The aged microenvironment impairs BCL6 and CD40L induction in CD4+ T follicular helper cell differentiation.

Weakened germinal center responses by the aged immune system result in diminished immunity against pathogens and reduced efficacy of vaccines. Prolonged contacts between activated B cells and CD4+ T cells are crucial to germinal center formation and T follicular helper cell (Tfh) differentiation, but it is unclear how aging impacts the quality of this interaction. Peptide immunization confirmed that aged mice have decreased expansion of antigen-specific germinal center B cells and reduced antibody titers. Furthermore, aging was associated with accumulated Tfh cells, even in naïve mice. Despite increased numbers, aged Tfh had reduced expression of master transcription factor BCL6 and increased expression of the ectonucleotidase CD39. In vitro activation revealed that proliferative capacity was maintained in aged CD4+ T cells, but not the costimulatory molecule CD40L. When activated in vitro by aged antigen-presenting cells, young CD4+ naïve T cells generated reduced numbers of activated cells with upregulated CD40L. To determine the contribution of cell-extrinsic influences on antigen-specific Tfh induction, young, antigen-specific B and CD4+ T cells were adoptively transferred into aged hosts prior to peptide immunization. Transferred cells had reduced expansion and differentiation into germinal center B cell and Tfh and reduced antigen-specific antibody titers when compared to young hosts. Young CD4+ T cells transferred aged hosts differentiated into Tfh cells with reduced PD-1 and BCL6 expression, and increased CD39 expression, though they maintained their mitochondrial capacity. These results highlight the role of the lymphoid microenvironment in modulating CD4+ T cell differentiation, which contributes to impaired establishment and maintenance of germinal centers.

Characteristics and risk factors of COVID-19 breakthrough infections in Idiopathic Inflammatory Myopathies: Results from the COVAD study.

OBJECTIVES: To explore prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIM) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. METHODS: A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after 2 vaccine doses. We compared BIs characteristics and severity among IIMs, other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HC). Multivariable Cox regression models assessed the risk factors for BI, severe BI and hospitalisations among IIMs. RESULTS: Among 9449 included response, BIs occurred in 1447 (15.3%) respondents, median age 44 years (IQR 21), 77.4% female, and 182 BIs (12.9%) occurred among 1406 IIMs. Multivariable Cox regression among IIMs showed age as a protective factor for BIs [Hazard Ratio (HR)=0.98, 95%CI = 0.97-0.99], hydroxychloroquine and sulfasalazine use were risk factors (HR = 1.81, 95%CI = 1.24-2.64, and HR = 3.79, 95%CI = 1.69-8.42, respectively). Glucocorticoid use was a risk factor for severe BI (HR = 3.61, 95%CI = 1.09-11.8). Non-White ethnicity (HR = 2.61, 95%CI = 1.03-6.59) was a risk factor for hospitalisation. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIM = 6.0% vs AIRD = 1.8%, nrAID = 2.2%, and HC = 0.9%), intensive care unit admission (IIM = 2.2% vs AIRD = 0.6%, nrAID, and HC = 0%), advanced treatment with antiviral or monoclonal antibodies (IIM = 34.1% vs AIRD = 25.8%, nrAID = 14.6%, and HC = 12.8%), and had more hospitalisation (IIM = 7.7% vs AIRD = 4.6%, nrAID = 1.1%, and HC = 1.5%). CONCLUSION: Patients with IIMs are susceptible to severe COVID-19 BI. Age and immunosuppressive treatments were related to the risk of BIs.

Differential roles of normal and lung cancer-associated fibroblasts in microvascular network formation.

Perfusable microvascular networks offer promising three-dimensional in vitro models to study normal and compromised vascular tissues as well as phenomena such as cancer cell metastasis. Engineering of these microvascular networks generally involves the use of endothelial cells stabilized by fibroblasts to generate robust and stable vasculature. However, fibroblasts are highly heterogenous and may contribute variably to the microvascular structure. Here, we study the effect of normal and cancer-associated lung fibroblasts on the formation and function of perfusable microvascular networks. We examine the influence of cancer-associated fibroblasts on microvascular networks when cultured in direct (juxtacrine) and indirect (paracrine) contacts with endothelial cells, discovering a generative inhibition of microvasculature in juxtacrine co-cultures and a functional inhibition in paracrine co-cultures. Furthermore, we probed the secreted factors differential between cancer-associated fibroblasts and normal human lung fibroblasts, identifying several cytokines putatively influencing the resulting microvasculature morphology and functionality. These findings suggest the potential contribution of cancer-associated fibroblasts in aberrant microvasculature associated with tumors and the plausible application of such in vitro platforms in identifying new therapeutic targets and/or agents that can prevent formation of aberrant vascular structures.

