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ID PMID Title PublicationDate abstract
24314164 [The clinical characteristics of primary Sjögren syndrome with neuromyelitis optica]. 2013 Sep OBJECTIVE: To investigate the clinical features of neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSD) with primary Sjögren's syndrome (pSS). METHODS: Eleven inpatients diagnosed as NMO secondary to pSS in Peking Union Medical College Hospital were retrospectively analyzed. RESULTS: Eleven patients of pSS with NMO were enrolled in this study, including 10 females and 1 male. The mean age was (35 ± 15) years old. The course of disease ranged from one month to 16 years, with a median of 10 months. The interval between optic nerve and spinal cord involvement was 3 months to 2 years.Eight patients had NMOSD as initial presentations of pSS. Eight patients had history of optic neuropathy. The most frequently involved spinal segment was cervical cord (10 cases) shown by magnetic resonance.Serum NMO-IgG antibodies were tested in 7 patients and 6 of them were positive. CONCLUSION: NMOSD may present as an important and initial clinical manifestation of pSS, which suggesting the involvement of central nervous system. Autoimmune antibodies, NMO-IgG and imaging were supposed to be done for further evaluation of prognosis and therapy regimens.
23889823 Spontaneous intracranial hemorrhage as an initial manifestation of primary Sjögren's synd 2013 Jul 29 BACKGROUND: Sjögren's syndrome can involve the central nervous system; however, spontaneous intracranial hemorrhage has rarely been reported as the initial manifestation. CASE PRESENTATION: We report a 39-year-old woman with primary Sjögren's syndrome presenting with intracranial hemorrhage. The diagnosis of primary Sjögren's syndrome was based on the presence of ocular dryness, salivary gland secretory and excretory dysfunction confirmed with dynamic tracer emission CT, and positive anti-Sjögren's syndrome A and anti-Sjögren's syndrome B antibodies. CONCLUSION: Primary Sjögren's syndrome can present with variable central nervous system signs, which may precede the classic sicca symptoms. Therefore, Sjögren's syndrome-associated indicators should be investigated in patients without the common risk factors for stroke who present with spontaneous intracranial hemorrhage.
23961524 Squamous cell carcinoma of the lip associated with adalimumab therapy for ankylosing spond 2013 Jul Adalimumab is an anti-tumor necrosis factor α (TNF-α) agent approved for the treatment of ankylosing spondylitis (AS); psoriatic arthritis; and moderate to severe cases of rheumatoid arthritis (RA), plaque psoriasis, Crohn disease, ulcerative colitis, and polyarticular juvenile idiopathic arthritis. Evidence suggests that anti-TNF-α agents may increase a patient's risk for some types of cancers, including cutaneous squamous cell carcinoma (SCC). Cutaneous nonmelanoma skin cancers (NMSCs) have occurred during treatment with etanercept, infliximab, and adalimumab in the setting of RA and psoriasis, but data related to AS are less clear. We report the case of a 29-year-old woman with AS treated with adalimumab for 2 years who developed invasive SCC of the lower lip. We advocate increased NMSC surveillance in patients undergoing treatment with anti-TNF-α agents.
23173750 Use of a whole-slide imaging system to assess the presence and alteration of lymphatic ves 2013 Nov We investigated the presence and alteration of lymphatic vessels in joints of arthritic mice using a whole-slide imaging system. Joints and long bone sections were cut from paraffin blocks of two mouse models of arthritis: meniscal-ligamentous injury (MLI)-induced osteoarthritis (OA) and TNF transgene (TNF-Tg)-induced rheumatoid arthritis (RA). MLI-OA mice were fed a high fat diet to accelerate OA development. TNF-Tg mice were treated with lymphatic growth factor VEGF-C virus to stimulate lymphangiogenesis. Sections were double immunofluorescence stained with anti-podoplanin and alpha-smooth muscle actin antibodies. The area and number of lymphatic capillaries and mature lymphatic vessels were determined using a whole-slide imaging system and its associated software. Lymphatic vessels in joints were distributed in soft tissues mainly around the joint capsule, ligaments, fat pads and muscles. In long bones, enriched lymphatic vessels were present in the periosteal areas adjacent to the blood vessels. Occasionally, lymphatic vessels were observed in the cortical bone. Increased lymphatic capillaries, but decreased mature lymphatic vessels, were detected in both OA and RA joints. VEGF-C treatment increased lymphatic capillary and mature vessel formation in RA joints. Our findings suggest that the lymphatic system may play an important role in arthritis pathogenesis and treatment.
