Mortality in Systemic Sclerosis-Associated Interstitial Lung Disease in Brazil: A Real-Life, Long-Term Follow-up Observational Study.

OBJECTIVES: The aim of this study was to identify risk factors associated with mortality in patients with systemic sclerosis (SSc), particularly those with interstitial lung disease (ILD), over a long-term follow-up in a large Brazilian SSc cohort. METHODS: We conducted a medical records review study of 380 scleroderma patients from 1982 to 2019. Systemic sclerosis ILD was considered in those with evidence of ILD on chest high-resolution computed tomography (HRCT). Causes of death were determined. RESULTS: Among the 380 SSc patients, SSc-ILD on chest HRCT was observed in 227 patients (59.7%). Seventy-two patients (18.9%) died during a mean follow-up of 7.2 years since the SSc diagnosis; among them, 57 (79.2%) had SSc-ILD, compared with 15 (20.8%) without SSc-ILD (p < 0.001). Of the 72 deaths, 51.4% were considered related to SSc, and ILD was the leading cause of death. The overall survival rates at 5, 10, and 15 years were 87.9%, 81.5%, and 74.9%, respectively. Kaplan-Meier analysis showed a significantly worse prognosis among patients with SSc-ILD than among those without ILD (p < 0.001). Among patients with SSc-ILD, disease duration of less than 4 years (p < 0.001), forced vital capacity <80% at baseline (p = 0.017), and pulmonary systolic arterial pressure ≥40 mm Hg on echocardiography (p < 0.001) were significantly associated with mortality by multivariate analysis. CONCLUSIONS: In Brazilian SSc patients, the presence of ILD was associated with a worse prognosis. The higher mortality among SSc-ILD patients, especially those with a shorter disease duration and forced vital capacity <80%, highlights the need for early screening and closer monitoring before irreversible lung function deterioration occurs.

Structural abnormalities associated with glaucoma using swept-source optical coherence tomography in patients with systemic sclerosis.

PURPOSE: Vasospasm represents an early event in systemic sclerosis (SSc). Ocular vasospasm may induce optic nerve head (ONH) damage and has been involved in the pathogenesis of glaucoma, especially normal-tension glaucoma (NTG). We aimed to investigate the presence of structural abnormalities associated with NTG using swept-source optical coherence tomography (SS-OCT) and to correlate the OCT parameters with clinical, capillaroscopy and digital blood flow measures in patients with SSc. METHODS: In this cross-sectional study, 40 patients with SSc and 23 age-matched controls were included. The following parameters were measured using SS-OCT: mean and sectoral retinal nerve fibre layer (RNFL) thickness, macular ganglion cell layer complex (GCC) thickness and ONH morphology. Nailfold capillaroscopy (NFC) and digital blood flow measurements using laser Doppler imaging (LDI) were performed in all subjects. RESULTS: Patients with SSc showed a thinner temporal RNFL than the controls (69.23 ± 11.74 versus 83.35 ± 20.19 µm, p = 0.001). The other parameters were similar between the two groups. In SSc patients, there was an inverse correlation between the disease duration and the average, superior and inferior RNFL thickness and the GCC thickness and between Raynaud's phenomenon duration and the average RNFL and GCC thickness (p < 0.05). NFC and LDI measurements did not show correlations with OCT parameters. CONCLUSION: A thinner temporal RNFL and the correlation between Raynaud's phenomenon and disease duration and structural abnormalities on OCT suggest the presence of early ganglion cell damage in patients with SSc. Although mild, these findings indicate the need to monitor ocular abnormalities in SSc.

Effect of probiotics on gastrointestinal symptoms and immune parameters in systemic sclerosis: a randomized placebo-controlled trial.

