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ID PMID Title PublicationDate abstract
34455440 COVID-19 vaccine use in immunocompromised patients: A commentary on evidence and recommend 2022 Jan 5 PURPOSE: While COVID-19 vaccine emergency use authorization (EUA) deemed the vaccines to be effective and safe for public use, the phase 3 trials leading to EUA predominantly excluded patients with immunocompromising conditions. Immunocompromised patients make up a significant proportion of the population, and in light of recent mass vaccination efforts, we aim to review current evidence and recommendations of COVID-19 vaccines in 4 patient populations with immunocompromising disorders or conditions: human immunodeficiency virus (HIV) infection, solid organ transplantation, rheumatoid arthritis, and inflammatory bowel disease. SUMMARY: Given the evolving data on the safety and efficacy of the approved COVID-19 vaccines in the immunocompromised population, it is vital that pharmacists and other immunizing providers understand the current data and recommendations and provide the public with accurate information. To date, the only immunocompromised subgroup included in phase 3 COVID-19 vaccine trials have been those with HIV infection. However, recent retrospective trials have provided reassuring data on the safety of the COVID-19 vaccine in immunocompromised patients, and the interim analysis of the Moderna phase 3 trial produced promising data on efficacy in HIV-infected patients. Presently, the US Centers for Disease Control and Prevention, British Society for Immunology, and various other governmental and professional societies and organizations endorse COVID-19 vaccination in the immunocompromised population. CONCLUSION: While additional data is needed to determine the effects of immunocompromising medical conditions and immunosuppressing medications on the efficacy of the vaccine, the benefits of vaccination is anticipated to outweigh theoretical risks. Thus, COVID-19 vaccination is recommended for immunocompromised patients at this time, and providers should make efforts to decrease vaccine hesitancy in this population through education and reassurance.
34274242 Clinical Outcomes After First Metatarsophalangeal Joint Arthrodesis by Flat Cut Joint Prep 2022 Jan Sagittal misalignment is a major cause of patient dissatisfaction and re-operation after first metatarsophalangeal (MTP) joint arthrodesis. The stereotypical application of the fixed angle would be undesirable, especially in cases of flat or cavus foot. We retrospectively reviewed 31 cases (27 patients) in which first MTP joint arthrodesis was performed using the flat cut joint preparation technique with reference to the plantar clearance beneath the pulp of the toe while simulating weightbearing by pushing a board against the sole. The most common underlying cause of surgery was rheumatoid arthritis (22 cases [71%]). Clinical outcomes were evaluated by the Japanese of Surgery of the Foot (JSSF) hallux scale and the self-administered foot evaluation questionnaire (SAFE-Q). Twenty-three cases were also examined by pedobarography to evaluate postoperative walking plantar pressure. At the most recent follow-up of a mean 19.6 months, the toe-to-floor distance of the hallux in static standing posture was a mean of 2.5 mm (range, 0-10 mm). All but 1 foot (97%) achieved bone union. There were no complications or revisions due to misalignment of the fused MTP joint. JSSF hallux scales improved significantly from 47 preoperatively to 82 postoperatively. All subscale scores except general health and well-being in the SAFE-Q improved significantly at final follow-up versus preoperative period. Plantar pressure under the hallux was correlated with the toe-to-floor distance but not radiographic parameter. In conclusion, first MTP joint arthrodesis achieved good clinical outcomes when using toe-to-floor distance and Kirschner wire template for flat cut joint preparation.
