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ID PMID Title PublicationDate abstract
33089733 Does Nonsurgical Periodontal Treatment Improve Systemic Health? 2021 Mar Clinicians frequently stress the importance of maintaining good oral health for multiple reasons, including its link to systemic health. Because periodontal treatment reduces inflammation in oral tissues, some hypothesize it may positively affect systemic outcomes by reducing inflammation in the body. A significant number of systematic reviews (SRs) and meta-analyses (MAs) have evaluated the effect of periodontal treatment on systemic outcomes. However, inconsistent findings and questionable methodological rigor make drawing conclusions difficult. We conducted a systematic review of reviews that studied the effect of nonsurgical periodontal treatment on systemic disease outcomes. We report on outcomes evaluated, categorizing them as biomarkers, and surrogate or clinical endpoints. In addition, we used A MeaSurement Tool to Access systematic Reviews 2 (AMSTAR 2) to evaluate the methodological quality of the reviews. Of the 52 studies included in our review, 21 focused on diabetes, 15 on adverse birth outcomes, 8 on cardiovascular disease, 3 each on obesity and rheumatoid arthritis, and 2 on chronic kidney disease. Across all studies, surrogate endpoints predominated as outcomes, followed by biomarkers and, rarely, actual disease endpoints. Ninety-two percent of studies had "low" or "critically low" AMSTAR 2 confidence ratings. Criteria not met most frequently included advance registration of the protocol, justification for excluding individual studies, risk of bias from individual studies being included in the review, and appropriateness of meta-analytical methods. There is a dearth of robust evidence on whether nonsurgical periodontal treatment improves systemic disease outcomes. Future reviews should adhere more closely to methodological guidelines for conducting and reporting SRs/MAs than has been the case to date. Beyond improved reviews, additional rigorous research on whether periodontal treatment affects systemic health is needed. We highlight the potential of large-scale databases containing matched medical and dental record data to inform and complement future clinical research studying the effect of periodontal treatment on systemic outcomes.
34360719 Uncovering the Mechanisms of Adenosine Receptor-Mediated Pain Control: Focus on the A(3) R 2021 Jul 26 Agonists of the G(i) protein-coupled A(3) adenosine receptor (A(3)AR) have shown important pain-relieving properties in preclinical settings of several pain models. Active as a monotherapy against chronic pain, A(3)AR agonists can also be used in combination with classic opioid analgesics. Their safe pharmacological profile, as shown by clinical trials for other pathologies, i.e., rheumatoid arthritis, psoriasis and fatty liver diseases, confers a realistic translational potential, thus encouraging research studies on the molecular mechanisms underpinning their antinociceptive actions. A number of pathways, involving central and peripheral mechanisms, have been proposed. Recent evidence showed that the prototypical A(3)AR agonist Cl-IB-MECA and the new, highly selective, A(3)AR agonist MRS5980 inhibit neuronal (N-type) voltage-dependent Ca(2+) currents in dorsal root ganglia, a known pain-related mechanism. Other proposed pathways involve reduced cytokine production, immune cell-mediated responses, as well as reduced microglia and astrocyte activation in the spinal cord. The aim of this review is to summarize up-to-date information on A(3)AR in the context of pain, including cellular and molecular mechanisms underlying this effect. Based on their safety profile shown in clinical trials for other pathologies, A(3)AR agonists are proposed as novel, promising non-narcotic agents for pain control.
34097669 Diagnosing Systemic Amyloidosis Presenting as Carpal Tunnel Syndrome: A Risk Nomogram to G 2021 Jul 21 BACKGROUND: As carpal tunnel syndrome often precedes other signs of systemic amyloidosis, tenosynovial biopsy at the time of carpal tunnel release may facilitate early diagnosis and treatment. However, evidence-based guidelines for amyloidosis screening during carpal tunnel release have not been established. We sought to develop a predictive model for amyloidosis after carpal tunnel release to inform screening efforts. METHODS: We performed a retrospective cohort study of adults without known amyloidosis undergoing at least 1 carpal tunnel release from 2000 to 2019 with use of the national Veterans Health Administration database. After estimating the cumulative incidence of amyloidosis after carpal tunnel release, we identified risk factors, constructed a predictive nomogram based on a multivariable subdistribution-hazard competing-risks model, and performed cross-validation. RESULTS: Among 89,981 patients undergoing at least 1 carpal tunnel release, 310 were subsequently diagnosed with amyloidosis at a median interval of 4.5 years, corresponding to a cumulative incidence of 0.55% (95% confidence interval [CI]: 0.47% to 0.63%) at 10 years. Amyloidosis diagnosis following carpal tunnel release was associated with an increased hazard of heart failure (hazard ratio [HR], 4.68; 95% CI: 4.26 to 5.55) and death (HR, 1.27; 95% CI: 1.07 to 1.51) after adjustment for potential confounders. Age, male sex, Black race, monoclonal gammopathy of undetermined significance or multiple myeloma, rheumatoid arthritis, atrial fibrillation, spinal stenosis, and bilateral carpal tunnel syndrome were independently associated with increased risk of amyloidosis diagnosis and were included in the risk nomogram. CONCLUSIONS: Amyloidosis diagnosis after carpal tunnel release is rare but is associated with poor outcomes. We present an amyloidosis-risk nomogram to help guide tenosynovial biopsy at time of carpal tunnel release. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