OBJECTIVES: Changes in the intestinal microbiota have been associated with the pathogenesis of SSc. Probiotics act by modulating the microbiome and the immune response. This study aimed to evaluate the efficacy of probiotics on gastrointestinal (GI) symptoms and immune responses in SSc patients. METHODS: Patients with SSc with a moderate-severe total score on the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (UCLA GIT 2.0) instrument were randomly assigned to receive a daily dose of probiotics (Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus acidophillus and Bifidobacterium lactis, 109 colony-forming units per capsule) or placebo for 8 weeks. The primary endpoint was improvement in the UCLA GIT 2.0 total score after 8 weeks. Secondary outcomes included changes in Th1, Th2, Th17 and regulatory T cell circulating levels and in the HAQ Disability Index (HAQ-DI) score. Parameters were assessed at baseline and after 4 and 8 weeks of treatment. RESULTS: A total of 73 patients were randomized to receive probiotics (n = 37) or placebo (n = 36). After 8 weeks, there was no difference in the UCLA GIT 2.0 score between the two groups. At week 8, the probiotic group showed a significant decrease in the proportion of Th17 cells compared with placebo (P = 0.003). There was no difference in the proportion of Th1, Th2 and regulatory T cells or in the HAQ-DI score between the groups. CONCLUSION: Probiotics did not improve GI symptoms in SSc patients. The reduction in Th17 cell levels suggests an immunomodulatory effect of probiotics on SSc. TRIAL REGISTRATION: ClinicalTrials.gov (http://clinicaltrials.gov), NCT02302352.

Less severe disease in patients with early systemic sclerosis?

Objectives: To evaluate the disease severity and activity in patients with a diagnosis of systemic sclerosis (SSc) after the 2013 American College of Rheumatology and the European League Against Rheumatism (ACR/EULAR) classification criteria development compared to patients diagnosed before 2013.Methods: One hundred and fifty-four subjects were included and assigned to the following groups: 120 SSc patients meeting the 1980 ACR criteria and with a diagnosis before 2013 (historical group), and 34 patients diagnosed after 2013, fulfilling the new ACR/EULAR criteria (early SSc group). Disease activity was assessed by the 2001 European Scleroderma Study Group Activity Index (EScSG-AI) and by the revised European Scleroderma Trials and Research group (EUSTAR) activity index. Disease severity was assessed using the Medsger Disease Severity Scale (DSS) and the summed DSS score.Results: The time between the first non-Raynaud's symptom and the diagnosis was shorter in early SSc than in the historical group (p = .001). The EScSG-AI and the EUSTAR activity index were similar between groups. The summed DSS score and the general, skin and gastrointestinal tract DSS scores were significantly lower in early SSc than in the historical group.Conclusion: SSc patients with a diagnosis after the new ACR/EULAR criteria development were diagnosed earlier and had a less severe disease than historical patients.

Evaluation of the effect of sildenafil on the microvascular blood flow in patients with systemic sclerosis: a randomised, double-blind, placebo-controlled study.

OBJECTIVES: To evaluate the effect of sildenafil as add-on therapy on the microvascular blood flow in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). METHODS: In this double-blind, placebo-controlled study, 41 patients with RP secondary to SSc were randomly assigned to receive oral sildenafil 100 mg/day (21 patients, mean age 47.2 years) or placebo (20 patients, mean age 41.6 years) for 8 weeks. Patients were evaluated at baseline, 8 weeks after treatment, and 2 weeks after the end of the treatment. The primary outcome measures were the mean changes in finger blood flow (FBF) measured using laser Doppler imaging before and after cold stimulus at 8 weeks of treatment. Secondary endpoints included frequency and duration of RP attacks, Visual Analog Scale (VAS) score for RP severity, Raynaud's condition score, and serum levels of VEGF and endothelial progenitor cells (EPCs). RESULTS: After 8 weeks of treatment, the sildenafil group presented a significantly higher mean percentage change from baseline in FBF before cold stimulus (p=0.026), and in FBF after cold stimulus (p=0.028) compared with the placebo group. There was a significant improvement in the duration of RP and in the percentage change from baseline to week 8 in the RP VAS score in sildenafil compared with placebo. There were no changes in EPCs and VEGF levels after treatment in either group. CONCLUSIONS: Sildenafil improved digital blood flow and RP symptoms in SSc patients after 8 weeks of treatment, and might be a good therapeutic option for secondary RP.

Validation of the ACR/EULAR classification criteria for systemic sclerosis in patients with early scleroderma.