Assessing the sensitivity and specificity of myositis-specific and associated autoantibodies: a sub-study from the MyoCite cohort.

OBJECTIVES: Myositis-specific and associated autoantibodies are important biomarkers in routine clinical use. We assessed local testing performance for myositis autoantibodies by comparing line immunoassay (LIA) to protein radio-immunoprecipitation and identifying clinical characteristics associated with each myositis autoantibody in the MyoCite cohort. METHODS: Serum samples from patients within the MyoCite cohort, a well-characterised retro-prospective dataset of adult and juvenile idiopathic inflammatory myopathy (IIM) patients in Lucknow, India (2017-2020), underwent LIA at Sanjay Gandhi Postgraduate Institute of Medical Science (SGPGIMS), Lucknow. Immunoprecipitation of 147 IIM patient serum samples (125 adult-onset, 22 juvenile-onset) was conducted at the University of Bath, with researchers blind to LIA results. LIA performance was assessed against Immunoprecipitation as the reference standard, measuring sensitivity, specificity, and inter-rater agreement. Univariate and multivariate logistic regression determined clinical associations for specific MSA. RESULTS: Immunoprecipitation identified myositis autoantibodies in 56.5% (n = 83) of patient samples, with anti-Jo1 (n = 16; 10.9%) as the most common, followed by anti-MDA5 (n = 14, 9.5%). While LIA showed good agreement for anti-Jo1, anti-PL7 and anti-PL12 (Cohen's κ 0.79, 0.83, and 1, respectively), poor agreement was observed in other subgroups, notably anti-TIF1γ (Cohen's κ 0.21). Strongly positive samples, especially in myositis-specific autoantibodies, correlated more with immunoprecipitation results. Overall, 59 (40.1%) samples exhibited non-congruence on LIA and Immunoprecipitation, and κ values for LIA's for anti-TIF1γ, anti-Ku, anti-PmScl, anti-Mi2, and anti-SAE ranged between 0.21-0.60. CONCLUSION: While LIA reliably detected anti-Jo1, anti-PL7, anti-PL12, anti-MDA5, and anti-NXP-2, it also displayed false positives and negatives. Its effectiveness in detecting other autoantibodies, such as anti-TIF1γ, was poor.

Evaluation of the Milled and Three-Dimensional Digital Manufacturing, 10-Degree and 20-Degree Preparation Taper, Groove and Box Auxiliary Retentive Features, and Conventional and Resin-Based Provisional Cement Type on the Adhesive Failure Stress of 3 mm Short Provisional Crowns.

BACKGROUND This study evaluated the effects of milling (CADCAM), 3D printing, preparation taper angles (10-degree and 20-degree), auxiliary retentive features (groove and box), and provisional cement types (conventional and resin-based) on the adhesive failure stress of 3-mm short provisional crowns (PC). The research was motivated by the need to understand how digital dentistry technologies impact the retention and durability of provisional crowns. MATERIAL AND METHODS A total of 160 working models (3D-printed) and PCs [80 milled (CopraTemp)/80 printed (Asiga)] were fabricated from two 10- and 20-degree typodont master models and two 20-degree 3D-printed master models (groove and box), simulating a 3 mm high all-ceramic short PC. After provisional cementation with conventional (Kerr TempBond) and resin-based (ProviTemp) cements, 16 subgroups (n=10 each) underwent thermocycling (10 000 cycles; 5-55°C) and pull-off tests on a universal testing machine. Statistical analysis was performed using one-way ANOVA and post hoc Tukey test. RESULTS Conventional cement failed at lower stress for milled (47.68 to 73.54) and printed (48.40 to 77.91) as compared to resin cement for milled (104.2 to 137.27) and printed (184.85 to 328.84), respectively, with significant differences. Increased taper and groove decreased failure load except for the printed PC/resin cement combination. Use of proximal box preparation increased retention significantly. Except for 20-degree taper cemented with conventional cement, the differences in auxiliary retentive features for milled and printed provisional crowns were statistically significant at P≤0.05. CONCLUSIONS 3D-printed PC, resin-based cement, 10-degree taper, and proximal box preparation were associated with higher retention than milled, conventional cements, 20-degree taper, and vertical groove.

