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ID PMID Title PublicationDate abstract
34964031 Methotrexate-Related Liver Cirrhosis in Psoriatic Arthritis: A Case Report and Review of t 2021 Sep Methotrexate is an anchor-drug for the treatment of inflammatory arthritides affecting peripheral joints, such as rheumatoid and psoriatic arthritis (PsA), but also for other immune-mediated diseases like psoriasis. Although it is generally a well-tolerated drug, adverse effects often occur. Reversible derangement of liver function test is the most common laboratory adverse event. However, in some cases, liver cirrhosis and/or fibrosis can occur. Besides, many of these diseases like PsA and psoriasis are closely linked with clinical conditions and risk factors that also contribute to liver damage/cirrhosis, such as increased body mass index, dyslipidaemia and diabetes mellitus (DM). It has been hypothesised that the aforementioned risk factors along with methotrexate usage can act synergistically, causing liver damage in these patients. Herein, we describe a PsA patient with DM who developed fatal liver cirrhosis after 10 years of treatment with MTX. We also review the literature about the liver toxicity of MTX in the context of PsA and psoriasis, describing concurring risk factors and histopathological findings. PubMed and Scopus were searched, without date limits. The keywords "methotrexate" AND "psoriatic arthritis" OR "psoriasis" AND "Liver damage" OR "liver fibrosis" OR "cirrhosis" were used. We found that although fibrosis/cirrhosis is present in about 10-25% of the patients, MTX can rarely cause liver damage itself. However, it can exert its effect when other factors, like increased alcohol consumption and obesity coexist. Prospective studies are needed, specifically examining the hepatotoxicity of MTX in individuals with immune-mediated diseases.
33477560 Association between Arthritis and Migraine: A US Nationally Representative Study Including 2021 Jan 18 This study aimed to investigate the cross-sectional association between arthritis and migraine in a large representative sample of the US adult population. The study used data from adults who participated in the RAND American Life Panel (ALP). Arthritis (excluding rheumatoid arthritis) and migraine were self-reported. Control variables included sex, age, ethnicity, marital status, education, employment, annual family income, stroke, epilepsy, coronary artery disease, asthma, depression, anxiety, bipolar disorder, and alcohol dependence. The association between arthritis and migraine was investigated using multivariable logistic regression models, while sex and age interaction analyses were also conducted. This study included 2649 adults (51.7% women; mean (SD) age 50.6 (15.9 years). The prevalence of migraine was 10.7% in the sample. After adjusting for several potential confounders, there was a significant association between arthritis and migraine (OR = 1.83, 95% CI = 1.20-2.81). Further sensitivity analyses revealed that the association was significant in women, adults aged ≤45 years, and those aged >65 years. The mere fact that arthritis and migraine may coexist is problematic, as this could lead to an important medical and economic burden. Therefore, strategies should be implemented to reduce the cooccurrence of these two chronic conditions.
33692019 TNF is a homoeostatic regulator of distinct epigenetically primed human osteoclast precurs 2021 Mar 10 OBJECTIVES: Circulating myeloid precursors are responsible for post-natal osteoclast (OC) differentiation and skeletal health, although the exact human precursors have not been defined. Enhanced osteoclastogenesis contributes to joint destruction in rheumatoid arthritis (RA) and tumour necrosis factor (TNF) is a well-known pro-osteoclastogenic factor. Herein, we investigated the interplay between receptor activator of nuclear factor kappa-Β ligand (RANK-L), indispensable for fusion of myeloid precursors and the normal development of OCs, and TNF in directing the differentiation of diverse pre-OC populations derived from human peripheral blood. METHODS: Flow cytometric cell sorting and analysis was used to assess the potential of myeloid populations to differentiate into OCs. Transcriptomic, epigenetic analysis, receptor expression and inhibitor experiments were used to unravel RANK-L and TNF signalling hierarchy. RESULTS: TNF can act as a critical homoeostatic regulator of CD14(+) monocyte (MO) differentiation into OCs by inhibiting osteoclastogenesis to favour macrophage development. In contrast, a distinct previously unidentified CD14(-)CD16(-)CD11c(+) myeloid pre-OC population was exempt from this negative regulation. In healthy CD14(+) MOs, TNF drove epigenetic modification of the RANK promoter via a TNFR1-IKKβ-dependent pathway and halted osteoclastogenesis. In a subset of patients with RA, CD14(+) MOs exhibited an altered epigenetic state that resulted in dysregulated TNF-mediated OC homoeostasis. CONCLUSIONS: These findings fundamentally re-define the relationship between RANK-L and TNF. Moreover, they have identified a novel pool of human circulating non-MO OC precursors that unlike MOs are epigenetically preconditioned to ignore TNF-mediated signalling. In RA, this epigenetic preconditioning occurs in the MO compartment providing a pathological consequence of failure of this pathway.
