent approval of CT-P13 (Remsima, Inflectra), a biosimilar of the reference infliximab (Remicade), by the European Medicines Agency (EMA) and several regulatory agencies has become a widely discussed topic in IBD, rheumatology, and other areas. Biologics are the main drivers of cost in current IBD units, and biosimilars can reduce prices thus increasing the availability of this type of treatment. The guidelines for evaluation of biosimilars are considerably different from those of the reference biologics, regulatory agencies relying on detailed in-vitro studies for defining 'high similarity', and requiring many fewer clinical data. 'High similarity' is considered sufficient for clinical trials, as the new molecule is demonstrated so structurally similar to the reference one that no significant difference in efficacy or safety is expected. Two trials in ankylosing spondylitis and rheumatoid arthritis gave no evidence of real difference and provided the required pharmacokinetic and PD data. The main controversy remains in the 'extrapolation' of indications, accepted by EMA but not by Health Canada. Position statements from several scientific societies and some expert's reviews have expressed concerns to the concept of extrapolation without direct IBD clinical evidence, whereas EMA experts have published detailed reviews supporting extrapolation. SUMMARY: Biosimilars in IBD are here to stay. New data are awaited to settle the controversy of extrapolation, but only the complex behavior of markets will show whether biosimilars fuel competition and extend access to biologics with significant cuts in drug costs.
26028048 Tuning T Cell Activation: The Function of CD6 At the Immunological Synapse and in T Cell R 2016 CD6 immunotherapy to treat psoriasis and rheumatoid arthritis has reached the clinical trial stage with apparent success, and targeting CD6 with mAbs is being used in several animal models of autoimmunity and neuroinflammation with promising indications. However, the mode of action of the therapeutic CD6 mAbs is far from being understood, reflecting the uncertainties and controversy surrounding the mechanistic and biological functions of CD6. Initially regarded as a co-stimulatory receptor of T lymphocytes, recent studies suggest that CD6 can instead modulate early as well as late T cell responses. Also, opposing the contribution of CD6 adhesiveness in the establishment and stabilization of immunological synapses, the actual triggering of CD6 might induce anti-proliferative signals to the T lymphocyte. CD6 has an unusually long cytoplasmic tail and its gene undergoes peculiar patterns of activation-dependent alternative splicing that can on one hand determine whether or not the CD6 protein binds to its ligand, and on the other include or exclude intracellular sequences that may transduce positive or negative signaling. In this review we discuss the multiple aspects that determine the nature of the signals transmitted via CD6 and the context that may define a dual role for this important T cell surface molecule.
25786337 Pemphigus and associated comorbidities: a cross-sectional study. 2015 Aug BACKGROUND: Pemphigus is a rare autoimmune blistering disease, reported to be associated with other coexisting and autoimmune diseases, including thyroid diseases, rheumatoid arthritis, alopecia areata, vitiligo, systemic lupus erythematosus, scleroderma and rare entities such as myasthenia gravis. AIM: To identify and describe patients with pemphigus with a diagnosed comorbidity, and to quantify the risk of additional comorbidities. METHODS: This was a cross-sectional study of patients with pemphigus treated at a tertiary referral centre. Prevalence rates of 15 comorbid diseases were calculated. Age-standardized prevalence ratio (SPR) and 95% CI were calculated in comparison with prevalence rates in the general Canadian population using data from the Canadian Community Health Survey. Data were analysed using SAS software. RESULTS: In total, 295 patients were identified. An increased risk of hypothyroidism (n = 38, SPR = 1.53, 95% CI 1.08-2.10) and inflammatory bowel disease (IBD) (SPR = 1.48, 95% CI 0.40-3.80), and a two-fold increased risk of diabetes (SPR = 2.20, 95% CI 1.64-2.87) were observed. CONCLUSIONS: Patients with pemphigus have a higher incidence of hypothyroidism, IBD and diabetes compared with the general population. As part of pemphigus investigations and surveillance, investigating for these conditions may be considered.
25725226 T cell chemokine receptor patterns as pathogenic signatures in autoimmunity. 2015 Feb Autoimmune diseases arise from aberrant activation of immune cells directed against endogenous autoantigens expressed throughout the human body. While the initiating triggers remain poorly understood, the self-perpetuating phase of these diseases is directly linked to the ongoing recruitment of inflammatory cells that traffic to the affected anatomical sites. T lymphocytes are prominent drivers of many autoimmune diseases and the targeted trafficking of these cells to infiltrate the affected organs is often a common denominator. The regulation of T cell trafficking involves the coordinated expression of specific patterns of chemokines and the reciprocal expression of cognate chemokine receptors on T cell membranes. Thereby, chemokines direct the specific trafficking of a wide array of responsive activated immune cells. Specific patterns of chemokine receptor expression can correlate with disease activity in an autoimmune disease, confirming the importance of further characterizing the T cells that infiltrate specific sites of autoimmunity. Herein, we will review our current understanding of the roles of chemokines in two common autoimmune diseases: rheumatoid arthritis and multiple sclerosis. We also discuss the implications for chemokine receptor signatures in autoimmune pathogenesis, and how these may provide novel targets for therapeutic intervention.