33957012 Pharmacologic activities of phytosteroids in inflammatory diseases: Mechanism of action an 2021 Sep Natural products and their derivatives are known to be useful for treating numerous diseases since ancient times. Because of their high therapeutic potentials, the use of different medicinal plants is possible to treat varied inflammation-mediated chronic diseases. Among natural products, phytosteroids have emerged as promising compounds mostly because they have diverse pharmacological activities. Currently, available medications exert numerous systemic toxicities, including hypertension, immune suppression, osteoporosis, and metabolic abnormalities. Thus, further research on phytosteroids to subside these complications is of significant importance. In this study, the information on phytosteroids, their types, and actions against inflammation, and allergic complications was collected by a systematic survey of literature on several scientific search engines. The literature review suggested that phytosteroids exhibit antiinflammatory action via different modes through transrepression or selective COX-2 enzymes. Also, in silico ADMET analysis was carried out on available phytosteroids to uncover their pharmacokinetic properties. Our analysis has shown that eight compounds: withaferin A, stigmasterol, β-sitosterol, guggulsterone, diosgenin, sarsasapogenin, physalin A, and dioscin, -isolated from medicinal plants show similar pharmacokinetic properties as compared to dexamethasone, commercially available glucocorticoid. These phytosteroids could be useful for the treatment of inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, asthma, and cardiovascular diseases. Thus, systematic research is required to explore potent phytosteroids with lesser side effects, which might substitute the current medications.
33746953 Activation of Bone Marrow Adaptive Immunity in Type 2 Diabetes: Rescue by Co-stimulation M 2021 Background: Chronic low-grade inflammation and alterations in innate and adaptive immunity were reported in Type 2 diabetes (T2D). Here, we investigated the abundance and activation of T cells in the bone marrow (BM) of patients with T2D. We then verified the human data in a murine model and tested if the activation of T cells can be rescued by treating mice with abatacept, an immunomodulatory drug employed for the treatment of rheumatoid arthritis. Clinical evidence indicated abatacept can slow the decline in beta-cell function. Methods: A cohort of 24 patients (12 with T2D) undergoing hip replacement surgery was enrolled in the study. Flow cytometry and cytokine analyses were performed on BM leftovers from surgery. We next compared the immune profile of db/db and control wt/db mice. In an additional study, db/db mice were randomized to receive abatacept or vehicle for 4 weeks, with endpoints being immune cell profile, indices of insulin sensitivity, and heart performance. Results: Patients with T2D showed increased frequencies of BM CD4(+) (2.8-fold, p = 0.001) and CD8(+) T cells (1.8-fold, p = 0.01), with the upregulation of the activation marker CD69 and the homing receptor CCR7 in CD4(+) (1.64-fold, p = 0.003 and 2.27-fold, p = 0.01, respectively) and CD8(+) fractions (1.79-fold, p = 0.05 and 1.69-fold, p = 0.02, respectively). These differences were confirmed in a multivariable regression model. CCL19 (CCR7 receptor ligand) and CXCL10/11 (CXCR3 receptor ligands), implicated in T-cell migration and activation, were the most differentially modulated chemokines. Studies in mice confirmed the activation of adaptive immunity in T2D. Abatacept reduced the activation of T cells and the levels of proinflammatory cytokines and improved cardiac function but not insulin sensitivity. Conclusions: Results provide proof-of-concept evidence for the activation of BM adaptive immunity in T2D. In mice, treatment with abatacept dampens the activation of adaptive immunity and protects from cardiac damage.
33468130 Production of biologically active human interleukin-10 by Bifidobacterium bifidum BGN4. 2021 Jan 19 BACKGROUND: Bifidobacterium spp. are representative probiotics that play an important role in the health of their hosts. Among various Bifidobacterium spp., B. bifidum BGN4 exhibits relatively high cell adhesion to colonic cells and has been reported to have various in vivo and in vitro bio functionalities (e.g., anti-allergic effect, anti-cancer effect, and modulatory effects on immune cells). Interleukin-10 (IL-10) has emerged as a major suppressor of immune response in macrophages and other antigen presenting cells and plays an essential role in the regulation and resolution of inflammation. In this study, recombinant B. bifidum BGN4 [pBESIL10] was developed to deliver human IL-10 effectively to the intestines. RESULTS: The vector pBESIL10 was constructed by cloning the human IL-10 gene under a gap promoter and signal peptide from Bifidobacterium spp. into the E. coli-Bifidobacterium shuttle vector pBES2. The secreted human IL-10 from B. bifidum BGN4 [pBESIL10] was analyzed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), Western Blotting, and enzyme-linked immunosorbent assay (ELISA). More than 1,473 ± 300 ng/mL (n = 4) of human IL-10 was obtained in the cell free culture supernatant of B. bifidum BGN4 [pBESIL10]. This productivity is significantly higher than other previously reported human IL-10 level from food grade bacteria. In vitro functional evaluation of the cell free culture supernatant of B. bifidum BGN4 [pBESIL10] revealed significantly inhibited interleukin-6 (IL-6) production in lipopolysaccharide (LPS)-induced Raw 264.7 cells (n = 6, p < 0.0001) and interleukin-8 (IL-8) production in LPS-induced HT-29 cells (n = 6, p < 0.01) or TNFα-induced HT-29 cells (n = 6, p < 0.001). CONCLUSION: B. bifidum BGN4 [pBESIL10] efficiently produces and secretes significant amounts of biologically active human IL-10. The human IL-10 production level in this study is the highest of all human IL-10 production reported to date. Further research should be pursued to evaluate B. bifidum BGN4 [pBESIL10] producing IL-10 as a treatment for various inflammation-related diseases, including inflammatory bowel disease, rheumatoid arthritis, allergic asthma, and cancer immunotherapy.
