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ID PMID Title PublicationDate abstract
31876066 Awareness and practices of general practitioners towards the oral-systemic disease relatio 2020 Dec RATIONALE, AIM, AND OBJECTIVE: "Periodontal medicine" is based on evidence of interactions between periodontal disease and overall health. The aim of the present study was to assess awareness of oral-systemic disease relationship among French general practitioners (GPs) and clarify how this influences their practices in a wider effort to better integrate oral health concerns into global health care delivery. METHOD: GPs registered in the north of France were invited to complete an online self-administered questionnaire through local divisions of the French Medical Board. The questionnaire was divided into four sections: socio-demographic aspects, knowledge, practices, and an overview. RESULTS: The questionnaire was completed by 253 GPs. Among these, 75% were aware of the association between periodontitis (PD) and diabetes, and 53% to 59% were aware of the impact of PD on cardiovascular diseases, inflammatory bowel diseases, and respiratory infections. Few GPs identified PD as a possible risk factor of rheumatoid arthritis and Alzheimer disease (35.18% and <15%, respectively); 74.31% of GPs reported never asking their patients about their periodontal health. However, a personal history of PD and professional experiences seem to influence the medical practices of GPs to include oral examination. GPs largely self-rated their knowledge of the oral-systemic disease connection as being insufficient and were favourable to completing an up-to-date training course (86.56%). CONCLUSION: French GPs' knowledge about the association of PD with systemic diseases seems to be fair, but discrepancies in their daily clinical routine were found. Promisingly, a positive attitude was observed towards improving their knowledge of oral-systemic diseases link. These results indicate the importance to reinforce collaboration between medical doctors and oral health care specialists.
31848527 [Progressive necrosis of lipid: A case report]. 2019 Dec 18 A 61-year-old woman was referred to our department with a 11-year-erythra. In the anterior tibia of both lower extremities, we could see large dark red infiltrating erythema, waxy luster, clear boundary, slight central atrophy, depression and capillary dilatation. He was diagnosed with "dermatitis contusiformis" in local hospitals, but the treatment of traditional Chinese medicine and external drugs was not effective. She had normal laboratory findings for blood routine test, biochemical indexes, C reactive protein(CRP) and erythrocyte sedimentation rate(ESR)．Furthermore, autoimmune antibodies were all negative. The skin pathology showed degeneration and necrosis of collagen fibers, chronic granulomatous inflammation in the dermis, and there were more acute and chronic inflammatory cell infiltration around the small vessels and in the wall of the tube. We eventually diagnosed it as necrobiosis lipoidica (NL) according to the history, erythra morphology and skin pathology. After treatment of low dose hormone and thalidomide for 1 year, the color and range of skin lesions gradually alleviated. NL was a rare chronic granulomatous inflammatory disease. There appeared to be a predominance in females. The incidence of NL was higher in patients with diabetes mellitus, although this asscoiation was currently questioned. NL might also be connected with autoimmune diseases, such as rheumatoid arthritis, sarcoidosis, ulcerative colitis and Crohn's disease. The pathological changes of the tissue were mainly in the dermis, including necrotic type, granulomatous type or mixed type. NL typically presented on the pretibial surface of lower extremities. Less typical locations included the face, scalp, vulva and upper limbs. Leisions usually began with small papules and nodules that gradually infiltrated into brownyellow patches and developed central wax-like atrophy. The diagnosis is often based on clinical examination and skin biopsy. NL is rare and easy to be misdiagnosed. For rheumatologists, we should carefully compare with the nodular erythema, the microscopic polyangitis and allergic purpura. It is significant for differential diagnosis to perform skin biopsy. Lacking of randomized controlled trials, no specific treatment has proven to be the gold standard. First-line therapy mainly consists of intralesional and systemic corticosteriods. Additionally, other reported treatment options include immunomodulator, biological agent, antiplatelet aggregation drug and plateletrich plasma. These patients need long term follow up continuously for progression of the disease, ulcerations, and possibility of malignant tranformation.
