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ID PMID Title PublicationDate abstract
33266300 TGF-β Pathway in Salivary Gland Fibrosis. 2020 Nov 30 Fibrosis is presented in various physiologic and pathologic conditions of the salivary gland. Transforming growth factor beta (TGF-β) pathway has a pivotal role in the pathogenesis of fibrosis in several organs, including the salivary glands. Among the TGF-β superfamily members, TGF-β1 and 2 are pro-fibrotic ligands, whereas TGF-β3 and some bone morphogenetic proteins (BMPs) are anti-fibrotic ligands. TGF-β1 is thought to be associated with the pro-fibrotic pathogenesis of sialadenitis, post-radiation salivary gland dysfunction, and Sjögren's syndrome. Potential therapeutic strategies that target multiple levels in the TGF-β pathway are under preclinical and clinical research for fibrosis. Despite the anti-fibrotic effect of BMPs, their in vivo delivery poses a challenge in terms of adequate clinical efficacy. In this article, we will review the relevance of TGF-β signaling in salivary gland fibrosis and advances of potential therapeutic options in the field.
33026728 [Sjögren Syndrome : the ENT specialist contributes to the workup]. 2020 Oct 7 Sjögren Syndrome is an autoimmune disorder presenting as Sicca syndrome (dry-eye, dry mouth) and most often multiorgan involvement with various clinical manifestations. The diagnostic criteria defined by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) include biologic, histologic parameters and functional measurements. Part of this workup can be performed by the ENT specialist. It encompasses minor salivary gland biopsy, sialometry, Schirmer lacrymal test and major salivary gland ultrasound. These tests and their performances are described. The growing importance of major salivary gland ultrasound as a follow-up and diagnostic tool is also discussed in this article.
33313242 Ginkgolide B attenuates collagen-induced rheumatoid arthritis and regulates fibroblast-lik 2020 Nov BACKGROUND: Rheumatoid arthritis (RA) is a systemic disease characterized by chronic synovial infiltration and proliferation, cartilage destruction, and joint injury. Ginkgolide B (GB) is an extract of the leaves of Ginkgo biloba, and pharmacological studies have shown that it has anti-inflammatory and anti-apoptotic activities. The purpose of this study was to investigate the anti-RA properties of GB. METHODS: In vivo, we established a collagen II-induced arthritis (CIA) mouse model. Mice were divided into five groups (n=10): sham, CIA, GB (10 µM), GB (20 µM), and GB (40 µM). We measured arthritis score, synovial histopathological change, and peripheral blood cytokine levels. In vitro, we used lipopolysaccharide (LPS)-induced-fibroblast-like synoviocytes (RA-FLSs) as the study subject. Cell viability, apoptosis, and inflammatory cytokines levels were detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, flow cytometry, and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), respectively. Finally, the protein expression of wingless-type family member 5A (Wnt5a), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 were detected by Western blot. RESULTS: Arthritis scores, synovial hyperplasia, and cartilage and bone destruction were significantly ameliorated by GB. Additionally, GB decreased the serum levels of interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α), matrix metalloproteinase (MMP)-3 and MMP-13, and increased IL-10. In vitro, we found that GB remarkably inhibited RA-FLSs viability at 24 or 48 h in a concentration-dependent manner. The apoptotic ratio was reduced by GB, and it increased the expression of cleaved-Caspase-3 and Bax while decreasing Bcl-2 expression in RA-FLSs. Furthermore, GB attenuated the progression of inflammation by mediating inflammatory cytokine release and MMPs gene expression. Meanwhile, GB inactivated the expression levels of Wnt5a, phosphorylated (p)-JNK, and p-P65 in the synovial tissues and RA-FLSs. CONCLUSIONS: This study was the first to demonstrate that the anti-RA effect of GB is related to reducing articular cartilage and bone destruction, inducing RA-FLSs apoptosis, and regulating inflammatory cytokine release and the Wnt5a/JNK/NF-κB axis. All the findings highlight that GB might provide a novel treatment approach for RA.