Clinical Outcomes of 27-Gauge Pars Plana Vitrectomy for Diabetic Tractional Retinal Detachment Repair.

Purpose: To analyze the clinical outcomes of 27-gauge pars plana vitrectomy (PPV) repair of diabetic tractional retinal detachment (TRD) of various severities. Methods: This retrospective case series examined the outcomes of 27-gauge PPV to repair diabetic TRD from 2016 to 2020. The effect of medical and ophthalmologic history parameters and baseline detachment characteristics on visual acuity (VA) and retinal reattachment was analyzed. A grading system was established to stage the severity of the baseline vitreoretinal traction or detachment and compare the visual and anatomic outcomes between stages. Results: The study comprised 79 eyes (79 patients). The overall redetachment rate was 10.1% (8/79). The proportion of eyes with severe visual impairment (worse than 20/200) decreased from 81.0% (64/79) preoperatively to 56.9% (37/65) 6 months postoperatively (P < .001). Worse preoperative logMAR VA was associated with greater odds of redetachment (P = .017) and worse postoperative VA (P < .001). Insulin dependence was associated with better VA at 6 months (P = .017). A shorter known duration of diabetes (P = .026) and evidence of neovascularization of the iris (NVI) or angle (P = .004) were associated with worse visual outcomes. Eyes with detachment involving the posterior pole extending beyond the equator had worse VA at 6 months (P = .048). Conclusions: The primary reattachment rate after 27-gauge PPV was 89.9%. There was significant VA improvement, with a roughly 40% reduction in the number of eyes with severe visual impairment by the final follow-up. Insulin dependence, duration of diabetes, presence of NVI before surgery, and baseline posterior pole detachment extending beyond the equator were predictors of visual outcomes.

Renal injury, biomarkers, and myositis, an understudied aspect of disease: prospective study in the MyoCite cohort.

Introduction: The mechanisms leading to chronic kidney disease (CKD) in patients with idiopathic inflammatory myopathies (IIMs) are poorly understood. We assessed the prevalence of subclinical renal injury in patients with IIMs, through elevation in biomarker levels of tubular injury and fibrosis (NGAL, KIM1, Activin A, CD163, and Cys-c), and assessed differences between subtypes of IIMs, and the effect of disease activity and duration. Materials and methods: Clinical data, core set measures, sera and urine were prospectively collected from all patients enrolled in the MyoCite cohort from 2017 to 2021. Twenty healthy subjects (HC) and 16 patients with acute kidney injury (AKI) were included as controls. Baseline and follow up data for IIMs were included. Enzyme-linked immunosorbent assay (ELISA) was used to measure urine NGAL (Human Lipocalin-2/NGAL Duoset ELISA, Cat no: DY1757), KIM1 (Human TIM-1/KIM 1/HAVCR Duoset ELISA, Cat.no: DY1750B), Activin A (Human Activin A Duoset ELISA, Cat no: DY338), CD163 (Human CD163 Duoset ELISA,Cat no: DY1607-05), and Cys-c (Human Cystatin C Duoset ELISA, Cat. no.: DY1196) levels, while eGFR (unit mL/min/1.73 m2) was calculated by the Cockcroft-Gault formula and CKD-EPI formula. Results: Analysis of 201 visits of 110 adult patients with IIMs indicated higher normalized biomarker levels compared to HCs, and comparable to patients with AKI, with the exception of NGAL, which was higher in the AKI group. Notably 72 (49%) patients with IIMs had eGFR<90; the levels of the 5 biomarkers were comparable between active and inactive IIMs, and different subtypes of IIMs. Similarly, a poor correlation between urine biomarker levels and core set measures of activity and damage was found. Changes in biomarker levels on follow-up did not correlate with eGFR changes. Discussion: This exploratory analysis of urinary biomarkers identified low eGFR and elevated biomarkers of CKD in nearly half of the patients with IIMs, comparable to patients with AKI and higher than HCs, indicative of potential renal damage in IIMs that may have a lead to complications in other systems.

