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ID PMID Title PublicationDate abstract
34424415 Treatment pattern in postmenopausal women with osteoporosis: a population-based cohort stu 2022 Jan INTRODUCTION: The treatment landscape of postmenopausal osteoporosis (OP) in an Asian population is yet to be explored. MATERIALS AND METHODS: We conducted a retrospective cohort study to explore treatment patterns and characteristics associated with treatment interruption in postmenopausal women diagnosed with OP between 2008 and 2014. Treatment pattern assessment included the initial distribution of OP medications and treatment interruption rate according to the treatment groups during a 3-year follow-up period. We used multivariate logistic regression to estimate odds ratio (OR) and 95% confidence interval (CI) to identify factors associated with treatment interruption. RESULTS: Of 21,813 patients, 87.9% initiated oral bisphosphonates (BP), followed by ibandronate intravenous (IV; 5.4%), selective estrogen receptor modulators (SERMs; 5.2%), pamidronate IV (1.4%) and zoledronic acid (0.06%). Treatment interruption was most notable in the first year of treatment, with cumulative treatment interruption rates highest for oral BP (76.3%) and lowest for pamidronate IV (50.5%). Compared to oral BP users, users of ibandronate IV (OR 0.34, 95% CI 0.30-0.39), pamidronate IV (0.49, 0.39-0.63), zoledronic acid (0.26, 0.09-0.77), and SERMs (0.50, 0.44-0.57) were less likely to interrupt treatment. Of characteristics assessed, presence of rheumatoid arthritis increased the odds of treatment interruption in ibandronate IV group (3.94, 2.12-7.33), and concomitant use of glucocorticoids for oral BP (1.11, 1.03-1.19) and pamidronate IV (2.04, 1.06-3.93) groups, respectively. CONCLUSION: Given the frequent treatment interruptions across all OP medications, our findings on the factors associated with treatment interruption will serve to implement targeted interventions in reinforcing persistence to OP treatment.
34134513 System-Level Variation in Multiple Sclerosis Care Outcomes: Initial Findings from the Mult 2022 Feb Multiple sclerosis (MS) is a "3C" (complex, chronic, costly) condition that is a common and disabling neurological illness affecting approximately 1 million adults in the United States. MS has been studied at the basic science, individual, and population levels, but not at the system level to assess small-area variation effects on MS population health outcomes. System-level effects have been observed in other 3C conditions including cystic fibrosis, rheumatoid arthritis, and inflammatory bowel disease. The authors report here on system-level variation findings from the baseline period during the first year of the Multiple Sclerosis Continuous Quality Improvement (MS-CQI) study. Stepwise binary logistic regression analyses were conducted to investigate system-level (small-area variation) effects on MS relapses (exacerbations), disease-modifying therapy (DMT) utilization, and brain MRI utilization, controlling for demographics (age and sex) and other potential confounders. Significant differences were observed in people with MS (PwMS) between centers for a number of demographic and disease characteristics, including sex, age, and MS subtype. Controlling for these factors, significant system-level effects were observed on outcomes, including DMT utilization, MRI utilization, and relapses. Significant relationships also were observed between outcomes and urgent care utilization, including emergency department visits and hospitalizations. This initial study provides evidence establishing the presence of system-level variation effects on MS outcomes in a multicenter population study - where PwMS get their care can influence their outcomes. Results support continued systems-level research and improvement initiatives to optimize MS population health outcomes in this challenging and costly complex chronic condition.
32928063 Proteome-wide mapping and reverse vaccinology-based B and T cell multi-epitope subunit vac 2022 Feb Porphyromonas gingivalis, a prominent pathogen responsible for acute periodontal diseases, is widely studied by the scientific community for its successful evasion of the host immune system. P. gingivalis is associated with rheumatoid arthritis, dementia, and Alzheimer's. The pathogen successfully survives itself against the heavy load of conventional antibiotics because of its ability to evade the host immune system. Subtractive proteomics and reverse vaccinology approaches were employed in order to prioritize the best proteins for vaccine designing. Three vaccine candidates with Uniprot ID: Q7MWZ2 (histidine Kinase), Q7MVL1 (Fe (2+) transporter), and Q7MWZ2 (Capsular polysaccharide transport protein) were identified for vaccine designing. These proteins are antigenic and essential for pathogen survival. A wide range of immunoinformatics tools was applied for the prediction of epitopes, B, and T cells, for the vaccine candidate proteins. Molecular docking of the predicted epitopes against the MHC molecules were carried out. In-silico vaccine was constructed using carefully evaluated epitopes and consequently modeled for docking with human Toll-like receptor 2. Chain C of Pam3CSK4 (PDB ID; 2Z7X) was linked to the vaccine as an adjuvant to boost immune response towards the vaccine. For stability evaluation of the vaccine-TLR-2 docked complex, Molecular Dynamics simulations were performed. The reverse-translated nucleotide sequence cloned in Eschericia coli to attain the maximal expression of the vaccine protein. The maximal expression was ensured by CAI score of 0.96. The current vaccine requires future experimental validation to confirm its effectiveness. The vaccine developed will be helpful to protect against P. gingivalis associated infections.Communicated by Ramaswamy H. Sarma.