34650827 Porcine-Derived Collagen-Augmented Chondrogenesis Technique for Treating Knee Cartilage De 2021 Jul Articular cartilage is virtually incapable of self-healing in the event of a defect. Microfracture is the most frequently used bone marrow stimulation technique(1), but there is the limitation of unpredictable quality of the cartilage repair following bone marrow stimulation(2). To resolve the shortcomings of the microfracture technique, various reinforcing technologies have been developed, including the porcine-derived collagen-augmented chondrogenesis technique (C-ACT)(3). The collagen gel utilized in that procedure is a product called CartiFill (Sewon Cellontech), made from highly purified pig-derived type-I collagen. It has been modified into an atelocollagen, by removing telopeptides, to virtually eliminate the risk of rejection. The collagen matrix provides not only a 3-dimensional structure for cartilage differentiation, but also mechanical support(3,4). DESCRIPTION: Porcine-derived C-ACT is initiated by creating a mixture of atelocollagen, thrombin, and fibrinogen. First, thrombin is mixed with atelocollagen and placed in one arm of an assembled Y-shaped syringe, and fibrinogen is placed in the other arm. The articular cartilage defect site is confirmed in a routine arthroscopic procedure. The articular margin is debrided, and the calcified lesion is cleanly removed. Then, microfractures are created. After creating a more extended incision at the anteromedial portal, the microfracture site is prepared by removing moisture. The prepared atelocollagen mixture is applied to the defect site as a single layer, although a second layer can be formed 1 to 2 minutes later. After 5 minutes, the stability is verified by range of motion of the knee.Indications for this procedure include (1) cartilage defects in the knee, including knee osteoarthritis and knee traumatic arthritis; (2) knee osteoarthritis with a Kellgren-Lawrence grade of 3 or less; (3) hip-knee-ankle malalignment of <5° or a deformity that is able to be surgically corrected; and (4) knee stability, or instability that is able to be surgically corrected.Contraindications for this procedure include (1) patient or family history of autoimmune disease, (2) history of anaphylactic reaction, (3) history of hypersensitivity to an implant, (4) history of allergy to porcine or bovine protein, and (5) inflammatory arthritis such as rheumatoid and gouty arthritis.C-ACT is a procedure for cartilage repair, and the effects of this procedure can be limited in cases with a deep subchondral bone defect; however, there is no limit to the size of the cartilage defect in terms of patient selection for C-ACT. ALTERNATIVES: There are several alternatives to C-ACT, ranging from the simple microfracture technique to autologous chondrocyte implantation(5), matrix-induced autologous chondrocyte implantation(6), autologous matrix-induced chondrogenesis(7), osteochondral autograft transplantation(8), and stem cell therapy. There are various ways to recover from an articular cartilage defect, but C-ACT does not require a 2-stage technique, as is necessary with both autologous chondrocyte implantation procedures. Therefore, C-ACT has the advantages of ease of operation and being a single-stage procedure(3,9). RATIONALE: C-ACT can be classified as an upgraded version of microfracture, which is the most common treatment method for articular cartilage defects. With the microfracture technique, repaired cartilage is limited to fibrous cartilage and does not include hyaline cartilage(3,4). However, a recent study reported that C-ACT exhibited a superior quality of repaired cartilage compared with microfracture(3,4). EXPECTED OUTCOMES: Previous studies have reported favorable results with the use of C-ACT(3,4). Kim et al.(4) compared atelocollagen augmentation with microfracture alone in patients undergoing medial opening wedge high tibial osteotomy for the treatment of medial compartment osteoarthritis. Although there was no clinical difference between the 2 groups, the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score and the International Cartilage Repair Society II score were superior in the atelocollagen augmentation group. In addition, the microfracture group formed fibrous-like cartilage compared with the hyaline-like cartilage created in the atelocollagen augmentation group. A recent multicenter randomized study compared the use of C-ACT and microfracture and found that C-ACT exhibited significantly better results in several MOCART subscores and quantitative T2 mapping, indicating a histologically superior form of repaired cartilage compared with microfracture(3). According to recent research, microfracture is superior to autologous chondrocyte implantation in terms of cost-effectiveness(10). Similar results appear to be applicable to C-ACT. C-ACT requires an additional $1,300 for material costs; however, C-ACT showed better cartilage regeneration on magnetic resonance imagining and histology(3,4), and higher rate of patients meeting the 20%-improvement rate in visual analogue scale pain scores at 24 months postoperatively compared with microfracture(3). Long-term studies will be needed to assess whether histological superiority of C-ACT is reflected in meaningful improvements to clinical outcomes. IMPORTANT TIPS: Debride all of the damaged cartilage to subchondral bone and remove the calcified layer without interfering with tissue repairTake special care when creating the atelocollagen mixture to ensure that it is accurately manufacturedDry the defect site with use of suction or gauze to aid in atelocollagen adhesion when applying atelocollagen.