25561460 Protein unfolding allows use of commercial antibodies in an apolipoprotein M sandwich ELIS 2015 Mar apoM is a member of the lipocalin superfamily and circulates in plasma attached to HDL particles. apoM plays a role in cholesterol metabolism and has recently been identified as transporter for the signaling lipid, sphingosine-1-phosphate (S1P), in plasma. S1P is implicated in several inflammatory diseases such as multiple sclerosis and rheumatoid arthritis. The ability to accurately measure apoM is crucial for investigating its biological functions and possible clinical implications. However, reliable commercial methods have been lacking so far. Therefore, we have developed an assay that specifically recognizes human apoM in plasma using commercially available reagents. Commercial apoM antibodies were screened for compatibility in a sandwich ELISA-based assay. One optimal pair of antibodies was chosen, and sample preparation, buffers, and incubation times were optimized to generate a simple and reproducible method. Validation and comparison to a previously described ELISA for apoM confirmed that the assay displays a high degree of sensitivity, specificity, and precision. Our results show that commercially available antibodies can be used to accurately measure human plasma apoM. This method can be implemented in every laboratory and will help promote high quality research.
25550090 Interdisciplinary exchange of ideas: progestagens for autoimmunity, biologics for pregnanc 2015 Feb In recent years, there has been a growing interest in the role of immune, alloimmune and autoimmune processes in the pathogenesis of spontaneous preterm birth and recurrent pregnancy loss. The association between an inflammatory response and preterm labor has been established. Indeed, many women suffering from preterm labor have elevated inflammatory markers such as tumor necrosis factor alpha, interleukin 6 and matrix metaloproeinase 8. The role of immune processes in the pathogenesis of recurrent pregnancy loss has also been widely researched. Progesterone induces many physiologic effects necessary for healthy pregnancy, and progestagens supplementation has been used as an approach to prevent preterm labor and recurrent pregnancy loss. Progestagens also have potent anti-inflammatory and immunomodulatory actions. Because preterm labor and recurrent pregnancy loss are associated with abnormal inflammation, progestagens may maintain healthy pregnancy through both endocrine and immunologic actions. These immunologic actions, such as suppression of Th1- and Th17-related responses, enhancement of regulatory T cell (Tregs) activity and suppression of inflammation, may also be involved in pregnancy-induced remission of certain autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Accordingly, there is growing interest in the potential therapeutic role of progestagens in the treatment of MS and RA. In this review, we suggest that biologic autoimmune modulators, especially those which affect immune pathways similar to progestagens, may provide more potent and specific effects, and hence better results than progestagens, in preventing preterm labor and recurrent pregnancy loss.
25323520 Aryl-acetic and cinnamic acids as lipoxygenase inhibitors with antioxidant, anti-inflammat 2015 Cinnamic acids have been identified as interesting compounds with cytotoxic, anti-inflammatory, and antioxidant properties. Lipoxygenase pathway, catalyzing the first two steps of the transformation of arachidonic acid into leukotrienes is implicated in several processes such as cell differentiation, inflammation and carcinogenesis. Development of drugs that interfere with the formation or effects of these metabolites would be important for the treatment of various diseases like asthma, psoriasis, ulcerative colitis, rheumatoid arthritis, atherosclerosis, cancer, and blood vessel disorders. Till now, asthma consists of the only pathological case in which improvement has been shown by lipoxygenase LO inhibitors. Thus, the research has been directed towards the development of drugs that interfere with the formation of leukotrienes. In order to explore the anti-inflammatory and cytotoxic effects of antioxidant acrylic/cinnamic acids a series of derivatives bearing the appropriate moieties have been synthesized via the Knoevenagel condensation and evaluated for their biological activities. The compounds have shown important antioxidant activity, anti-inflammatory activity and very good inhibition of soybean lipoxygenase while some of them were tested for their anticancer activity.