35638589 Immunogenicity of the mRNA-1273 and ChAdOx1 nCoV-19 vaccines in Asian patients with autoim 2022 May 31 OBJECTIVE: Nucleic acid-based vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are effective in the general population. However, it is unknown whether this is true in Asian patients with autoimmune rheumatic diseases (ARDs) who have received various combinations of disease-modifying anti-rheumatic drugs (DMARDs). METHOD: We designed a large prospective observational study recruiting 228 patients with ARDs in a tertiary rheumatology centre in Taiwan. Altogether, 142 received biological or targeted synthetic DMARDs and 86 received only conventional synthetic (cs) DMARDs. Serum levels of immunoglobulin G antibody against SARS-CoV-2 spike proteins were measured 2-6 weeks after COVID-19 vaccination with mRNA-1273 (Moderna®) or ChAdOx1 nCoV-19 (Oxford/AstraZeneca®). The immunomodulatory therapies were not modified before or after vaccination. RESULTS: Overall, 194 patients (85.09%) exhibited antibodies (758.33 ± 808.43 ng/mL) but 34 patients did not (103.24 ± 41.08 ng/mL). Patients with systemic lupus erythematosus or rheumatoid arthritis had significantly lower humoral responses to COVID-19 vaccination than those with other ARDs (p < 0.05). There was no significant difference in immunogenicity among patients on different csDMARD treatments. Compared to patients treated with only csDMARDs, those on rituximab or abatacept therapy had significantly lower immune response to the vaccination (p = 0.008 and p = 0.035, respectively). Patients who were treated with anti-tumour necrosis factor-α or interleukin-6 inhibitor exhibited higher titres of vaccination antibodies than those treated with direct lymphocyte inhibitors. CONCLUSIONS: mRNA-1273 and ChAdOx1 nCoV-19 vaccines were immunogenic in the majority of ARD patients. Rituximab and abatacept were associated with significantly diminished COVID-19 vaccination immunogenicity.
35450955 Autoantibodies against specific post-translationally modified proteins are present in pati 2022 Apr BACKGROUND: Although autoantibodies are an important hallmark of systemic lupus erythematosus (SLE), most are not specific for SLE or any of its clinical manifestations. Autoantibodies against post-translationally modified (PTM) proteins have been studied extensively in rheumatoid arthritis and associate with disease progression. While PTMs have also been detected in patients with SLE, studies on anti-PTM antibodies remain scarce. We studied the presence of anti-PTM antibodies in SLE and neuropsychiatric SLE (NPSLE), a manifestation that lacks serological markers. METHODS: IgG antibody responses against six PTMs (malondialdehyde-acetaldehyde adducts (MAA), advanced glycation end-products (AGE), carbamylation (CarP), citrullination, acetylation and nitration) were tested using ELISA in sera of 349 patients with SLE (mean age 44±13 years; 87% female) and compared with 108 healthy controls. Levels and positivity were correlated with clinical features and SLE manifestations. RESULTS: Anti-MAA, anti-AGE and anti-CarP antibodies were more prevalent in SLE compared with controls (MAA: 29% vs 3%, AGE: 18% vs 4%, CarP: 14% vs 5%, all p≤0.0001). Anti-MAA and anti-AGE antibodies correlated with clinical manifestations and serological inflammatory markers. Patients with major NPSLE showed higher positivity of anti-MAA (39% vs 24%, p=0.01) and anti-CarP antibodies (20% vs 11%, p=0.04) than patients without major NPSLE. In addition, anti-PTM antibody levels correlated with brain volumes, an objective measure of nervous system involvement. CONCLUSIONS: In our NPSLE cohort, a subset of patients with SLE have anti-PTM antibodies against MAA, AGE and CarP modified proteins. Interestingly, anti-MAA and anti-CarP were more prevalent in NPSLE, a manifestation for which no biomarkers exist.
