Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 34152881 | T cell transgressions: Tales of T cell form and function in diverse disease states. | 2021 Jun 21 | Insights into T cell form, function, and dysfunction are rapidly evolving. T cells have remarkably varied effector functions including protecting the host from infection, activating cells of the innate immune system, releasing cytokines and chemokines, and heavily contributing to immunological memory. Under healthy conditions, T cells orchestrate a finely tuned attack on invading pathogens while minimizing damage to the host. The dark side of T cells is that they also exhibit autoreactivity and inflict harm to host cells, creating autoimmunity. The mechanisms of T cell autoreactivity are complex and dynamic. Emerging research is elucidating the mechanisms leading T cells to become autoreactive and how such responses cause or contribute to diverse disease states, both peripherally and within the central nervous system. This review provides foundational information on T cell development, differentiation, and functions. Key T cell subtypes, cytokines that create their effector roles, and sex differences are highlighted. Pathological T cell contributions to diverse peripheral and central disease states, arising from errors in reactivity, are highlighted, with a focus on multiple sclerosis, rheumatoid arthritis, osteoarthritis, neuropathic pain, and type 1 diabetes. | |
| 33875273 | Emerging Roles of Coronavirus in Autoimmune Diseases. | 2021 Oct | Virus infection can alter immune regulatory activity, and thus may be involved in the occurrence of autoimmune diseases. Recently, the pandemic of COVID-19 has posed a huge threat to public health and emerging evidence suggests that coronavirus may be implicated in the development and pathogenesis of autoimmune diseases. However, how coronavirus infection impacts the risk of autoimmune disease remains largely unknown. In this review, we focused on the association between coronavirus and autoimmunity, and elucidated the molecular mechanisms linking coronavirus exposure to autoimmunity. Additionally, we briefly introduced the role that coronavirus plays in several autoimmune diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and idiopathicthrombocytopenic purpura (ITP). | |
| 33806595 | Bleeding by Bruton Tyrosine Kinase-Inhibitors: Dependency on Drug Type and Disease. | 2021 Mar 4 | Bruton tyrosine kinase (Btk) is expressed in B-lymphocytes, myeloid cells and platelets, and Btk-inhibitors (BTKi) are used to treat patients with B-cell malignancies, developed against autoimmune diseases, have been proposed as novel antithrombotic drugs, and been tested in patients with severe COVID-19. However, mild bleeding is frequent in patients with B-cell malignancies treated with the irreversible BTKi ibrutinib and the recently approved 2nd generation BTKi acalabrutinib, zanubrutinib and tirabrutinib, and also in volunteers receiving in a phase-1 study the novel irreversible BTKi BI-705564. In contrast, no bleeding has been reported in clinical trials of other BTKi. These include the brain-penetrant irreversible tolebrutinib and evobrutinib (against multiple sclerosis), the irreversible branebrutinib, the reversible BMS-986142 and fenebrutinib (targeting rheumatoid arthritis and lupus erythematodes), and the reversible covalent rilzabrutinib (against pemphigus and immune thrombocytopenia). Remibrutinib, a novel highly selective covalent BTKi, is currently in clinical studies of autoimmune dermatological disorders. This review describes twelve BTKi approved or in clinical trials. By focusing on their pharmacological properties, targeted disease, bleeding side effects and actions on platelets it attempts to clarify the mechanisms underlying bleeding. Specific platelet function tests in blood might help to estimate the probability of bleeding of newly developed BTKi. | |
| 33746917 | Predictive Metagenomic Analysis of Autoimmune Disease Identifies Robust Autoimmunity and D | 2021 | Within the last decade, numerous studies have demonstrated changes in the gut microbiome associated with specific autoimmune diseases. Due to differences in study design, data quality control, analysis and statistical methods, many results of these studies are inconsistent and incomparable. To better understand the relationship between the intestinal microbiome and autoimmunity, we have completed a comprehensive re-analysis of 42 studies focusing on the gut microbiome in 12 autoimmune diseases to identify a microbial signature predictive of multiple sclerosis (MS), inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and general autoimmune disease using both 16S rRNA sequencing data and