35579338 Comparison of drug retention of TNF inhibitors, other biologics and JAK inhibitors in RA p 2022 May 17 OBJECTIVES: JAK Inhibitors (JAKi) are recommended DMARDs for patients with moderate-to severe rheumatoid arthritis (RA) who failed first-line therapy with methotrexate. There is a lack of data allowing an evidence-based choice of subsequent disease modifying anti-rheumatic drug (DMARD) therapy for patients who had discontinued JAKi treatment. We aimed to compare the effectiveness of TNF inhibitor (TNFi) therapy vs JAKi vs other mode of action (OMA) biologic DMARD (bDMARD) in RA patients who were previously treated with a JAKi. METHODS: RA patients who discontinued JAKi treatment within the Swiss RA registry SCQM were included for this observational prospective cohort study. Primary outcome was drug retention for either TNFi, OMA bDMARD or JAKi. The hazard ratio for treatment discontinuation was calculated adjusting for potential confounders. A descriptive analysis of the reasons for discontinuation was performed. RESULTS: 400 treatment courses of JAKi were included, with a subsequent switch to either JAKi, TNFi or OMA bDMARD. The crude overall drug retention was higher in patients switching to another JAKi as compared with TNFi and comparable to OMA. A significant difference of JAKi vs TNFi persisted after adjusting for potential confounders. CONCLUSION: In a real-world population of RA patients who discontinued treatment with a JAKi, switching to another JAKi resulted in a higher drug retention than switching to a TNFi. A switch to a second JAKi seems an effective therapeutic option.
35131488 The multifaced role of HtrA1 in the development of joint and skeletal disorders. 2022 Apr HtrA1 (High temperature requirement A1) family proteins include four members, widely conserved from prokaryotes to eukaryotes, named HtrA1, HtrA2, HtrA3 and HtrA4. HtrA1 is a serine protease involved in a variety of biological functions regulating many signaling pathways degrading specific components and playing key roles in many human diseases such as neurodegenerative disorders, pregnancy complications and cancer. Due to its role in the breakdown of many ExtraCellular Matrix (ECM) components of articular cartilage such as fibronectin, decorin and aggrecan, HtrA1 encouraged many researches on studying its role in several skeletal diseases (SDs). These studies were further inspired by the fact that HtrA1 is able to regulate the signaling of one of the most important cytokines involved in SDs, the TGFβ-1. This review aims to summarize the data currently available on the role of HtrA1 in skeletal diseases such as Osteoporosis, Rheumatoid Arthritis, Osteoarthritis and Intervertebral Disc Degeneration (IDD). The use of HtrA1 as a marker of frailty in geriatric medicine would represent a powerful tool for identifying older individuals at risk of developing skeletal disorders, evaluating an appropriate intervention to improve quality care in these people avoiding or improving age-related SDs in the elderly population.
35338108 Negative-Pressure Pulmonary Edema After Difficult Endotracheal Intubation in a Patient wit 2022 Mar 26 BACKGROUND Difficult tracheal intubation (DTI) is common in patients with rheumatoid arthritis (RA) because of the subluxation of atlas and axis, the fusion of the cervical spine as a result of arthritis. We report a case of negative-pressure pulmonary edema (NPPE) caused by DTI in a patient with juvenile RA (JRA) who underwent surgery for spigelian hernia. CASE REPORT A 35-year-old man was referred to our department for repeated abdominal pain and a left-lower quadrant mass. Spigelian hernia was diagnosed with abdominal computed tomography (CT), and surgery was scheduled. Despite careful preoperative preparation and intubation strategy, fiber-optic intubation and laryngeal mask ventilation failed; nasal fiber-optic tracheal intubation was subsequently successfully performed. During induction, upper airway obstruction caused NPPE. CT findings showed bilateral infiltration and diffuse ground-glass opacity suggestive of pulmonary edema. Surgery for the spigelian hernia was canceled as the patient required intensive care as a result of NPPE. After 48 h of initiating treatment, the patient's respiratory condition gradually improved. Seven days after DTI, he underwent laparoscopy-assisted surgery for the spigelian hernia. The patient was discharged after 2 weeks of hospitalization. Four years have passed since the surgical procedure; the outcome has remained favorable and there has been no recurrence. CONCLUSIONS Normal ventilation may be the most important factor for preventing NPPE. It is vital that patients with RA receive treatment in an environment with advanced airway equipment and staff fully trained in its use. Similarly, the necessary staff and equipment for emergency cricothyroidotomies should also be readily available.