COVID-19 vaccine safety during pregnancy and breastfeeding in women with autoimmune diseases: results from the COVAD study.

OBJECTIVES: We investigated COVID-19 vaccine safety in pregnant and breastfeeding women with autoimmune diseases (AID) in the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. METHODS: Delayed-onset (>7 days) vaccine-related adverse events (AE), disease flares (DF), and AID-related treatment modifications were analyzed upon diagnosis of AID versus healthy controls (HC) and the pregnancy/breastfeeding status at the time of at least one dose of vaccine. RESULTS: Among the 9201 participants to the self-administered online survey, 6787 (73.8%) were women. Forty pregnant and 52 breastfeeding patients with AID were identified, of whom the majority had received at least one dose of COVID-19 vaccine (100% and 96.2%, respectively). AE were reported significantly more frequently in pregnant than in non-pregnant patients (overall AE 45% vs 26%, p= 0.01; minor AE 40% vs 25.9%, p= 0.03; major AE 17.5% vs 4.6%, p< 0.01), but no difference was found in comparison with pregnant HC. No difference was observed between breastfeeding patients and HC with respect to AE. Post-vaccination DF were reported by 17.5% of pregnant and 20% of breastfeeding patients, and by 18.3% of age- and disease-matched non-pregnant and non-breastfeeding patients (n = 262). All pregnant/breastfeeding patients who experienced a DF were managed with glucocorticoids; 28.6% and 20% of them required initiation or change in immunosuppressants, respectively. CONCLUSION: This study provides reassuring insights into the safety of COVID-19 vaccines administered to women with AID during the gestational and post-partum periods, helping overcome hesitant attitudes, as the benefits for the mother and the fetus by passive immunization appear to outweigh potential risks.

Perioperative systemic blood pressure parameters and clinical outcomes following 27g vitrectomy for diabetic tractional detachment repair.

BACKGROUND: Extremes in perioperative blood pressures are known risk factors for adverse outcomes after surgical interventions. There is scarce literature studying these parameters as predictors of outcomes after ocular surgery. METHODS: This was a retrospective single-centre interventional cohort analysis to evaluate the relationship between perioperative (preoperative and intraoperative) blood pressure value and variability and postoperative visual and anatomic outcomes. Included were patients who underwent primary 27-gauge (27g) vitrectomy for repair of diabetic tractional retinal detachment (DM-TRD) with at least 6 months of follow-up. Univariate analyses were conducted via independent two-sided t-tests and Pearson's χ2 tests. Multivariate analyses were conducted via generalised estimating equations. RESULTS: 71 eyes of 57 patients were included in the study. Higher preprocedure mean arterial pressure (MAP) was associated with fewer Snellen lines of improvement at postoperative month 6 (POM6) (p<0.01). Higher mean intraoperative systolic blood pressure (SBP), diastolic blood pressure and MAP were associated with visual acuity 20/200 or worse at POM6 (p<0.05). Patients with sustained intraoperative hypertension had 1.77 times the risk of visual acuity 20/200 or worse at POM6 compared with those without sustained intraoperative hypertension (p=0.006). Higher SBP variability was associated with worse visual outcomes at POM6 (p<0.05). Blood pressure was not associated with macular detachment at POM6 (p>0.10). CONCLUSIONS: Higher average perioperative blood pressure and blood pressure variability are associated with worse visual outcomes in patients undergoing 27g vitrectomy for DM-TRD repair. Patients with sustained intraoperative hypertension were approximately twice as likely to have visual acuity 20/200 or worse at POM6 compared to those without sustained intraoperative hypertension.

Pain in individuals with idiopathic inflammatory myopathies, other systemic autoimmune rheumatic diseases, and without rheumatic diseases: A report from the COVAD study.