shotgun metagenomics data. To do this, we used four machine learning algorithms, random forest, eXtreme Gradient Boosting (XGBoost), ridge regression, and support vector machine with radial kernel and recursive feature elimination to rank disease predictive taxa comparing disease vs. healthy participants and pairwise comparisons of each disease. Comparing the performance of these models, we found the two tree-based methods, XGBoost and random forest, most capable of handling sparse multidimensional data, to consistently produce the best results. Through this modeling, we identified a number of taxa consistently identified as dysregulated in a general autoimmune disease model including Odoribacter, Lachnospiraceae Clostridium, and Mogibacteriaceae implicating all as potential factors connecting the gut microbiome to autoimmune response. Further, we computed pairwise comparison models to identify disease specific taxa signatures highlighting a role for Peptostreptococcaceae and Ruminococcaceae Gemmiger in IBD and Akkermansia, Butyricicoccus, and Mogibacteriaceae in MS. We then connected a subset of these taxa with potential metabolic alterations based on metagenomic/metabolomic correlation analysis, identifying 215 metabolites associated with autoimmunity-predictive taxa. | |
| 33634114 | Targeting NR4A Nuclear Receptors to Control Stromal Cell Inflammation, Metabolism, Angioge | 2021 | The NR4A1-NR4A3 (Nur77, Nurr1, and Nor-1) subfamily of nuclear receptors is a group of immediate early genes induced by a pleiotropy of stimuli including peptide hormones, growth factors, cytokines, inflammatory, and physiological stimuli, and cellular stress. NR4A receptors function as potent sensors of changes in the cellular microenvironment to control physiological and pathological processes through genomic and non-genomic actions. NR4A receptors control metabolism and cardiovascular and neurological functions and mediate immune cell homeostasis in inflammation and cancer. This receptor subfamily is increasingly recognized as an important molecular connection between chronic inflammation, altered immune cell responses, and cancer development. In this review, we examine how transcriptome analysis identified NR4A1/NR4A2 receptors as transcriptional regulators in mesenchymal stromal cell (MSC) migration, cell cycle progression, and cytokine production to control local immune responses. In chronic inflammatory conditions, such as rheumatoid arthritis, NR4A receptors have been shown to modify the activity of MSC and fibroblast-like stromal cells to regulate synovial tissue hyperplasia, pathological angiogenesis, and cartilage turnover in vivo. Additionally, as NR4A1 has been observed as a major transcriptional regulator in tumor-stromal communication controlling tumorigenesis, we discuss how advances in the pharmacological control of these receptors lead to important new mechanistic insights into understanding the role of the tumor microenvironment in health and disease. | |
| 33569898 | Case study: An older COVID-19 patient in a Turkish intensive care unit with prolonged stay | 2021 Feb 10 | This paper reports the presentation and management of an older female patient who was diagnosed with Coronavirus disease (COVID-19) and discharged from an intensive care unit (ICU) after prolonged hospitalization. The patient's COVID-19 test was negative; therefore, she was monitored in the COVID-19 general clinic with normal levels of oxygen saturation (SpO(2) ). The patient had been taking Plaquenil for rheumatoid arthritis for a long time. Azithromycin was administered first, and then, the treatment continued with favipiravir according to the national treatment protocol in Turkey. On the third day in the COVID-19 general clinic, she was transferred to the ICU because of decreased saturation levels. Owing to worsening respiratory status and SpO(2) <70%, the patient was intubated on the sixth day in the ICU, and every day, she was nursed in a prone position for >16 hours. We believe that the treatment and care activities under qualified and effective nursing care, such as providing appropriate respiratory support at the right time, early initiation and maintenance of anticoagulant therapy, long-term prone positioning, maintaining sufficient fluid resuscitation, and early commencement of balanced enteral nutrition, contributed to the successful discharge of the patient from the ICU. The patient was finally extubated on the 23rd day. Respiratory support was continued with oxygen administered at 2 lt/min through a nasal canula with SpO(2) at 94%. We believe that by combining all these factors, the patient's results improved. She was discharged from the ICU after 25 days without any organ dysfunction. During the 25 days of care in the ICU, infectious disease protection and isolation rules were strictly adhered to, and personal protective equipment was worn. | |