33530719 Evaluation of the effect of topical tacrolimus 0.03% versus cyclosporine 0.05% in the trea 2022 Jan PURPOSE: To compare the effect of topical application of tacrolimus 0.03% eyedrops versus cyclosporine 0.05% in Sjogren syndrome subjects with severe dry eyes. DESIGN: A prospective single-blinded simply randomized controlled study. METHODOLOGY: 60 Sjogren patients were randomized intoGroup A: 30 patients were instructed to put tacrolimus 0.03% eyedrops in one eye for 6 months and placebo eyedrops in the other eye, (N = 30, 44.9 ± 12.58 years).Group B: 30 patients were instructed to put cyclosporine 0.05% eyedrops in one eye for 6 months and placebo eyedrops in the other eye (N = 30, 49.4 ± 12.92 years).Main outcome measures: Patients were evaluated at day 0, 90, and 180 for Ocular Surface Disease Index Questionnaire (OSDI), frequency of use of artificial tears, average fluorescein tear break up time (TBUT), ocular surface staining scores, Schirmer I test, meibum quality, and expressibility scores. RESULTS: Upon comparing both eyedrops, the mean value of OSDI decrease was 38.25 ± 18.29% versus 31.69 ± 18.57% (p-value 0.09), SICCA score decrease was 2.97 ± 1.92 versus 2.27 ± 2.02 (p-value 0.124) the decrease in artificial tear substitute use was 3.90 ± 2.22 versus 3.63 ± 1.92 (p-value 0.616), increase in Schirmer I values were 4.10 ± 4.21 and 4.26 ± 2.00 (p-value 0.590) in eyes treated with tacrolimus and cyclosporine respectively. Neither of them affected meibum quality or expressibility scores. CONCLUSION: Both tacrolimus and cyclosporine significantly improved patient symptoms, frequency of artificial tears use and ocular surface staining compared to placebo-controlled eyes. However, no significant difference regarding the efficacy of both eyedrops at the end of 6 months treatment of severe dry eyes of Sjögren syndrome patients. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT03865888.
35396234 Sjogren syndrome presenting as atrioventricular block in an adult. 2022 Apr 8 A woman in her late teens with a history of Juvenile idiopathic arthritis (JIA) and ongoing sicca symptoms presented with syncope. Upon admission, she was found to be bradycardic with a second-degree atrioventricular (AV) block. After infectious, structural and metabolic aetiologies had been ruled out, she was worked up for rheumatologic causes.Our patient had elevated titres of anti-Sjogren syndrome (SS) antibodies anti-Ro antibodies and was diagnosed with AV block secondary to SS. She was treated with a permanent pacemaker. Patient was followed up in clinic where she denied further syncopal episodes and was started on secretagogues for sicca symptoms.
35032460 Glytabastan B, a coumestan isolated from Glycine tabacina, alleviated synovial inflammatio 2022 Mar The roots of Glycine tabacina are used to treat rheumatoid arthritis (RA) and joint infection in folk medicine. Glytabastan B (GlyB), a newly reported coumestan isolated from this species, was found to significantly attenuate IL-1β-induced inflammation in SW982 human synovial cells at 3 and 6 μM, as evidenced by the decreased levels of pro-inflammatory mediators and matrix metalloproteinases (MMPs). GlyB also suppressed RANKL-induced osteoclastogenesis, decreased the expression of osteoclastogenic markers (NFATc1, CTSK, MMP-9) and osteoclast-mediated bone resorption. Further, GlyB administration (12.5 and 25 mg/kg) significantly inhibited inflammation, osteoclast formation and disease progression in collagen-induced arthritis (CIA) mice. Integration of network pharmacology, quantitative phosphoproteomic and experimental pharmacology results revealed that these beneficial actions were closely associated with the blockade of GlyB on the activation of MAPK, PI3K/AKT and their downstream signals including NF-κB and GSK3β/NFATc1. Drug affinity responsive target stability (DARTS) assay, cellular thermal shift (CETSA) assay and molecular docking analysis confirmed that there were direct interactions between GlyB and its target proteins ERK2, JNK1 and class Ⅰ PI3K catalytic subunit p110 (α, β, δ and γ), which significantly contributed to the inhibition of activation of MAPK and PI3K/AKT pathways. In conclusion, these results strongly suggest GlyB is a promising multiple-target candidate for the development of agents for the prevention and treatment of RA.
