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Introduction: Endothelial progenitor cells (EPCs) are essential for maintenance of vascular homeostasis and stability, key processes in the pathogenesis of systemic lupus erythematosus (SLE). However, the role and phenotypic characterization of EPCs populations in SLE have not been completely elucidated., Objective: To identify EPCs specific subpopulations in patients with SLE using a novel flow cytometry tool., Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SLE and healthy controls (HC). mRNA and surface protein expression were determined by quantitative PCR (qPCR) and flow cytometry. Clusters identification and characterization were performed using tSNE-CUDA dimensionality reduction algorithms., Results: tSNE-CUDA analysis identified eight different clusters in PBMCs from HC and patients with SLE. Three of these clusters had EPC-like phenotype and the expression was elevated in patients with SLE. Moreover, four SLE-associated subclusters were found mainly expressed in patients with SLE, being only present in patients in remission with SLE and significantly associated with the 2021 Definition of Remission in SLE. Importantly, we also identified specific clusters in SLE patients with organ damage, according to the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology damage index (SDI). These clusters showed an EPC-like phenotype, but the expression of angiogenic markers was lower compared to HC or patients without organ damage, suggesting an impaired angiogenic function., Conclusion: Our novel approach identified clusters of EPCs in patients with SLE that are associated with remission and damage. Therefore, these clusters might be useful biomarkers to predict disease progression and severity in SLE pathogenesis., (© 2024. The Author(s).)

Immobilizing different enzymes on membranes can result in biocatalytic active membranes with a self-cleaning capacity toward a complex mixture of foulants. The membrane modification can reduce fouling and enhance filtration performance. Protease, lipase, and amylase were immobilized on poly(vinylidene fluoride) (PVDF) microfiltration membranes using a polydopamine coating in a one-step method. The concentrations of polydopamine precursor and enzymes were optimized during the immobilization. The higher hydrolytic activities were obtained using 0.2 mg/mL of dopamine hydrochloride and 4 mg/mL of enzymes: 0.90 mg starch /min·cm 2 for amylase, 10.16 nmol tyrosine /min·cm 2 for protease, and 20.48 µmol p-nitrophenol /min·cm 2 for lipase. Filtration tests using a protein, lipid, and carbohydrate mixture showed that the modified membrane retained 41%, 29%, and 28% of its initial water permeance (1808 ± 39 L/m 2 ·h·bar) after three consecutive filtration cycles, respectively. In contrast, the pristine membrane (initial water permeance of 2016 ± 40 L/m 2 ·h·bar) retained only 23%, 12%, and 8%. Filtrations of milk powder solution were also performed to simulate dairy industry wastewater: the modified membrane maintained 28%, 26%, and 26% of its initial water permeance after three consecutive filtration cycles, respectively, and the pristine membrane retained 34%, 21%, and 7%. The modified membrane showed increased fouling resistance against a mixture of foulants and presented a similar water permeance after three cycles of simulated dairy wastewater filtration. Membrane fouling is reduced by the immobilized enzymes through two mechanisms: increased membrane hydrophilicity (evidenced by the reduced water contact angle after modification) and the enzymatic hydrolysis of foulants as they accumulate on the membrane surface.