34305940 Desiccation Induced Conjunctival Monocyte Recruitment and Activation - Implications for Ke 2021 BACKGROUND: Lacrimal gland secretory dysfunction in Sjögren syndrome (SS) causes ocular surface desiccation that is associated with increased cytokine expression and number of antigen-presenting cells (APCs) in the conjunctiva. This study evaluated the hypothesis that desiccating stress (DS) alters the percentage and gene expression of myeloid cell populations in the conjunctiva. METHODS: DS was induced by pharmacologic suppression of tear secretion and exposure to drafty low humidity environment. Bone marrow chimeras and adoptive transfer of CD45.1(+) bone marrow cells to CD45.2(+) C-C chemokine receptor 2 knockout (CCR2(-/-)) mice were used to track DS-induced myeloid cell recruitment to the conjunctiva. Flow cytometry evaluated myeloid cell populations in conjunctivae obtained from non-stressed eyes and those exposed to DS for 5 days. CD11b(+) myeloid lineage cells were gated on monocyte (Ly6C), macrophage (CD64, MHCII) and DC (CD11c, MHCII) lineage markers. NanoString immune arrays were performed on sorted MHCII(+) and MHCII(-) monocyte/macrophage cell populations. RESULTS: DS significantly increased the recruitment of adoptively transferred MHCII positive and negative myeloid cells to the conjunctiva in a CCR2 dependent fashion. The percentage of resident conjunctival monocytes (Ly6C(+)CD64(-)) significantly decreased while CD64(+)MHCII(+) macrophages increased over 5 days of DS (P<0.05 for both). Comparison of gene expression between the MHCII(-) monocyte and MHCII(+) populations in non-stressed conjunctiva revealed a ≥ 2 log(2) fold increase in 95 genes and decrease in 46 genes. Upregulated genes are associated with antigen presentation, cytokine/chemokine, M1 macrophage and NLRP3 inflammasome pathways. DS increased innate inflammatory genes in monocytes and MHCII(+) cells and increased M1 macrophage (Trem1, Ido1, Il12b, Stat5b) and decreased homeostasis (Mertk) and M2 macrophage (Arg1) genes in MHCII(+) cells. CONCLUSIONS: There are myeloid cell populations in the conjunctiva with distinct phenotype and gene expression patterns. DS recruits myeloid cells from the blood and significantly changes their phenotype in the conjunctiva. DS also alters expression of an array of innate inflammatory genes. Immature monocytes in the unstressed conjunctiva appear to cascade to MHCII(+) macrophages during DS, suggesting that DS promotes maturation of monocytes to antigen presenting cells with increased expression of inflammatory genes that may contribute to the pathogenesis of SS keratoconjunctivitis sicca.