34409540 Meibomian gland atrophy with duration of Sjogren's syndrome in adult females. 2022 Jan BACKGROUND: To investigate the correlation between the duration of Sjögren syndrome (SS) and ocular surface parameters in patients with SS-related dry eye. METHODS: We analyzed 108 eyes of 108 female patients with primary SS-related dry eye. All patients underwent rheumatoid serologic tests and ocular surface assessments. The ocular surface assessment included the Standard Patient Evaluation of Eye Dryness (SPEED) score, meibomian gland (MG) atrophy, lipid layer thickness (LLT), partial and total blinking, partial blinking rate, Schirmer's I test, non-invasive tear break-up time, and ocular surface staining score. Correlations between the duration of SS and ocular surface assessments were calculated. RESULTS: The average age and SS duration of the participants were 56.7 ± 10.2 (range 21-78) years and 54.15 ± 41.10 (range 1-134) months, respectively. There was a strong positive correlation between SS duration and MG atrophy (r = 0.766, p < 0.001). The correlation between SS duration and MG atrophy rate remained significant after controlling for age (r = 0.559, p < 0.001). Average, maximum, and minimum LLTs showed weak negative correlations with SS duration (r = - 0.310, - 0.211, and-0.304, respectively, p = 0.014, 0.028, and 0.022, respectively) and MG atrophy (r = - 0.191, - 0.326, and - 0.299, respectively, p = 0.049, 0.002, and 0.009, respectively). SPEED score showed a weak positive correlation to SS duration (r = 0.303, p = 0.042) and a moderate positive correlation to MG atrophy (r = 0.450, p = 0.029). CONCLUSIONS: Longer duration of primary SS was related to more severe MG atrophy. Therefore, it is necessary to perform meibography in SS patients to verify MG atrophy status. A comparative study with non-SS dry eye patients is required to validate this study.
35628481 The Involvement of Alarmins in the Pathogenesis of Sjögren's Syndrome. 2022 May 18 Sjögren's syndrome (SS) is a chronic autoimmune disease that affects exocrine glands, primarily the salivary and lachrymal glands. It is characterized by lymphoplasmacytic infiltration of the glandular tissues, ultimately leading to their dysfunction and destruction. Besides classic dry eyes and dry mouth defined as sicca syndrome, patients affected by the disease also typically display symptoms such as fatigue, pain and in more than 50% of cases, systemic manifestations such as arthritis, interstitial lung involvement, neurological involvement and an increased risk of lymphoma. The pathophysiological mechanisms underlying SS still remain elusive. The crucial role of innate immunity has been advocated in recent years regarding the pathogenesis of pSS, especially in the initiation and progression toward autoimmunity. Alarmins are endogenous molecules that belong to the large family of damage associated molecular pattern (DAMP). Alarmins are rapidly released, ensuing cell injury and interacting with pattern recognition receptors (PRR) such as toll-like receptors (TLR) to recruit and activate cells of the innate immune system and to promote adaptive immunity responses. This review highlights the current knowledge of various alarmins and their role in the pathogenesis of pSS.
