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ID PMID Title PublicationDate abstract
31182410 Surgical Treatment of Chronic Periprosthetic Joint Infection: Fate of Spacer Exchanges. 2019 Sep BACKGROUND: Patients with periprosthetic joint infection (PJI) undergoing 2-stage exchange arthroplasty may undergo an interim spacer exchange for a variety of reasons including mechanical failure of spacer or persistence of infection. The objective of this study is to understand the risk factors and outcomes of patients who undergo spacer exchange during the course of a planned 2-stage exchange arthroplasty. METHODS: Our institutional database was used to identify 533 patients who underwent a 2-stage exchange arthroplasty for PJI, including 90 patients with a spacer exchange, from 2000 to 2017. A retrospective review was performed to extract relevant clinical information. Treatment outcomes included (1) progression to reimplantation and (2) treatment success as defined by a Delphi-based criterion. Both univariate and multivariate Cox regression models were performed to investigate whether spacer exchange was associated with failure. Additionally, a propensity score analysis was performed based on a 1:2 match. RESULTS: A spacer exchange was required in 16.9%. Patients who underwent spacer exchanges had a higher body mass index (P < .001), rheumatoid arthritis (P = .018), and were more likely to have PJI caused by resistant (0.048) and polymicrobial organisms (P = .007). Patients undergoing a spacer exchange demonstrated lower survivorship and an increased risk of failure in the multivariate and propensity score matched analysis compared to patients who did not require a spacer exchange. DISCUSSION: Despite an additional load of local antibiotics and repeat debridement, patients who underwent a spacer exchange demonstrated poor outcomes, including failure to undergo reimplantation and twice the failure rate. The findings of this study may need to be borne in mind when managing patients who require spacer exchange.
31648579 Indonesians Human Leukocyte Antigen (HLA) Distributions and Correlations with Global Disea 2020 Apr In Human, Major Histocompatibility Complex known as Human Leukocyte Antigen (HLA). The HLA grouped into three subclasses regions: the class I region, the class II region, and the class III region. There are thousands of polymorphic HLAs, many of them are proven to have correlations with diseases. Indonesia consists of diverse ethnicity people and populations. It carries a unique genetic diversity between one and another geographical positions. This paper aims to extract Indonesians HLA allele data, mapping the data, and correlating them with global diseases. From the study, it is found that global diseases, like Crohn's disease, rheumatoid arthritis, Graves' disease, gelatin allergy, T1D, HIV, systemic lupus erythematosus, juvenile chronic arthritis, and Mycobacterial disease (tuberculosis and leprosy) suspected associated with the Indonesian HLA profiles.
31495827 A Novel Chinese Medicine, Xinfeng Capsule, Modulates Proinflammatory Cytokines via Regulat 2019 Sep 9 BACKGROUND Rheumatoid arthritis (RA) is a chronic autoimmune disease targeting joints. This research aimed to explore the effects of Xinfeng capsules (XFC) on cardiac injury in adjuvant arthritis (AA) model rats and assessed the associated mechanism. MATERIAL AND METHODS An adjuvant arthritis (AA) rat model was established by intracutaneously injection with Freund's complete adjuvant (FCA). Model rats were divided into 4 groups: an AA model group, an astragalus polysaccharides (APS) group, a methotrexate (MTX) group, and an XFC and triptolide (TPT) group. Hematoxylin-eosin (HE) staining was used to observe histopathologic changes. TUNEL assay was utilized to evaluate the apoptosis of cardiomyocytes. ELISA was utilized to evaluate levels of tumor necrosis factor alpha (TNF-alpha), interleukin 17 (IL-17), and interleukin 6 (IL-6) in myocardial tissues. Quantitative RT-PCR (qRT-PCR) was used to detect microRNA-21 (miRNA21) levels. Mitogen-activated protein kinase (MAPK)/p38, Toll-like receptor 4 (TLR4), and nuclear kappa B (NF-kappaB)/p65 levels were evaluated using Western blot. RESULTS XFC significantly improved proinflammatory response compared to the AA model group (p<0.05). XFC treatment significantly decreased the number of cells staining TUNEL-positive compared with the model group (p<0.05). XFC treatment significantly reduced TNF-alpha, IL-17, and IL-6 levels in myocardial tissues compared to the model group (p<0.05). Levels of miRNA21 were significantly lower in the XFC group compared to the AA model group (p<0.05). TLR4, MAPK/p38, and NF-kappaB/p65 expression levels were significantly lower in the XFC group than in the model group (p<0.05). CONCLUSIONS Xinfeng capsule, a traditional Chinese medicine preparation, protects against cardiac injury in AA rats by modulating proinflammatory cytokines expression via the TLR4/MAPK/NF-kappaB signaling pathway.