| 33446772 | Autophagy facilitates type I collagen synthesis in periodontal ligament cells. | 2021 Jan 14 | Autophagy is a lysosomal protein degradation system in which the cell self-digests its intracellular protein components and organelles. Defects in autophagy contribute to the pathogenesis of age-related chronic diseases, such as myocardial infarction and rheumatoid arthritis, through defects in the extracellular matrix (ECM). However, little is known about autophagy in periodontal diseases characterised by the breakdown of periodontal tissue. Tooth-supportive periodontal ligament (PDL) tissue contains PDL cells that produce various ECM proteins such as collagen to maintain homeostasis in periodontal tissue. In this study, we aimed to clarify the physiological role of autophagy in periodontal tissue. We found that autophagy regulated type I collagen synthesis by elimination of misfolded proteins in human PDL (HPDL) cells. Inhibition of autophagy by E-64d and pepstatin A (PSA) or siATG5 treatment suppressed collagen production in HPDL cells at mRNA and protein levels. Immunoelectron microscopy revealed collagen fragments in autolysosomes. Accumulation of misfolded collagen in HPDL cells was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. E-64d and PSA treatment suppressed and rapamycin treatment accelerated the hard tissue-forming ability of HPDL cells. Our findings suggest that autophagy is a crucial regulatory process that facilitates type I collagen synthesis and partly regulates osteoblastic differentiation of PDL cells. | |
| 32985460 | Regulation of neuroimmune processes by damage- and resolution-associated molecular pattern | 2021 Mar | Sterile inflammatory processes are essential for the maintenance of central nervous system homeostasis, but they also contribute to various neurological disorders, including neurotrauma, stroke, and demyelinating or neurodegenerative diseases. Immune mechanisms in the central nervous system and periphery are regulated by a diverse group of endogenous proteins, which can be broadly divided into the pro-inflammatory damage-associated molecular patterns (DAMPs) and anti-inflammatory resolution-associated molecular patterns (RAMPs), even though there is notable overlap between the DAMP- and RAMP-like activities for some of these molecules. Both groups of molecular patterns were initially described in peripheral immune processes and pathologies; however, it is now evident that at least some, if not all, of these immunomodulators also regulate neuroimmune processes and contribute to neuroinflammation in diverse central nervous system disorders. The review of recent literature demonstrates that studies on DAMPs and RAMPs of the central nervous system still lag behind the much broader research effort focused on their peripheral counterparts. Nevertheless, this review also reveals that over the last five years, significant advances have been made in our understanding of the neuroimmune functions of several well-established DAMPs, including high-mobility group box 1 protein and interleukin 33. Novel neuroimmune functions have been demonstrated for other DAMPs that previously were considered almost exclusively as peripheral immune regulators; they include mitochondrial transcription factor A and cytochrome C. RAMPs of the central nervous system are an emerging area of neuroimmunology with very high translational potential since some of these molecules have already been used in preclinical and clinical studies as candidate therapeutic agents for inflammatory conditions, such as multiple sclerosis and rheumatoid arthritis. The therapeutic potential of DAMP antagonists and neutralizing antibodies in central nervous system neuroinflammatory diseases is also supported by several of the identified studies. It can be concluded that further studies of DAMPs and RAMPs of the central nervous system will continue to be an important and productive field of neuroimmunology. | |