35309355 Abnormal Changes of Monocyte Subsets in Patients With Sjögren's Syndrome. 2022 BACKGROUND: Recent studies have proven the existence of distinct monocyte subsets, which play a significant role in the development of some rheumatic diseases such as systemic lupus erythematosus (SLE). This study was performed to define the changes of monocyte subsets in patients with Sjögren's Syndrome (SjS). METHODS: Single cell RNA-sequencing (scRNA-seq) data of monocytes from SjS patients and controls were analyzed. The transcriptomic changes in monocyte subsets between SjS and controls were identified and potential key functional pathways involved in SjS development were also explored. RESULTS: A total of 11 monocyte subsets were identified in the scRNA-seq analyses of monocytes. A new monocyte subset characterized by higher expression of VNN2 (GPI-80) and S100A12 (Monocyte cluster 3) was identified, and it was increased in SjS patients. Compared with controls, almost all monocyte subsets from SjS patients had increased expression of TNFSF10 (TRAIL). Moreover, interferon (IFN)-related and neutrophil activation-associated pathways were main up-regulated pathways in the monocytes of SjS patients. CONCLUSION: This study uncovered the abnormal changes in monocyte subsets and their transcriptomic changes in SjS patients, and identified TNFSF10 (high/+) monocytes as a potential key player in SjS pathogenesis and a promising target for SjS treatment.
35592328 Association Between Endometriosis and Subsequent Risk of Sjögren's Syndrome: A Nationwide 2022 OBJECTIVE: The relationship between endometriosis and the ensuing risk of Sjögren's syndrome has remained unclear. This study aims to present epidemiological evidence for this connection. METHODS: This is a retrospective cohort study of endometriosis patients (ICD-9-CM 617.0-617.9 and 621.3) and matched comparison group between 2000 and 2012 in the National Taiwan Insurance Research Database. After age matching, we analyzed the association between endometriosis and Sjögren's syndrome (ICD-9-CM 710.2). We used the Cox proportional hazard model to examine the hazard ratio of incidental Sjögren's syndrome. Subgroup analyses on age, comorbidities, and disease duration were also performed. RESULTS: A total of 73,665 individuals were included in this study. We identified 14733 newly diagnosed endometriosis patients and 58,932 non-endometriosis comparison group. The adjusted hazard ratio (HR) for incidental Sjögren's syndrome was 1.45 (95% confidence interval CI=1.27-1.65) in the endometriosis group, compared to the non-endometriosis comparison group. In subgroup analysis, the adjusted HR was 1.53 (95% CI=1.25-1.88) in the age group of 20-39 and 1.41 (95% CI =1.18-1.68) in the age of 40-64. Time-vary analysis showed that endometriosis who have a follow-up time of fewer than five years (adjusted HR=1.57, 95% CI=1.32-1.87) have a significantly highest risk of having subsequent Sjögren's syndrome. CONCLUSION: This population-based cohort study indicated that having a history of endometriosis puts patients at an increased risk of getting Sjögren's syndrome afterward, especially in the age group of 20-39 and within the first five years after the diagnosis of endometriosis. Clinicians should recognize this possible association in managing endometriosis or Sjögren's syndrome patients.
35000785 Recurrent or persistent salivary gland enlargement in children: When is it Sjögren's? 2022 Feb OBJECTIVES: To describe characteristic features in children with recurrent or persistent salivary gland enlargement and to propose a diagnostic algorithm with specific consideration for Sjögren's disease (SD). METHODS: In this single-center, prospective study, 45 patients < 18 years, with recurrent or persistent salivary gland enlargement of unknown etiology were enrolled from 2006 to 2019. We collected detailed clinical information to characterize this group of patients including specific details of their major salivary gland signs and symptoms. We compared clinical, laboratory and radiological parameters between 4 groups based on the results of labial salivary gland biopsy (LSGB) and between patients who met existing SD criteria or not. RESULTS: 44 patients, with a mean age of 6.8 years and female to male ratio 21:23 were observed over a mean of 3.8 years. Characteristics of salivary gland swelling episodes varied considerably between individuals, but the majority experienced ≤5 episodes per year, lasting ≤ 1 week, with swelling affecting either or both glands. Ocular and oral dryness symptoms were observed only in 25% and 59% patients, respectively. The majority were positive for ANA, but negative for SD-specific antibodies. A total of 75% patients fulfilled at least one of the existing SD criteria. CONCLUSION: SD is a major cause of recurrent salivary gland enlargement in children. For children meeting adult criteria, the diagnosis of SD is clear. However, for the many children without dryness symptoms, objective dryness, or SD-specific antibodies, further workup including a combination of salivary gland imaging and histopathological examination can help establish the diagnosis of SD.