35248101 α-Mangostin inhibits LPS-induced bone resorption by restricting osteoclastogenesis via NF 2022 Mar 5 BACKGROUND: Excessive osteoclast activation is an important cause of imbalanced bone remodeling that leads to pathological bone destruction. This is a clear feature of many osteolytic diseases such as rheumatoid arthritis, osteoporosis, and osteolysis around prostheses. Because many natural compounds have therapeutic potential for treating these diseases by suppressing osteoclast formation and function, we hypothesized that α-mangostin, a natural compound isolated from mangosteen, might be a promising treatment as it exhibits anti-inflammatory, anticancer, and cardioprotective effects. METHODS: We evaluated the therapeutic effect of α-mangostin on the processes of osteoclast formation and bone resorption. The receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) induces osteoclast formation in vitro, and potential pathways of α-mangostin to inhibit osteoclast differentiation and function were explored. A mouse model of lipopolysaccharide-induced calvarial osteolysis was established. Subsequently, micro-computed tomography and histological assays were used to evaluate the effect of α-mangostin in preventing inflammatory osteolysis. RESULTS: We found that α-mangostin could inhibit RANKL-induced osteoclastogenesis and reduced osteoclast-related gene expression in vitro. F-actin ring immunofluorescence and resorption pit assays indicated that α-mangostin also inhibited osteoclast functions. It achieved these effects by disrupting the activation of NF-κB/mitogen-activated protein kinase signaling pathways. Our in vivo data revealed that α-mangostin could protect mouse calvarial bone from osteolysis. CONCLUSIONS: Our findings demonstrate that α-mangostin can inhibit osteoclastogenesis both in vitro and in vivo and may be a potential option for treating osteoclast-related diseases.
34724085 ArthroRad trial: multicentric prospective and randomized single-blinded trial on the effec 2022 Apr PURPOSE: Randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard-dose vs. a very-low-dose regime PATIENTS AND METHODS: Patients with OA of the hand and knee joints were included. Further inclusion criteria: symptoms for more than 3 months, favorable general health status, age above 40 years. Patients with prior local radiotherapy, trauma, rheumatoid arthritis, or vascular diseases were excluded. After randomization (every joint was randomized separately), the following protocols were applied: standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice weekly; experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice weekly. The dosage was not known to the patients. The patients were examined 3 and 12 months after radiotherapy. Scores like VAS (visual analogue scale), KOOS-SF (the knee injugy and osteoarthritis outcome score), SF-SACRAH (short form score for the assessment and quantification of chronic rheumatic affections of the hands), and SF-12 (short form 12) were used. RESULTS: A total of 64 knees and 172 hands were randomized. 3.0 Gy was applied to 87 hands and 34 knees, 0.3 Gy was given to 85 hands and 30 knees. After 3 months, we observed good pain relief after 3 Gy and after 0.3 Gy, there was no statistically significant difference. Side effects were not recorded. The trial was closed prematurely due to slow recruitment. CONCLUSION: We found favorable pain relief and a limited response in the functional and quality of life scores in both arms. The effect of low doses such as 0.3 Gy on pain is widely unknown. Further trials are necessary to compare a conventional dose to placebo and to further explore the effect of low doses on inflammatory disorders.