33996408 Biological drug and drug delivery-mediated immunotherapy. 2021 Apr The initiation and development of major inflammatory diseases, i.e., cancer, vascular inflammation, and some autoimmune diseases are closely linked to the immune system. Biologics-based immunotherapy is exerting a critical role against these diseases, whereas the usage of the immunomodulators is always limited by various factors such as susceptibility to digestion by enzymes in vivo, poor penetration across biological barriers, and rapid clearance by the reticuloendothelial system. Drug delivery strategies are potent to promote their delivery. Herein, we reviewed the potential targets for immunotherapy against the major inflammatory diseases, discussed the biologics and drug delivery systems involved in the immunotherapy, particularly highlighted the approved therapy tactics, and finally offer perspectives in this field.
33626984 Clinical analyses of ultrasound-guided nerve block in lower-extremity surgery: A retrospec 2021 Jan PURPOSE: The purpose of this study is to examine the clinical effects and results of lower-extremity surgery under ultrasound-guided nerve block; time required for nerve block, anesthesia onset time, duration of anesthesia, duration of analgesia, tolerable tourniquet time, visual analog scale (VAS) satisfaction score, and anesthetic-related complications. METHODS: A total of 3312 cases (2597 patients) from January 2010 to April 2015 were analyzed retrospectively. A senior author performed ultrasound-guided nerve block of the lateral femoral cutaneous nerve (LFCN, 630 cases), femoral nerve (FN, 2503 cases), obturator nerve (ON, 366 cases), sciatic nerve (SN, 3271 cases), or posterior femoral cutaneous nerve (PFCN, 222 cases) depending on the type of surgery. Time required for nerve block, anesthesia onset time, duration of anesthesia, duration of analgesia, tolerable tourniquet time, VAS satisfaction score, and anesthetic-related complications were analyzed. RESULTS: The mean times required were 1.1 min for SN block, 2.5 min for FN/SN block (1762 cases), and 4.8 min for FN/SN/LFCN/ON block. The mean anesthesia onset time was 48 min. The mean durations of anesthesia were 4.5 h for FN dermatome and 5.6 h for SN dermatome. The mean duration of analgesia was 11.5 h. The mean tolerable tourniquet times after were 35, 51, and 84 min after SN block, FN/SN block, and FN/SN/LFCN/ON block, respectively. The mean VAS satisfaction score was 9.3. There were no anesthetic-related complications, such as infection, hematoma, paralysis, or nerve irritation. CONCLUSION: Selective block of the LFCN, FN, ON, SN, and PFCN based on the locations of lesions and type of surgery showed favorable clinical results with high efficacy. Ultrasound-guided nerve block may be a good option for anesthesia and analgesia in lower-extremity surgery.
33571819 Leflunomide an immunomodulator with antineoplastic and antiviral potentials but drug-induc 2021 Apr Leflunomide (LF) represents the prototype member of dihydroorotate dehydrogenase (DHODH) enzyme inhibitors. DHODH is a mitochondrial inner membrane enzyme responsible for catalytic conversion of dihydroorotate into orotate, a rate-limiting step in the de novo synthesis of the pyrimidine nucleotides. LF produces cellular depletion of pyrimidine nucleotides required for cell growth and proliferation. Based on the affected cells the outcome can be attainable as immunosuppression, antiproliferative, and/or the recently gained attention of the antiviral potentials of LF and its new congeners. Also, protein tyrosine kinase inhibition is an additional mechanistic benefit of LF, which inhibits immunological events such as cellular expansion and immunoglobulin production with an enhanced release of immunosuppressant cytokines. LF is approved for the treatment of autoimmune arthritis of rheumatoid and psoriatic pathogenesis. Also, LF has been used off-label for the treatment of relapsing-remitting multiple sclerosis. However, LF antiviral activity is repurposed and under investigation with related compounds under a phase-I trial as a SARS CoV-2 antiviral in cases with COVID-19. Despite success in improving patients' mobility and reducing joint destruction, reported events of LF-induced liver injury necessitated regulatory precautions. LF should not be used in patients with hepatic impairment or in combination with drugs elaborating a burden on the liver without regular monitoring of liver enzymes and serum bilirubin as safety biomarkers. This study aims to review the pharmacological and safety profile of LF with a focus on the LF-induced hepatic injury from the perspective of pathophysiology and possible protective agents.