35529439 Orphan Nuclear Receptor NR4A2 Is Constitutively Expressed in Cartilage and Upregulated in 2022 Orphan nuclear receptor 4A2 (NR4A2/Nurr1) is a constitutively active transcription factor with potential roles in the onset and progression of inflammatory arthropathies. NR4A2 is overexpressed in synovium and cartilage from individuals with rheumatoid arthritis (RA), psoriatic arthritis, and osteoarthritis. This study documents the expression and tissue localization of NR4A2 and upstream regulator nuclear factor kappa B (NF-κB) in the human tumor necrosis factor-alpha (hTNF-α) transgenic mouse model of RA. Since TNF-α is a potent inducer of NR4A2 in vitro, we hypothesized that NR4A2 would also be upregulated and active during disease progression in this model. Expression levels of NR4A2, related receptors NR4A1 (Nur77) and 3 (NOR1), and NF-κB(1) transcripts were quantified by RT-qPCR in hTNF-α and wild-type joints at three stages of disease. The protein distribution of NR4A2 and NF-κB subunit RelA (p65) was analyzed by quantitative immunohistochemistry. Global gene expression of 88 RA-related genes was also screened and compared between groups. Consistent with previous reports on the hTNF-α model, transgenic mice exhibited significant weight loss and severely swollen paws by 19 weeks of age compared to age-matched wild-type controls. NR4A1-3 and NF-κB(1) were constitutively expressed at disease onset and in healthy joints. NF-κB(1) transcript levels increased 2-fold in hTNF-α paws with established disease (12 weeks), followed by a 2-fold increase in NR4A2 at the late disease stage (19 weeks). NR4A2 and RelA proteins were overexpressed in inflamed synovium prior to symptoms of arthritis, suggesting that gene expression changes documented in whole paws were largely driven by elevated expression in diseased synovium. Broader screening of RA-related genes by RT-qPCR identified several differentially expressed genes in hTNF-α joints including those encoding inflammatory cytokines and chemokines, matrix-degrading enzymes and inhibitors, cell surface receptors, intracellular signaling proteins and transcription factors. Consensus binding sites for NR4A receptors and NF-κB(1) were enriched in the promoters of differentially expressed genes suggesting central roles for these transcription factors in this model. This study is the first comprehensive analysis of NR4A2 in an animal model of RA and validates the hTNF-α model for testing of small molecules and genetic strategies targeting this transcription factor.
35593968 Impaired GATE16-mediated exocytosis in exocrine tissues causes Sjögren's syndrome-like ex 2022 May 20 Sjögren's syndrome (SjS) is a chronic autoimmune disease characterized by immune cell infiltration of the exocrine glands, mainly the salivary and lacrimal glands. Despite recent advances in the clinical and mechanistic characterization of the disease, its etiology remains largely unknown. Here, we report that mice with a deficiency for either Atg7 or Atg3, which are enzymes involved in the ubiquitin modification pathway, in the salivary glands exhibit a SjS-like phenotype, characterized by immune cell infiltration with autoantibody detection, acinar cell death, and dry mouth. Prior to the onset of the SjS-like phenotype in these null mice, we detected an accumulation of secretory vesicles in the acinar cells of the salivary glands and found that GATE16, an uncharacterized autophagy-related molecule activated by ATG7 (E1-like enzyme) and ATG3 (E2-like enzyme), was highly expressed in these cells. Notably, GATE16 was activated by isoproterenol, an exocytosis inducer, and localized on the secretory vesicles in the acinar cells of the salivary glands. Failure to activate GATE16 was correlated with exocytosis defects in the acinar cells of the salivary glands in Atg7 and Atg3 cKO mice. Taken together, our results show that GATE16 activation regulated by the autophagic machinery is crucial for exocytosis and that defects in this pathway cause SjS.