| 32807053 | Novel Aceclofenac Cocrystals with l-Cystine: Virtual Coformer Screening, Mechanochemical S | 2021 | AIM: Current work focuses on the improvement of the solubility and dissolution of ACF by the cocrystal approach. BACKGROUND: Aceclofenac (ACF) is one of the commonly used Nonsteroidal Anti-Inflammatory Drug (NSAID) representing a variety of therapeutic applications including management of pain, inflammation, rheumatoid arthritis, and osteoarthritis, etc. But very low solubility and dissolution rate of ACF compromise its therapeutic utility. Now a day's cocrystallization technique has emerged as a novel technique for modulation of the said problems. OBJECTIVE: The Specific objectives of this research work were mechanochemical synthesis, characterization, and performance evaluation of aceclofenac cocrystal. METHODS: ACF was screened with various pharmaceutically acceptable coformers (Selected from GRAS and EAFUS list) using MOPAC software and physical screening method to find out novel cocrystals of ACF with enhanced solubility and dissolution rate. Novel cocrystals (multi-component crystalline solid) of ACF with l-cystine were prepared by a neat grinding method and by liquid assisted grinding method. The synthesized cocrystals (ACF-l-CYS NG and ACF-l-CYS LAG) were characterized carefully by Differential Scanning Calorimetry (DSC), Infrared Spectroscopy (IR), and Powder XRay Diffraction (PXRD) to verify the formation of the cocrystals. Pharmaceutically significant properties such as powder dissolution rate, solubility, and stability of the prepared cocrystals were evaluated. RESULTS: Compared to pure ACF, the prepared cocrystals showed superior solubility and dissolution rate. The prepared cocrystals were found to be stable and non-hygroscopic under study conditions. CONCLUSION: The cocrystallization technique was successfully utilized to increase the solubility and dissolution rate of aceclofenac. | |
| 35082759 | Distinct Glucocorticoid Receptor Actions in Bone Homeostasis and Bone Diseases. | 2021 | Glucocorticoids (GCs) are steroid hormones that respond to stress and the circadian rhythm. Pharmacological GCs are widely used to treat autoimmune and chronic inflammatory diseases despite their adverse effects on bone after long-term therapy. GCs regulate bone homeostasis in a cell-type specific manner, affecting osteoblasts, osteoclasts, and osteocytes. Endogenous physiological and exogenous/excessive GCs act via nuclear receptors, mainly via the GC receptor (GR). Endogenous GCs have anabolic effects on bone mass regulation, while excessive or exogenous GCs can cause detrimental effects on bone. GC-induced osteoporosis (GIO) is a common adverse effect after GC therapy, which increases the risk of fractures. Exogenous GC treatment impairs osteoblastogenesis, survival of the osteoblasts/osteocytes and prolongs the longevity of osteoclasts. Under normal physiological conditions, endogenous GCs are regulated by the circadian rhythm and circadian genes display oscillatory rhythmicity in bone cells. However, exogenous GCs treatment disturbs the circadian rhythm. Recent evidence suggests that the disturbed circadian rhythm by continuous exogenous GCs treatment can in itself hamper bone integrity. GC signaling is also important for fracture healing and rheumatoid arthritis, where crosstalk among several cell types including macrophages and stromal cells is indispensable. This review summarizes the complexity of GC actions via GR in bone cells at cellular and molecular levels, including the effect on circadian rhythmicity, and outlines new therapeutic possibilities for the treatment of their adverse effects. | |
| 34898994 | Progranulin as a Potential Therapeutic Target in Immune-Mediated Diseases. | 2021 | Progranulin (PGRN), a secretory glycoprotein consisting of 593 amino acid residues, is a key actor and regulator of multiple system functions such as innate immune response and inflammation, as well as tissue regeneration. Recently, there is emerging evidence that PGRN is protective in the development of a variety of immune-mediated diseases, including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS) by regulating signaling pathways known to be critical for immunology, particularly the tumor necrosis factor alpha/TNF receptor (TNF-α/TNFR) signaling pathway. Whereas, the role of PGRN in psoriasis, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is controversial. This review summarizes the immunological functions of PGRN and its role in the pathogenesis of several immune-mediated diseases, in order to provide new ideas for developing therapeutic strategies for these diseases. | |