33744132 Impaired Coronary Vasodilator Reserve and Adverse Prognosis in Patients With Systemic Infl 2021 Nov OBJECTIVES: The purpose of this study was to evaluate the prognostic value of quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR), reflecting the integrated effects of diffuse atherosclerosis and microvascular dysfunction in patients with systemic inflammatory disorders. BACKGROUND: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis (PsO) are common inflammatory conditions with excess cardiovascular (CV) risk compared to the general population. Systemic inflammation perturbs endothelial function and has been linked to coronary vasomotor dysfunction. However, the prognostic significance of this vascular dysfunction is not known. METHODS: This was a retrospective study of patients with RA, SLE, and PsO undergoing clinically indicated rest and stress myocardial perfusion positron emission tomography (PET). Patients with an abnormal myocardial perfusion study or left ventricular dysfunction were excluded. MFR was calculated as the ratio of myocardial blood flow (MBF, ml/min/g) at peak stress compared to that at rest. RESULTS: Among the 198 patients (median age: 65 years; 80% female), 20.7% had SLE, 31.8% had PsO, and 47.5% had RA. There were no differences in mean MFR between these conditions. Over a median follow-up of 7.8 years, there were 51 deaths and 63 major adverse cardiovascular events (MACE). Patients in the lowest tertile (MFR <1.65) had higher all-cause mortality than the highest tertile, which remained significant after adjusting for age, sex, and the pre-test clinical risk score (hazard ratio [HR]: 2.4; 95% confidence interval [CI]: 1.05 to 5.4; p = 0.038). Similarly, compared to the highest MFR tertile, those in the lowest tertile had a lower MACE-free survival after adjusting for age, sex, and the pre-test clinical risk score (HR: 3.6; 95% CI: 1.7 to 7.6; p = 0.001). CONCLUSIONS: In patients with systemic inflammatory disorders, impaired coronary vasodilator reserve was associated with worse cardiovascular outcomes and all-cause mortality.
33150702 Prevalence, Deaths, and Disability-Adjusted Life Years Due to Musculoskeletal Disorders fo 2021 Apr OBJECTIVE: To report the levels and trends of prevalence, deaths, and disability-adjusted life years (DALYs) due to musculoskeletal disorders, categorized as low back pain, neck pain, osteoarthritis (OA), rheumatoid arthritis (RA), gout, and other musculoskeletal disorders, across 195 countries and territories from 1990 to 2017 according to age, sex, and Sociodemographic Index (SDI; a composite of sociodemographic factors). METHODS: Data were obtained from the Global Burden of Disease (GBD) Study 2017. The fatal and nonfatal burdens of musculoskeletal disorders were estimated using the Cause of Death Ensemble model and Bayesian meta-regression tool, respectively. Estimates were provided for all musculoskeletal disorders and the corresponding 6 categories at global, regional, and national levels from 1990 to 2017. Counts and age-standardized rates per 100,000 population along with 95% uncertainty intervals (95% UIs) were reported for prevalence, deaths, and DALYs. RESULTS: Globally, there were ~1.3 billion prevalent cases (95% UI 1.2 billion, 1.4 billion), 121.3 thousand deaths (95% UI 105.6 thousand, 126.2 thousand), and 138.7 million DALYs (95% UI 101.9 million, 182.6 million) due to musculoskeletal disorders in 2017. Age-standardized prevalence, death, and DALY rates per 100,000 population were 16,276.2 (95% UI 15,495.5, 17,145.8), 1.6 (95% UI 1.4, 1.6), and 1,720 (95% UI 1,264.4, 2,259.2), respectively. Age-standardized prevalence (-1.6% [95% UI -2.4, -0.8]) and DALY rates (-3.5% [95% UI -4.7, -2.3]) decreased slightly from 1990. The global point prevalence rate of musculoskeletal disorders in 2017 was higher in women than in men and increased with age up to the oldest age group. Globally, the proportion of prevalent cases according to category of musculoskeletal disorders in 2017 was greatest for low back pain (36.8%), followed by other musculoskeletal disorders (21.5%), OA (19.3%), neck pain (18.4%), gout (2.6%), and RA (1.3%). These proportions did not change appreciably compared with 1990. The burden due to musculoskeletal conditions was higher in developed countries. The countries with the highest age-standardized prevalence rates of musculoskeletal disorders in 2017 were Switzerland (23,346.0 [95% UI 22,392.6, 24,329.8]), Chile (23,007.9 [95% UI 21,746.5, 24,165.8]), and Denmark (22,166.1 [95% UI 20,817.2, 23,542.1]). The greatest increases from 1990 were found in Chile (10.8% [95% UI 6.6, 15.4]), Benin (8.8% [95% UI 6.7, 11.1]), and El Salvador (8.5% [95% UI 5.5, 11.9]). CONCLUSION: There is a large burden of musculoskeletal disorders globally, with some notable inter-country variation. Some countries have twice the burden of other countries. Increasing population awareness regarding risk factors, consequences, and evidence-informed treatment strategies for musculoskeletal disorders with a focus on the older female population in developed countries is needed, particularly for low back and neck pain and OA, which contribute a large burden among this cohort.