31782357 Prediction of Citrullination Sites on the Basis of mRMR Method and SNN. 2019 BACKGROUND: Citrullination, an important post-translational modification of proteins, alters the molecular weight and electrostatic charge of the protein side chains. Citrulline, in protein sequences, is catalyzed by a class of Peptidyl Arginine Deiminases (PADs). Dependent on Ca2+, PADs include five isozymes: PAD 1, 2, 3, 4/5, and 6. Citrullinated proteins have been identified in many biological and pathological processes. Among them, abnormal protein citrullination modification can lead to serious human diseases, including multiple sclerosis and rheumatoid arthritis. OBJECTIVE: It is important to identify the citrullination sites in protein sequences. The accurate identification of citrullination sites may contribute to the studies on the molecular functions and pathological mechanisms of related diseases. METHODS AND RESULTS: In this study, after an encoded training set (containing 116 positive and 348 negative samples) into the feature matrix, the mRMR method was used to analyze the 941- dimensional features which were sorted on the basis of their importance. Then, a predictive model based on a self-normalizing neural network (SNN) was proposed to predict the citrullination sites in protein sequences. Incremental Feature Selection (IFS) and 10-fold cross-validation were used as the model evaluation method. Three classical machine learning models, namely random forest, support vector machine, and k-nearest neighbor algorithm, were selected and compared with the SNN prediction model using the same evaluation methods. SNN may be the best tool for citrullination site prediction. The maximum value of the Matthews Correlation Coefficient (MCC) reached 0.672404 on the basis of the optimal classifier of SNN. CONCLUSION: The results showed that the SNN-based prediction methods performed better when evaluated by some common metrics, such as MCC, accuracy, and F1-Measure. SNN prediction model also achieved a better balance in the classification and recognition of positive and negative samples from datasets compared with the other three models.
31679663 First Metatarsophalangeal Joint Arthrodesis Using an Intraosseous Post and Lag Screw With 2019 Nov Arthrodesis is the gold standard procedure for advanced arthrosis of the first metatarsophalangeal joint. Having a strong construct is preferable for allowing immediate bearing of weight, which facilitates patient rehabilitation. Plate and screw fixation is currently in favor but can lead to prominent metalware necessitating removal. The aim of this study is to report the results of a series of 54 first metatarsophalangeal joint arthrodeses performed in 52 patients treated with an implant composed of an intraosseous post and lag screw. All of the patients had a minimum follow-up of 1 year, and the indication for the surgery was end-stage hallux rigidus in 44 (81.5%) feet, severe hallux valgus in 8 (14.8%) feet, and rheumatoid arthritis in 2 (3.7%) feet. Arthrodesis was achieved in 52 (96.3%) feet at a mean of 61 ± 16 (range 39 to 201) days with nonunion observed in 2 (3.7%) feet; neither of the 2 patients had known risk factors. Metalware impinging on soft tissues necessitating removal was observed in 3 (5.6%) feet, and there were no cases of loss of position or implant breakage. The mean Manchester-Oxford Foot Questionnaire score improved from 46.4 ± 13.3 to 18.4 ± 9.4 (p < .001) at latest follow-up. In conclusion, our results suggest the intraosseous post and lag screw device was safe and effective, and it can be considered an alternative method of stabilizing the first metatarsophalangeal joint when undertaking arthrodesis surgery.