25580792 Group G Streptococcus bacteremia in recurrent cellulitis. 2014 In recent years, group G Streptococcus has been reported with increasing frequency as the cause of a variety of human infections. Underlying host factors such as immunosuppression, malignancy, diabetes mellitus, and rheumatoid arthritis may be predisposing conditions leading to infection. Toxic involvement and post-streptococcal sequalae, once believed to be exclusive to infections caused by group A Streptococcus, are now known to occur following acute group G Streptococcus and group C Streptococcus infections. We report on a case of group G Streptococcus bacteremia and recurrent cellulitis with toxic involvement. Patient blood cultures were always negative for β-hemolytic Streptococci in all the recurrences, except during the last one. Antibiotic therapy based on antibiogram quickly resolved the infection. A regimen of intramuscular injection of 1.2 million units of benzathine penicillin every 15 days for one year prevented recurrences of cellulitis.
25506031 Necrotising myositis, the deadly impersonator. 2014 We report two cases of patients with necrotising myositis who presented initially with limb pain and swelling on a background of respiratory complaints. Patient 1, a previously well 38-year-old female, underwent various investigations in the emergency department for excessive lower limb pain and a skin rash. Patient 2, a 61-year-old female with a background of rheumatoid arthritis and hypertension, presented to accident and emergency feeling generally unwell and was treated for presumed respiratory sepsis. Both deteriorated rapidly and were referred to the plastic surgery team with soft tissue necrosis, impending multiorgan failure and toxaemia. Large areas of necrotic muscle and skin were debrided, which grew group A streptococci, Streptococcus pyogenes. Patient 1 had a high above knee amputation of the left leg with extensive debridement of the right. Despite aggressive surgical intervention and microbiological input with intensive care support, patient 2 died. These two cases highlight the importance of early diagnosis and prompt surgical and pharmacological intervention in managing this life-threatening disease. Pain is the primary symptom with skin changes being a late and subtle sign in a septic patient. The Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) may be of use if there is concern to aid diagnosis of this life-threatening disease.
25407369 Small-molecule inhibitors of spleen tyrosine kinase as therapeutic agents for immune disor 2014 Following on the heels of the US FDA approval of tofacitinib (Xeljanz, Pfizer, USA), an inhibitor of the JAK family members, and ibrutinib (Imbruvica, Janssen, Belgium), an inhibitor of BTK, for the treatment of rheumatoid arthritis and chronic lymphocytic leukemia, respectively, there is now renewed interest in the biopharmaceutical industry in the development of orally active small-molecule agents targeting key protein kinases implicated in immune regulation. One such 'immunokinase' target is SYK, a non-receptor tyrosine protein kinase critical for transducing intracellular signaling cascades for various immune recognition receptors, such as the B-cell receptor and the Fc receptor. Here, we review and discuss the progress and challenges in the development of small-molecule inhibitors of SYK and their potential as a new class of disease-modifying immunosuppressive agents for certain inflammatory and autoimmune disorders.
25182149 Intra-articular glucocorticoid injections and their effect on hypothalamic-pituitary-adren 2015 Mar The use of intra-articular (IA) glucocorticoids for reducing pain and inflammation in patients with osteoarthritis, rheumatoid arthritis, and other inflammatory arthropathies is widespread among primary care physicians, specialists, and non-specialists in the United States. Injectable glucocorticoids have anti-inflammatory and analgesic properties which can be effective in improving clinical parameters such as pain, range of motion, and quality of life. After injection into the IA space, glucocorticoids may be systemically absorbed; the degree of absorption can depend on the size of the joint injected, the injectable glucocorticoid preparation used, the dosage, and the frequency of the injection. The adverse effects of intra-articular glucocorticoid injections (IAGC) can often be overlooked by both the patient and physicians who administer them, in particular the potential deleterious effect on the hypothalamic-pituitary-adrenal (HPA)-axis which can result in adrenal suppression and/or iatrogenic Cushing syndrome. In this paper we provide an overview on the often under-recognized effects of IAGC on HPA-axis function.