33034861 Implementation and Evaluation of Audit and Feedback for Monitoring Treat-to-Target (T2T) S 2020 Dec INTRODUCTION: In collaboration with the Alberta Medical Association's Physician Learning Program we developed individualized physician reports and held a group feedback session on rheumatoid arthritis (RA) performance measures (PM) to facilitate treat-to-target (T2T) strategies and evaluated physician experiences with this process. METHODS: 5 PMs addressing T2T concepts from an established Canadian quality framework were operationalized for physician practice reports at 2 university-affiliated rheumatology clinics. Rheum4U, a quality improvement and research platform, was the data source. The audit results were reviewed in a facilitated group feedback session. Rheumatologists provided experiential feedback on the process through survey and/or an interview. Transcripts from interviews were analyzed using a 6-step thematic analysis. RESULTS: 11 of 12 eligible rheumatologists consented to receive practice reports and provided feedback through surveys (n = 5) and interviews (n = 6). The practice reports from Rheum4U (n = 448 patients) revealed high rates of yearly follow-up (> 85%, PM1) and 100% performance on documentation of disease activity at ≥ 50% of visits (PM2). Only 34% of patients were seen within 3 months if not in remission (PM3) with 62% (2017) and 69% (2018) of those with active RA achieving a LDA state within 6 months (PM4). Approximately 70% of patients were in remission at any time point (PM5). All survey respondents agreed or strongly agreed comparison to peers was valuable and helped them reflect on their practice. Several strategies for improvement were identified, including but not limited to, leveraging of electronic records for future audit and feedback reports, providing additional granularity of results, additional stratification of results, and using high-performing peers as the comparator rather than the group mean. CONCLUSIONS: Audit and feedback was perceived by clinicians as a useful strategy for evaluating T2T efforts in RA. Future work will focus on longitudinal evaluation of the clinical impact of this quality improvement initiative.
32314938 Fibromyalgia, Sjogren's & depression: linked? 2020 Sep Health care has become increasingly fragmented, partly due to advancing medical technology. Patients are often managed by various specialty teams when presenting with symptoms that could be manifestations of different diseases. Approximately one third of them are referred to specialists, at over half for outpatient appointments. Fatigue, pain, depression, dry mouth, headaches, and arthralgia are common complaints and frequently require referral to specialist physicians. Differential diagnoses include fibromyalgia (FM), Sjogren's syndrome (SS), and depression. Evaluations involve various sub-specialist especially physicians like those practicing pain management, rheumatology, and psychiatry. Thresholds for referring vary. Patients sometime feel lost in a 'medical maze'. Disagreement is frequent between specialties regarding management. Each discipline has its own diagnostic and treatment protocols and there is little consensus about shared decision-making. Communication between doctors could improve continuity. There are many differences and similarities in the pathophysiology, symptomatology, diagnosis, and treatment of fibromyalgia, Sjogren's syndrome, and depression. Understanding the associations between fibromyalgia, Sjogren's syndrome and depression should improve clinical outcome via a common holistic approach.