31677967 Retrotransposons shuttling genetic and epigenetic information from the nuclear to the mito 2019 Oct Endogenous retroelements are a class of ancient defective viral insertions contained in the genome of host cells, where they account for up to 40% of all DNA. Centuries of co-existence in host genome have led to the development of immunotolerance to endogenous retroelements, most of which are defective and unable to replicate or transcribe functional proteins. However, given their capacity to move across the nuclear and mitochondrial genome and recombine, they could mix phenotypes and give rise to infections that may trigger innate and adaptive immune responses by sensing receptors capable of recognising foreign nucleic acids and proteins. It has recently been suggested that they play a role in the pathogenesis of autoimmune diseases on the grounds of their partial reactivation or the epigenetic control of host gene transcription. A number of studies have confirmed their contribution to the development of rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus, but there is still a lack of data concerning systemic sclerosis (SSc). Their role in the pathogenesis of SSc can be hypothesised on the basis of mitochondrial and nuclear chromatinic damage, and hyper-activation of the immune pathway involved in antiviral defense. SSc is characterised by genetic and immunological evidence of a viral infection but, as no viral agent has yet been isolated from SSc patients, the hypothesis that partial reactivation of endogenous retroviruses may trigger the disease cannot be excluded and deserves further investigation.
31431995 Eight-year survival study of first-line tumour necrosis factor α inhibitors in rheumatoid 2019 OBJECTIVE: This study aimed to investigate the efficacy, safety and survival of TNF-α inhibitors in patients with RA. METHODS: A total of 178 patients >18 years of age were treated with TNF-α inhibitors. A total of 74 patients were treated with infliximab, 75 with adalimumab and 29 with etanercept. Each patient was followed-up for a period of 8 years. RESULTS: Anti-TNF-α therapy resulted in rapid clinical improvement. The rate of good/moderate response according to EULAR response criteria for the index 28-joint DAS with CRP in the first 6 months was 82% for infliximab, 89.6% for adalimumab and 95.6% for etanercept. The rate of withdrawal in 8 years was 80% for patients on infliximab, 61.4% for patients on adalimumab and 47.6% for patients on etanercept. The main reasons for discontinuation were allergic reactions for infliximab (rate of discontinuation 25.7%) and inefficacy for adalimumab and etanercept (17.5% and 23.8%, respectively). Systemic allergic reactions and infections were significantly more frequent in the infliximab group (P < 0.05 and P < 0.001, respectively). However, there was no significant difference among the three drugs concerning serious infections. According to Kaplan-Meier survival analysis, a significantly faster withdrawal for infliximab patients was depicted compared with adalimumab (P = 0.003) and etanercept (P = 0.019), while adalimumab and etanercept were not statistically different (P = 0.089). CONCLUSIONS: TNF-α inhibitors establish an effective therapeutic option in RA showing an acceptable safety profile. Infections and allergic reactions appear more often with infliximab, while serious infections did not differ among them. RA patients treated with infliximab are more likely to discontinue treatment earlier compared with the other alternatives.
31384329 Immunologic adverse reactions of β-blockers and the skin. 2019 Aug β-Blockers are a widely utilised class of medication. They have been in use for a variety of systemic disorders including hypertension, heart failure and intention tremors. Their use in dermatology has garnered growing interest with the discovery of their therapeutic effects in the treatment of haemangiomas, their potential positive effects in wound healing, Kaposi sarcoma, melanoma and pyogenic granuloma, and, more recently, pemphigus. Since β-blockers are deployed in a variety of disorders, which have cutaneous co-morbidities such as psoriasis, their pertinence to dermatologists cannot be overstated. Likewise, β-blockers, like any other drug category, carry risks of side effects, some of which are dermatologic. These include triggering and exacerbation of psoriasis, psoriatic and rheumatoid arthritis, anaphylaxis, contact dermatitis, occupational contact dermatitis, Raynaud's disease, alopecia, lichen planus-like drug eruption, hyperhydrosis and vitiligo. While recent articles have focussed on the positive uses of β-blockers, it may also be wise to call our attention to the potential dermatologic adverse effects that may follow β-blocker use, as well as possible therapeutic approaches to these. This short review will focus on those dermatoses resulting from β-blocker use, which have an immunologic basis.