25101275 Biomechanical assessment of a patient-specific knee implant design using finite element me 2014 Rheumatoid arthritis is the leading cause of disability in young adults. Total knee arthroplasty has been successfully used to restore the joint function. Due to small bone size, osteoporosis, and severe soft tissue disease, standard knee implant sometimes cannot be directly applied clinically and patient-specific designs may be a more rational choice. The purpose of this study was to evaluate the biomechanical behavior of a patient-specific knee implant. A three-dimensional finite element of total knee arthroplasty was developed. The mechanical strength and the wear damage of the articular surfaces were analyzed. The results show that there exist high risks of component fracture and wear damage; the proposed implant design should be abandoned. The presurgery analysis is helpful in avoiding the potential failure.
24969281 Are we under- or mistreating patients at the time of presentation? 2014 Treatment goals in Crohn's disease (CD) are evolving beyond the control of symptoms towards deep remission, which encompasses clinical remission and mucosal healing. The ultimate goals are to prevent bowel damage, reduce long-term disability, and maintain normal quality of life. Until recently, goals of CD management focused on induction and maintenance of a symptomatic response, and little attention was paid to the delay or even prevention of disease progression. A very different approach is taken with other chronic diseases, such as hypertension, diabetes, and rheumatoid arthritis. This more comprehensive approach is often referred to as 'treat-to-target' strategy. The treat-to-target strategy defines a new treatment objective that aims to achieve and sustain both clinical remission and control of inflammation. With our new understanding of the etiopathophysiology of inflammatory bowel disease, are we mistreating our patients? The most convincing concept at this time is that of a defective mucosal barrier due to inappropriate recognition of the luminal flora or a defective defense against those bacteria. These recent theories indicate that the paradigm of immune suppression may not be the optimal concept. Therefore, a variety of approaches to improve the barrier function or to modulate luminal components have to be considered. We still have much to learn about these concepts in order to achieve the treatment goals of avoiding structural damage and complications.
26052544 MFG-E8, a novel homeostatic regulator of osteoclastogenesis. 2014 Although the glycoprotein MFG-E8 (milk fat globule-epidermal growth factor-factor 8) has been investigated extensively as an anti-inflammatory and homeostatic molecule, a possible role in bone homeostasis and disease was not addressed until recently. Our group has now shown that MFG-E8 is expressed by human and mouse osteoclasts and regulates their differentiation and function (Abe et al., J Immunol 2014;193:1383-1391). Whereas genetic deficiency or antibody-mediated neutralization of MFG-E8 enhances osteoclastogenesis and promotes inflammation-induced bone loss in mice, local administration of recombinant MFG-E8 blocks bone loss. These findings establish MFG-E8 as a novel homeostatic regulator of osteoclastogenesis and suggest that MFG-E8 could be exploited therapeutically to treat disorders associated with inflammatory bone loss, such as periodontitis and rheumatoid arthritis.
24139612 Toll-like receptors in atherosclerosis: a 'Pandora's box' of advances and controversies. 2013 Nov Seminal research over the past 20 years has revealed atherosclerosis to be a chronic inflammatory process that shares features with traditional inflammatory diseases including rheumatoid arthritis. More recently, emphasis has been placed on the role of innate immunity in the development and progression of atherosclerosis. In particular, pattern recognition receptors, including Toll-like receptors (TLRs), have been the focus of much attention as modulators of atherogenesis. This review provides an update on the developments in this area of research in the past 2 years, with a specific focus on the current controversies and how these may affect the design of therapeutics. Specifically, we will address the recent evidence that TLRs elicit both protective and detrimental effects in atherosclerosis and the emerging observation that the outcome of TLR signaling is dependent on the agonist and responding cell type.