29623845 Is Treat-to-target in Lupus Nephritis Realistic in Clinical Practice? 2019 The Treat-to-Target (T2T) principle has been advocated in a number of inflammatory and non-inflammatory medical illnesses. Tight control of disease activity has been shown to improve the outcome of rheumatoid arthritis and psoriatic arthritis as compared to the conventional approach. However, whether T2T can be applied to patients with lupus nephritis is still under emerging discussion. Treatment of lupus nephritis should target at inducing and maintaining remission of the kidney inflammation so as to preserve renal function and improve survival in the longterm. However, there is no universal agreement on the definition of remission or low disease activity state of nephritis, as well as the time points for switching of therapies. Moreover, despite the availability of objective parameters for monitoring such as proteinuria and urinary sediments, differentiation between ongoing activity and damage in some patients with persistent urinary abnormalities remains difficult without a renal biopsy. A large number of serum and urinary biomarkers have been tested in lupus nephritis but none of them have been validated for routine clinical use. In real life practice, therapeutic options for lupus nephritis are limited. As patients with lupus nephritis are more prone to infective complications, tight disease control with aggressive immunosuppressive therapies may have safety concern. Not until the feasibility, efficacy, safety and cost-effectiveness of T2T in lupus nephritis is confirmed by comparative trials, this approach should not be routinely recommended with the current treatment armamentarium and monitoring regimes.
31703794 Taking the patient and the patient's perspective into account to improve outcomes of care 2019 Jun Patient-reported outcome measures are commonly used in the assessment of patients with musculoskeletal diseases. The present review provides an overview of historic and recent developments, including core set recommendations for assessing patient-reported outcomes in patients with fibromyalgia, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. The evidence supporting commonly used patient-reported outcomes measures is reviewed. Furthermore, various methodological approaches that can be utilized to evaluate validity and measurement precision of patient reported outcomes are introduced. Commonly used methods based on the classical test theory as well as modern approaches based on item response theory will be discussed. The review finally describes the increasing use of item response theory-based approaches used in patient-reported outcomes assessment in the musculoskeletal diseases.
31316589 Scoping review: Diagnosis and management of periprosthetic joint infection in elbow arthro 2019 Aug BACKGROUND: Total elbow arthroplasty is an effective treatment for patients with painful elbow arthritis. Infection can be a serious complication. The aim of this scoping review was to document the available evidence on periprosthetic elbow infection. METHODS: A search of Medline, Embase and PubMed was performed; two authors screened results independently. Systematic reviews, randomised controlled trials, cohort studies, case-control studies and case series including periprosthetic elbow infection were eligible. RESULTS: A total of 46 studies were included. The median rate of periprosthetic elbow infection reported from recent published studies is 3.3%. The most commonly identified causative organisms are Staphylococcus aureus and Staphylococcus epidermidis. Risk factors include younger age, rheumatoid arthritis, obesity, previous surgery or infection to the elbow, and postoperative wound complications. Debridement, antibiotics and implant retention results in implant survival rates of 50-90%. Two-stage revision results in improved functional outcome scores, but with recurrent infection rates of 12-28%. CONCLUSIONS: Total elbow arthroplasty carries a higher risk of infection when compared to other major joint replacements. The current body of literature is limited and is almost exclusively low volume retrospective case series. The best management of periprosthetic elbow infection is difficult to determine, but two-stage revision appears to be the gold standard.