25274075 Managing chronic pain in adults with haemophilia: current status and call to action. 2015 Jan Haemophilic arthroses are associated with acute pain during bleeding episodes and with chronic pain caused by arthritic complications of repeated bleeding into joints. Unlike other conditions (e.g. osteoarthritis, rheumatoid arthritis, sickle cell disease), there are limited data on pain management in haemophilia. Management of arthritic individuals and those with sickle cell disease relies heavily on administration of acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics. In haemophilia, acetaminophen often has limited efficacy at therapeutic doses, offering a narrow dosing range in those with liver disease due to chronic hepatitis C. NSAIDs can effectively manage pain in patients with haemophilia, but these agents are potentially associated with a significant risk of precipitating or exacerbating bleeding complications in an already coagulopathic population. Opioids have proven effective in osteoarthritis and sickle cell disease, but outcomes data in those with haemophilia are virtually non-existent. Patients with haemophilia are at least as vulnerable as other chronic pain populations to opioid-related adverse events and to developing abusive behaviours and addiction. Despite pain management strategies for patients with haemophilia being far from optimal, the predominant precept of haemophilia management still applies. As such, it is critically important to aggressively reverse or prevent acute symptomatic bleeding in a timely and effective manner to at least minimize pain and progressive joint damage. This review should serve as a call to action to prioritize pain management in haemophilia care and spur interest in the development, improvement and standardization of tools to assess and manage acute and chronic pain in haemophilia.
26179062 Increased carotid artery intima-media thickness and myeloperoxidase level in children with 2015 Jul 16 INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a frequent childhood rheumatic disease characterized by chronic inflammation. The latter has been related to impairment of arterial functional-structural properties, atherogenesis and later cardiovascular events. The objective of this study was to examine intima-media thickness (IMT) and the parameters of arterial stiffness in children with JIA at diagnosis and their correlation with JIA subtype and markers of inflammation and atherosclerosis. METHODS: Thirty-nine newly diagnosed patients with JIA (26 girls; mean age, 13.2 ± 2.6 years) and 27 healthy controls (9 girls; mean age, 13.6 ± 3.4 years) were included in the study. Twelve patients had oligoarthritis, fifteen had extended oligoarthritis and twelve had rheumatoid factor-negative polyarthritis. IMT of the common carotid artery was determined by ultrasonography, carotid-femoral pulse wave velocity (cfPWV) and augmentation index adjusted to a heart rate of 75 beats/min (AIx@75) were determined by applanation tonometry. The serum levels of atherosclerosis-related biomarkers, such as asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and adiponectin, were measured by enzyme-linked immunosorbent assay. RESULTS: Mean IMT (0.46 ± 0.04 vs. 0.42 ± 0.04 mm; p = 0.0003) and MPO concentration (115.2 [95% confidence interval {95% CI}, 97.4-136.3] vs. 57.6 [95% CI, 47.1-70.3] ng/ml; p < 0.0001) were higher in the patients with JIA than in the control subjects. The cfPWV, AIx@75 and serum ADMA and adiponectin levels did not significantly differ between the groups and JIA subtypes. Serum adiponectin level correlated negatively with AIx@75 in patients with JIA (r = -0.38; p < 0.05). CONCLUSIONS: Patients with JIA have increased mean IMT and elevated MPO levels at early stages of the disease. AIx@75 was inversely independently associated with adiponectin level in the patients, suggesting that lower adiponectin levels might influence arterial subclinical stiffening in patients with newly diagnosed JIA.
27959806 Bayesian Quantification of Contrast-Enhanced Ultrasound Images With Adaptive Inclusion of 2017 Apr Contrast Enhanced Ultrasound (CEUS) is a sensitive imaging technique to assess tissue vascularity and it can be particularly useful in early detection and grading of arthritis. In a recent study we have shown that a Gamma-variate can accurately quantify synovial perfusion and it is flexible enough to describe many heterogeneous patterns. However, in some cases the heterogeneity of the kinetics can be such that even the Gamma model does not properly describe the curve, with a high number of outliers. In this work we apply to CEUS data the single compartment recirculation model (SCR) which takes explicitly into account the trapping of the microbubbles contrast agent by adding to the single Gamma-variate model its integral. The SCR model, originally proposed for dynamic-susceptibility magnetic resonance imaging, is solved here at pixel level within a Bayesian framework using Variational Bayes (VB). We also include the automatic relevant determination (ARD) algorithm to automatically infer the model complexity (SCR vs. Gamma model) from the data. We demonstrate that the inclusion of trapping best describes the CEUS patterns in 50% of the pixels, with the other 50% best fitted by a single Gamma. Such results highlight the necessity of the use ARD, to automatically exclude the irreversible component where not supported by the data. VB with ARD returns precise estimates in the majority of the kinetics (88% of total percentage of pixels) in a limited computational time (on average, 3.6 min per subject). Moreover, the impact of the additional trapping component has been evaluated for the differentiation of rheumatoid and non-rheumatoid patients, by means of a support vector machine classifier with backward feature selection. The results show that the trapping parameter is always present in the selected feature set, and improves the classification.