24062860 Perioperative management of patients with rheumatic diseases. 2013 This paper aims to explore the assessment of patients with rheumatologic diseases, especially rheumatoid arthritis (RA), before undergoing orthopedic surgery. Perioperative assessment ensures an early diagnosis of the patient's medical condition, overall health, medical co-morbidities, and the assessment of the risk factors associated with the proposed procedures. Perioperative assessment allows for proper postoperative management of complications and of the management of drugs such as disease-modifying anti-rheumatic drugs (DMARD) and anti-platelets, and corticosteroids. The assessment also supports follow up plans, and patient education. Perioperative assessment enables the discussion of the proposed treatment plans and the factors associated with them in each case among the different specialists involved to facilitate an appropriate early decision-making about the assessment and treatment of patients with rheumatologic diseases. It also enables the discussion of both condition and procedure with the patient to ensure a good postoperative care. The article identifies the components of perioperative medical evaluation, discusses perioperative management of co-morbidities and the management of specific clinical problems related to RA, systemic lupus erythematosus, the management of DMARDs, like methotrexate (MTX) and biologic therapies, prophylactic antibiotics, and postoperative follow up, including patient education and rehabilitation.
23929799 Imaging of inflammation by PET, conventional scintigraphy, and other imaging techniques. 2013 Sep Nuclear medicine imaging procedures play an important role in the assessment of inflammatory diseases. With the advent of 3-dimensional anatomic imaging, there has been a tendency to replace traditional planar scintigraphy by CT or MRI. Furthermore, scintigraphic techniques may have to be combined with other imaging modalities to achieve high sensitivity and specificity, and some may require time-consuming labeling procedures. On the other hand, new developments such as combined SPECT/CT increase the diagnostic power of scintigraphy. Also, the advent of PET had a considerable impact on the use of nuclear medicine imaging techniques. In this review, we aim to provide nuclear medicine specialists and clinicians with the relevant information on rational and efficient use of nuclear medicine imaging techniques in the assessment of patients with osteomyelitis, infected vascular prostheses, metastatic infectious disease, rheumatoid arthritis, vasculitis, inflammatory bowel disease, sarcoidosis, and fever of unknown origin.
23864901 Monoester-Diterpene Aconitum Alkaloid Metabolism in Human Liver Microsomes: Predominant Ro 2013 Aconitum, widely used to treat rheumatoid arthritis for thousands of years, is a toxic herb that can frequently cause fatal cardiac poisoning. Aconitum toxicity could be decreased by properly hydrolyzing diester-diterpene alkaloids into monoester-diterpene alkaloids. Monoester-diterpene alkaloids, including benzoylaconine (BAC), benzoylmesaconine (BMA), and benzoylhypaconine (BHA), are the primary active and toxic constituents of processed Aconitum. Cytochrome P450 (CYP) enzymes protect the human body by functioning as the defense line that limits the invasion of toxicants. Our purposes were to identify the CYP metabolites of BAC, BMA, and BHA in human liver microsomes and to distinguish which isozymes are responsible for their metabolism through the use of chemical inhibitors, monoclonal antibodies, and cDNA-expressed CYP enzyme. High-resolution mass spectrometry was used to characterize the metabolites. A total of 7, 8, and 9 metabolites were detected for BAC, BMA, and BHA, respectively. The main metabolic pathways were demethylation, dehydrogenation, demethylation-dehydrogenation, hydroxylation and didemethylation, which produced less toxic metabolites by decomposing the group responsible for the toxicity of the parent compound. Taken together, the results of the chemical inhibitors, monoclonal antibodies, and cDNA-expressed CYP enzymes experiments demonstrated that CYP3A4 and CYP3A5 have essential functions in the metabolism of BAC, BMA, and BHA.
23676145 Aspergillosis after liver transplantation in the context of common variable immunodeficien 2013 Oct Common variable immunodeficiency (CVID) is the most common primary immune defect, resulting in hypogammaglobulinemia as well as deficits in cell-mediated immunity. Although it mainly manifests in immunodeficiency and related infection, CVID can also be associated with autoimmune phenomena such as immune thrombocytopenic purpura, hemolytic anemia, rheumatoid arthritis, lupus, primary biliary cirrhosis, and autoimmune hepatitis (AIH). AIH is a less common but serious complication of CVID, which can result in early cirrhosis, ascites, and even hepatocellular carcinoma. Here, we discuss a recent case of transplantation for cirrhosis secondary to AIH in the context of CVID. Although the patient's surgery occurred without complication, he rapidly developed fulminant alveolar hemorrhage and seizures, and died secondary to disseminated neuroaspergillosis.