35600593 Central Diabetes Insipidus Following Immunization With BNT162b2 mRNA COVID-19 Vaccine: A C 2022 INTRODUCTION: Cases of central diabetes insipidus (CDI) have been reported after COVID-19 infection, with hypophysitis being the most likely cause. COVID-19 vaccines potential adverse effects may mimetize some of these complications. CASE REPORT: Woman 37 years old, with rheumatoid arthritis under adalimumab (40 mg twice a month) since December 2018. She was in her usual state of health when she has received the second dose of BNT162b2 mRNA COVID-19 vaccine (June 2021). Seven days later, she started reporting intense thirst and polyuria and consulted her family physician. BLOOD ANALYSIS: creatinine 0.7 mg/dL, glucose 95mg/dL, Na+ 141mEq/L, K+ 3.9 mEq/L, TSH 3.8 mcUI/L (0.38-5.33), FT4 0.9 ng/dL (0.6-1.1), cortisol 215.4 nmol/L (185-624), ACTH 21.9 pg/mL (6- 48), FSH 4.76 UI/L, LH5.62 UI/L, estradiol 323 pmol/L, IGF1 74.8 ng/mL (88-209), PRL 24.7mcg/L (3.3-26.7) osmolality 298.2 mOs/Kg (250- 325); Urine analysis: volume 10200 mL/24h, osmolality 75 mOs/Kg (300-900), density 1.002. On water restriction test: 0' - Serum osmolality 308.8mOsm/Kg vs. urine osmolality 61.0 mOsm/Kg; 60' - urine osmolality 102 mOsm/Kg; urine osmolality 1 h after desmopressine was 511mOsm/kg. MRI revealed no abnormal signs consistent with hypophysitis except for the loss of the posterior pituitary bright spot on T1 weighted imaging. Diagnosis of CDI was assumed, and started therapy with desmopressine. A report of potential adverse effect was addressed to national health authorities. CONCLUSION: In hypophysitis MRI often shows loss of posterior pituitary bright spot on T1 weighted imaging, pituitary enlargement or stalk thickening but those findings were not present in this patient. To the best of our knowledge, CDI has never been reported following administration of a COVID-19 vaccine.
35066538 Risk Factors for 30-day and 90-day Readmission After Lumbar Decompression. 2022 May 1 STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To assess readmission rates and risk factors for 30-day and 90-day readmission after elective lumbar decompression at a single institution. SUMMARY OF BACKGROUND DATA: Hospital readmission is an undesirable aspect of interventional treatment. Studies evaluating readmissions after elective lumbar decompression typically analyze national databases, and therefore have several drawbacks inherent to their macroscopic nature that limit their clinical utility. METHODS: Patients undergoing primary one- to four-level lumbar decompression surgery were retrospectively identified. Demographic, surgical, and readmission data within "30-days" (0-30 days) and "90-days" (31-90 days) postoperatively were extracted from electronic medical records. Patients were categorized into four groups: (1) no readmission, (2) readmission during the 30-day or 90-day postoperative period, (3) complication related to surgery, and (4) Emergency Department (ED)/Observational (OBs)/Urgent (UC) care. RESULTS: A total of 2635 patients were included. Seventy-six (2.9%) were readmitted at some point within the 30- (2.3%) or 90-day (0.3%) postoperative periods. Patients in the pooled readmitted group were older (63.1 yr, P  < 0.001), had a higher American Society of Anesthesiologists (ASA) grade (31.2% with ASA of 3, P = 0.03), and more often had liver disease (8.1%, P = 0.004) or rheumatoid arthritis (12.0%, P = 0.02) than other cohorts. A greater proportion of 90-day readmissions and complications had surgical-related diagnoses or a diagnosis of recurrent disc herniation than 30-day readmissions and complications (66.7% vs. 44.5%, P = 0.04 and 33.3% vs. 5.5%, P < 0.001, respectively). Age (Odds ratio [OR]: 1.02, P = 0.01), current smoking status (OR: 2.38, P < 0.001), longer length of stay (OR: 1.14, P < 0.001), and a history of renal failure (OR: 2.59, P = 0.03) were independently associated with readmission or complication. CONCLUSION: Increased age, current smoking status, hospital length of stay, and a history of renal failure were found to be significant independent predictors of inpatient readmission or complication after lumbar decompression.
35019195 The key role of organic anion transporter 3 in the drug-drug interaction between tranilast 2022 Apr Tranilast, N-(3',4'-dimethoxycinnamoyl)-anthranilic acid, is an anti-allergic drug and is considered for use in the treatment of rheumatoid arthritis. Methotrexate, an antimetabolite and folate antagonist to treat some cancers, is also a first-line drug for RA. The aim of this study was to understand whether tranilast could inhibit renal uptake transporters (Oat1, Oat3, and Oct2) and whether MTX combined with TL would have drug-drug interactions. The results of kidney slices and HEK293T-OAT3 cell uptake experiments showed that TL (10 μM) could inhibit the uptake of penicillin G and MTX, which are substrates of OAT3. When TL (10 mg/kg) was combined with MTX (5 mg/kg), the area under the curve and peak concentration of MTX increased by 46.46% and 113.51%, respectively, while the pharmacokinetic process of tranilast (10 mg/kg) was not changed by methotrexate (5 mg/kg). TL could increase plasma exposure of MTX by inhibiting Oat3 in vitro and in vivo.