32550868 Acute mental health service use is increased in rheumatoid arthritis and ankylosing spondy 2020 BACKGROUND: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with mental illness. Whether acute mental health (MH) service utilization (i.e. emergency visits or hospitalizations) is increased in RA or AS is not known. METHODS: Two population-based cohorts were created where individuals with RA (n = 53,240) or AS (n = 13,964) were each matched by age, sex, and year to unaffected comparators (2002-2016). Incidence rates per 1000 person-years (PY) were calculated for a first MH emergency department (ED) presentation or MH hospitalization. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated, adjusting for demographic, clinical, and health service use variables. RESULTS: Individuals with RA had higher rates of ED visits [6.59/1000 person-years (PY) versus 4.39/1000 PY in comparators] and hospitalizations for MH (3.11/1000 PY versus 1.80/1000 PY in comparators). Higher rates of ED visits (7.92/1000 PY versus 5.62/1000 PY in comparators) and hospitalizations (3.03/1000 PY versus 1.94/1000 PY in comparators) were also observed in AS. Overall, RA was associated with a 34% increased risk for MH hospitalization (HR 1.34, 95% CI 1.22-1.47) and AS was associated with a 36% increased risk of hospitalization (HR 1.36, 95% CI 1.12-1.63). The risk of ED presentation was attenuated, but remained significant, after adjustment in both RA (HR 1.08, 95% CI 1.01-1.15) and AS (HR 1.14, 95% CI 1.02-1.28). CONCLUSIONS: RA and AS are both independently associated with a higher rate and risk of acute ED presentations and hospitalizations for mental health conditions. These findings underscore the need for routine evaluation of MH as part of the management of chronic inflammatory arthritis. Additional research is needed to identify the underlying individual characteristics, as well as system-level variation, which may explain these differences, and to help plan interventions to make MH service use more responsive to the needs of individuals living with RA and AS.
32570853 Exposure to Aggregatibacter actinomycetemcomitans before Symptom Onset and the Risk of Evo 2020 Jun 18 Periodontal disease has been implicated in the pathogenesis of rheumatoid arthritis (RA), an autoimmune disease characterized by immune-mediated synovial damage, and antibodies to citrullinated antigens. Here, we investigate the association between exposure to the periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa) and the development of RA. IgM, IgG and IgA antibodies to Aa leukotoxin A (LtxA) were detected by ELISA in plasma from a cohort of Swedish adults at different stages of RA development, from before onset of symptoms to established disease. Patients with early and established RA had increased levels of anti-LtxA IgM compared with matched non-RA controls and periodontally healthy individuals. Logistic regression revealed that anti-LtxA IgM levels were associated with RA during early disease (OR 1.012, 95%CI 1.007, 1.017), which was maintained after adjustment for smoking, anti-CCP antibodies, rheumatoid factor, HLA-DRB1 shared epitope alleles and sex. We found no association between anti-LtxA IgG/IgA antibodies and RA at any stage of disease development. The data support a temporal association between anti-LtxA IgM antibodies and the development of RA, suggesting that a subset of RA patients may have been exposed to Aa around the time of transition from being asymptomatic to become a patient with RA.
33327432 Impact of Mediterranean Diet on Disease Activity and Gut Microbiota Composition of Rheumat 2020 Dec 14 Rheumatoid arthritis (RA) is an autoimmune disorder in which gut and oral microbiota play a crucial role. Diet is a modifiable factor that can influence both microbiota composition and arthritis outcome; previous studies have suggested associations between dietary habits and RA, with contrasting results. We investigate the protective effect of the Mediterranean diet (MD) on disease activity and the gut microbiota profile in RA patients. Sixty consecutive RA patients were enrolled upon filling a validated 14-item questionnaire for the assessment of adherence to the Mediterranean diet (Prevention with Mediterranean Diet-PREDIMED). Then, 16S analysis was employed to explore the gut microbiota within the two cohorts of patients. Patients with high adherence to MD (20) had a significantly lower C-reactive protein (p < 0.037) and disease activity (p < 0.034) than the 40 patients with low/moderate adherence to MD. An inverse association between MD and disease activity was confirmed by multivariate analysis after adjustments for all the different demographic, clinical and serologic variables. A healthier gut microbiota composition was observed in the high adherence group, with a significant decrease in Lactobacillaceae and an almost complete absence of Prevotella copri with respect to the low/moderate adherence group. In conclusion, our findings support the protective role of MD on disease activity and microbiota composition in RA patients, and suggest the feasibility of shifting the habitual diet to modulate the gut microbiota and promote the benefits associated with MD.