31060597 Correction to: Drug tolerability and reasons for discontinuation of seven biologics in 446 2019 May 6 Following publication of the original article [1], the authors noticed that two corrections were not implemented during the production process.
30881306 Triggering the Resolution of Immune Mediated Inflammatory Diseases: Can Targeting Leukocyt 2019 Leukocyte recruitment is a pivotal process in the regulation and resolution of an inflammatory episode. It is vital for the protective responses to microbial infection and tissue damage, but is the unwanted reaction contributing to pathology in many immune mediated inflammatory diseases (IMIDs). Indeed, it is now recognized that patients with IMIDs have defects in at least one, if not multiple, check-points regulating the entry and exit of leukocytes from the inflamed site. In this review, we will explore our understanding of the imbalance in recruitment that permits the accumulation and persistence of leukocytes in IMIDs. We will highlight old and novel pharmacological tools targeting these processes in an attempt to trigger resolution of the inflammatory response. In this context, we will focus on cytokines, chemokines, known pro-resolving lipid mediators and potential novel lipids (e.g., sphingosine-1-phosphate), along with the actions of glucocorticoids mediated by 11-beta hydroxysteroid dehydrogenase 1 and 2.
30789012 Practical Guidelines for Managing Patients With Psoriasis on Biologics: An Update. 2019 Jan/Feb The paradigm for treating inflammatory diseases has shifted dramatically in the past 10 to 20 years with the discovery of targeted therapeutics or "biologic" agents. Patients with rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis, and psoriasis, among others, are reaping the benefits of decades of bench to bedside research, allowing them to live more productive lives with less side effects than traditional systemic therapies. Despite these advances, many physicians unfamiliar with biologics are left to care for the basic needs of these patients and may be unaware of the multisystem comorbidities associated with psoriasis and the screening, monitoring, and other special considerations required of biologics patients. This can be overwhelming to primary care physicians and inadvertently expose patients to undue risks. The aim of this review is to provide a practical approach for all health care providers caring for patients with psoriasis being treated with biologics to facilitate communication with their treating dermatologist and ultimately provide patients with more comprehensive care.
31649847 Kinsenoside attenuates osteoarthritis by repolarizing macrophages through inactivating NF- 2019 Sep The objective was to investigate the effect of kinsenoside (Kin) treatments on macrophage polarity and evaluate the resulting protection of chondrocytes to attenuate osteoarthritis (OA) progression. RAW264.7 macrophages were polarized to M1/M2 subtypes then administered with different concentrations of Kin. The polarization transitions were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR), confocal observation and flow cytometry analysis. The mechanism of Kin repolarizing M1 macrophages was evaluated by Western blot. Further, macrophage conditioned medium (CM) and IL-1β were administered to chondrocytes. Micro-CT scanning and histological observations were conducted in vivo on anterior cruciate ligament transection (ACLT) mice with or without Kin treatment. We found that Kin repolarized M1 macrophages to the M2 phenotype. Mechanistically, Kin inhibited the phosphorylation of IκBα, which further reduced the downstream phosphorylation of P65 in nuclear factor-κB (NF-κB) signaling. Moreover, Kin inhibited mitogen-activated protein kinases (MAPK) signaling molecules p-JNK, p-ERK and p-P38. Additionally, Kin attenuated macrophage CM and IL-1β-induced chondrocyte damage. In vivo, Kin reduced the infiltration of M1 macrophages, promoted M2 macrophages in the synovium, inhibited subchondral bone destruction and reduced articular cartilage damage induced by ACLT. All the results indicated that Kin is an effective therapeutic candidate for OA treatment.