34716913 A comprehensive review of IL-26 to pave a new way for a profound understanding of the path 2022 Jan Cytokines are considered vital mediators of the immune system. Down- or upregulation of these mediators is linked to several inflammatory and pathologic situations. IL-26 is referred to as an identified member of the IL-10 family and IL-20 subfamily. Due to having a unique cationic structure, IL-26 exerts diverse functions in several diseases. Since IL-26 is mainly secreted from Th17, it is primarily considered a pro-inflammatory cytokine. Upon binding to its receptor complex (IL-10R1/IL-20R2), IL-26 activates multiple signalling mediators, especially STAT1/STAT3. In cancer, IL-26 induces IL-22-producing cells, which consequently decrease cytotoxic T-cell functions and promote tumour growth through activating anti-apoptotic proteins. In hypersensitivity conditions such as rheumatoid arthritis, multiple sclerosis, psoriasis and allergic disease, this cytokine functions primarily as the disease-promoting mediator and might be considered a biomarker for disease prognosis. Although IL-26 exerts antimicrobial function in infections such as hepatitis, tuberculosis and leprosy, it has also been shown that IL-26 might be involved in the pathogenesis and exacerbation of sepsis. Besides, the involvement of IL-26 has been confirmed in other conditions, including graft-versus-host disease and chronic obstructive pulmonary disease. Therefore, due to the multifarious function of this cytokine, it is proposed that the underlying mechanism regarding IL-26 function should be elucidated. Collectively, it is hoped that the examination of IL-26 in several contexts might be promising in predicting disease prognosis and might introduce novel approaches in the treatment of various diseases.
34433776 At my own pace, space, and place: a systematic review of qualitative studies of enablers a 2022 Feb 1 Telehealth is a promising approach to support self-management with the potential to overcome geographical barriers. Understanding patient perspectives will identify practical challenges to delivering self-management strategies by telehealth. The aim of this study was to synthesize the perceptions of people with chronic musculoskeletal pain for engaging in interventions delivered using telehealth. We searched MEDLINE, Embase, CINAHL, LILACS, and PsycINFO databases. We included qualitative studies that explored perceptions or experiences or attitudes of people with chronic musculoskeletal pain engaging with telehealth. We assessed the methodological quality using the Critical Appraisal Skills Programme checklist. Meta-synthesis was guided by a thematic synthesis approach. The level of confidence of review findings was assessed using the Confidence in the Evidence from Reviews of Qualitative Studies (GRADE-CERQual). Twenty-one studies were included (n = 429). Telehealth comprised web-based, videoconference-based, telephone-based, video-based, and smartphone app-based programs delivered solely or combined. Chronic musculoskeletal conditions included people with knee or hip osteoarthritis, chronic low back pain, persistent pain (chronic joint pain or nonspecific chronic musculoskeletal pain), rheumatoid arthritis, and functional fatigue syndrome. The enablers for engaging in telehealth interventions were as follows: (1) "at my own pace, space, and place" and (2) empowered patient. Barriers to engaging in telehealth interventions were as follows: (1) impersonal, (2) technological challenges, (3) irrelevant content, and (4) limited digital (health) literacy. Telehealth interventions with well-designed interactive platforms, flexibility to fit patients' routine, and the broad availability of material may favor better engagement. Encouragement of self-efficacy is linked to successful telehealth-delivered self-management programs.