31902746 Silencing of Long Non-coding RNA HOTTIP Reduces Inflammation in Rheumatoid Arthritis by De 2020 Mar 6 Accumulating evidence suggests long non-coding RNAs (lncRNAs) play crucial roles in the pathogenesis of rheumatoid arthritis (RA). Here, we aimed to define the role of HOXA transcript at the distal tip (HOTTIP) in RA pathogenesis in relation to SFRP1 methylation and Wnt signaling pathway. HOTTIP was found highly expressed, and SFRP1 was hypermethylated in RA synovial fibroblasts (RASFs). Next, gain- or loss-of-function experiments were conducted in RASFs to explore the effects of HOTTIP on the biological behaviors of RASFs. Silencing of HOTTIP or overexpression of SFRP1 inhibited RASF proliferation, invasion, and migration, while enhancing apoptosis. The relationship among HOTTIP, SFRP1, and Dnmt3b was determined using methylation-specific PCR (MSP), bisulfite sequencing PCR (BSP), RNA pull-down, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) assays. The regulatory mechanisms of HOTTIP/Dnmt3b/SFRP1 were explored by altering their expression in RASFs. It was noted that HOTTIP could induce SFRP1 promoter methylation through recruitment of Dnmt3b and activate the Wnt signaling pathway. Finally, a rat RA model was established in order to evaluate the in vivo effects of HOTTIP and SFRP1, which suggested that HOTTIP silencing or SFRP1 elevation inhibited the progression of RA in vivo. Our key findings demonstrate the anti-inflammatory ability of HOTTIP silencing in RA through SFRP1 promoter demethylation. These findings support HOTTIP as a candidate anti-arthritis target.
31950322 Anti-arthritic Effect of the Spirocyclopiperazinium Salt Compound LXM-15 in Rats and Its 2020 Jun In this study, we aimed to evaluate the effects of the spirocyclopiperazinium salt compound LXM-15 on rheumatoid arthritis induced by complete Freund's adjuvant (CFA) in rats and investigate the underlying mechanism. The results showed that LXM-15 significantly inhibited the paw edema and ankle swelling, and alleviated the mechanical allodynia and thermal hyperalgesia responses in the CFA rats. The histopathological results revealed that LXM-15 ameliorated the infiltration of inflammatory cells and joint destruction. The micro-CT scan showed that LXM-15 alleviated bone erosion and increased BMD in the ankle joints of the CFA rats. Western blot analyses showed that LXM-15 significantly reduced the upregulation of phospho-JAK2, phospho-STAT3, phospho-IκBα, and phospho-NF-κBp65, and the overexpression of BDNF in the dorsal root ganglions. ELISA result showed that the protein level of TNF-α in the paw tissue was decreased upon LXM-15 treatment. RT-PCR analysis showed that the mRNA expression levels of c-fos and BDNF were reduced in the dorsal root ganglions by LXM-15 treatment. The LXM-15-mediated anti-arthritic effects were abolished by treatment with hexamethonium (a peripheral nicotinic receptor antagonist), atropine methylnitrate (a peripheral muscarinic receptor antagonist), methyllycaconitine citrate (a selective α7 nicotinic receptor antagonist), and tropicamide (a selective M4 muscarinic receptor antagonist). Collectively, our results demonstrate that LXM-15 exerts anti-arthritic effects in CFA rats. The underlying mechanism may be related to the activation of the peripheral α7 nicotinic receptor and M4 muscarinic receptor by LXM-15, further suppressing the activation of the JAK2/STAT3 and IκBα/NF-κBp65 signaling pathways and, eventually, inhibiting the expression levels of TNF-α, BDNF, and c-fos.