| 34924008 | Malignancy and immune disorders in patients with hereditary angioedema. | 2021 Dec 19 | BACKGROUND: Hereditary angioedema (HAE) is an inherited condition manifesting as recurrent angioedema episodes which is caused by deficiency or dysfunction of C1 inhibitor. Although complement dysregulation has historically been shown to be associated with various malignancy and immune disorders, it is currently not known if HAE patients are at an increased risk of developing malignancy or autoimmune conditions. CASE PRESENTATION: We reviewed the charts of 49 HAE patients and identified 6 patients who had a co-existing malignancy diagnosis (two with breast cancer, one with melanoma, one with pancreatic cancer, one with renal cancer and one with cervical dysplasia) and 6 patients who had a diagnosis of a co-existing immune disorder (two with rheumatoid arthritis, two with ulcerative colitis, one with chronic urticaria with hypothyroidism and one with Sjogren's syndrome). Nearly all malignancy cases occurred in older HAE patients (> 50 years) and malignancy was diagnosed before HAE in 3 of the patients. CONCLUSIONS: Our case series identified multiple hereditary angioedema (HAE) patients with co-existing malignancy and immune disorders. Based on these findings, we would advocate that physicians managing HAE patients should maintain a high index of suspicion for these conditions and that in patients with angioedema, C1 inhibitor deficiency and malignancy, a diagnosis of HAE should still be considered in addition to acquired angioedema (AAE). | |
| 34881119 | Pericarditis Following Recovery From COVID-19 Infection in a 15-Year-Old Boy: A Postinflam | 2021 Nov | As the COVID-19 pandemic evolves, the medical community continues to report a variety of clinical manifestations of SARS-CoV-2 in the pediatric population. Although younger age groups experience less severe disease, attention is given to the immunologic manifestations of the disease. Pericarditis is a rare cardiac complication of COVID-19 infection. We discuss the first case of delayed presentation of pericarditis following recovery from COVID-19 infection in the pediatric population. A 15-year-old male adolescent presented to the emergency department (ED) with a two-day history of left-sided, sub-sternal chest pain that worsened during inspiration and a low-grade fever. Twenty days prior to this presentation, the patient experienced fever and was tested positive for SARS-CoV-2. His family history was remarkable for Hashimoto thyroiditis and rheumatoid arthritis, with his mother having experienced 18 episodes of pericarditis during the exacerbations of her disease. RT-PCR for SARS-CoV-2 was negative on this occasion and the serology assay identified positive IgG antibodies against the virus. The ECG was suggestive for pericarditis and the diagnosis was confirmed by the presence of pericardial effusion on ECHO. The rest of the aetiological investigations for pericarditis were negative. In view of the strong family history of autoimmunity, questions were raised in the medical team of our hospital regarding the etiology of his pericarditis and on whether it represented a postinflammatory immune-mediated presentation of SARS-CoV-2 or a new-onset autoimmune disease. | |
| 34626163 | The pathogenic mechanism of oral bacteria and treatment with inhibitors. | 2022 Feb | OBJECTIVES: The objective of this study was to introduce the evidence obtained through extensive research that periodontitis increases risk of many systemic diseases. METHOD: Analysis of some oral bacteria (P. gingivalis, T. denticola, T. forsythia, A. actinomycetemcomitans, and F. nucleatum) and its related treatments and mediators by the specific methods (western blot, ELISA, etc). RESULTS: This article reviews in detail the evidence obtained through extensive research that periodontitis increases risk of many systemic diseases, including cardiovascular disease, rheumatoid arthritis, and Alzheimer's disease. These diseases are known to be associated with some certain specific gram-negative bacteria as periodontal pathogens, which induce inflammation and related diseases through TLR receptors, kinases, transcriptional factors and other cytokines. We also reviewed the latest research for inhibitors against inflammation and related diseases that have potential to be further applied clinically. In addition, based on a large amount of research evidence, we draw two tables about the mechanism of disease caused by periodontal bacteria, so that readers can easily search and analyze these research results. DISCUSSION: This review details how the periodontal bacteria and their virulence factors can trigger host immune defense and induce many systemic diseases via inflammation and invasion. This Review also addressed the latest research around inhibitors against inflammation. | |
| 34539413 | The Pathological Mechanism and Potential Application of IL-38 in Autoimmune Diseases. | 2021 | Interleukin-38 (IL-38), a new cytokine of interleukin-1 family (IL-1F), is expressed in the human heart, kidney, skin, etc. Recently, new evidence indicated that IL-38 is involved in the process of different autoimmune diseases. Autoimmune diseases are a cluster of diseases accompanied with tissue damage caused by autoimmune reactions, including rheumatoid arthritis (RA), psoriasis, etc. This review summarized the links between IL-38 and autoimmune diseases, as well as the latest knowledge about the function and regulatory mechanism of IL-38 in autoimmune diseases. Especially, this review focused on the differentiation of immune cells and explore future prospects, such as the application of IL-38 in new technologies. Understanding the function of IL-38 is helpful to shed light on the progress of autoimmune diseases. | |