The aim of this study was to validate the 2013 ACR/EULAR classification criteria for systemic sclerosis (SSc) in patients with SSc, including patients with early SSc. Fifty-six consecutive patients with early SSc (2001 LeRoy and Medsger criteria), 122 patients with established SSc (1980 ACR classification criteria), and 141 patients with SSc-like disorders were included in this cross-sectional study. The diagnostic performance of the 2013 ACR/EULAR criteria was compared with the 1980 ACR criteria in several subsets of patients. The performance of individual variables was also obtained. Receiver operating characteristic (ROC) curves and optimal cut-off values were computed. The sensitivity and specificity in the whole cohort of 178 SSc patients were 77.6 and 98.5%, respectively, using the 2013 ACR/EULAR criteria and 68.5 and 100%, respectively, using the 1980 ACR criteria. Twenty-eight percent of the patients with early SSc met the 2013 ACR/EULAR criteria. Among the patients with early SSc, 53% of those who had Raynaud's phenomenon, abnormal capillaroscopy and positive SSc-related antibodies met the 2013 ACR/EULAR criteria. The area under the ROC curve was 0.975 (95% confidence interval 0.962-0.987). The best cut-off value for the total score was ≥8 (sensitivity 82%; specificity 97.9%). The individual variables with the highest specificity values were proximal skin thickening, sclerodactyly (specificity 100%), telangiectasia and SSc-related antibodies (specificity 98.6%). Raynaud's phenomenon had the best sensitivity (99.4%) but had low specificity (4.2%). In conclusion, the 2013 ACR/EULAR classification criteria showed high accuracy and increased sensitivity in the classification of patients with early SSc.

Nailfold videocapillaroscopy in healthy children and adolescents: description of normal patterns.

OBJECTIVES: to describe normal patterns of nailfold videocapillaroscopy (NVC) in healthy children and adolescents; to quantify the relationship between age and capillary dimensions, intercapillary distance and number of capillaries/mm; to evaluate the inter and intraobserver concordance. METHODS: Cross-sectional study including 100 healthy participants aged 5 to 18 years. Capillary dimensions (capillary loop length, capillary width and intercapillary distance) and number of capillaries/mm were evaluated in 900 capillaries using stereomicroscope under 100x magnification. Intra and inter observer agreements were tested. RESULTS: The capillary dimensions (mean ± SD) were: capillary loop length 278.6±60.3 µm, intercapillary distance 124.1±28.1 µm, capillary width 15.0±2.6 µm. Teenagers between 15 and 18 years had longer and more enlarged capillaries than the other age groups (p<0.001 and p=0.012 respectively). We also found a significant increase in the number of capillaries/mm with age (p<0.001). There was a positive correlation between age and number of capillaries/mm, capillary length, and capillary width (p<0.001, R=0.796; p<0.001, R=0.368; p=0.004, R=0.285, respectively). There was a good intra and interobserver concordance. Enlarged capillary and avascular areas were present in 11% and 10% of capillaries respectively. A weak negative correlation was found between the intercapillary distance and the number of capillaries/mm (p=0.05; R=-0.20). CONCLUSIONS: There is a wide variability in the capillary morphology among healthy individuals. There was a positive correlation between age and number of capillaries/mm, capillary length, and capillary width. In addition, NVC has been shown to be a reproducible method.

Decreased numbers of endothelial progenitor cells in patients in the early stages of systemic sclerosis.

INTRODUCTION: Microangiopathy and endothelial dysfunction are present in the early stages of systemic sclerosis (SSc). Defective vasculogenesis mediated by bone marrow-derived endothelial progenitor cells (EPCs) might be involved in the vascular abnormalities found in SSc. OBJECTIVES: To evaluate the circulating EPC levels and EPC subtypes via flow cytometry and early outgrowth colony-forming units (CFUs) in patients with SSc compared to healthy subjects. METHODS: Thirty-nine female SSc patients (30 in the early stages of SSc) and 44 age-matched healthy women were included. Peripheral blood EPCs were quantified using flow cytometry and by counting the early outgrowth CFUs. RESULTS: The EPCs quantified with flow cytometry and the CFU numbers were significantly lower in SSc patients than in control subjects (155.1 ± 95.1 vs. 241.3 ± 184.2 EPC/10(6) lymphomononuclear cells, p=0.011; 15.4 ± 8.6 vs. 23.5 ± 10.9 CFU, p<0.001; respectively), as well as in the group of patients in the early stages of SSc compared to the controls. Patients with digital ulcers had significantly higher CFU counts than those without ulcers (p=0.013). Among patients with the scleroderma pattern on nailfold capillaroscopy, patients with the late pattern had significantly lower EPC levels than those with the early and active patterns (p=0.046). There were no significant correlations of EPCs or CFU levels with RP duration. CONCLUSIONS: The present study revealed decreased EPCs in SSc patients, including those with early disease onset. These findings suggest that defective vasculogenesis occurs in the early phases of the disease. Therefore, EPCs might be an important therapeutic target for the prevention of vascular complications in SSc patients.