31364806 Identification of most damaging nsSNPs in human CCR6 gene: In silico analyses. 2019 Dec Single nucleotide polymorphisms in CCR6 (C-C chemokine receptor type 6) gene have been found to be the possible cause of many diseases like rheumatoid arthritis, psoriasis, lupus nephritis and systemic sclerosis and other autoimmune diseases. Therefore, identification of structurally and functionally important polymorphisms in CCR6 is important in order to study its potential malfunctioning and discovering therapeutic targets. Several bioinformatics tools were used to identify most damaging nsSNPs that might be vital for CCR6 structure and function. The in silico tools included PROVEAN, SIFT, SNP&GO and PolyPhen2 followed by I-Mutant MutPred and ConSurf. Phyre2 and I-TASSER were used for protein 3-D Modelling while gene-gene interaction was predicted by STRING and GeneMANIA. Our study suggested that three nsSNPs rs1376162684, rs751102128 and rs1185426631 are the most damaging in CCR6 gene while 7 missense SNPs rs1438637216, rs139697820, rs768420505, rs1282264186, rs1394647982, rs769360638 and rs1263402382 are found to revert into stop codons. Prediction of post-transcriptional modifications highlighted the significance of rs1376162684 because it effected potential phosphorylation site. Gene-gene interactions showed relation of CCR6 with other genes depicting its importance in several pathways and co-expressions. In future, studying diseases related to CCR6 should include investigation of these 10 nsSNPs. Being the first of its type, this study also proposes future perspectives that will help in precision medicines. For such purposes, CCR6 proteins from patients of autoimmune diseases should be explored. Animal models can also be of significance find out the effects of CCR6 in diseases.
31498576 2019 Jun 25 Chronic pain is a pervasive health issue that adversely affects both the patient and society, including loss of productivity, decreased quality of life, and an increased burden on the health care system.(–) The International Classification of Diseases (ICD) of the World Health Organization defines chronic pain as persistent or recurrent pain lasting longer than three months. Non-malignant (non-cancer) related types of chronic pain may include low back pain, osteoarthritis, rheumatoid arthritis, headache, neck pain, fibromyalgia, and irritable bowel syndrome. The prevalence of chronic pain is estimated to be 21% among the general Canadian population, a prevalence rate that has increased over time. Chronic pain has substantial economic implications and has been estimated to cost Canada over six billion dollars per year in direct health care costs and 37 billion per year in productivity costs (e.g., job loss, sick days).(,)(,) Given the prevalence and burden of chronic pain, a variety of treatment options have been explored to help patients manage their symptoms of pain, including pharmacological approaches (i.e., prescription or non-prescription drugs), physical therapy, exercise, surgery, psychological therapy, and complementary and alternative therapies. In order to decide what treatment is best for the patient, careful consideration should be given to the benefits and risks of the available treatment options. Medications, such as opioids, are commonly prescribed for pain, with approximately three to four percent of the adult population in the United States prescribed long-term opioid therapy.(,) However, long-term opioid therapy presents some serious risks, including addiction, accidental overdose, hyperalgesia, and diversion for non-medical use. Mindfulness training is another potential treatment option for individuals who suffer from chronic pain. Mindfulness is defined as the intentional and non-judgmental conscious awareness of the present moment. A previous CADTH rapid response report that was published in 2012 examined the clinical effectiveness and evidence-based guidelines regarding the use of mindfulness training for chronic pain management in adults and found insufficient evidence to draw conclusions about its potential effectiveness. An update is needed to determine if the evidence surrounding mindfulness for chronic pain management is more conclusive to inform future policy decisions. The aim of this report is to summarize the evidence regarding both the clinical and cost-effectiveness, as well as guidelines for the use of mindfulness training for chronic non-malignant pain management.