33787627 Clinical and laboratory features of patients with focal lymphocytic sialadenitis on minor 2021 Apr 2 Minor salivary gland biopsy (MSGB) is often used in patients lacking specific autoantibodies (seronegative patients) to confirm the presence of focal lymphocytic sialadenitis (FLS), which would suggest a diagnosis of Sjogren syndrome. There are no current guidelines indicating when to refer patients for MSGB. The objective of our study was to ascertain distinguishing clinical and laboratory features among individuals with sicca symptoms based on their serologic and histopathologic status, and to identify factors associated with FLS.Using a cross-sectional study design, patients ages 18 years or older with sicca symptoms who had MSGB performed at the University of Iowa from January 2000 to December 2016 were selected for chart reviews. The clinical and laboratory features of patients with and without FLS were analyzed using exact univariate and multivariable logistic regression, with Bonferroni correction for multiple comparisons.We identified 177 patients who had MSGB performed and available clinical data. A total of 133 patients had FLS, 37 (27.8%) were seropositive (positive-anti-Sjogren syndrome type A [SSA] and/or anti-Sjogren syndrome type B) and 96 (72.2%) were seronegative. Dry eyes (unadjusted odds ratio [OR]: 5.17, 95% confidence interval [CI]: 1.16-26.30; adjusted odds ratio [aOR]: 12.58, 95% CI: 1.70-167.77) and the presence of anti-SSA (OR: 7.16, 95% CI: 1.70-64.24; aOR: 8.82, 95% CI: 1.73-93.93) were associated with FLS. Smoking (aOR 0.27, 95% CI: 0.11-0.63) and antihistamine use (aOR 0.23, 95% CI: 0.08-0.63) were associated with lower odds of FLS.Our study suggests that dry eyes and anti-SSA positivity are associated with FLS. Smoking and antihistamine use were associated with lower odds of FLS. In the appropriate clinical context, seronegative patients with sicca symptoms and no smoking history could be considered for MSGB. A thorough medication and smoking history should be performed in all patients before referral for MSGB.
33631650 Short-chain fatty acid butyrate induces IL-10-producing B cells by regulating circadian-cl 2021 May OBJECTIVES: Sjögren's syndrome (SS) is an autoimmune disease caused by inflammation of the exocrine gland. The pathological hallmark of SS is the infiltration of lymphocytes into the salivary glands. Increased infiltration of T and B cells into salivary glands exacerbates symptoms of SS. Several recent studies have identified the role of gut microbiota in SS. Butyrate, one of the metabolites of the gut microbiota, regulates T cells; however, its effects on B cells and SS remain unknown. This study determined the therapeutic effect of butyrate on regulating B cells in SS. METHODS: Various concentrations of butyrate were intraperitoneally injected three times per week in NOD/ShiLtJ (NOD) mice, the prototype animal model for SS, and observed for more than 10 weeks. Whole salivary flow rate and the histopathology of salivary glands were investigated. Human submandibular gland (HSG) cells and B cells in mouse spleen were used to confirm the anti-inflammatory and immunomodulatory effects of butyrate. RESULTS: Butyrate increased salivary flow rate in NOD mice and reduced inflammation of salivary gland tissues. It also regulated cell death and the expression of circadian-clock-related genes in HSG cells. Butyrate induced B cell regulation by increasing IL-10-producing B (B10) cells and decreasing IL-17-producing B cells, through the circadian clock genes RAR-related orphan receptor alpha and nuclear receptor subfamily 1 group D member 1. CONCLUSION: The findings of this study imply that butyrate may ameliorate SS via reciprocal regulation of IL-10- and IL-17-producing B cells.
34168654 CD27(-)CD38(low)CD21(low) B-Cells Are Increased in Axial Spondyloarthritis. 2021 B-cells have received little attention in axial spondyloarthritis (axSpA) and for this reason their role in pathogenesis remains unclear. However, there are indications that B-cells may be involved in the disease process. Our objective was to obtain insights into the composition of the peripheral B-cell compartment of axSpA patients compared to healthy donors (HD) and patients with primary Sjögren's syndrome (pSS), a typical B-cell-associated autoimmune disease. Special emphasis was given to CD27-negative B-cells expressing low levels of CD21 (CD21(low) B-cells), since this subset is implicated in autoimmune diseases with strong involvement of B-cells. Transitional B-cells (CD38(hi)) were excluded from the analysis of the CD27(-)CD21(low) B-cell compartment. This study included 45 axSpA patients, 20 pSS patients and 30 HDs. Intriguingly, compared to HDs the frequency of CD27(-)CD38(low)CD21(low) B-cells was significantly elevated in both axSpA and pSS patients (P<0.0001 for both comparisons). The frequency of CD27(-)CD38(low)CD21(low) B-cells expressing the activation-induced immune markers T-bet and CD11c was decreased in axSpA patients compared to HDs. A higher proportion of CD27(-)CD38(low)CD21(low) B-cells expressed the chemokine receptor CXCR3 in axSpA compared to HDs, suggestive for active involvement of these cells in an inflammatory process. The frequency of CD27(-)CD38(low)CD21(low) B-cells in axSpA patients correlated positively with age and erythrocyte sedimentation rate. Furthermore, axSpA patients with extra-skeletal manifestations (ESM) showed increased frequencies of CD27(-)CD38(low)CD21(low) B-cells compared to patients without ESM. In conclusion, our findings are suggestive of active B-cell involvement in the pathogenesis of axSpA, against prevailing dogma.