33513531 Juvenile idiopathic arthritis, gait characteristics and relation to function. 2021 Mar BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is a chronic inflammatory arthritis that impacts biomechanical features of gait. This systematic review describes the effects of JIA on gait motion parameters and walking performance. METHODS: Six databases were searched (PubMed/Medline, Cochrane, the EBSCOHost database SPORTDiscus, Web of Science, and Embase). Studies were restricted to children with any subtype of JIA who were assessed for gait motion features (kinematic, kinetic, temporalspatial) or walking performance (velocity or distance covered); could include intervention or treatment exposure with measures of gait and gait speed; could involve comparison of gait in JIA to healthy controls. Quality of evidence was assessed using the GRADE system. This systematic review was registered at PROSPERO (CRD42018109582) RESULTS: The search yielded 625 papers, 23 of which described biomechanical features of gait and/or assessed walking performance. Twenty studies measured walking velocity and walking ability using simple field tests or laboratory methods. Eleven studies measured temporalspatial parameters such as cadence, step length, stride length, step width, single and double support time. Nine studies evaluated kinetic measurements including joint power, flexion and extension and joint moments. Nine studies evaluated kinematic parameters including range of motion, pelvic tilt, center of motion and trunk sway. CONCLUSIONS: Key features of gait in children with JIA include slower gait velocity, shortened step length, decreased range of motion at the hip, knee and ankle with trend towards flexion, decreased joint power, anteriorly tilted pelvis and trunk with shifted center of motion. There is a potential to ameliorate JIA-related gait changes with exercise and/or pharmaceutical interventions.
32176556 Personalized medicine in rheumatic diseases: how close are we to being able to use genetic 2020 Apr Introduction: A genetic biomarker to select which drug will work best for which patients with rheumatic diseases is a goal of pharmacogenetic precision medicine approaches and one that patients and the public support. However, studies to date have yielded inconsistent findings with no robustly replicated or clinically useful genetic biomarkers emerging.Areas covered: Using studies investigating biomarkers to predict response to tumor necrosis factor inhibitor therapies in rheumatoid arthritis as an exemplar, we consider factors that reduce the power to detect such predictive biomarkers, including non-adherence, immunogenicity, the use of clinical outcome measures comprising composite scores and sample size. We argue that the biologic therapies were developed to target joint inflammation and so the outcome measure should be closer to the biology and, ideally, should be a biological measure. Given that heritability studies have shown a substantial genetic contribution, there is merit in designing studies to optimize the chance of identifying robust genetic markers and that includes testing drug levels for adherence.Expert opinion: Ultimately, we think that genetics will be used as part of an algorithm to assess likely response to individual drugs but that other factors will also be important including clinical and environmental factors.
33090496 Revisiting B cell tolerance and autoantibodies in seropositive and seronegative autoimmune 2021 Feb Autoimmune rheumatic diseases (AIRD) are categorized seropositive or seronegative, dependent upon the presence or absence of specific autoreactive antibodies, including rheumatoid factor and anti-citrullinated protein antibodies. Autoantibody-based diagnostics have proved helpful in patient care, not only for diagnosis but also for monitoring of disease activity and prediction of therapy responsiveness. Recent work demonstrates that AIRD patients develop autoantibodies beyond those contained in the original categorization. In this study we discuss key mechanisms that underlie autoantibody development in AIRD: defects in early B cell development, genetic variants involved in regulating B cell and T cell tolerance, environmental triggers and antigen modification. We describe how autoantibodies can directly contribute to AIRD pathogenesis through innate and adaptive immune mechanisms, eventually culminating in systemic inflammation and localized tissue damage. We conclude by discussing recent insights that suggest distinct AIRD have incorrectly been denominated seronegative.
33106703 Seronegative Oligoarthritis Preceding Psoriasis by 9.5 Years. 2020 Oct We report a case of psoriatic arthritis where oligoarthritis preceded the skin lesions. A 57-year-old man complained of left third-finger pain. Laboratory examinations were negative for anti-cyclic citrullinated peptide antibodies and rheumatoid factor; he was treated for suspected rheumatoid arthritis. Six years later, X-ray revealed enthesitis of his fingers and wrist joint. At 9.5 years after the initial visit, skin lesions appeared in the left auricular region and buttock and dermatopathology findings indicated psoriasis vulgaris. The final diagnosis was psoriatic arthritis. In cases of seronegative oligoarthritis, psoriatic arthritis must be considered because some patients demonstrate osteoarticular lesions preceding skin lesions.