27683430 Calcium Influx Characteristics During T Lymphocyte Activation Measured with Flow Cytometry 2013 Jan T lymphocytes are of paramount importance in many intercellular reactions, such as the regulation of the inflammatory response and immune reactivity. Until the recent past, single-cell techniques were used for the investigation of calcium influx during T lymphocyte activation. Therefore, over the recent years we have created a novel approach that allows simultaneous recording of calcium influx in several lymphocyte subsets using flow cytometry. Our research group developed a robust algorithm (FacsKin) for the evaluation of the acquired data that fits functions to median values of the fluorescent marker of interest and calculates relevant parameters describing each function. Over the recent years, we have investigated calcium influx characteristics applying this method in a number of autoimmune disorders and under different physiological conditions (such as the neonatal period and pregnancy). In this review, we aim to give a brief summary of our findings and of the common characteristics of calcium influx in the investigated disorders, namely: multiple sclerosis (MS), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), ankylosing spondylitis (AS), and preeclampsia (PE). Based on our results, a number of dominant features were identified that were present in most of the investigated autoimmune diseases.
22785549 Endobronchial Watanabe spigot embolisation in the treatment of bronchopleural fistula due 2013 Tuberculosis may be complicated with empyema and fistula in patients with cellular immune deficiency. The case presented was a 39-year-old male patient with diagnosis of rheumatoid arthritis developed hydropneumothorax while taking steroid and immunosuppressive treatment and examination of pleural fluid revealed acid-fast bacilli. The patient was admitted to the intensive care unit due to respiratory failure and underwent bronchoscopic examination due to air leakage. The right middle lobe was obliterated by using an endobronchial Watanabe Spigot (EWS), and the amount of leakage decreased considerably after the procedure. On day 7, chest tube drainage was removed, and empyema was drained with a Pezzer drain. On day 50, upon the cessation of empyema drainage, spigots were removed with rigid and flexible bronchoscope. In conclusion, EWS use in the treatment of bronchopleural fistula is an effective, safe and a reversible procedure.
25198784 Catching the therapeutic window of opportunity in early Crohn's disease. 2014 Crohn's disease (CD) is a chronic, disabling, progressive and destructive disease. The general goal of conventional step-up strategy in CD treatment is to treat and control symptoms. This strategy did not change the disease course and is now being replaced with a treat-to-target approach. Achieving deep remission (clinical remission and absence of mucosal ulcerations) is the target in CD in 2014. Inducing and maintaining deep remission is needed to prevent long-term outcomes such as bowel damage and disability in CD. Diagnostic delay is a common issue in CD and is associated with an increased risk of bowel damage over time. Identification of poor prognostic factors, risk stratification together with the development of "red flags" may result in early intervention with disease-modifying agents such as anti-TNF agents with the final aim of preventing overtreatment and avoiding undertreatment. Similar to rheumatoid arthritis, by catching the therapeutic window of opportunity in early CD and achieving deep remission, this could be the best way to change disease course (hospitalizations, surgeries, bowel damage, and disability) and patients' life.
24999308 Interleukin-32 in inflammatory autoimmune diseases. 2014 Jun Interleukin-32 (IL-32) is a cytokine inducing crucial inflammatory cytokines such as tumor necrosis factor-α (TNFα) and IL-6 and its expression is elevated in various inflammatory autoimmune diseases, certain cancers, as well as viral infections. IL-32 gene was first cloned from activated T cells, however IL-32 expression was also found in other immune cells and non-immune cells. IL-32 gene was identified in most mammals except rodents. It is transcribed as multiple-spliced variants in the absence of a specific activity of each isoform. IL-32 has been studied mostly in clinical fields such as infection, autoimmune, cancer, vascular disease, and pulmonary diseases. It is difficult to investigate the precise role of IL-32 in vivo due to the absence of IL-32 gene in mouse. The lack of mouse IL-32 gene restricts in vivo studies and restrains further development of IL-32 research in clinical applications although IL-32 new cytokine getting a spotlight as an immune regulatory molecule processing important roles in autoimmune, infection, and cancer. In this review, we discuss the regulation and function of IL-32 in inflammatory bowel diseases and rheumatoid arthritis.