31211245 Leflunomide Synergizes with Gemcitabine in Growth Inhibition of PC Cells and Impairs c-Myc 2019 Sep 27 The immunosuppressive agent leflunomide has been used in the treatment of over 300,000 patients with rheumatoid arthritis. Its active metabolite, teriflunomide (Ter), directly inhibits dihydroorotate dehydrogenase (DHODH), an enzyme involved in nucleoside synthesis. We report that Ter not only shows in vitro anti-proliferative activity in pancreatic cancer (PC) cells as a single agent but also synergizes with the chemotherapeutic gemcitabine (Gem) in growth inhibition of PC cells. The growth-inhibitory effects of Ter are not solely caused by inhibition of DHODH. Through a kinase screening approach, we identified the PIM-3 serine-threonine kinase as a novel direct target. Subsequent dose-response kinase assays showed that Ter directly inhibited all three PIM family members, with the highest activities against PIM-3 and -1. The PIM-3 kinase was the PIM family member most often associated with PC oncogenesis and was also the kinase inhibited the most by Ter among more than 600 kinases investigated. Ter in PC cells induced changes in phosphorylation and expression of PIM downstream targets, consistent with the effects achieved by overexpression or downregulation of PIM-3. Finally, pharmacological inhibition of PIM proteins not only diminished PC cell proliferation, but also small-molecule pan-PIM and PIM-3 inhibitors synergized with Gem in growth inhibition of PC cells.
31115802 Myelopathy associated with mixed connective tissue disease: clinical manifestation, diagno 2019 Sep Mixed connective tissue disease (MCTD) is a chronic autoimmune disease, which has a broad range of clinical manifestations shared by systemic lupus erythematosus, systemic sclerosis, polymyositis/dermatomyositis, and rheumatoid arthritis. MCTD is featured with high serum titers of anti-ribonucleoprotein antibodies and multiple system involvement. Its spinal cord involvement mainly manifests as transverse myelopathy (TM) and longitudinal extensive transverse myelopathy (LETM). Myelopathy in MCTD is extremely rare, and is usually characterized by serious neurological complications, such as paralysis or muscular paresis, sensory impairment, and smooth muscle dysfunction. Progressive clinical manifestations combined with laboratory examinations and magnetic resonance imaging examinations play important roles in the diagnosis of this disease. In order to prevent permanent neurological damage to the spinal cord, plasmapheresis and intravenous immunoglobulin can be performed in patients at the early disease stage. Early high-dose corticosteroids combined with cyclophosphamide, followed by low doses of immunosuppressors, can improve the long-term prognosis of patients. There are only nine global cases reported on MCTD associated with myelopathy at present. The death rate and disability rate of myelopathy in MCTD are extremely high. In this review, the pathomechanisms, clinical manifestations, auxiliary examination, diagnosis, differential diagnosis, treatment, and prognosis of myelopathy in MCTD were systematically elucidated.
31084231 Development and exacerbation of pulmonary nontuberculous mycobacterial infection in patien 2020 May Objectives: To examine the development and exacerbation of pulmonary nontuberculous mycobacterial (NTM) infection in patients with systemic autoimmune rheumatic diseases (SARD).Methods: We conducted a case-control study. Seventeen of 7013 patients with SARD fulfilling the criteria for pulmonary NTM infection were enrolled in the NTM group. The control group was matched for age, sex, and SARD at a ratio of 2:1.Results: Eight patients with rheumatoid arthritis, four with systemic vasculitis, three with Sjögren's syndrome, and one each with dermatomyositis and systemic lupus erythematosus were included in the NTM group. Mycobacterium avium was detected in 12 (71%) patients, M. chelonae in 2, and M. intracellulare, M. abscessus, and M. kansasii in 1 patient each. Preexisting lung disease was more common in the NTM group than in the control group (88% versus 38%, p = .0009), particularly bronchiectasis (65% versus 29%, p = .033). The body mass index and serum albumin level were significantly lower in the NTM group than in the control group. Six patients (35%) experienced NTM exacerbation during observation. Clinical immune status at the time of NTM diagnosis, as indicated by the peripheral blood leukocyte/lymphocyte count and serum immunoglobulin G level, was unremarkable and comparable between patients with and without exacerbation, as were the treatments for SARD.Conclusions: In patients with SARD, pulmonary NTM infection may develop and exacerbate without clinically apparent immunosuppression.