32100456 Alteration of the gut microbiota in tumor necrosis factor-α antagonist-treated collagen-i 2020 Apr AIM: Gut microbiota play an important role in rheumatoid arthritis (RA). Biological therapies targeting tumor necrosis factor-α (TNF-α) have been used for treatment in RA patients. However, whether TNF-α antagonist has some influence on gut microbiota is still unknown. This study aims to investigate the distribution of gut microbiota in collagen-induced arthritis (CIA) mice treated with the TNF-α antagonist etanercept. METHODS: Collagen-induced arthritis mice were induced by type II collagen. Cytokine expression was detected by real-time polymerase chain reaction. 16S ribosomal RNA sequencing was performed to characterize the gut microbiota in CIA mice treated with vehicle or etanercept. Sequencing reads were processed by Microbial Ecology software program. RESULTS: Compared with vehicle-treated mice, we showed that CIA mice treated with etanercept led to attenuation of inflammation and reduced expression of TNF-α, interferon (IFN)-γ, interleukin (IL)-6 and IL-21. Meanwhile, results showed operational taxonomic units, richness estimators and the diversity indices of gut microbiota in etanercept-treated mice were lower than that in vehicle-treated mice. Moreover, bacterial abundance analyses showed that genus Escherichia/Shigella was more abundant in etanercept-treated mice, and Lactobacillus, Clostridium XlVa, Tannerella were less abundant. The altered bacterial genus was correlated with TNF-α, IFN-γ, IL-6, IL-21 and IL-10. CONCLUSION: Our results revealed that TNF-α antagonist treatment can reduce the abundance and diversity of gut microbiota in CIA mice. Targeted gut microbiota may be a new therapeutic strategy for the treatment of RA.
32851395 Adaptive treatment strategies for chronic conditions: shared-parameter G-estimation with a 2020 Aug 27 Most estimation algorithms for adaptive treatment strategies assume that treatment rules at each decision point are independent from one another in the sense that they do not possess any common parameters. This is often unrealistic, as the same decisions may be made repeatedly over time. Sharing treatment-decision parameters across decision points offers several advantages, including estimation of fewer parameters and the clinical ease of a single, time-invariant decision to implement. We propose a new computational approach to estimation of shared-parameter G-estimation, which is efficient and shares the double robustness of the "unshared" sequential G-estimation. We use this approach to analyze data from the Scottish Early Rheumatoid Arthritis (SERA) Inception Cohort.
32476683 Osteosarcopenia in rheumatoid arthritis treated with glucocorticosteroids - essence, signi 2020 Rheumatoid arthritis (RA) is one of the most common rheumatic diseases, associated with cooccurrence of serious side effects. This study discusses the problems associated with chronic RA, well-known as osteoporosis, but also recently recognized as sarcopenia. Relationships between sarcopenia and rheumatic diseases are not yet fully understood. Co-occurrence of osteoporosis and sarcopenia, referred to as osteosarcopenia, is becoming increasingly important. The overlap of the effects of RA and osteosarcopenia and the adverse effects of glucocorticosteroids leads to progressive impairment of the musculoskeletal system, increasing the risk of falls, fractures, institutionalization and death, and it is a source of dramatic socioeconomic burden on society. Very limited options for effective treatment of developed osteosarcopenia, as well as the severity of complications caused by it, advocates for the need of broad education and raising public awareness, especially among health care workers, in order to implement the prevention of osteosarcopenia as early as possible.