33971778 Budget impact analysis of medicines: estimated values versus real-world evidence and the i 2022 Mar OBJECTIVES: Budget Impact Analyses (BIA) of medicines helps managers in promoting health systems' sustainability when assessing the role and value of new medicines. However, it is not clear whether BIAs typically underestimate or overestimate the impact on real-world budgets. This retroactive analysis seeks to compare estimated values obtained by a BIA and Real-World Evidence (RWE) to guide discussions. METHODS: The estimated values were obtained through a BIA concerning the incorporation of adalimumab for the treatment of Rheumatoid Arthritis into the Brazilian Unified Health System (SUS) carried out retroactively and per international guidelines. RWE data was extracted from SUS computerized systems. We subsequently compared the number of treatments, costs, and Incremental Budget Impact (IBI). RESULTS: - The total number of treatments was underestimated by 10% (6,243) and the total expenditure was overestimated by 463% (US$ 4.7 billion). In five years, the total difference between the estimated values and real IBI reached US$ 1.1 billion. A current expenditure of US$ 1.0 was observed for every US$ 5.60 of estimated expenditure. CONCLUSION: - The higher estimates from the BIA might cause decision makers to be more cautious with the introduction of a new medicine to reduce the opportunity costs for other interventions.
35347476 Health-related quality of life (HRQoL) from HIV patients' perspective: comparison of patie 2022 Mar 26 BACKGROUND: People living with HIV (PLWH) are generally known to suffer from a lower quality of life compared to the one of general population, but still very few is known about the self-perception of quality of life when comparing HIV to non-communicable diseases. We performed a comprehensive assessment of patient's reported outcomes measures (PROMs) among PLWH and patients affected by other chronic conditions (OC) such as diabetes mellitus type 1, rheumatoid arthritis, breast cancer in hormonal therapy, in order to investigate differences in PROMs outcomes between PLWH and other pathologies. METHODS: A cross-sectional observational study was performed by using questionnaires investigating health-related quality of life (Medical Outcomes Study Short Form 36-item Health Survey), work productivity (WPI), and global health status (EQ-5D-3L). They were administered to patients affected by chronic diseases consecutively observed at a single University Hospital during a 10 months period, with comparable disease related aspects. Logistic regression analysis was used to analyze the association between disease group (HIV vs OC) and PROMs. RESULTS: 230 patients were enrolled (89 PLWH, 143 OC). Mean age: 49 years (SD 10), mean time of disease 12 years (10), 96% were Caucasian, 35% assumed polypharmacy, 42% of male were PLWH versus 16% OC (p < 0.001), 19% PLWH versus 6% OC had clinical complications (p < 0.001). HIV infection was independently associated to a better health-related quality of life in several domains compared with the other conditions, except in mental health, whereas a worst health-related quality of life in most domains was reported by older patients and those experiencing polypharmacy. CONCLUSIONS: In this cohort of patients with chronic conditions followed within the same health setting, PLWH showed better self-reported health outcomes compared to other chronic conditions with comparable characteristics of chronicity. The potential detrimental role of older age and polypharmacy in most outcomes suggests the need of longitudinal assessment of PROMs in clinical practice.
35342454 A comparison of Remdesivir versus gold cluster in COVID-19 animal model: A better therapeu 2022 Jun While gold compound have been approved for Rheumatoid arthritis treatment as it well suppresses inflammatory cytokines of patients, no such treatment is currently available for COVID-19 treatment in vivo . We firstly disclose gold cluster yields better therapeutic outcome than Remdesivir in COVID-19 hamster treatments as it is armed with direct inhibition viral replication and intrinsic suppression inflammatory cytokines expression. Crystal data reveals that Au (I), released from gold cluster (GA), covalently binds thiolate of Cys145 of SARS-CoV-2 M(pro). GA directly decreases SARS-CoV-2 viral replication and intrinsically down-regulates NFκB pathway therefore significantly inhibiting expression of inflammatory cytokines in cells. The inflammatory cytokines in GA-treated COVID-19 transgenic mice are found to be significantly lower than that of control mice. When COVID-19 golden hamsters are treated by GA, the lung inflammatory cytokines levels are significantly lower than that of Remdesivir. The pathological results show that GA treatment significantly reduce lung inflammatory injuries when compared to that of Remdesivir-treated COVID-19 hamsters.