34477358 Tetrahedral Framework Nucleic Acids Reestablish Immune Tolerance and Restore Saliva Secret 2021 Sep 15 As one of the most frequent autoimmune diseases, Sjogren's syndrome (SS) is characterized by overactive lymphocytic infiltration in the exocrine glands, with ensuing dry mouth and dry eyes. Unfortunately, so far, there are no appropriate therapies without causing overall immunosuppression. Tetrahedral framework nucleic acids (tFNAs) were regarded as promising nanoscale materials whose immunomodulatory capabilities have already been verified. Herein, we reveal, for the first time, that tFNAs were utilized to treat SS in female nonobese diabetic (NOD) mice, the animal model used for SS. We proved a 250 nM tFNA treatment was successful in suppressing inflammation and stimulating saliva secretion in NOD mice. Specialised proteins for the secretory function and structure of acinar cells in submandibular glands (SMGs) were restored. It has been the permanent goal for SS treatment to establish immune tolerance and stop disease development. Surprisingly, tFNA treatment guided T cells toward regulatory T cells (Tregs), while suppressing T helper (Th) cell responses. Th cells include Th1, Th17, and follicular helper T (Tfh) cells. Tregs are highly significant in immune tolerance. Inducing Tregs is a promising approach to reestablish immune tolerance. Comparable results were also observed in B cell responses. Reductions in the percentage of germinal center (GC) B cells and plasma cells were detected, and a marked increase in the percentage of regulatory B cells (Bregs) was also noticed. The mechanisms of inducing Tregs may associated with cytokine changes. Changes of T cell subsets, especially changes of Tfh, may influence the differentiation of B cells accordingly. Collectively, our results demonstrated the immunomodulatory capacities of tFNAs once again, which may provide a novel, safe, and effective option for the treatment of SS and other autoimmune diseases.
34431883 Sterile, recurrent, and bilateral corneal perforation related to primary biliary cirrhosis 2021 Nov Primary biliary cirrhosis is a rare progressive autoimmune liver disease that causes chronic cholestasis. Of patients with primary biliary cirrhosis, 75% develop secondary Sjogren syndrome and could develop vitamin A deficiency. Here, we report the case of a patient with primary biliary cirrhosis who developed a secondary Sjogren syndrome and vitamin A deficiency, which led to severe and unusual eye involvement with multiple and recurrent spontaneous corneal perforations. Corneal perforations in patients with primary biliary cirrhosis and secondary Sjogren syndrome are rare but devastating complications, in contrast to other eye clinical manifestations of the disease.