34748096 The effects of resistance training in patients with primary Sjogren's syndrome. 2022 Apr INTRODUCTION: Resistance training (RT) is well tolerated and has shown promise for decreasing fatigue. However, the effects of RT have never been examined in primary Sjogren's syndrome (pSS). OBJECTIVE: To assess the feasibility, effectiveness, and safety of a resistance exercise program on fatigue in patients with pSS. METHODS: This is a parallel, single-blind randomized trial. Women aged 18 years or older, diagnosed with pSS according to the American-European criteria, were included. We randomized 59 participants to a resistance training group (RT) or a control group (CG). Participants in the RT group performed a 16-week resistance exercise program. The sessions consisted of three sets of resistance exercises (10 repetitions each) at 60 to 80% of 1 repetition maximum, designed to improve whole-body strength. The participants in the CG received their usual pharmacological treatment and instructions regarding disease control, pain management, sleep hygiene, and activities of daily living. To compare intergroup and intragroup variability, a one-factor repeated-measures analysis of variance (ANOVA) was used. RESULTS: RT effectively improved fatigue, pain, functional capacity, emotional aspects, vitality, and subjective perception of disease activity by the patient. No between-group differences were found in the ESSPRI mental score, ESSDAI, SF-36-Physical Aspects, SF-36-General Health, SF-36-Social aspects, and SF-36-Mental Health after the training period. CONCLUSION: An RT program was safe and effective in improving fatigue, pain, functional capacity, emotional aspects, vitality, and subjective perception of disease activity by the patient in women with pSS. Key Points • This is the first study to evaluate the effects of a resistance training program on fatigue in patients with primary Sjogren's syndrome. • A resistance training program was shown to be effective in improving fatigue in patients with primary Sjogren's syndrome. • A resistance training program is well-tolerated, has good compliance, and is not associated with serious adverse effects in patients with primary Sjogren's syndrome.
35292563 Association between long-term exposure to air pollution and immune-mediated diseases: a po 2022 Feb OBJECTIVE: Environmental air pollution has been associated with disruption of the immune system at a molecular level. The primary aim of the present study was to describe the association between long-term exposure to air pollution and risk of developing immune-mediated conditions. METHODS: We conducted a retrospective observational study on a nationwide dataset of women and men. Diagnoses of various immune-mediated diseases (IMIDs) were retrieved. Data on the monitoring of particulate matter (PM)10 and PM2.5 concentrations were retrieved from the Italian Institute of Environmental Protection and Research. Generalised linear models were employed to determine the relationship between autoimmune diseases prevalence and PM. RESULTS: 81 363 subjects were included in the study. We found a positive association between PM10 and the risk of autoimmune diseases (ρ+0.007, p 0.014). Every 10 µg/m(3) increase in PM10 concentration was associated with an incremental 7% risk of having autoimmune disease. Exposure to PM10 above 30 µg/m3 and PM2.5 above 20 µg/m(3) was associated with a 12% and 13% higher risk of autoimmune disease, respectively (adjusted OR (aOR) 1.12, 95% CI 1.05 to 1.20, and aOR 1.13, 95% CI 1.06 to 1.20). Exposure to PM10 was associated with an increased risk of rheumatoid arthritis; exposure to PM2.5 was associated with an increased risk of rheumatoid arthritis, connective tissue diseases (CTDs) and inflammatory bowel diseases (IBD). CONCLUSION: Long-term exposure to air pollution was associated with higher risk of developing autoimmune diseases, in particular rheumatoid arthritis, CTDs and IBD. Chronic exposure to levels above the threshold for human protection was associated with a 10% higher risk of developing IMIDs.