35311690 The Use of Telehealth for Psychological Counselling of Vulnerable Adult Patients With Rheu 2022 Mar 21 BACKGROUND: Video consultation is increasingly used in different health care settings to reach patients. However, little is known about telehealth in psychological counselling for vulnerable patients with somatic and chronic conditions such as rheumatoid arthritis and diabetes. OBJECTIVE: This study aimed to develop and pilot test a telepsychology module for inclusion in the app My Hospital (Mit Sygehus) to provide remote psychological counselling to vulnerable adults with either rheumatic diseases or diabetes. METHODS: With inspiration from participatory design, the content of the telepsychology module was developed through user involvement and evaluated by individual interviews with patients and psychologists as well as questionnaires. RESULTS: We developed a module with our patient partners that targeted patients with rheumatic diseases and diabetes in relation to the psychological challenges of living with chronic diseases. The module included information, tools, exercises, and videoconferencing. In total, 16 patients and 3 psychologists participated in the pilot test. Psychological counselling was described by 4 themes: "The good relation despite physical distance," "The comfort of being at home," "The pros of saving time on transport and energy," and "A therapeutic alliance at a distance." CONCLUSIONS: Psychological counselling in relation to somatic care can be provided by videoconferencing supported by web-based or mobile delivery of tailored information, tools, and exercises without compromising on the quality of care. To ensure a good alliance between the patient and psychologist, a first face-to-face meeting is important. The home location provided patients with a safe environment and increased accessibility and reduced travel time to the hospital.
35639644 Strong response after 4th dose of mRNA COVID-19 vaccine in autoimmune rheumatic diseases p 2022 May 26 OBJECTIVES: To assess immunogenicity of a heterologous 4th dose of a mRNA (BNT162b2) SARS-CoV-2 vaccine in autoimmune rheumatic diseases (ARD) patients with poor/non-response to inactivated vaccine (Sinovac-CoronaVac). METHODS: 164 ARD patients who were COVID-19 poor/non-responders (negative anti-SARS-CoV-2 S1/S2 IgG and/or neutralising antibodies-NAb) to the 3rd dose of Sinovac-CoronaVac received an additional heterologous dose of mRNA (BNT162b2) three months after last dose. IgG and NAb were evaluated before and after the 4th dose. RESULTS: Significant increases were observed after 4th dose in IgG (66.4% vs 95.1%, p< 0.001), NAb positivity (5.5% vs 83.5%, p< 0.001) and GMT (29.5 vs 215.8 AU/ml, p< 0.001), and 28 (17.1%) remained poor/non-responders. Patients with negative IgG after 4th dose were more frequently under rituximab (p= 0.001). Negative NAb was associated with older age (p= 0.015), rheumatoid arthritis (p= 0.002), systemic sclerosis (p= 0.026), leflunomide (p= 0.016), and rituximab use (p= 0.007). In multiple logistic regression analysis, prednisone dose ≥7.5 mg/day (OR = 0.34; p= 0.047), leflunomide (OR = 0.32, p= 0.036) and rituximab use (OR = 0.19, p= 0.022) were independently associated with negative NAb after the 4th vaccine dose. CONCLUSIONS: This is the largest study to provide evidence of a remarkable humoral response after the 4th dose of heterologous mRNA SARS-CoV-2 vaccination in ARD patients with poor/no-response to the 3rd dose of an inactivated vaccine. We further identified that treatment, particularly rituximab and prednisone, impaired antibody response to this additional dose. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, CoronavRheum #NCT04754698.
35432314 Humoral and Cellular Immunogenicity and Safety of Five Different SARS-CoV-2 Vaccines in Pa 2022 BACKGROUND: Vaccine-induced immunity is essential for controlling the COVID-19 pandemic. Data on humoral and cellular immunogenicity and safety of different SARS-CoV-2 vaccines in patients with autoimmune rheumatic and musculoskeletal diseases (RMDs) are limited. METHODS: A single center observational study evaluated the immunogenicity and safety of the two-dose regimen of the BBIBP-CorV inactivated, Gam-COVID-Vac and AZD1222 adenovirus-based, and BNT162b2 and mRNA-1273 mRNA-based vaccines in patients with RMDs (n = 89) compared with healthy controls (n = 74). Neutralizing anti-RBD (receptor binding domain) specific antibodies and SARS-CoV-2 specific T-cell response were measured one and four months after the second vaccine dose in parallel with vaccination efficacy and safety. RESULTS: Disease-specific comparison showed that antibody response at four months was higher in spondylarthropathies compared to rheumatoid arthritis and autoimmune RMDs. Risk factors for reduced immunogenicity included longer disease duration, positive immunoserological profile and anti-CD20 therapy of patients. The rate of positive anti-RBD antibody response for healthy controls versus patients after 4 months post vaccination was 69% vs. 55% for the inactivated viral vaccine BBIBP-CorV, 97% vs. 53% for the pooled data of adenovirus vector-based vaccines Gam-COVID-Vac and AZD1222, or 100% vs. 81% for the pooled data of mRNA vaccines BNT162b2 and mRNA-1273, respectively. Patients who received the Gam-COVID-Vac or mRNA-1273 vaccines had a higher proportion of TNF-α producing CD4+ T-cells upon SARS-CoV-2 antigen stimulation compared to the inactivated viral vaccine. CONCLUSION: All five investigated vaccines were immunogenic in the majority of patients and healthy controls with variable antibody and T-cell response and an acceptable safety profile.