28284487 Toll-like receptors as a key regulator of mesenchymal stem cell function: An up-to-date re 2017 May Understanding the role of toll-like receptors (TLRs) in the immunomodulation potential, differentiation, migration, and survival of mesenchymal stem cells (MSCs) is absolutely vital to fully exploiting their MSC-based therapeutic potential. Furthermore, through recognition of exogenous or endogenous ligands produced upon injury, TLRs have been linked to allograft rejection and maintenance of chronic inflammatory diseases, including Crohn's disease, rheumatoid arthritis. Characterizing the effect of TLRs in biological control of MSCs fate and function could improve our knowledge about the MSC-based cell therapy and immunotherapy. In this paper, we outline the impacts of TLR activation and mechanisms on MSCs immunomodulatory functions, differentiation, migration, and survivability. Moreover, we indicate that the expression patterns of TLRs in MSCs from different sources.
28110701 Potential relationship between periodontal diseases and eye diseases. 2017 Feb Periodontal diseases are inflammatory lesions initiated by oral bacteria and lead to the destruction of the supporting structures of the teeth (gingiva, periodontal ligament and alveolar bone) in susceptible patient. Via several biological mechanisms, periodontal diseases have been associated with multiple systemic diseases, such as rheumatoid arthritis, diabetes, cardiovascular diseases, Alzheimer's disease and adverse pregnancy outcomes. Similarly certain eye diseases have been associated with systemic diseases of the inflammatory pathway. We hypothesized that periodontal diseases are associated with eye diseases. Thus using literature data we find that several studies have reported that eye disorders are associated with the presence of periodontal diseases. But the mechanisms of this relationship are not clear. However the innate immune response involvement, the sharing of similar risk factors in pathogenesis and the changes of eye choroid thickness may be suggested as several hypotheses to explain this potential association.
28031726 Complex regional pain syndrome: medical and legal ramifications of clinical variability an 2017 OBJECTIVE: The aim of this study was to demonstrate the ramifications of clinical variability of complex regional pain syndrome (CRPS) and how they can affect the various aspects of this condition, favorably or unfavorably, for both patients and participating medical and legal professionals. METHODS: Twelve patients diagnosed with CRPS at different times in the past 25 years were followed up, and their signs and symptoms were reviewed for variability. None had preexisting or ongoing medical disorders and prior injury to the peripheral nerves or musculoskeletal tissues. None had been involved in litigation. Physical traumas that triggered CRPS were job-related, vehicular accidents, and personal injuries. The presence of vasomotor symptoms (eg, swelling, skin discoloration, and temperature changes) and allodynia in the affected extremity was the basis for clinical diagnosis in all the patients. The need for imaging studies was precluded in some patients owing to the presence of vasomotor symptoms, which either fluctuated or were steady. Seven of the patients had type 1 CRPS, and five patients had type 2 CRPS. RESULTS: Most patients encountered delay in diagnosis and treatment and legal obstacles owing to the lack of "typical" objective signs of CRPS. The patients' symptoms fluctuated at different times of the day. Eight patients experienced spread of vasomotor symptoms and varying degree of allodynia in the opposite extremity. One patient, who developed signs and symptoms of rheumatoid arthritis, 2 months after the injury, continued to have CRPS symptoms in the injured hand. Treatment modalities administered in all the patients were essentially ineffective. All the patients, except one, were unable to return to their original line of work, and their symptoms persisted regardless of the outcome of their legal claims. CONCLUSION: It is likely that patients who continue to complain of pain and vasomotor symptoms followed by a physical injury have CRPS. The complex interaction between the peripheral, autonomic, and central nervous system in this condition makes it challenging to diagnose, treat, and prognosticate.
27787362 A novel method of C1-C2 transarticular screw insertion for symptomatic atlantoaxial instab 2016 Oct Atlantoaxial instability treated with the C1-2 transarticular screw fixation is biomechanically more stable; however, the technique demanding and the potential risk of neurovascular injury create difficulties for clinical usage, and there is still lack of clinical experience till now.We reported an adult female patient with symptomatic atlantoaxial instability due to rheumatoid arthritis that was successfully treated with a bilateral C1-C2 transarticular screw fixation using a customized guiding block. We preoperatively determined the trajectories for bilateral C1-C2 transarticular screws on a 3-dimensional reconstruction model from the computed tomography (CT) and self-developed computer software, and designed a rapid prototyping customized guiding block in order to offer a guide for the entry point and insertion angle of the C1-C2 transarticular screws.The clinical outcome was good, and the follow-up period was >3 years. The accuracy of the screws is good in comparison with preoperative and postoperative CT findings, and no neurovascular injury occurred.The patient was accurately and successfully treated with a bilateral C1-C2 transarticular screw fixation using a customized guiding block.