31056931 Clinical Outcomes of Total Ankle Arthroplasty With Total Talar Prosthesis. 2019 Aug BACKGROUND: Total ankle arthroplasty (TAA) has been developed to treat patients with end-stage ankle osteoarthritis (OA). However, there is often difficulty in treating complicated pathologies such as ankle OA with subtalar joint OA and severe talar collapse. Therefore, this study aimed to explore the short-term results and complications of TAA with total talar prosthesis, known as combined TAA, as the new techniques to treat such complicated pathology. METHODS: We examined postoperative results including ankle range of motion, Japanese Society for Surgery of the Foot (JSSF) scale, and complications. There were 22 patients (15 women), with mean follow-up of 34.9 (range, 24-53 months), and the mean age was 72 (range, 62-80) years. The main indications for combined TAA included osteoarthritis (18 patients), rheumatoid arthritis (3 patients), and talar osteonecrosis with osteoarthritis (one patient). RESULTS: The mean range of motion improved from 4.0 to 14.4 degrees in dorsiflexion and from 23.8 to 32.0 degrees in plantarflexion. The JSSF scale improved from 50.5 to 91.5 points. Prolonged wound healing occurred in 3 patients, and medial malleolus fracture occurred in 4 patients. CONCLUSION: Combined TAA was a reliable procedure for the treatment of not only ankle OA following avascular necrosis of talus but also of degeneration of both ankle and subtalar joints. LEVEL OF EVIDENCE: Level IV, case series.
31021170 Validation of a population pharmacokinetic model of adalimumab in a cohort of patients wit 2019 Jun BACKGROUND: therapeutic monitoring of anti-TNF drugs and anti-drug antibody levels are useful for clinical decision-making, via the rationalization and optimization of the use of anti-TNF treatments. The objective of the present study was to validate the model of Ternant et al., in a cohort of patients with inflammatory bowel diseases (IBD). This model was originally established for patients with rheumatoid arthritis and was used in this study to optimize the adalimumab (ADA) dose and predict ADA trough levels (ATL). METHODS: this study used concentration data points from 30 IBD patients who received ADA treatment between 2014 and 2015. A goodness-of-fit of the model was determined by evaluating the relationship between the observed ATL values and population model-predicted values (PRED) or individual model-predicted values (IPRED). RESULTS: a total of 51 ADA concentration points were analyzed. The bias of the model was 2.39 (95% CI, 1.63-3.15) for PRED and 0.63 (95% CI, 0.23-1.03) for IPRED. The precision was 3.57 (95% CI, 2.90-4.13) and 1.53 (95% CI, 1.22-1.80), respectively. CONCLUSIONS: therapeutic drug monitoring involving ATL may allow the optimization of the treatment of IBD patients. The validation results of the phamacokinectic (PK) model for ADA in IBD patients are inadequate. However, additional studies will strengthen the bias and precision of the model.
30954362 The potential use of l-sulforaphane for the treatment of chronic inflammatory diseases: A 2020 Mar According to the World Health Organisation, 70% of all deaths globally can be attributed to chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, respiratory conditions, cardiovascular diseases, diabetes and cancer. Chronic inflammation has a significant impact on the quality of life of affected individuals with an increased risk of developing other chronic inflammatory diseases. Given the limitations of current pharmaceuticals, there is an intense research interest in identifying novel dietary interventions that can regulate and alleviate inflammation. A diet rich in cruciferous vegetables has been extensively studied for its immediate and long-term health benefits, particularly in the context of cardiovascular disease and cancer. Cruciferous vegetables contain the precursor glucoraphanin, which is hydrolysed upon consumption to form l-sulforaphane (LSF), the primary active compound that mediates potential cardio-protective and anti-carcinogenic effects. LSF has been shown to have beneficial effects in vitro and in animal studies through its classical antioxidant and anti-inflammatory properties, and more recently its chromatin modifying effects. This review discusses the clinical evidence to date in relation to the use of LSF in the context of chronic inflammatory diseases as well as provide key mechanistic insights for these effects.