34204342 Cardiovascular Risk and Endothelial Dysfunction in Primary Sjogren Syndrome Is Related to 2021 Jun 17 The aim of our study was to evaluate if endothelial-dysfunction (ED) occurs in patients with primary Sjogren syndrome (pSS) and whether it is associated with the disease characteristics and activity. A total of 46 patients with pSS and 30 controls, without known cardiovascular disease, were enrolled in this study. A flow-mediated-dilation (FMD) of the brachial artery, plasma concentrations of the nitric oxide (NO) metabolic pathway (ADMA, L-arginine, SDMA, cGMP), and markers of endothelial inflammatory function (PAI-1, sE-selectin) and angiogenesis (angiostatin, VEGF) were analyzed. The FMD was significantly lower in pSS patients (7.56 ± 3.08 vs. 10.91 ± 1.02%, p = 0.043) and positively correlated with the Ro/SS-A-antibodies (r = 0.34, p = 0.03), pulmonary involvement (r = 0.52, p = 0.001) and inversely with ADMA (r = -0.35, p = 0.04). Plasma ADMA, L-arginine and angiostatin levels were significantly higher in pSS patients (0.39 ± 0.08 vs. 0.36 ± 0.06 µmol/L, p = 0.05; 29.07 ± 6.7 vs. 25.4 ± 5.23 µmol/L, p = 0.01; 152.25 ± 60.99 vs. 120.07 ± 38.7 pg/mL, p = 0.0, respectively). ADMA was associated with ESSDAI (r = 0.33, p = 0.02), SCORE (r = 0.57, p = 0.00003) and focus score (r = 0.38, p = 0.04). In the multiple regression analysis, the ESSDAI was significantly and independently associated with plasma ADMA levels (β = 0.24, p = 0.04). Moreover, plasma cGMP concentrations were negatively correlated with the disease duration (r = -0.31, p = 0.03). Endothelial function is impaired in patients with pSS and associated with the measures of disease activity, which supports the key-role of inflammation in developing and maintaining accelerated atherosclerosis.
33803026 Role of the Innate Immunity Signaling Pathway in the Pathogenesis of Sjögren's Syndrome. 2021 Mar 17 Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of the salivary and lacrimal glands and extra-glandular lesions. Adaptive immune response including T- and B-cell activation contributes to the development of SS. However, its pathogenesis has not yet been elucidated. In addition, several patients with SS present with the type I interferon (IFN) signature, which is the upregulation of the IFN-stimulated genes induced by type I IFN. Thus, innate immune responses including type I IFN activity are associated with SS pathogenesis. Recent studies have revealed the presence of activation pattern recognition receptors (PRRs) including Toll-like receptors, RNA sensor retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, and inflammasomes in infiltrating and epithelial cells of the salivary glands among patients with SS. In addition, the activation of PRRs via the downstream pathway such as the type I IFN signature and nuclear factor kappa B can directly cause organ inflammation, and it is correlated with the activation of adaptive immune responses. Therefore, this study assessed the role of the innate immune signal pathway in the development of inflammation and immune abnormalities in SS.
34599320 Fatigue in inflammatory rheumatic diseases: current knowledge and areas for future researc 2021 Nov Fatigue is a complex phenomenon and an important health concern for many people with chronic inflammatory rheumatic diseases, such as rheumatoid arthritis, psoriatic arthritis, primary Sjögren syndrome and systemic lupus erythematosus. Although some clinical trials have shown the benefits of cognitive behavioural therapy in fatigue management, the effect of this approach is relatively modest, and no curative treatment has been identified. The pathogenesis of fatigue remains unclear. Despite many challenges and limitations, a growing body of research points to roles for the immune system, the central and autonomic nervous systems and the neuroendocrine system in the induction and maintenance of fatigue in chronic diseases. New insights indicate that sleep, genetic susceptibility, metabolic disturbances and other biological and physiological mechanisms contribute to fatigue. Furthermore, understanding of the relationships between psychosocial factors and fatigue is increasing. However, the interrelationships between these diverse mechanisms and fatigue remain poorly defined. In this Review, we outline various biological, physiological and psychosocial determinants of fatigue in inflammatory rheumatic diseases, and propose mechanistic and conceptual models of fatigue to summarize current understanding, stimulate debate and develop further research ideas.
34480164 The endothelium-bone axis in development, homeostasis and bone and joint disease. 2021 Oct Blood vessels form a versatile transport network that is best known for its critical roles in processes such as tissue oxygenation, metabolism and immune surveillance. The vasculature also provides local, often organ-specific, molecular signals that control the behaviour of other cell types in their vicinity during development, homeostasis and regeneration, and also in disease processes. In the skeletal system, the local vasculature is actively involved in both bone formation and resorption. In addition, blood vessels participate in inflammatory processes and contribute to the pathogenesis of diseases that affect the joints, such as rheumatoid arthritis and osteoarthritis. This Review summarizes the current understanding of the architecture, angiogenic growth and functional properties of the bone vasculature. The effects of ageing and pathological conditions, including arthritis and osteoporosis, are also discussed.