27758933 Deletion of mPGES-1 affects platelet functions in mice. 2016 Dec 1 Microsomal prostaglandin E(2) synthase-1 (mPGES-1) constitutes an essential player in inflammation and is involved in the pathogenesis of rheumatoid arthritis. Platelets participate in the regulation of inflammatory processes by the release of proinflammatory mediators and platelet-derived microparticles (PMPs). However, the role of the inducible mPGES-1/PGE(2) pathway in platelet functions has not been investigated. In the present study we report a significant impact of mPGES-1 on platelet functions during inflammation. Wild-type (WT) and mPGES-1(-/-) knockout (KO) mice were stimulated with lipopolysaccharide (LPS) for 24 h. Platelet counts and activation were assessed by flow cytometry analysing CD62P-CD154 expression, PMP numbers, platelet-leukocyte aggregates and platelet aggregation. The accumulation of platelets and fibrinogen in the liver was analysed by immunofluorescent staining. In native platelets from WT and mPGES-1 KO mice, there were no differences among the investigated functions. After LPS treatment, the number of platelets was significantly decreased in WT, but not in KO mice. Platelet activation, platelet-leukocyte aggregates and PMP numbers were all significantly lower in KO mice compared with WT mice after LPS treatment. In addition, KO mice displayed a significant reduction in platelet aggregation ex vivo In the liver of LPS-stimulated WT and KO mice, there were no differences in platelet accumulation, although the percentage of total vessel area in the KO liver was significantly lower compared with the WT one. Our results demonstrate that systemic inhibition of mPGES-1 prevents platelet activation, which should have important implications with regard to the cardiovascular safety of mPGES-1 inhibitors.
27408505 Evaluation of lower limb axial alignment using digital radiography stitched films in pre-o 2016 Dec BACKGROUND: For patients with knee osteoarthritis, even slight anatomical variations in the femur or the tibia could affect total limb alignment during total knee replacement (TKR). Our hypothesis implies that the femoral valgus correction angle (VCA) in patients indicated for TKR, is variable and higher than the reported norm of 6° utilized in most intramedullary instrumentation systems, and that tibial bowing may result to a disparity of the tibial mechanical axis to the anatomical axis. METHODS: Our study is a retrospective review of 216 pre-operative arthritic knees, which investigated the lower limb axial alignment using digitally-stitched films. Patients excluded from the study are those with history of previous tibial or femoral osteotomy, secondary gonarthrosis, rheumatoid arthritis, previous femoral or tibial fracture, patients for bilateral TKR, or history of hip surgery. RESULTS: The mean age was 68-years old (range 39-86 years). The mean VCA was 7° (4.7-9.3) for men and 6.6° (4.9-9) for women. However, 71 patients (33%) had more than 7° VCA. Subsequently, 46 patients (21%) had tibial bowing producing an angle >1.5° between its mechanical and anatomic axis. CONCLUSIONS: The 6° standard when used as a guide may result in suboptimal prosthesis positioning during conventional TKR surgery. Therefore our findings suggest that the femoral valgus correction angle has a broad range, and using standard femoral intramedullary guides should not be overlooked.
27388717 IL-33 circulating serum levels are increased in patients with non-segmental generalized vi 2016 Sep IL-33 is a recently identified cytokine, encoded by the IL-33 gene, which is a member of the IL-1 family that drives the production of T-helper-2 (Th-2)-associated cytokines. Serum levels of IL-33 have been reported to be up-regulated in various T-helper (Th)-1/Th-17-mediated diseases, such as psoriasis, rheumatoid arthritis, and inflammatory bowel. To investigate whether cytokine imbalance plays a role in the pathogenesis of vitiligo, we performed a case-control association study by enzyme-linked immunosorbent assay of IL-33 in our patients. IL-33 serum levels were measured by a quantitative enzyme immunoassay technique in patients with non-segmental generalized vitiligo and compared with those of healthy controls. IL-33 serum levels in patients with vitiligo were significantly increased than those in healthy controls. There was a positive correlation of IL-33 serum levels with extension of vitiligo and disease activity. This study suggests a possible systemic role of IL-33 in the pathogenesis of vitiligo. Inhibiting IL-33 activity might be a novel therapeutic strategy in the treatment of autoimmune inflammatory disease, like vitiligo.