34920373 Increased circulating levels of High Mobility Group Box 1 (HMGB1) in acute-phase Chikungun 2022 Jan BACKGROUND: Chikungunya virus (CHIKV) causes a febrile syndrome with intense and debilitating arthralgia that can persist for several months or years after complete virus clearance. As there is no specific antiviral treatment or vaccine against CHIKV, identification of serological markers that help clinical management of CHIKV patients is urgent. The High Mobility Group Box 1 (HMGB1) protein is secreted to extracellular milieu and triggers an intense inflammatory process by inducing the overexpression of pro-inflammatory cytokines. HMGB1 plays an important role in several virus diseases as well as in rheumatoid arthritis. OBJECTIVES: This study focus on the investigation of HMGB1 serum levels in a sera panel from CHIKV-infected patients in an attempt to assess its potential as a biomarker for chikungunya clinical management. STUDY DESIGN: Eighty CHIKV-positive samples and 32 samples from healthy donors were subjected to a quantitative HMGB1 ELISA assay to assess the HMGB1 circulating levels. RESULTS: HMGB1 levels were significantly higher in CHIKV-positive samples (516.12 ng/mL, SEM ± 48.83 ng/mL) compared to negative control (31.20 ng/mL, SEM ± 3.24 ng/mL, p < 0.0001). Circulating levels of HMGB1 persisted elevated during the whole acute-phase of disease and correlated with virus titer (p < 0.05). CONCLUSIONS: The present study is the first to describe increased serum levels of HMGB1 in CHIKV infection and its positive correlation with virus titer, suggesting its potential use as a biomarker for diagnosis and treatment of chikungunya fever.
34696484 Transcriptome Analysis for Genes Associated with Small Ruminant Lentiviruses Infection in 2021 Oct 13 Small ruminant lentiviruses (SRLV) are economically important viral pathogens of sheep and goats. SRLV infection may interfere in the innate and adaptive immunity of the host, and genes associated with resistance or susceptibility to infection with SRLV have not been fully recognized. The presence of animals with relatively high and low proviral load suggests that some host factors are involved in the control of virus replication. To better understand the role of the genes involved in the host response to SRLV infection, RNA sequencing (RNA-seq) method was used to compare whole gene expression profiles in goats carrying both a high (HPL) and low (LPL) proviral load of SRLV and uninfected animals. Data enabled the identification of 1130 significant differentially expressed genes (DEGs) between control and LPL groups: 411 between control and HPL groups and 1434 DEGs between HPL and LPL groups. DEGs detected between the control group and groups with a proviral load were found to be significantly enriched in several gene ontology (GO) terms, including an integral component of membrane, extracellular region, response to growth factor, inflammatory and innate immune response, transmembrane signaling receptor activity, myeloid differentiation primary response gene 88 (MyD88)-dependent toll-like receptor signaling pathway as well as regulation of cytokine secretion. Our results also demonstrated significant deregulation of selected pathways in response to viral infection. The presence of SRLV proviral load in blood resulted in the modification of gene expression belonging to the toll-like receptor signaling pathway, the tumor necrosis factor (TNF) signaling pathway, the cytokine-cytokine receptor interaction, the phagosome, the Ras signaling pathway, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) (PI3K-Akt) signaling pathway and rheumatoid arthritis. It is worth mentioning that the most predominant in all pathways were genes represented by toll-like receptors, tubulins, growth factors as well as interferon gamma receptors. DEGs detected between LPL and HPL groups were found to have significantly enriched regulation of signaling receptor activity, the response to toxic substances, nicotinamide adenine dinucleotide (NADH) dehydrogenase complex assembly, cytokine production, vesicle, and vacuole organization. In turn, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway tool classified DEGs that enrich molecular processes such as B and T-cell receptor signaling pathways, natural killer cell-mediated cytotoxicity, Fc gamma R-mediated phagocytosis, toll-like receptor signaling pathways, TNF, mammalian target of rapamycin (mTOR) signaling and forkhead box O (Foxo) signaling pathways, etc. Our data indicate that changes in SRLV proviral load induced altered expression of genes related to different biological processes such as immune response, inflammation, cell locomotion, and cytokine production. These findings provide significant insights into defense mechanisms against SRLV infection. Furthermore, these data can be useful to develop strategies against SRLV infection by selection of animals with reduced SRLV proviral concentration that may lead to a reduction in the spread of the virus.
34640586 Impact of Infliximab Biosimilar CT-P13 Dose and Infusion Interval on Real-World Drug Survi 2021 Oct 1 CT-P13 is an infliximab biosimilar approved for indications including ankylosing spondylitis (AS); the approved maintenance regimen is 5 mg/kg infused every 6-8 weeks. In clinical practice, modifications to infliximab dose and/or infusion interval can be beneficial to the patient. For CT-P13, real-world data on dose and/or interval adjustment are lacking. This analysis investigated the impact of such treatment pattern changes on effectiveness and drug survival up to five years for adult (≥18 years old) patients with AS in the Korean, real-world, retrospective rheumatoid arthritis and ankylosing spondylitis (RAAS) study. Overall, 337 patients with AS were identified: 219 who initiated infliximab treatment with CT-P13 ('naïve') and 118 who switched from reference infliximab to CT-P13 ('switched'). Overall, 18/235 (7.7%), 110/224 (49.1%), and 101/186 (54.3%) evaluable patients had dose, infusion interval, or combined treatment pattern changes, respectively. More naïve (61.0%) versus switched (42.6%) patients had treatment pattern changes. Overall, Bath Ankylosing Spondylitis Disease Activity Index scores decreased from baseline to week 54, then remained stable; improvements were greater for patients with than without treatment pattern changes. Drug survival did not differ significantly between patients with or without treatment pattern changes. Findings suggest that adjusting dose and/or infusion interval can improve clinical outcomes for CT-P13-treated patients with AS.