34941008 Hydroxychloroquine Use and Cardiovascular Events Among Patients with Systemic Lupus Erythe 2021 Dec 23 OBJECTIVE: We evaluated the potential temporal association between Hydroxychloroquine (HCQ) use and cardiovascular (CV) events among patients with SLE or RA. METHODS: We conducted a nested case-control study within inception cohorts of SLE and RA patients using administrative health databases including the entire population of British Columbia, Canada. We identified cases with incident CV events, including myocardial infarction (MI), stroke, or venous thromboembolism (VTE). We matched each case with up to three controls on age, sex, and rheumatic disease. HCQ exposure was categorized by the time between the last HCQ prescription date covered and the index date as current use, recent use, remote use, or never used. We used conditional logistic regression to assess the association between HCQ exposure and CV events, using remote use as the reference group. RESULTS: We identified 10,268 cases and 29,969 controls. Adjusted conditional odd ratios (cORs) (95% CI) for current HCQ use relative to remote use were 0.86 (0.77-0.97) for combined CV events, 0.88 (0.74, 1.05) for MI, 0.87 (0.74, 1.03) for stroke, and 0.74 (0.59, 0.94) for VTE. Recent HCQ users and non-users had similar odds of combined CV events as remote users (cORs 0.93 ([95% CI, 0.77-1.13] and 0.96 [95% CI, 0.88-1.04], respectively). CONCLUSION: In this nested case-control study of patents with SLE and RA, we found a reduced risk of overall CV events associated with current HCQ use including reductions in VTE and trends towards reductions in MI and stroke. These findings suggest a possible cardiovascular preventative benefit of HCQ use.
34254500 A case report of intracranial hypertension and aseptic meningitis: anti-tumor necrosis fac 2021 BACKGROUND: The adverse effects of tumor necrosis factor alpha inhibitors (TNFi) are well characterized but rare adverse events are increasing day by day. CASE: We presented an 18-year-old girl with rheumatoid factor positive polyarticular juvenile idiopathic arthritis (JIA) who developed fever, headache, and nausea after the second dose of adalimumab. In addition to her suspicious complaints for meningitis, she had bilateral papilledema and partial abducens nerve palsy. Leptomeningeal contrast enhancement was noted in magnetic resonance imaging (MRI) of the brain. Brain MRI venography was normal. The cerebrospinal fluid (CSF) opening pressure was high but CSF analysis was normal. She was diagnosed with non-infectious subacute meningitis. Since brain biopsy was not performed, no definite distinction could be made between TNFi related aseptic meningitis or cerebral involvement of JIA. Due to the onset of neurological complaints after initiation of adalimumab treatment and rare cerebral involvement in JIA, the drug-associated aseptic meningitis was likely to be responsible in our patient. Adalimumab was discontinued and methylprednisolone followed by methotrexate treatment were initiated. Her symptoms resolved and control brain MRI was normal. CONCLUSION: Pediatric rheumatologists should be aware of this potentially severe side effect of anti-TNF treatment.
35000348 Upper Cervical Compression Myelopathy Caused by the Retro-Odontoid Pseudotumor With Degene 2021 Dec The retro-odontoid pseudotumor is often concurrent with atlantoaxial subluxation (AAS). Therefore, the pseudotumor is relatively common in rheumatoid arthritis (RA) but rare in primary osteoarthritis (OA). This is a case report of an elderly male patient suffering from neck pain and compression myelopathy caused by the craniocervical pseudotumor with OA but without atlantoaxial instability. He had long-lasting peripheral and spinal pain treated by nonsteroidal anti-inflammatory drugs. Imaging found upper cervical spondylosis without AAS or dynamic instability but with periodontoid calcifications and ossifications, suggesting calcium pyrophosphate dihydrate (CPPD) crystal deposition. Based on a comprehensive literature search and review, CPPD disease around the atlantodental joint is a possible contributor to secondary OA development and retro-odontoid pannus formation through chronic inflammation, which can be enough severe to induce compression myelopathy in non-RA patients without AAS. The global increase in the aged population advises caution regarding more prevalent upper cervical spine disorders associated with OA and CPPD.