30895813 Trends in Primary Proximal Interphalangeal Joint System and Revisions for Osteoarthritis o 2020 Nov Background: Proximal interphalangeal arthroplasty (PIPA) has been indicated for patients suffering from osteoarthritis (OA) or rheumatoid arthritis of the hand. Although there is extensive literature showing the outcomes of PIPA, there is paucity in the literature regarding trends of PIPA in patients with OA of the hand. The purpose of this study was to determine annual primary utilization and revision PIPA trends within the Medicare population with the use of an administrative database. Methods: A retrospective query was performed using the Medicare Standard Analytical Files from the PearlDiver database. Patients undergoing primary and revision PIPA with hand OA were queried using International Classification of Disease, Ninth Revision, and Current Procedural Terminology coding. Primary outcomes analyzed included annual and revision utilization of PIPA and demographic comparison of age, gender, and geographic location. Statistical analysis was primarily descriptive. An α value less than 0.05 was considered statistically significant. Results: The query returned 10 191 patients who underwent primary and revision PIPA between 2005 and 2013. Calculated annual growth rate for primary and revision PIPA was 2.40% and -0.03%, respectively (P < .001). Patients between the ages of 70 and 74 years represented most of the patients undergoing a primary PIPA, whereas patients between 65 and 69 years most commonly underwent a revision procedure. Regionally, primary and revision PIPA were most commonly performed in the South. Conclusion: The data demonstrate an increased use of primary PIPA utilization for patients with OA, whereas revision PIPA decreased. The increased use indicates the increasing demand for PIPA in the United States.
30854861 The effect of time to surgery on outcomes and complication rates following total hip arthr 2019 May INTRODUCTION: Total hip arthroplasty is recommended for elderly patients with fractured neck of femur who are independently mobile, have few co-morbidities and are not cognitively impaired. Providing a daily total hip arthroplasty service is challenging for some units in the UK and considering that these patients may be physiologically distinct from the average hip fracture patient, loss of the best practice tariff as a result of surgical delay may be unjustified. The aim of this study was to determine whether time to surgical intervention for patients eligible for total hip arthroplasty had a negative impact on patient complications, length of stay and functional outcomes. METHODS: All patients undergoing total hip arthroplasty for fractured neck of femur at our institution over a ten-year period were identified. Complications and functional outcomes were compared between patients receiving total hip arthroplasty before and after 36 hours. RESULTS: Of 112 consecutive patients undergoing total hip arthroplasty, 70 responded to a questionnaire or telephone consultation. Four patients were excluded owing to delayed presentation, the presence of advanced rheumatoid arthritis or a pathological fracture. Two-thirds (64%) of the remaining 66 patients underwent surgery within 36 hours of presentation. There were no significant differences between the groups of patients receiving surgery before or after 36 hours with regard to postoperative length of stay, complications, Oxford hip scores or visual analogue scale scores for state of health. CONCLUSIONS: Delaying surgery for patients eligible for total hip arthroplasty as per the National Institute for Health and Care Excellence guidelines is justified and should not incur loss of the best practice tariff.