| 34313205 | Biological Importance, Therapeutic Benefit and Analytical Aspects of Bioactive Flavonoid P | 2021 | BACKGROUNDS: Plants and their derived products have been used in the traditional system of medicine for the treatment of various forms of human disorders since very ancient times. In the traditional system of medicine and modern allopathic medicine, numerous phytoconstituents have been used for the preparation of various types of formulation. Flavonoidal class phytochemicals are the main active phytoconstituents of plants, fruit, vegetables and beverages. Flavonoidal class phytochemicals are more referred as "nutraceuticals" due to their important pharmacological activities in the mammalian body. METHODS: In order to understand the beneficial health effects of flavonoidal class chemical, the present work summarized the health beneficial aspects of pectolinarin. Present work summarized the medicinal importance, pharmacological activities and analytical aspects of pectolinarin with various experimental models and advance analytical methods. However, all the collected scientific information's have been analyzed in the present work for their health beneficial potential. RESULTS: From the analysis of all the collected scientific information in the present work, it was found that pectolinarin is an important phytochemical present in numerous medicinal plants but especially found in Cirsium japonicum, which is an important medicinal herb of Korea, China and Japan. Pharmacological activities data analysis signified the health beneficial potential of pectolinarin for their anti-rheumatoid arthritis, analgesic, anti-inflammatory, hepatoprotective, anti-diabetic, anti-tumor, anti-dengue, antiviral, neuroprotective and antidepressant activity. However, the effectiveness of pectolinarin in central nervous system, bone, liver and cancerous disorders have been also reported in the literature. Analysis of present scientific information revealed the health beneficial potential of pectolinarin in modern medicine due to their numerous pharmacological activities in different parts of biological systems. Due to their biological importance in food and human health, a better understanding of their biological activities indicates their potentials as therapeutic agents. CONCLUSION: Scientific data of the present work signified the biological potential and therapeutic benefit of pectolinarin. | |
| 34247774 | A systematic review of pharmacological activities, toxicological mechanisms and pharmacoki | 2021 Jul | The tubers and roots of Aconitum (Ranunculaceae) are widely used as heart medicine or analgesic agents for the treatment of coronary heart disease, chronic heart failure, rheumatoid arthritis and neuropathic pain since ancient times. As a type of natural products mainly extracted from Aconitum plants, Aconitum alkaloids have complex chemical structures and exert remarkable biological activity, which are mainly responsible for significant effects of Aconitum plants. The present review is to summarize the progress of the pharmacological, toxicological, and pharmacokinetic studies of Aconitum alkaloids, so as to provide evidence for better clinical application. Research data concerning pharmacological, toxicological and pharmacokinetic studies of Aconitum alkaloids were collected from different scientific databases (PubMed, CNKI, Google Scholar, Baidu Scholar, and Web of Science) using the phrase Aconitum alkaloids, as well as generic synonyms. Aconitum alkaloids are both bioactive compounds and toxic ingredients in Aconitum plants. They produce a wide range of pharmacological activities, including protecting the cardiovascular system, nervous system, and immune system and anti-cancer effects. Notably, Aconitum alkaloids also exert strong cardiac toxicity, neurotoxicity and liver toxicity, which are supported by clinical studies. Finally, pharmacokinetic studies indicated that cytochrome P450 proteins (CYPs) and efflux transporters (ETs) are closely related to the low bioavailability of Aconitum alkaloids and play an important role in their metabolism and detoxification in vivo. | |