OBJECTIVES: To compare pain intensity among individuals with idiopathic inflammatory myopathies (IIMs), other systemic autoimmune rheumatic diseases (AIRDs), and without rheumatic disease (wAIDs). METHODS: Data were collected from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an international cross-sectional online survey, from December 2020 to August 2021. Pain experienced in the preceding week was assessed using numeral rating scale (NRS). We performed a negative binomial regression analysis to assess pain in IIMs subtypes and whether demographics, disease activity, general health status, and physical function had an impact on pain scores. RESULTS: Of 6988 participants included, 15.1% had IIMs, 27.9% had other AIRDs, and 57.0% were wAIDs. The median pain NRS in patients with IIMs, other AIRDs, and wAIDs were 2.0 (interquartile range [IQR] = 1.0-5.0), 3.0 (IQR = 1.0-6.0), and 1.0 (IQR = 0-2.0), respectively (P < 0.001). Regression analysis adjusted for gender, age, and ethnicity revealed that overlap myositis and antisynthetase syndrome had the highest pain (NRS = 4.0, 95% CI = 3.5-4.5, and NRS = 3.6, 95% CI = 3.1-4.1, respectively). An additional association between pain and poor functional status was observed in all groups. Female gender was associated with higher pain scores in almost all scenarios. Increasing age was associated with higher pain NRS scores in some scenarios of disease activity, and Asian and Hispanic ethnicities had reduced pain scores in some functional status scenarios. CONCLUSION: Patients with IIMs reported higher pain levels than wAIDs, but less than patients with other AIRDs. Pain is a disabling manifestation of IIMs and is associated with a poor functional status.

Systemic sclerosis and COVID-19 vaccine safety: short-term insights from the global COVID-19 vaccination in autoimmune disease (COVAD) survey.

The safety profile of COVID-19 vaccines is understudied in patients with systemic sclerosis (SSc). We compared short-term adverse events (AEs) 7 days following vaccination in patients with SSc vs other rheumatic (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs). The COVID-19 Vaccination in autoimmune diseases (COVAD) self-reporting e-survey was circulated by a group of > 110 collaborators in 94 countries from March to December 2021. AEs were analyzed between different groups using regression models. Of 10,679 complete respondents [73.8% females, mean age 43 years, 53% Caucasians], 478 had SSc. 83% had completed two vaccine doses, Pfizer-BioNTech (BNT162b2) (51%) was the most common. Minor and major AEs were reported by 81.2% and 3.3% SSc patients, respectively, and did not differ significantly with disease activity or different vaccine types, though with minor symptom differences. Frequencies of AEs were not affected by background immunosuppression, though SSc patients receiving hydroxychloroquine experienced fatigue less commonly (OR 0.4; 95% CI 0.2-0.8). Frequency of AEs and hospitalisations were similar to other AIRDs, nrAIDs, and HC except a higher risk of chills (OR 1.3; 95% CI 1.0-1.7) and fatigue (OR 1.3; 95% CI 1.0-1.6) compared to other AIRDs. COVID-19 vaccines were largely safe and well tolerated in SSc patients in the short term. Background immunosuppression and disease activity did not influence the vaccination-related short-term AEs.

Flares in autoimmune rheumatic diseases in the post-COVID-19 vaccination period-a cross-sequential study based on COVAD surveys.

OBJECTIVE: Flares of autoimmune rheumatic diseases (AIRDs) following COVID-19 vaccination are a particular concern in vaccine-hesitant individuals. Therefore, we investigated the incidence, predictors and patterns of flares following vaccination in individuals living with AIRDs, using global COVID-19 Vaccination in Autoimmune Diseases (COVAD) surveys. METHODS: The COVAD surveys were used to extract data on flare demographics, comorbidities, COVID-19 history, and vaccination details for patients with AIRDs. Flares following vaccination were identified as patient-reported (a), increased immunosuppression (b), clinical exacerbations (c) and worsening of PROMIS scores (d). We studied flare characteristics and used regression models to differentiate flares among various AIRDs. RESULTS: Of 15 165 total responses, the incidence of flares in 3453 patients with AIRDs was 11.3%, 14.8%, 9.5% and 26.7% by definitions a-d, respectively. There was moderate agreement between patient-reported and immunosuppression-defined flares (K = 0.403, P = 0.022). Arthritis (61.6%) and fatigue (58.8%) were the most commonly reported symptoms. Self-reported flares were associated with higher comorbidities (P = 0.013), mental health disorders (MHDs) (P < 0.001) and autoimmune disease multimorbidity (AIDm) (P < 0.001).In regression analysis, the presence of AIDm [odds ratio (OR) = 1.4; 95% CI: 1.1, 1.7; P = 0.003), or a MHD (OR = 1.7; 95% CI: 1.1, 2.6; P = 0.007), or being a Moderna vaccine recipient (OR = 1.5; 95% CI: 1.09, 2.2; P = 0.014) were predictors of flares. Use of MMF (OR = 0.5; 95% CI: 0.3, 0.8; P = 0.009) and glucocorticoids (OR = 0.6; 95% CI: 0.5, 0.8; P = 0.003) were protective.A higher frequency of patients with AIRDs reported overall active disease post-vaccination compared with before vaccination (OR = 1.3; 95% CI: 1.1, 1.5; P < 0.001). CONCLUSION: Flares occur in nearly 1 in 10 individuals with AIRDs after COVID vaccination; people with comorbidities (especially AIDm), MHDs and those receiving the Moderna vaccine are particularly vulnerable. Future avenues include exploring flare profiles and optimizing vaccine strategies for this group.