Laser Doppler imaging for assessment of microcirculation in juvenile systemic sclerosis.

OBJECTIVES: The objectives of this study were to evaluate the dynamic behaviour of digital skin microvascular blood flow before and after cold stimulation using laser Doppler imaging (LDI) in children and adolescents with RP secondary to juvenile systemic sclerosis (JSS), primary RP (PRP) and healthy controls and to compare functional abnormalities measured by LDI with structural microvascular abnormalities evaluated by nailfold capillaroscopy (NFC). METHODS: Five JSS patients, five children and adolescents with PRP and five healthy controls matched for gender and age were included. All subjects had NFC performed. Finger blood flow (FBF) was measured using the LDI system (Moor Instruments) at baseline and after cold stimulus (CS). RESULTS: There were a decreased number of capillaries, a greater number of enlarged capillaries and a higher deletion score in JSS patients compared with controls and patients with PRP. The mean baseline FBF was significantly lower in JSS patients compared with controls. There was no difference between the mean baseline FBF in JSS patients compared with patients with PRP. There was a significant decrease in FBF 1 min after CS in all groups followed by blood flow recovery at 20 min after CS in comparison with basal FBF values in controls, but not in JSS and PRP patients. CONCLUSION: In JSS patients, LDI showed a lower FBF before and after CS compared with healthy controls and may be an objective and sensitive method for the measurement of digital skin blood flow in RP children.

2023 Brazilian Society of Rheumatology guidelines for the treatment of systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. METHODS: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. RESULTS: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud's phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. CONCLUSION: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.

Safety of CoronaVac and ChAdOx1 vaccines against SARS-CoV-2 in patients with rheumatoid arthritis: data from the Brazilian multicentric study safer.

BACKGROUND: Patients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with associated comorbidities. However, few studies have assessed the safety of the COVID-19 vaccine in patients with RA. OBJECTIVE: To evaluate the safety of vaccines against SARS-CoV-2 in patients with RA. METHODS: This data are from the study "Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases," a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 (Oxford/AstraZeneca) or CoronaVac (Sinovac/Butantan). Stratification of postvaccination AEs was performed using a diary, filled out daily and returned at the end of 28 days for each dose. RESULTS: A total of 188 patients with RA were include, 90% female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed, mainly after the first dose. The most common AEs after the first dose were pain at the injection (46,7%), headache (39,4%), arthralgia (39,4%), myalgia (30,5%) and fatigue (26,6%), and ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0.001) arthralgia (62% vs 22%, p < 0.001) and myalgia (45% vs 20%, p < 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection (37%), arthralgia (31%), myalgia (23%), headache (21%) and fatigue (18%). Arthralgia (41,4% vs 25%, p = 0.02) and pain at injection (51,4% vs 27%, p = 0.001) were more common with ChAdOx1. No serious AEs were related. With Regard to RA activity level, no significant difference was observed between the three time periods for both COVID-19 vaccines. CONCLUSION: In the comparison between the two immunizers in patients with RA, local reactions and musculoskeletal symptoms were more frequent with ChAdOx1 than with CoronaVac, especially after the first dose. In summary, the AE occurred mainly after the first dose, and were mild, like previous data from others immunizing agents in patients with rheumatoid arthritis. Vaccination did not worsen the degree of disease activity.

Nailfold capillaroscopy abnormalities as predictors of mortality in patients with systemic sclerosis.

OBJECTIVES: Peripheral microangiopathy is a hallmark of systemic sclerosis (SSc) and can be early detected by nailfold capillaroscopy (NFC). This study aimed to examine whether more severe peripheral microangiopathy at NFC are predictive factor for death in SSc patients. METHODS: 135 SSc patients who performed NFC between June 2001 and July 2009 were included. The following NFC parameters were evaluated: number of capillary loops/mm, avascular score (scored from 0 to 3), and number of enlarged and giant capillary loops. Univariate and multivariate regression models were used to analyse the association of mortality with NFC and clinical parameters. RESULTS: At the time of the analysis (August 2010), 123 patients were alive, and 12 were dead. By univariate analysis, male gender, forced vital capacity <75% predicted, higher number of giant capillary loops, and an avascular score >1.5 on NFC were associated with a significantly increase risk of death. By multivariate analysis, an avascular score >1.5 was the only independent predictor of death (hazard ratio 2.265). Survival rates from diagnosis at 1, 5 and 10 years were lower in patients with avascular score >1.5 (97%, 86%, and 59%, respectively) compared with those with avascular score ≤1.5 (97%, 97%, and 91% respectively) (p=0.009 by log rank test). CONCLUSIONS: Avascular scores higher than 1.5 at NFC was an independent predictor of death in SSc, suggesting that NFC can be useful for predicting SSc outcome.