34416426 The Prevalence of Autoimmune Diseases in Patients with Primary Open-Angle Glaucoma Undergo 2022 Mar PURPOSE: To assess the prevalence of autoimmune disease (AiD) in patients with primary open-angle glaucoma (POAG) undergoing ophthalmic surgery. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: Patients with POAG undergoing any ophthalmic surgery and control subjects undergoing cataract surgery at the Massachusetts Eye and Ear from March 2019 to April 2020. METHODS: All available medical records with patient demographics, ocular, and medical conditions were reviewed. Differences in AiD prevalence were assessed and adjusted for covariates using multiple logistic regression. Additionally, a subgroup analysis comparing the POAG patients with and without AiD was performed. MAIN OUTCOME MEASURES: To assess the prevalence of AiD based on the American Autoimmune Related Diseases Association list. RESULTS: A total of 172 patients with POAG and 179 controls were included. The overall prevalence of AiD was 17.4% in the POAG group and 10.1% in the controls (P = 0.044); 6.4% of POAG patients and 3.4% of controls had more than 1 AiD (P = 0.18). The most prevalent AiDs in POAG group were rheumatoid arthritis (4.6%) and psoriasis (4.1%), which were also the most common in controls (2.8% each). In a fully adjusted multiple logistic regression analysis accounting for steroid use, having an AiD was associated with 2.62-fold increased odds of POAG relative to controls (95% confidence interval, 1.27-5.36, P = 0.009); other risk factors for POAG derived from the analysis included age (odds ratio [OR], 1.04, P = 0.006), diabetes mellitus (OR, 2.31, P = 0.008), and non-White ethnicity (OR, 4.75, P < 0.001). In a case-only analysis involving the eye with worse glaucoma, there was no statistical difference in visual field mean deviation or retinal nerve fiber layer (RNFL) thickness in POAG patients with AiD (n = 30) and without AiD (n = 142, P > 0.13, for both). CONCLUSIONS: A higher prevalence of AiD was found in POAG patients compared with control patients undergoing ophthalmic surgery. The presence of AiD was associated with increased risk for POAG after adjusting for covariates. Additional factors may have prevented a difference in RNFL thickness in POAG patients with and without AiD. Autoimmunity should be explored further in the pathogenesis of POAG.
33940428 Assessment of risk factors for bone fractures in patients with type 2 diabetes mellitus: A 2021 May BACKGROUND AND AIMS: This study aimed to estimate the prevalence of bone fractures and analyze their associated risk factors in people with and without type 2 diabetes (T2D) in Saudi Arabia. METHODS: This study was conducted among 1188 people (581 type 2 diabetes) in Prince Sultan Military Medical City, Riyadh, Saudi Arabia. In addition to the demographic variables, glycated hemoglobin (HbA1c), creatinine, estimated glomerular filtration rate (eGFR), use of teriparatide, presence of rheumatoid arthritis, presence of chronic obstructive pulmonary disease (COPD), Bone mineral density (BMD), Trabecular Bone Score (TBS) and Fracture Risk using the Fracture Risk Assessment Tool (FRAX) were also collected. RESULTS: There were 1188 people (mean age 66.5 ± 8.7yrs) included in this study, of which 1068 (89.9%) were female, and 120 (10.1%) were male. A total of 112 (9.4%) individuals had a fracture history. Female, use of teriparatide, TBS (partially degraded and degraded), FRAX with TBS (MOF), and FRAX with TBS (Hip fx) were identified as independent risk factors for fracture in the whole study population. Teriparatide use and FRAX with TBS (MOF) were observed as independent risk factors for fracture in the non-diabetic population, whereas age, creatinine, eGFR, teriparatide, osteopenia, osteoporosis, TBS (partially degraded, degraded), FRAX with TBS (MOF), FRAX with TBS (Hip fx) were determined as independent risk factors for fracture among patients with diabetes. CONCLUSION: Patients with T2D were observed to have a higher risk for fractures. The findings of the study highlight the requirement for fracture prevention strategies in patients with diabetes.