Recent updates in enthesitis-related arthritis.

Enthesitis-related arthritis (ERA) is a category of juvenile idiopathic arthritis which belongs to the spectrum of diseases that are included in juvenile spondyloarthropathy. In recent years, there have been significant advances in understanding pathogenesis, tools to assess disease activity, early recognition of the axial disease, and targeted therapy using IL-17 inhibitors and small molecule inhibitors. The current narrative review highlights these new advances. Among many hypotheses linking HLA B27 to ERA, one of them is the effect of HLA B27 on gut dysbiosis. However, recent data suggest that gut dysbiosis is probably not determined by HLA B27. Though children present with arthritis and enthesitis, axial disease is present in 50-60% on MRI. Using data-driven approach, discriminative MRI finding for active and chronic diseases has been defined for children. This will help in the early recognition of disease. An abridged version of juvenile spondyloarthropathy disease activity (JSpADA) score without the need for acute phase reactants and Schober test performed as well as the original score may increase its acceptance in routine practice. Secukinumab (anti-IL-17 antibody) has shown a more than 75% response rate in children with ERA and may be a good alternative to anti-TNF therapy. Initial data with tofacitinib also look promising. All these will translate into better outcomes for children with ERA.

Safety and tolerance of vaccines against SARS-CoV-2 infection in systemic lupus erythematosus: results from the COVAD study.

OBJECTIVE: To determine COVID-19 vaccine-related adverse events (AEs) in the seven-day post-vaccination period in patients with SLE vs autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HC). METHODS: Data were captured through the COVID-19 Vaccination in Autoimmune Diseases (COVAD) questionnaire (March-December 2021). Multivariable regression models accounted for age, gender, ethnicity, vaccine type and background treatment. RESULTS: Among 9462 complete respondents, 583 (6.2%) were SLE patients (mean age: 40.1 years; 94.5% females; 40.5% Asian; 42.9% Pfizer-recipients). Minor AEs were reported by 83.0% of SLE patients, major by 2.6%, hospitalization by 0.2%. AE and hospitalization frequencies were similar between patients with active and inactive SLE. Rashes were more frequent in SLE patients vs HC (OR; 95% CI: 1.2; 1.0, 1.5), chills less frequent in SLE vs AIRDs (0.6; 0.4, 0.8) and nrAIDs (0.5; 0.3, 0.8), and fatigue less frequent in SLE vs nrAIDs (0.6; 0.4, 0.9). Pfizer-recipients reported higher overall AE (2.2; 1.1, 4.2) and injection site pain (2.9; 1.6, 5.0) frequencies than recipients of other vaccines, Oxford/AstraZeneca-recipients more body ache, fever, chills (OR: 2.5, 3.0), Moderna-recipients more body ache, fever, chills, rashes (OR: 2.6, 4.3). Hospitalization frequencies were similar across vaccine types. AE frequencies were similar across treatment groups, although chills were less frequent in antimalarial users vs non-users (0.5; 0.3, 0.9). CONCLUSION: While COVID-19 vaccination-related AEs were reported by four-fifths of SLE patients, those were mostly minor and comparable to AEs reported by healthy individuals, providing reassurance regarding COVID-19 vaccination safety in SLE.

Evaluation of split-cast techniques for remounting casts on a dental articulator: A survey and an in vitro study.