31271739 Elevated circulating IL-17 level is associated with inflammatory arthritis and disease act 2019 Sep OBJECTIVES: Previous studies found that the interleukin (IL)-17 level was elevated in inflammatory arthritis, but results were inconsistent. This meta-analysis aimed to investigate the association of IL-17 cytokine with osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: Relevant studies were searched using databases. Standardized mean difference (SMD) was calculated. Correlation coefficient was utilized to evaluate the relationship between IL-17 and disease activity of AS and RA. Subgroup analysis, sensitivity analysis and meta-regression were applied to explore the sources of heterogeneity. RESULTS: 83 records were enrolled. The IL-17 level was elevated in AS (SMD = 2.348, P < .001), RA (SMD = 1.502, P < .001), PsA (SMD = 1.710, P < .001) and OA (SMD = 1.192, P = .016), and similar results occurred in subgroup analysis. Furthermore, the IL-17 level was positively associated with disease activity of AS and RA. CONCLUSION: Circulating IL-17 level is significantly elevated in inflammatory arthritis and is related to the disease activity of AS and RA, suggesting that it plays an important role in the pathogenesis and progression of inflammatory arthritis (especially in AS and RA).
31173610 Upregulation of sphingosine-1-phosphate receptor 3 on fibroblast-like synoviocytes is asso 2019 BACKGROUND: Sphingosine-1-phosphate receptor 3 (S1P3) is one of five receptors for sphingosine-1-phosphate (S1P). S1P/S1P3 signaling is involved in numerous physiological and pathological processes including bone metabolism, sepsis, cancer, and immunity. In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLSs) are activated by several factors and promote abundant proinflammatory cytokine production and bone destruction. The aim of this study was to investigate whether S1P3 is associated with the development of autoimmune arthritis and the pathogenic function of FLSs. METHODS: Wild-type (WT) and S1P3 knockout (S1P3-KO) collagen-induced arthritis (CIA) mice were evaluated with respect to clinical and histological disease severity, along with the levels of anti-collagen antibodies and expression of tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6). S1P3 expression in the synovium was analyzed by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining. FLSs isolated from CIA mice were activated with TNFα and S1P3 expression was analyzed by real-time RT-PCR. The role of S1P/S1P3 signaling in activated and non-activated FLSs was investigated by measuring cell proliferation and cyto/chemokine production by real-time RT-PCR and/or enzyme-linked immunosorbent assay. RESULTS: Clinical and histological scores, and synovial IL-6 expression were significantly lower in S1P3-KO mice with CIA than in WT mice. Arthritic synovia had higher S1P3 expression than intact synovia and FLSs in arthritic joints expressed S1P3 in vivo. Primary cultured FLSs produced IL-6 in a time-dependent manner in response to S1P stimulation and exhibited higher levels of S1P3 expression after activation with TNFα. S1P3-induced production of IL-6 and MMP-3 was increased in FLSs pre-activated with TNFα. CONCLUSION: In this study, we demonstrated that S1P3 expression is associated with the development of autoimmune arthritis via inflammation-induced increases in S1P/S1P3 signaling that increase production of IL-6 in FLSs. Inhibition of S1P/S1P3 signaling could open the door to the development of new therapies for RA.
31842923 Oral health and plaque microbial profile in juvenile idiopathic arthritis. 2019 Dec 16 BACKGROUND: The oral microbiota has been implicated in the pathogenesis of rheumatoid arthritis through activation of mucosal immunity. This study tested for associations between oral health, microbial communities and juvenile idiopathic arthritis (JIA). METHODS: A cross-sectional exploratory study of subjects aged 10-18 years with oligoarticular, extended oligoarticular and polyarticular JIA was conducted. Control groups included pediatric dental clinic patients and healthy volunteers. The primary aim was to test for an association between dental health indices and JIA; the secondary aim was to characterize the microbial profile of supragingival plaque using 16S rRNA gene sequencing. RESULTS: The study included 85 patients with JIA, 62 dental patients and 11 healthy child controls. JIA patients overall had significantly more gingival inflammation compared to dental patients, as evidenced by bleeding on probing of the gingiva, the most specific sign of active inflammation (p = 0.02). Overall, however, there was a trend towards better dental hygiene in the JIA patients compared to dental patients, based on indices for plaque, decay, and periodontitis. In the JIA patients, plaque microbiota analysis revealed bacteria belonging to genera Haemophilus or Kingella elevated, and Corynebacterium underrepresented. In poly JIA, bacteria belonging to the genus Porphyromonas was overrepresented and Prevotella was underrepresented. CONCLUSION: Increased gingival inflammation in JIA was independent of general oral health, and thus cannot be attributed to poor dental hygiene secondary to disability. The variation of microbial profile in JIA patients could indicate a possible link between gingivitis and synovial inflammation.