32929753 Finite sample variance estimation for optimal dynamic treatment regimes of survival outcom 2020 Dec 20 Deriving valid confidence intervals for complex estimators is a challenging task in practice. Estimators of dynamic weighted survival modeling (DWSurv), a method to estimate an optimal dynamic treatment regime of censored outcomes, are asymptotically normal and consistent for their target parameters when at least a subset of the nuisance models is correctly specified. However, their behavior in finite samples and the impact of model misspecification on inferences remain unclear. In addition, the estimators' nonregularity may negatively affect the inferences under some specific data generating mechanisms. Our objective was to compare five methods, two asymptotic variance formulas (adjusting or not for the estimation of nuisance parameters) to three bootstrap approaches, to construct confidence intervals for the DWSurv parameters in finite samples. Via simulations, we considered practical scenarios, for example, when some nuisance models are misspecified or when nonregularity is problematic. We also compared the five methods in an application about the treatment of rheumatoid arthritis. We found that the bootstrap approaches performed consistently well at the cost of longer computational times. The asymptotic variance with adjustments generally yielded conservative confidence intervals. The asymptotic variance without adjustments yielded nominal coverages for large sample sizes. We recommend using the asymptotic variance with adjustments in small samples and the bootstrap if computationally feasible. Caution should be taken when nonregularity may be an issue.
32304030 Bioactive Lipids in Age-Related Disorders. 2020 Our own studies and those of others have shown that defects in essential fatty acid (EFA) metabolism occurs in age-related disorders such as obesity, type 2 diabetes mellitus, hypertension, atherosclerosis, coronary heart disease, immune dysfunction and cancer. It has been noted that in all these disorders there could occur a defect in the activities of desaturases, cyclo-oxygenase (COX), and lipoxygenase (LOX) enzymes leading to a decrease in the formation of their long-chain products gamma-linolenic acid (GLA), arachidonic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). This leads to an increase in the production of pro-inflammatory prostaglandin E2 (PGE2), thromboxanes (TXs), and leukotrienes (LTs) and a decrease in anti-inflammatory lipoxin A4, resolvins, protectins and maresins. All these bioactive molecules are termed as bioactive lipids (BALs). This imbalance in the metabolites of EFAs leads to low-grade systemic inflammation and at times acute inflammatory events at specific local sites that trigger the development of various age-related disorders such as obesity, type 2 diabetes mellitus, hypertension, coronary heart disease, atherosclerosis, and immune dysfunction as seen in rheumatoid arthritis, lupus, nephritis and other localized inflammatory conditions. This evidence implies that methods designed to restore BALs to normal can prevent age-related disorders and enhance longevity and health.
32021491 From Reactive Lymphadenopathy to Systemic Vasculitis, the Importance of Providing Sufficie 2020 INTRODUCTION: Pathology must aim at a correct diagnosis, which is complete and useful for clinicians. However, in routine practice, there are multiple sources of errors in the pathology results, which have several impacts on the patient's treatment and outcome. CASE PRESENTATION: Our patient is a 66 years old man, case of rheumatoid arthritis with lymphadenopathy due to vasculitis, which was underdiagnosed due to lack of complete clinical data during pathologic examination. Since the patient was extremely ill, and the workup was inconclusive, the pathology slides were sent to our center for consultation and molecular study to rule out lymphoma. The slide review was done with complete access to the patient's history and status. In addition to reactive follicular hyperplasia, there was inter-follicular/paracortical plasma cell infiltration and remarkable leukocytoclastic vasculitis of small vessels. DISCUSSION: Most frequent errors in the laboratories are preanalytical, due to clinical failures (wrong clinical procedure, inappropriate ordering, erroneous, incomplete or misleading clinical information), and specimen transportation and delivery. Surgical pathology by its nature depends heavily on the input of clinicians and surgeons who are fully aware of patient condition. CONCLUSION: This case clearly shows the importance of communication between the pathologist and clinicians and the impact on patient care. Clinicians should also provide complete clinical data for the pathologist. Full access to clinical information improves the pathologist's ability to make an accurate diagnosis.