Treatment of early diffuse systemic sclerosis skin disease.

Diffuse systemic sclerosis carries a high morbidity and mortality. The Prospective Registry of Early Systemic Sclerosis (PRESS), a multicentre incident cohort study of patients with early diffuse cutaneous systemic sclerosis, has the goal of advancing the understanding of disease pathogenesis and identifying novel biomarkers. In this review, PRESS investigators discuss the evidence pertaining to the more commonly used treatments for early diffuse SSc skin disease including methotrexate, mycophenolate, cyclophosphamide, azathioprine, and intravenous immunoglobulin. This review highlights the unmet need for effective treatment in early diffuse SSc as well as its more rigorous study. Nonetheless, the PRESS investigators aim to decrease intra- and inter-institutional variability in prescribing in order to improve the understanding of the clinical course of early diffuse SSc skin disease.

Treatment of Inflammatory Arthritis in Systemic Sclerosis.

Joint involvement, including arthralgia, inflammatory arthritis, joint contractures and overlapping with rheumatoid arthritis, is a common manifestation and is associated with impared quality of life in systemic sclerosis (SSc). Few studies have evaluated the treatment of arthritis in SSc. Pharmacological approach includes low-dose corticosteroids, methotrexate, and hydroxychloroquine. Non-tumor necrosis factor biologics, especially rituximab and tocilizumab, may be a promising option for refractory cases.

Microparticles: potential new contributors to the pathogenesis of systemic sclerosis?

BACKGROUND: Microparticles (MPs) are membrane-derived vesicles released from cells undergoing activation or apoptosis with diverse proinflammatory and prothrombotic activities, that have been implicated in the pathogenesis of systemic sclerosis (SSc). We aimed to evaluate the plasma levels of platelet-derived microparticles (PMPs), endothelial cell-derived microparticles (EMPs), and monocyte-derived microparticles (MMPs) in SSc patients, and the association between MPs and the clinical features of SSc. METHODS: In this cross-sectional study, 70 patients with SSc and 35 age- and sex-matched healthy controls were evaluated. Clinical and nailfold capillaroscopy (NFC) data were obtained from all patients. Plasma levels of PMPs (CD42+/31+), EMPs (CD105+), and MMPs (CD14+) were quantified by flow cytometry. RESULTS: Patients were mainly females (90%), with a mean age of 48.9 years old. PMP, EMP, and MMP levels were significantly increased in SSc patients compared to controls (79.2% ± 17.3% vs. 71.0% ± 19.8%, p = 0.033; 43.5% ± 8.7% vs. 37.8% ± 10.4%, p = 0.004; and 3.5% ± 1.3% vs. 1.1% ± 0.5%, p < 0.0001, respectively). PMP levels were significantly higher in patients with positive anti-topoisomerase-I antibodies (p = 0.030) and in patients with a disease duration > 3 years (p = 0.038). EMP levels were lower in patients with a higher modified Rodnan skin score (p = 0.015), and in those with an avascular score > 1.5 in NFC (p = 0.042). CONCLUSION: The increased levels of PMPs, EMPs and MMPs in scleroderma patients might indicate a possible role for these agents in the pathogenesis of this challenging disease.

Peripheral Microvascular Abnormalities Associated with Open-Angle Glaucoma.