30765202 IL-17 and limits of success. 2019 May Interleukin-17 (IL-17) is a potent proinflammatory cytokine that protects a host against fungal and extracellular bacterial infections. On the other hand, excessive or dysregulated production of IL-17 underlines susceptibility to autoimmune disease. Consequently, blocking IL-17 has become an effective strategy for modulating several autoimmune diseases, including multiple sclerosis (MS), psoriasis, and rheumatoid arthritis (RA). Notably, however, IL-17 blockade remains ineffective or even pathogenic against important autoimmune diseases such as inflammatory bowel disease (IBD). Furthermore, the efficacy of IL-17 blockade against other autoimmune diseases, including type 1 diabetes (T1D) is currently unknown and waiting results of ongoing clinical trials. Coming years will determine whether the efficacy of IL-17 blockade is limited to certain autoimmune diseases or can be expanded to other autoimmune diseases. These efforts include new clinical trials aimed at testing second-generation agents with the goal of increasing the efficiency, spectrum, and ameliorating side effects of IL-17 blockade. Here we briefly review the roles of IL-17 in the pathogenesis of selected autoimmune diseases and provide updates on ongoing and recently completed trials of IL-17 based immunotherapies.
30728673 The Differential Influence of Immunological Process of Autoimmune Disease on Lipid Metabol 2019 Jan Metabolic parameters like uric acid, lipids and homocysteine are influenced by immunopathological mechanisms underlying the autoimmune disease processes. The current study examined the differences in these parameters and the correlation between inflammatory and metabolic variables in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. The cross-sectional prospective study included 24 treatment-naïve patients with moderate to severe diseases-15 subjects had RA and 9 had SLE. Atherogenic index of plasma (AIP) was used to assess the cardiovascular risk of the patients. Spearman's correlation was performed to verify the relationship between inflammatory and metabolic parameters. A two-tailed P < 0.05 was considered statistically significant for all the analysis. SLE patients had higher uric acid levels, very low density lipoprotein-cholesterol, total cholesterol/high density lipoprotein-cholesterol ratio (TC/HDL-C) and logarithmic ratio of triglycerides to HDL-cholesterol (log[TG/HDL-C]) than RA. Whereas, reduced total lymphocyte count, lipoprotein(a), and low density lipoprotein cholesterol were noted in the former than latter group. Majority of the SLE patients had increased risk of cardiovascular diseases (> 0.24 AIP score) and RA patients in comparison had lower risk. Correlation among serum uric acid, lipid profile constituents and AIP was noted. The immunological process of SLE has greater impact on the metabolic parameters. Higher uric acid levels are suggestive of dysfunctional lipid profile. Understanding the implications of risk factors and its inflammatory role in autoimmune processes may assist in disease management.
30706927 Comprehensive bioinformation analysis of methylated and differentially expressed genes in 2019 Feb 11 Differentially methylated genes (DMGs) play a crucial role in the etiology and pathogenesis of esophageal squamous cell carcinoma (ESCC). This study aimed to ascertain aberrant DMGs and pathways by comprehensive bioinformatics analysis. We downloaded the gene expression microarray of GSE51287 from the Gene Expression Omnibus (GEO). Aberrant DMGs were obtained using the GEO2R tool. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome pathway enrichment analyses were performed on selected genes by using the Database for Annotation Visualization and Integrated Discovery. A protein-protein interaction (PPI) network was constructed with the Retrieval of Interacting Genes (STRING) and visualized in Cytoscape. Then, the modules in the PPI networks were analyzed with Molecular Complex Detection, and the hub genes derived from the PPI networks were verified by using the Cancer Genome Atlas. A total of 271 DMGs, including 173 hypermethylated genes, were enriched in the biological processes of peptidyl-tyrosine phosphorylation, positive regulation of transcription from RNA polymerase II promoters, and autophosphorylation. Pathway analysis enrichment revealed cancer, PI3K-Akt, and Ras signaling pathways, and 98 hypomethylated genes were enriched in the biological processes of the immune response, extracellular matrix disassembly, and macrophage differentiation. Pathway enrichment showed rheumatoid arthritis, cytokine-cytokine receptor interaction, and toxoplasmosis. Furthermore, bioinformatics analysis indicated feasible aberrant DMGs and pathways in ESCC. The results provided valuable information on the pathogenesis of ESCC. The significant DMGs may provide novel insights into their potential predictive and prognostic value as methylation-based biomarkers for the precise diagnosis and treatment of ESCC.