34902604 The autoimmune aetiology of unexplained chronic pain. 2022 Mar Chronic pain is the leading cause of life years lived with disability worldwide. The aetiology of most chronic pain conditions has remained poorly understood and there is a dearth of effective therapies. The WHO ICD-11 has categorised unexplained chronic pain states as 'chronic primary pains' (CPP), which are further defined by their association with significant distress and/or dysfunction. The new mechanistic term, 'nociplasticic pain' has been developed to illustrate their presumed generation by a structurally intact, but abnormally functioning nociceptive system. Recently, researchers have unravelled the surprising, ubiquitous presence of pain-sensitising autoantibodies in four investigated CPP indicating autoimmune causation. In persistent complex regional pain syndrome, fibromyalgia syndrome, chronic post-traumatic limb pain, and non-inflammatory joint pain associated with rheumatoid arthritis, passive transfer experiments have shown that either IgG or IgM antibodies from patient-donors cause symptoms upon injection to rodents that closely resemble those of the clinical disorders. Targets of antibody-binding and downstream effects vary between conditions, and more research is needed to elucidate the molecular and cellular details. The central nervous system appears largely unaffected by antibody binding, suggesting that the clinically evident CNS symptoms associated with CPP might arise downstream of peripheral processes. In this narrative review pertinent findings are described, and it is suggested that additional symptom-based disorders might be examined for the contribution of antibody-mediated autoimmune mechanisms.
34923222 Balance between Interleukin-18 and Interleukin-18 binding protein in auto-inflammatory dis 2022 Feb Interleukin (IL)-18 is a member of the IL-1 family of cytokines with pleiotropic and potent pro-inflammatory activities that are tightly controlled at the level of production and in the extracellular space. Indeed, IL-18 is translated as a leaderless biologically inert pro-peptide that is cleaved by caspase-1 in its N-terminus domain to become active. Mature Il-18 is then released out of the cells via a phenomenon of inflammatory cell death termed pyroptosis. The biological activity of IL-18 is also regulated by a naturally-occurring soluble inhibitor, IL-18 binding protein (IL-18BP) that binds IL-18 and forms high affinity complexes, thus preventing IL-18 to signal through its cell surface receptors. IL-18BP is present in high amount in the circulation, thus unbound free Il-18 is virtually absent in normal and most pathological conditions. Recent findings showed that IL-18 is present in remarkably high concentrations in some autoinflammatory diseases, including adult-onset Still's disease, systemic juvenile idiopathic arthritis and in various conditions associated with hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Furthermore, elevated levels of free IL-18 are present in correlation with clinical and biological signs of disease activity. Most importantly, some patients with these diseases responded remarkably well to the administration of recombinant human IL-18BP, further indicating the pathogenic role of Il-18 and providing a strong rational for the use of IL-18 inhibitors in some of these difficult to treat auto-inflammatory diseases.
34363247 Adverse post-operative events of salivary gland biopsies: A systematic review and meta-an 2022 Feb OBJECTIVES: The study aimed to perform a systematic review and meta-analysis of the complications following major and minor salivary gland biopsy. MATERIALS AND METHODS: Observational studies assessing postoperative complications of minor salivary gland biopsy and indexed at Medline/PubMed, EMBASE, Cinahl, LILACS, or Scopus were selected. This review was registered under the protocol number: CRD42020211169. The level of significance considered was 0.05, and the R software (The R Foundation) was used for the meta-analysis. RESULTS: Twenty-seven studies reporting 3208 patients were included in this review. The combined prevalence of postsurgical complications was 11% (95% CI, 8 to 13%, p = 0.01). The percentage of the combined prevalence of neurological complications was 3% (95% CI, 1-6%, p = 0.01). The surgical technique did not influence the frequency of overall and neurological complications. CONCLUSION: Minor salivary gland biopsies are a safe and predictable procedure that should be performed on the lower lip. Postoperative complications are more common than previously reported, but permanent complaints are uncommon.