| 34239951 | Late Acute Hematogenous Infections after Total Knee Arthroplasty: Results of Debridement, | 2021 May | The frequency of late acute hematogenous infection (LAHI) following total knee arthroplasty (TKA) is between 0.2% and 0.5%. There is controversy over the results of patients treated for LAHIs by surgical debridement, antibiotics, and implant retention (DAIR). This narrative review of the literature aims to establish the role of DAIR in LAHIs after TKA. The published success rate (retention of the prosthesis) after DAIR is between 50% and 100%. The success rate is associated with a shorter duration of symptoms (5-14 days from the onset of symptoms). Factors associated with failure are an accompanying infection and the diagnosis of rheumatoid arthritis before the TKA is performed. It is not recommended to indicate a DAIR in patients with atrial fibrillation, chronic obstructive pulmonary disease, the presence of >15 cells per high-powered field, preoperative C-reactive protein >500 mg/L or methicillin-resistant S. aureus. In such patients, a two-stage revision arthroplasty should be recommended. Arthroscopic DAIR has a limited effect. It is most efficacious in the very early stage of acute presentations of infected TKA. It can be useful in patients with extreme frailty as an adjunct to suppressive antibiotic therapy. If carried out, high volumes of fluid should be utilized. The indications for an open DAIR are the following: duration of clinical signs and symptoms is less than 3 weeks; patients with a well-fixed implant; no abscess or sinus tract; low-virulence bacteria; elderly patients with multiple comorbidities; and nonimmunocompromised patients. Open DAIR should not be advised in cases with chronic infection (>4 weeks postoperatively, insidious beginning of symptoms). | |
| 34159026 | A Rare Presentation of Acute Respiratory Distress Due to Diffuse Large B-Cell Lymphoma of | 2021 May 19 | Primary diffuse large B-cell lymphoma of the tongue base (BOT) is an extremely rare entity with only a few cases described in the English literature to date. The incidence of BOT non-Hodgkin's lymphoma (NHL) increases with age, most commonly after the sixth decade of life with no observed gender differences. Our patient presented with a six-month history of right neck swelling, one-month history of dysphagia, a change in voice, and ultimately acute airway distress, which led to a tracheostomy. We report an extremely rare case of a diffuse large B-cell lymphoma presenting with airway distress. The patient was treated using rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) chemotherapy, a five-day steroid course, and one intrathecal methotrexate. The patient recovered completely and is alive at the time of this writing. NHLs occur more commonly in patients like ours with a prior history of congenital immunodeficiency and celiac disease, exposure to radiation, acquired immune deficiency syndrome, rheumatoid arthritis, or Sjögren's syndrome. Most reported cases of BOT NHLs may cause dysphagia, pharyngeal foreign body sensation, or progressive dyspnea. This case highlights that although NHL of the tongue is a very rare entity, it should not be overlooked and should always be in the differential diagnosis among various benign and malignant tumors and may cause rapid respiratory deterioration. | |
| 34124070 | Metformin Reverses Hashimoto's Thyroiditis by Regulating Key Immune Events. | 2021 | BACKGROUND: Hashimoto's thyroiditis (HT) is a common autoimmune disease characterized by high levels of thyroid peroxidase antibody (TPOAb) and thyroid globulin antibody (TgAb) as well as infiltration of lymphocytes in thyroid. In recent years, metformin has been proven to be effective in a variety of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. METHODS: This study systematically explored the therapeutic effect of metformin on HT and its underlying mechanism by comprehensively utilizing methods including animal model, in vitro cell culture and differentiation, mRNA sequencing and 16S rRNA sequencing. FINDINGS: We found that metformin indeed had a therapeutic effect on mice with HT mainly by reducing TgAb and lymphocyte infiltration in thyroid tissue. In addition, metformin also significantly suppressed the number and function of Th17 cells and M1 macrophages polarization in HT mice. Furthermore, metformin can inhibit the differentiation and function of Th17 in vitro. The results of mRNA sequencing of thyroid tissue illustrated that the therapeutic effect of metformin on HT was mainly achieved by regulating immune pathways. 16S RNA sequencing of the intestinal flora found that the intestinal flora of HT mice differs significantly from that of the normal mice and also were altered by metformin treatment. INTERPRETATION: These experiments provided a preliminary theoretical basis for the clinical application of metformin in the treatment of HT. |