31777836 Prevalence and Characteristics of Metabolic Syndrome Differ in Men and Women with Early Rh 2019 Nov OBJECTIVE: Metabolic syndrome (MetS) prevalence in early rheumatoid arthritis (ERA) is conflicting. The impact of sex, including menopause, has not been described. We estimated the prevalence and factors associated with MetS in men and women with ERA. METHODS: A cross-sectional study of the Canadian Early Arthritis Cohort (CATCH) was performed. Participants with baseline data to estimate key MetS components were included. Sex-stratified logistic regression identified baseline variables associated with MetS. RESULTS: The sample included 1543 participants; 71% were female and the mean age was 54 (SD 15) years. MetS prevalence was higher in men 188 (42%) than women 288 (26%, P < 0.0001) and increased with age. Frequent MetS components in men were hypertension (62%), impaired glucose tolerance (IGT, 40%), obesity (36%), and low high-density lipoprotein cholesterol (36%). Postmenopausal women had greater frequency of hypertension (65%), IGT (32%), and high triglycerides (21%) compared with premenopausal women (P < 0.001). In multivariate analysis, MetS was negatively associated with seropositivity and pulmonary disease in men. Increasing age was associated with MetS in women. In postmenopausal women, corticosteroid use was associated with MetS. Psychiatric comorbidity was associated with MetS in premenopausal women. MetS status was not explained by disease activity or core RA measures. CONCLUSION: The characteristics and associations of MetS differed in men and women with ERA. Sex differences, including postmenopausal status, should be considered in comorbidity screening. With this knowledge, the interplay of MetS, sex, and RA therapeutic response on cardiovascular outcomes should be investigated.
31153707 Elevated serum globulin gap as a highly reliable marker of elevated erythrocyte sedimentat 2019 Dec OBJECTIVE: Serum C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) are the two most commonly used markers of inflammation in clinical practice. Reducing the need for these tests could lead to considerable cost savings without sacrificing the quality of patient care. METHODS: The electronic medical records of patients with systemic rheumatic diseases seen between May 2015 and June 2017 in the rheumatology clinics at a single academic medical center were retrospectively reviewed. Correlations and receiver operator characteristic (ROC) curves between serum CRP level and ESR vs serum globulin gap (the difference between levels of total protein and albumin) and albumin-to-globulin (A:G) ratio were determined. RESULTS: In two independent cohorts (discovery: 263 subjects, 446 entries; validation: 438 subjects, 1959 entries), the globulin gap and A:G ratio correlated (p < 0.001) with CRP level and ESR, with correlation coefficients being greater for ESR than for CRP level. ROC curve analyses demonstrated better area-under-curve for ESR than for CRP level. The percentages of entries with elevated globulin gap (≥4.0 g/dl) and low A:G ratio (<0.8) were ∼8.4% and ∼2.6%, respectively, and each had a positive predictive value of ≥0.960 for elevated ESR. Among patients with high globulin gap, the change in globulin gap over time faithfully reflected changes in ESR. CONCLUSION: In the subset of systemic rheumatic disease patients who harbor an elevated globulin gap, the ESR is almost always elevated. This novel observation sets the conceptual foundation and rationale for subsequent prospective studies that assess whether ESR testing in this subset of rheumatic disease patients could be reduced without sacrificing patient care. Ultimately, ordering an ESR test may often be unnecessary, thereby resulting in cost savings.