PURPOSE: To investigate peripheral microvascular abnormalities associated with patients with open-angle glaucoma (OAG). DESIGN: This was a cross-sectional study. PARTICIPANTS: Patients with OAG and controls. METHODS: All subjects underwent detailed ophthalmic evaluation, including Humphrey visual field (HVF) tests and swept source OCT. To evaluate peripheral microvascular abnormalities, nailfold capillaroscopy (NFC) and laser Doppler imaging (LDI) were performed. The presence of microhemorrhages, tortuous capillaries, dilated capillaries, avascular areas, and the capillary density, among other characteristics, were recorded using NFC; fingertip blood flow (FBF) was measured using LDI at different time points, before and 1, 10, and 20 minutes after exposure to a cold stimulus. In addition, venous blood samples were collected to measure serum endothelin-1 (ET-1) concentrations as well as serum autoantibodies. MAIN OUTCOME MEASURES: Presence of microhemorrhages, tortuous capillaries, and dilated capillaries; FBF; ET-1; and autoantibodies. RESULTS: Sixty-eight subjects (43 patients with OAG and 25 controls) were enrolled in the study. Microhemorrhages were found in the nail bed of 65.1% of the patients with OAG compared with 25.0% of the controls (P = 0.003). There was a significant difference in the mean FBF at the baseline in patients with OAG versus controls (293.6 ± 100.2 vs 388.8 ± 52.0 perfusion units, respectively, P < 0.001), together with a significant decrease in the mean FBF 10 and 20 minutes after cold stimulus in patients with OAG in comparison to controls (P < 0.001 for all comparisons). There was a positive correlation between mean baseline FBF and HVF mean deviation (r = 0.27, P = 0.03) and between mean baseline FBF and average retinal nerve fiber layer thickness (r = 0.44, P = 0.001). Neither the analysis of ET-1 concentrations (P= 0.71) nor the autoantibodies measurements (P > 0.05, for all) showed any difference between the 2 groups. CONCLUSIONS: Significant peripheral microvascular abnormalities were found in patients with OAG compared to controls, suggesting that microvascular changes might play a role in the pathogenesis of the disease. In addition, part of these peripheral microvascular abnormalities seems to be correlated with both functional and structural glaucomatous damage. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Vascular parameters and endothelin-1 measurements in glaucoma patients with low- and high-tension optic disc hemorrhages.

This prospective study aimed to compare vascular parameters (endothelin-1 [ET-1] blood levels, laser Doppler imaging [LDI] of distal phalanxes, and nailfold capillaroscopy) between open-angle glaucoma patients with low- and high-tension optic disc hemorrhages (LTDH and HTDH, respectively). The 33 enrolled patients (mean age, 62.3 ± 13 years) were classified as LTDH or HTDH if they presented at the time of DH detection an intraocular pressure (IOP) < 16 mmHg or ≥ 16 mmHg, respectively. Demographic and ophthalmological data, ET-1 concentrations, LDI (before and 1, 10, and 20 min after cold stimulation), and nailfold capillaroscopy findings were evaluated. The ET-1 blood level was 65% higher in the LTDH (2.27 ± 1.46 pg/ml) than in the HTDH (1.37 ± 0.57 pg/ml; p = 0.03) group. Moreover, there was a statistically significant negative correlation between ET-1 blood concentration and IOP at the time of DH detection (r = -0.45, p = 0.02). Blood flow measurements 10 and 20 min after cold stimulation were lower in the LTDH group than in the HTDH group (p < 0.01). Patients developing DH with lower IOPs have higher ET-1 blood levels and more peripheral vascular dysfunction as estimated by LDI than those with higher IOPs. These findings suggest that distinct underlying mechanisms may be involved in patients developing DH within different IOP ranges.

The Role of Autoantibody Testing in Modern Personalized Medicine.

Personalized medicine (PM) aims individualized approach to prevention, diagnosis, and treatment. Precision Medicine applies the paradigm of PM by defining groups of individuals with akin characteristics. Often the two terms have been used interchangeably. The quest for PM has been advancing for centuries as traditional nosology classification defines groups of clinical conditions with relatively similar prognoses and treatment options. However, any individual is characterized by a unique set of multiple characteristics and therefore the achievement of PM implies the determination of myriad demographic, epidemiological, clinical, laboratory, and imaging parameters. The accelerated identification of numerous biological variables associated with diverse health conditions contributes to the fulfillment of one of the pre-requisites for PM. The advent of multiplex analytical platforms contributes to the determination of thousands of biological parameters using minute amounts of serum or other biological matrixes. Finally, big data analysis and machine learning contribute to the processing and integration of the multiplexed data at the individual level, allowing for the personalized definition of susceptibility, diagnosis, prognosis, prevention, and treatment. Autoantibodies are traditional biomarkers for autoimmune diseases and can contribute to PM in many aspects, including identification of individuals at risk, early diagnosis, disease sub-phenotyping, definition of prognosis, and treatment, as well as monitoring disease activity. Herein we address how autoantibodies can promote PM in autoimmune diseases using the examples of systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, Sjögren syndrome, systemic sclerosis, idiopathic inflammatory myopathies, autoimmune hepatitis, primary biliary cholangitis, and autoimmune neurologic diseases.