INTRODUCTION: This study aimed to investigate the difference between senior dental students and prosthodontic faculty members regarding their opinions, attitudes and adoption of six split-cast techniques for remounting complete dentures. The accuracy of each technique for measurements of the vertical and the anteroposterior dimensions was assessed. MATERIALS AND METHODS: Six split-cast techniques to remove the casts were compared. A total of 115 participants removed a set of casts on six different articulators, and a questionnaire survey was administered. A digital Vernier caliper was used to measure the linear dimensional changes between the laterally pindexed references on each cast. The data were statistically analysed at α = 0.05. RESULTS: There were significant differences between senior dental students and prosthodontic faculty members in their responses regarding adoption of daily practice and techniques requiring more skill (p = .001). To adopt a specific technique in daily practice, most students and faculty members chose long round die pins (36.4%) and central groove indexing (CGI; 40.7%), respectively. For techniques requiring more skills, most students and faculty members chose long rectangular die pins (30.7%) and short round dowel pins (33.3%), respectively. CONCLUSION: Dental students preferred ShRP, whilst faculty members preferred LReP. All participants considered CGI to be the easiest amongst the techniques. For comparison with baseline measurements, both senior dental students and prosthodontic faculty members considered side notch indexing and double dowel pins to be the most accurate techniques for vertical measurements, and CGI for anteroposterior measurements.

COVID-19 vaccination in autoimmune diseases (COVAD) study: vaccine safety and tolerance in rheumatoid arthritis.

OBJECTIVES: The COVID-19 vaccination in autoimmune diseases (COVAD) study aimed to assess short-term COVID-19 vaccination-related adverse events (AEs) in RA patients. METHODS: An online self-reported questionnaire (March-December 2021) was used to capture data related to COVID-19 vaccination-related AEs in RA, other autoimmune rheumatic diseases (AIRDs) (excluding RA and inflammatory myositis), non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs). Descriptive and multivariable regression analyses were performed. RESULTS: Of the 9462 complete respondents, 14.2% (n = 1347) had been diagnosed with RA; they had a mean (s.d.) age of 50.7 (13.7) years, 74.2% were women and 49.3% were Caucasian. In total, 76.9% and 4.2% of patients with RA reported minor and major AEs, respectively. Patients with active and inactive RA had similar AE and hospitalization frequencies. Overall, AEs were reported more frequently by BNT162b2 and mRNA-1273 recipients and less frequently by BBV152 recipients compared with the rest. Major AE and hospitalization frequencies were similar across recipients of different vaccines. Patients receiving methotrexate and hydroxychloroquine reported fewer minor AEs than those patients not on them. Compared with HCs and patients with other AIRDs, patients with RA reported similar total AEs, overall minor AEs, and hospitalizations. Compared with nrAIDs, patients with RA reported lower frequencies of overall AEs, minor AEs (both odds ratio [OR] = 0.7; 95% CI: 0.5, 0.9), and injection site pain (OR = 0.6; 95% CI: 0.5, 0.8) with similar major AE and hospitalization frequencies. CONCLUSION: Despite the differences in AE frequency across different COVID-19 vaccines, all were well tolerated in patients with RA and were comparable to HCs, providing reassurance as to the safety of COVID-19 vaccination.

Retinal changes in patients with idiopathic inflammatory myopathies: A case-control study in the MyoCite cohort.