31777827 Joint Estimation of Remission and Response for Methotrexate-Based DMARD Options in Rheumat 2019 Oct OBJECTIVE: To jointly estimate American College of Rheumatology (ACR50) response (a more commonly reported outcome) and remission (a more clinically relevant outcome) for methotrexate (MTX)-based treatment options in rheumatoid arthritis (RA). METHODS: We conducted a bivariate network meta-analysis (NMA) to compare MTX monotherapy and MTX-based conventional and biologic disease-modifying antirheumatic drug (DMARD) combinations for RA. The correlation between the outcomes was derived from an incident RA cohort study, whereas the treatment effects were derived from randomized trials in the network of evidence. The analyses were conducted separately for MTX-naïve and MTX-inadequate response (IR) populations in a Bayesian framework with uninformative priors. RESULTS: From the cohort study, the correlation between ACR50 response and Disease Activity Score 28 remission at 6 months was moderate (Pearson correlation coefficient = 0.58). In the bivariate NMA for MTX-naïve populations, most combinations of MTX with either biologic or tofacitinib were statistically superior to MTX alone for both ACR50 response and remission. Triple therapy (MTX + sulfasalazine + hydroxychloroquine) was the only nonbiologic DMARD statistically superior to MTX for either ACR50 response (odds ratio [OR] 95% credible interval: 2.1 [1.0, 4.3]) or remission (OR: 2.5 [1.0, 5.8]). In the MTX-IR analysis, all treatments except MTX + sulfasalazine were statistically superior to MTX alone. Compared to analyzing the outcomes separately, the bivariate model often resulted in more precise estimates and allowed remission to be estimated for all treatments. CONCLUSION: Borrowing the strength of correlation between outcomes allowed us to demonstrate a statistically significant benefit for remission across most MTX-based DMARD combinations, including triple therapy.
31515140 Early Antibody-Mediated Kidney Transplant Rejection Associated With Anti-Vimentin Antibodi 2020 Jan Improving precision in predicting alloreactivity is an important unmet need and may require individualized consideration of non-HLA antibodies. We report a 21-year-old man with kidney failure from immunoglobulin A nephropathy who met all traditional criteria for a "low-risk" transplant for immune memory. He was unsensitized and received a haplotype-matched living donor kidney transplant from his mother. There were no anti-HLA donor-specific antibodies and flow cross-match was negative. After immediate function, he developed delayed graft function on postoperative day 2. The transplant biopsy specimen was suggestive of antibody-mediated rejection and acute tubular injury with increased vimentin proximal tubular expression compared to the implantation biopsy specimen. He had a history of juvenile idiopathic arthritis, and non-HLA antibody screening demonstrated preformed anti-vimentin antibody. He was successfully treated with plasmapheresis, intravenous immunoglobulin, antithymocyte globulin, and methylprednisolone, with renal recovery. The follow-up biopsy specimen demonstrated decreased vimentin expression with decreased alloinflammation, and graft function remains stable at 1 year posttransplantation (estimated glomerular filtration rate, 62mL/min/1.73m(2)). We postulate that preformed anti-vimentin autoantibodies bound to vimentin expressed on apoptotic tubular epithelial cells induced by ischemia-reperfusion injury and to constitutively expressed vimentin on peritubular capillaries and podocytes. Our case is suggestive of the involvement of anti-vimentin antibody, for which the pathogenic epitopes may be exposed during ischemia-reperfusion injury.