33913080 Evaluation of a novel particle-based multi-analyte technology for the detection of anti-fi 2021 Jun Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several anti-nuclear antibodies (ANA), including those in the classification criteria (anti-centromere, anti-topoisomerase I (Scl-70), anti-RNA Pol III). However, the presence of less common antibodies such as anti-fibrillarin (U3-RNP) that generate a clumpy nucleolar pattern by HEp-2 indirect immunofluorescence assay (IFA, ICAP AC-9) are considered disease specific and are with clinical subsets of SSc, therefore playing a role in diagnosis and prognosis. A specific and sensitive anti-fibrillarin assay would be an important addition to serological diagnosis and evaluation of SSc. The goal of this study was to evaluate a new particle-based multi-analyte technology (PMAT) for the measurement of anti-fibrillarin antibodies. A total of 149 patient samples were collected including 47 samples from France (Lyon and Paris, n = 32) and Italy (Careggi Hospital, Florence, n = 15) selected based on AC-9 HEp-2 IFA staining (> 1:640, clumpy nucleolar pattern) and 102 non-SSc controls (inflammatory bowel disease (IBD) n = 20, Sjögren's syndrome (SjS) n = 20, infectious disease (ID) n = 7, systemic lupus erythematosus (SLE) n = 17, rheumatoid arthritis (RA) n = 17, and healthy individuals (HI) n = 21). All samples were tested on the anti-fibrillarin PMAT assay (research use only, Inova Diagnostics, USA). Additionally, the 47 anti-fibrillarin positive samples were also tested on PMAT assays for detecting other autoantibodies in ANA-associated rheumatic diseases (AARD). Anti-fibrillarin antibody data performed by fluorescence enzyme immunoassay (FEIA, Thermo Fisher, Germany) was available for 34 samples. The anti-fibrillarin PMAT assay was positive in 31/32 (96.9%, France) and 12/15 (80.0%, Italy) of samples preselected based on the AC-9 IIF pattern (difference p = 0.09). Collectively, the PMAT assay showed 91.5% (95% confidence interval (CI): 80.1-96.6%) sensitivity with 100.0% (95% CI: 96.4-100.0%) specificity in non-SSc controls. Strong agreement was found between PMAT and FEIA with 100.0% positive qualitative agreement (34/34) and quantitative agreement (Spearman's rho = 0.89, 95% CI: 0.77.9-0.95%, p < 0.0001). Although most anti-fibrillarin positive samples were mono-specific (69.8%), some expressed additional antibodies (namely Scl-70, centromere, dsDNA, Ro52, Ro60, SS-B, Ribo-P, DFS70, and EJ). In conclusion, this first study on anti-fibrillarin antibodies measured using a novel PMAT assay shows promising results where the new PMAT assay had high level of agreement to FEIA for the detection of anti-fibrillarin antibodies. The availability of novel AFA assays such as PMAT might facilitate the clinical deployment, additional studies, standardization efforts, and potentially consideration of AFA for next generations of the classification criteria.
33821765 Transcriptomic profiling as biological markers of depression - A pilot study in unipolar a 2021 Dec OBJECTIVES: A significant challenge in psychiatry is the differential diagnosis of depressive episodes in the course of mood disorders. Gene expression profiling may provide an opportunity for such distinguishment. METHODS: We studied differentially expressed genes in women with a depressive episode in the course of unipolar depression (UD) (n = 24) and bipolar disorder types I (BDI) (n = 13) and II (BDII) (n = 19), and healthy controls (n = 15). RESULTS: Different types of depression varied in the number and type of up or down-regulated genes. The pathway analysis showed: in UD, up-regulated rheumatoid arthritis pathway (including ITGB2, CXCL8, TEK, TLR4 genes), and down-regulated taste transduction pathway (TAS2R10, TAS2R46, TAS2R14, TAS2R43, TAS2R45, TAS2R19, TAS2R13, TAS2R20, GNG13); in BDI, eight down-regulated pathways: glutamatergic synapse, retrograde endocannabinoid signalling, axon guidance, calcium signalling, nicotine addiction, PI3K-Akt signalling, drug metabolism - cytochrome P450, and morphine addiction; in BDII, up-regulated osteoclast differentiation and Notch signalling pathway, and down-regulated type I diabetes mellitus pathway. Distinct expression markers analysis uncovered the unique for UD, up-regulated bladder cancer pathway (HBEGF and CXCL8 genes). CONCLUSIONS: This pilot study suggests a probability of differentiating depression in the course of UD, BDI, and II, based on transcriptomic profiling.
33248709 Acute Myocardial Infarction in Autoimmune Rheumatologic Disease: A Nationwide Analysis of 2021 Feb OBJECTIVES: To examine national-level differences in management strategies and outcomes in patients with autoimmune rheumatic disease (AIRD) with acute myocardial infarction (AMI) from 2004 through 2014. METHODS: All AMI hospitalizations were analyzed from the National Inpatient Sample, stratified according to AIRD diagnosis into 4 groups: no AIRD, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSC). The associations between AIRD subtypes and (1) receipt of coronary angiography and percutaneous coronary intervention (PCI) and (2) clinical outcomes were examined compared with patients without AIRD. RESULTS: Of 6,747,797 AMI hospitalizations, 109,983 patients (1.6%) had an AIRD diagnosis (RA: 1.3%, SLE: 0.3%, and SSC: 0.1%). The prevalence of RA rose from 1.0% (2004) to 1.5% (2014), and SLE and SSC remained stable. Patients with SLE were less likely to receive invasive management (odds ratio [OR] [95% CI]: coronary angiography-0.87; 0.84 to 0.91; PCI-0.93; 0.90 to 0.96), whereas no statistically significant differences were found in the RA and SSC groups. Subsequently, the ORs (95% CIs) of mortality (1.15; 1.07 to 1.23) and bleeding (1.24; 1.16 to 1.31) were increased in patients with SLE; SSC was associated with increased ORs (95% CIs) of major adverse cardiovascular and cerebrovascular events (1.52; 1.38 to 1.68) and mortality (1.81; 1.62 to 2.02) but not bleeding or stroke; the RA group was at no increased risk for any complication. CONCLUSION: In a nationwide cohort of AMI hospitalizations we found lower use of invasive management in patients with SLE and worse outcomes after AMI in patients with SLE and SSC compared with those without AIRD.