Background: Retinal changes are the window to systemic vasculature. Therefore, we explored retinal changes in patients with Idiopathic inflammatory myopathies (IIM) as a surrogate for vascular health. Methods: Adult and Juvenile IIM patients (2017 ACR/EULAR criteria), visiting a tertiary care center in 2021 were enrolled for detailed ophthalmic examination in comparison with healthy controls (HC). Patients with conditions that precluded thorough posterior chamber examination were excluded. Scale variables are expressed as median (IQR). Multivariate analysis (binary logistic regression-BLR) was conducted, adjusting for age, gender, and comorbidities besides factors significant in univariate analysis. Results: 43 patients with IIM [31 females; age 36 (23-45) years; disease duration 5.5 (2-12) months] were enrolled for participation. DM (44%) was the most common diagnosis. IIM patients exhibited frequent attenuation of retinal vessels (32.6 vs. 4.3%, p < 0.001), AV nicking (14 vs. 2.2%, p = 0.053), and vascular tortuosity (18.6 vs. 2.2%, p = 0.012), besides decreased visual acuity (53.5 vs. 10.9%, p<0.001) and immature cataracts (34.9 vs. 2.2%, p < 0.001). Attenuation of vessels [OR 10.9 (1.7-71), p = 0.004] emerged as significantly different from HC after adjusting for covariates in BLR. Notably, adults with IIM were more predisposed to retinal abnormalities [21 (57%) vs. 1 (16%), p = 0.068], especially attenuation of vessels [14(38%) vs. 0(0), p = 0.067] than jIIM. However, no difference was found in retinal features amongst the subtypes of adult IIM, nor did they correlate with MDAAT, MDI, or HAQ-DI. Conclusion: Retinal microvasculopathy and diminution of vision occur in nearly one-thirds to half of the patients with IIM. Microvasculopathy occurs across subtypes of IIM, and more so in adults, calling for further investigation as a surrogate for damage assessment and potentially even systemic vascular health.

Tissue glue for management of large iris cyst.

Purpose: To present a novel technique utilizing fibrin glue-assisted adhesion as adjuvant to fine needle aspiration for management of post-surgical peripheral iris stromal cyst. Observations: A 61 year-old male presented with a 4.20 × 7.56 × 8.22 mm well-circumscribed, fluid-filled peripheral cystic lesion involving the central visual axis with local posterior displacement of the intraocular lens. Surgical drainage was performed with the adjuvant use of fibrin glue to enhance the annealing of cyst walls. The patient tolerated the procedure without significant complications. At final post-operative visit, vision improved to 20/30 and there was no recurrence of the cyst. Conclusions and importance: To our knowledge, this is the first report describing the use of fibrin glue to successfully treat a post-surgical peripheral iris stromal cyst. Fibrin glue may serve as an effective alternative to ethanol and sclerosing agents in the management of iris cysts.

"Constrained Medical Oxygen Supply Chain in India During COVID-19: Red-tapism, the Elephant in the Room?"

BACKGROUND: Recent disruption of medical oxygen during the second wave of coronavirus disease 2019 (COVID-19) has caused nationwide panic. This study attempts to objectively analyze the medical oxygen supply chain in India along the principles of value stream mapping (VSM), identify bottlenecks, and recommend systemic improvements. METHODS: Process mapping of the medical oxygen supply chain in India was done. Different licenses and approvals, their conditions, compliances, renewals, among others were factored in. All relevant circulars (Government Notices), official orders, amendments, and gazette notifications pertaining to medical oxygen from April 2020 to April 2021 were studied and corroborated with information from Petroleum and Explosives Safety Organization (PESO) official website. RESULTS: Steps of medical oxygen supply chain right from oxygen manufacture to filling, storage, and transport up to the end users; have regulatory bottlenecks. Consequently, flow of materials is sluggish and very poor information flow has aggravated the inherent inefficiencies of the system. Government of India has been loosening regulatory norms at every stage to alleviate the crisis. CONCLUSIONS: Regulatory bottlenecks have indirectly fueled the informal sector over the years, which is not under Government's control with difficulty in controlling black-marketing and hoarding. Technology enabled, data-driven regulatory processes with minimum discretionary human interface can make the system more resilient.

Patient-derived micro-organospheres enable clinical precision oncology.

Patient-derived xenografts (PDXs) and patient-derived organoids (PDOs) have been shown to model clinical response to cancer therapy. However, it remains challenging to use these models to guide timely clinical decisions for cancer patients. Here, we used droplet emulsion microfluidics with temperature control and dead-volume minimization to rapidly generate thousands of micro-organospheres (MOSs) from low-volume patient tissues, which serve as an ideal patient-derived model for clinical precision oncology. A clinical study of recently diagnosed metastatic colorectal cancer (CRC) patients using an MOS-based precision oncology pipeline reliably assessed tumor drug response within 14 days, a timeline suitable for guiding treatment decisions in the clinic. Furthermore, MOSs capture original stromal cells and allow T cell penetration, providing a clinical assay for testing immuno-oncology (IO) therapies such as PD-1 blockade, bispecific antibodies, and T cell therapies on patient tumors.