31523783 Interleukin-6 inhibition in the management of non-infectious uveitis and beyond. 2019 Sep 16 BACKGROUND: Uveitis consists of a spectrum of inflammatory disorders characterized by ocular inflammation. The underlying pathophysiology consists of a complex interplay of various inflammatory pathways. Interleukin 6 is an important mediator of inflammation in uveitis and constitutes focus of research toward development of newer biological therapies in the management of non-infectious uveitis. MAIN BODY: Pan-blockade of the inflammatory pathways with steroids is generally the first step in the management of acute non-infectious uveitis. However, long-term therapy with steroids is associated with systemic and ocular side effects, thereby necessitating the need for development of steroid sparing agents. IL-6 is a cytokine produced by various immune cells, in response to molecular patterns and affects multiple inflammatory cells. In particular, IL-6 is involved in differentiation of CD-4 cells into Th-17 cells that have been shown to play a significant role in various immune-mediated diseases such as uveitis. This broad-spectrum immunomodulatory activity makes IL-6 an excellent target for immunomodulatory therapy. Tocilizumab was the first IL-6 inhibitor to demonstrate efficacy in humans. It inhibits IL-6 from binding to both membrane-bound and soluble receptor and can be administered via intravenous (IV) and subcutaneous (SC) routes. It has been FDA approved for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Following the approval in systemic diseases, its efficacy was demonstrated in various uveitis studies including a phase 2 clinical trial (STOP-Uveitis). Overall, tocilizumab has shown a good safety profile with the risk of malignancy consistent with that expected in patients with rheumatoid arthritis. However, tocilizumab therapy has been shown to increase the risk for gastrointestinal perforation and dose-dependent neutropenia. Following the success of tocilizumab, several other agents targeting the IL-6 pathway are in the pipeline. These include sirukumab, siltuximab, olokizumab, clazakizumab, and EBI-031 which target IL-6; Sarilumab and ALX-0061 act on the IL-6 receptor. CONCLUSION: Studies have shown that IL-6 inhibitors can be effective in the management of NIU. In addition, the levels of IL-6 are elevated in other ocular vascular diseases such as retinal vein occlusion and diabetic macular edema. The roles of IL-6 inhibition may be broadened in the future to include the management of retinal vascular diseases and non-uveitic macular edema.
31157683 Acquired von Willebrand syndrome in a patient with small lymphocytic lymphoma and Sjögren 2019 Jul : Acquired von Willebrand syndrome (AVWS) is a rare hemorrhagic condition that poses both a diagnostic and a therapeutic challenge. Here we report a singular case of AVWS with two associated conditions, small lymphocytic lymphoma (SLL) and Sjögren's syndrome. The patient presented with recurrent and severe digestive bleeding that forced us to raise a curative attempt of AVWS. A first immunosuppressive therapy with immunoglobulins was unsuccessful and it was later decided to treat lymphoproliferative entity with bendamustine and rituximab effectively achieving SLL and AVWS remission. On the basis of our case and through literature review, we discuss potential strategies to achieve AVWS remission when it appears in the setting of several causative associated conditions.
31570207 Non- Hodgkin lymphoma of the lips: A rare entity. 2019 Nov AIM: To investigate clinico-pathological features of lymphoma of the lips, and review the literature. MATERIALS AND METHODS: Retrospective analysis and review of English literature, 1996-2016. RESULTS: Analysis included 23 cases, 7 new cases and 16 from literature, 12 M: 11 F, age 7-82 years. Four occurred in children, mean age 10.1; 19 in adults, mean 61.1 years. The lower lip was involved in the majority of cases (16, 69.56%). 14 (60.87%) were isolated to the lips, 8 (34.78%) were multifocal. Nine (39.13%) occurred in association with Sjogren's syndrome, of which one also had Hashimoto thyroiditis. IgG4-related disease and HIV were reported in one case each. The lip salivary glands were involved in most cases (19, 82.6%); 3 (13.6%) showed only cutaneous involvement. The typical presentation was single or multiple nodules (15, 65.21%), with surface ulceration in only two (8.69%). Constituent symptoms were absent in all cases, paresthesia was reported in one (4.34%). The majority (18, 78.26%) was extranodal marginal zone B-cell lymphoma - mucosa-associated lymphoid tissue lymphoma (EMZB-MALT), and one case each was mantle cell, NK-T cell, CD30 positive and plasmablastic lymphoma. CONCLUSION: The lips seem to have a unique pattern of non-Hodgkin lymphoma dominated by EMZB-MALT lymphoma, rarely other types. In more than half, neither Sjogren's syndrome nor other chronic inflammation was identified. Lesions tend to present as asymptomatic slowly progressing, non-ulcerated submucosal masses. Lymphoma should be considered even in the absence of constituent symptoms, as most cases showed none. Although the number of reported cases is rather small, disease course is usually prolonged and prognosis seems to be good.