34985300 Characterization of the O-Glycoproteome of Porphyromonas gingivalis. 2022 Feb 23 Porphyromonas gingivalis is an important human pathogen and also a model organism for the Bacteroidetes phylum. O-glycosylation has been reported in this phylum with findings that include the O-glycosylation motif, the structure of the O-glycans in a few species, and an extensive O-glycoproteome analysis in Tannerella forsythia. However, O-glycosylation has not yet been confirmed in P. gingivalis. We therefore used glycoproteomics approaches including partial deglycosylation with trifluoromethanesulfonic acid as well as both HILIC and FAIMS based glycopeptide enrichment strategies leading to the identification of 257 putative glycosylation sites in 145 glycoproteins. The sequence of the major O-glycan was elucidated to be HexNAc-HexNAc(P-Gro-[Ac](0-2))-dHex-Hex-HexA-Hex(dHex). Western blot analyses of mutants lacking the glycosyltransferases PGN_1134 and PGN_1135 demonstrated their involvement in the biosynthesis of the glycan while mass spectrometry analysis of the truncated O-glycans suggested that PGN_1134 and PGN_1135 transfer the two HexNAc sugars. Interestingly, a strong bias against the O-glycosylation of abundant proteins exposed to the cell surface such as abundant T9SS cargo proteins, surface lipoproteins, and outer membrane β-barrel proteins was observed. In contrast, the great majority of proteins associated with the inner membrane or periplasm were glycosylated irrespective of their abundance. The P. gingivalis O-glycosylation system may therefore function to establish the desired physicochemical properties of the periplasm. IMPORTANCE Porphyromonas gingivalis is an oral pathogen primarily associated with severe periodontal disease and further associated with rheumatoid arthritis, dementia, cardiovascular disease, and certain cancers. Protein glycosylation can be important for a variety of reasons including protein function, solubility, protease resistance, and thermodynamic stability. This study has for the first time demonstrated the presence of O-linked glycosylation in this organism by determining the basic structure of the O-glycans and identifying 257 glycosylation sites in 145 proteins. It was found that most proteins exposed to the periplasm were O-glycosylated; however, the abundant surface exposed proteins were not. The O-glycans consisted of seven monosaccharides and a glycerol phosphate with 0-2 acetyl groups. These glycans are likely to have a stabilizing role to the proteins that bear them and must be taken into account when the proteins are produced in heterologous organisms.
34957554 New-onset autoimmune phenomena post-COVID-19 vaccination. 2022 Apr Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented setback for global economy and health. Vaccination is one of the most effective interventions to substantially reduce severe disease and death due to SARS-CoV-2 infection. Vaccination programmes are being rolled out globally, but most of these vaccines have been approved without extensive studies on their side-effects and efficacy. Recently, new-onset autoimmune phenomena after COVID-19 vaccination have been reported increasingly (e.g. immune thrombotic thrombocytopenia, autoimmune liver diseases, Guillain-Barré syndrome, IgA nephropathy, rheumatoid arthritis and systemic lupus erythematosus). Molecular mimicry, the production of particular autoantibodies and the role of certain vaccine adjuvants seem to be substantial contributors to autoimmune phenomena. However, whether the association between COVID-19 vaccine and autoimmune manifestations is coincidental or causal remains to be elucidated. Here, we summarize the emerging evidence about autoimmune manifestations occurring in response to certain COVID-19 vaccines. Although information pertaining to the risk of autoimmune disease as a consequence of vaccination is controversial, we merely propose our current understanding of autoimmune manifestations associated with COVID-19 vaccine. In fact, we do not aim to disavow the overwhelming benefits of mass COVID-19 vaccination in preventing COVID-19 morbidity and mortality. These reports could help guide clinical assessment and management of autoimmune manifestations after COVID-19 vaccination.