34950546 Peanut-Related Perforated Diverticulitis Before the Age of 60. 2021 Nov We present a case in which a 55-year-old male with a past medical history of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) presented with sharp, worsening right-sided abdominal pain radiating across the entire abdomen after eating peanuts. Computed tomography (CT) imaging showed evidence of acute sigmoid diverticulitis complicated by a walled-off perforation. The patient's past medical history suggested previous recurrent episodes of diverticulitis. Our patient underwent exploratory laparotomy, sigmoid colon resection with low anterior anastomosis and proctocolectomy, and loop ileostomy. During treatment, the sigmoid colon was found to be very indurated and abnormally going all the way down to the peritoneal reflection. Appropriate identification of the patient's condition and timely intervention resulted in a successful outcome.
34925027 Liriopogons (Genera Ophiopogon and Liriope, Asparagaceae): A Critical Review of the Phytoc 2021 The closely related genera Liriope and Ophiopogon (Asparagaceae), collectively known in English as liriopogons, have similar therapeutic uses in treating cough, rheumatoid arthritis, and cleaning heat. The main aim of this review is to understand the current phytochemical and pharmacological knowledge including an assessment of the quality of the scientific evidence. A literature search was conducted in line with PRISMA guidelines, by retrieving available information up to 2020 from five online resources. The bioactive metabolites of liriopogons include steroidal saponins, flavonoids, polysaccharides, organic acids, phenols. Cardiovascular protective, anti-inflammatory, anti-diabetic, anti-oxidant, anti-cancer, neuroprotective, anti-viral, anti-acute myeloid leukemia and hepatoprotective effects have been at the center of attention. From a toxicological perspective Ophiopogon japonicus seems to be safe. Some problems with the quality of the pharmacological evidence stand out including the application of excessive dose level and methodological problems in the design. Additionally, a reasonable link between local/traditional uses and pharmacological assessment is often vague or not reflected in the text. Future researches on liriopogons are required to use rigorous scientific approaches in research on evidence-based natural products for the future benefits of patients.
34854586 [An asymptomatic patient with lactate acidosis and hypercapnia]. 2021 Sep 23 BACKGROUND: Blood gas analyses are used to identify acid-base and respiratory disturbances. Blood gas abnormalities can be first signs of serious underlying disease. CASE DESCRIPTION: An 82-year old women with chronic kidney disease (eGFR 35 ml/min/1.73m2) and rheumatoid arthritis was admitted to the geriatric ward due to a urinary tract infection and bloody diarrhea. She repeatedly had a low oxygen saturation, although without symptoms. Capillary blood gas analysis was evidently disturbed (pH 6.96, pCO2 9.3 kPa, lactate 8.4 mmol/l), and led to consultation of the intensivist. Careful physical examination demonstrated that the patients' hands had blue discoloration, typical for Raynaud's phenomenon. Arterial blood gas demonstrated normal results. CONCLUSION: Capillary blood gas analysis is less reliable when peripheral circulation is disturbed. When the results are aberrant, it is important to distinguish between peripheral vascular disease and diminished systemic circulation. Arterial blood gas analysis can be used to support the diagnosis.
34513612 Clinical Pharmacology Aspects in Patients Treated with TNF Inhibitors During SARS-Cov-2 Pa 2021 May In this period of global pandemic caused by SARS-Cov-2, it is of paramount importance to recognize all risk factors that may increase the likelihood of infection. In addition to the risk factors known as pre-existing diseases and old age, risk factors could be drug treatments for chronic diseases, such as immunomodulating drugs that can alter immune defences and response to infectious agents. Antibodies that inhibit tumor necrosis factor (TNF) such as adalimumab infliximab etanercept and golimumab have been used for over 20 years in severe cases of autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease or ankylosing spondylitis. Due to their mechanism of action they reduce inflammation and can stop the progression of the disease by inhibiting a key factor of inflammation such as TNF. In this article we want to examine the possible correlation between therapy with TNF inhibitors and the increased risk of SARS-CoV-2 infection, and the possible paradoxical therapeutic efficacy in patients with ongoing infection, especially in phase two and three. We express our opinion on this very complex and sensitive topic which is the subject of discussion among physicians and experts, based on current knowledge of the literature.