Background: Recent guidelines on acute coronary syndromes (ACS) recommend initiating lipid-lowering therapy (LLT) as early as possible to obtain >50% low-density-lipoprotein cholesterol (LDL-c) reduction and an LDL-c < 1.4 mmol/l., Methods: A multinational European survey study of ACS patients between 2021-2022 and acquired data on LLT and lipid levels on admission and during 1-year posthospitalization. We compared plasma lipid changes and adherence to post-ACS lipid targets across two in-hospital LLT groups: high-intensity statin (HIS) monotherapy (mono-HIS) and a combination of HIS and ezetimibe (combo-HIS)., Results: Of 286 patients, 268 (94%) received in-hospital HIS and were included in the final analysis. Patients (median age: 61.1 years) had a median baseline LDL-c of 3.3 mmol/l. Mono-HIS was the predominant in-hospital LLT (72.4%). In-hospital combo-HIS was administered in 27.6% of the cases. Patients from high-income countries (n = 141) were more likely to receive in-hospital combo-HIS than patients from middle-income countries [n = 127; 38.3% vs. 15.7% patients, P < 0.001). One-year post-ACS, 50 (26.5%) patients from the mono-HIS group received ezetimibe. The target of LDL-c ≤ 55 mg/dl was reached in 85 patients (31.7%), without significant difference between study groups [mono-HIS: 56 (28.9%) and combo-HIS: 29 (39.2%) patients, P = 0.10]. The target of >50% reduction was achieved more frequently among the combo-HIS group than in the mono-HIS group (50.0% vs. 29.9%, respectively, P = 0.002)., Conclusion: LDL-c targets were achieved in less than half of the patients post-ACS, regardless of the LLT regimen. Combo-HIS was initiated in-hospital post-ACS in only 28% and was associated with greater LDL-c reduction compared to a staged approach of mono-HIS with up-titration at follow-up., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Previous works from our group show that Semaphorin3B (Sema3B) is reduced in RA and plays a protective role in a mouse arthritis model. In turn, MerTK plays a protective function in murine arthritis models, is expressed by synovial tissue macrophages and is linked to remission in patients with RA. In this study, we examined the role of Sema3B in the phenotypic characteristics of RA macrophages and the implication of MerTK. Peripheral blood monocytes from RA patients were differentiated into IFN-γ (RA MØ IFN-γ ) or M-CSF (RA MØ M-CSF ) macrophages and stimulated with LPS, Sema3B or their combination. Alternatively, RA fibroblast like synoviocytes (FLS) were stimulated with RA MØ IFN-γ and RA MØ M-CSF supernatants. Gene expression was determined by qPCR and protein expression and activation by flow cytometry, ELISA and western blot. Sema3B down-regulated the expression of pro-inflammatory mediators, in both RA MØ IFN-γ and RA MØ M-CSF . We observed a similar reduction in RA FLS stimulated with the supernatant of Sema3B-treated RA MØ IFN-γ and RA MØ M-CSF . Sema3B also modulated cell surface markers in macrophages towards an anti-inflammatory phenotype. Besides, MerTK expression and activation was up-regulated by Sema3B, just as GAS6 expression, Resolvin D1 secretion and the phagocytic activity of macrophages. Importantly, the inhibition of MerTK and neuropilins 1 and 2 abrogated the anti-inflammatory effect of Sema3B. Our data demonstrate that Sema3B modulates the macrophage characteristics in RA, inducing a skewing towards an anti-inflammatory/pro-resolving phenotype in a MerTK-dependant manner. Therefore, here we identify a new mechanism supporting the protective role of Sema3B in RA pathogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martínez-Ramos, Rafael-Vidal, Malvar-Fernández, Pérez, Mouriño, Pérez, Maceiras Pan, Conde, Pego-Reigosa and García.)

Endothelial cell (EC) dysfunction is a hallmark of Systemic Lupus Erythematosus (SLE) and Tie2 is a receptor essential for vascular stability. Inflammatory processes promote inhibition of Tie2 homeostatic activation, driving vascular dysfunction. In this work we determined whether type I Interferons (IFN) induce Tie2 signalling-mediated endothelial dysfunction in patients with SLE. Serum levels of Angiopoietin (Ang)-1, Ang-2 and soluble (s)Tie1 in patients with SLE and healthy controls were measured by ELISA. Monocytes from patients with SLE and Human Umbilical Vein EC (HUVEC) were stimulated with IFN-α, IFN-β (1000 I.U.) or SLE serum (20%). mRNA and protein expression, phosphorylation and translocation were determined by quantitative PCR, ELISA, Western Blot, flow cytometry and confocal microscopy. Viability and angiogenic capacity were determined by calcein and tube formation assays. We found that sTie1 and Ang-2 serum levels were increased and Ang-1 decreased in patients with SLE and were associated with clinical characteristics. Type I IFN significantly decreased Ang-1 and increased Ang-2 in monocytes from patients with SLE. Type I IFN increased sTie1 and Ang-2 secretion and reduced Tie2 activation in HUVEC. Functionally, type I IFN significantly reduced EC viability and impaired angiogenesis in a Tie2 signalling-dependent manner. Finally, SLE serum increased Ang-2 and sTie1 secretion and significantly decreased tube formation. Importantly, Tie1 and IFNAR1 knockdown reversed these effects in tube formation. Overall, type I IFN play an important role in the stability of EC by inhibiting Tie2 signalling, suggesting that these processes may be implicated in the cardiovascular events observed in patients with SLE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rafael-Vidal, Martínez-Ramos, Malvar-Fernández, Altabás-González, Mouriño, Veale, Floudas, Fearon, Reigosa and García.)

Background: Tumor budding (TB) has been investigated in several types of solid tumors. In oral cancer, studies show its association with survival. However, for its implementation in routine histological analyses, results with a high certainty of evidence are needed. Therefore, the aim of this systematic review is to explore the association between tumor budding and overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in oral cancer., Methods: A search was performed in Embase, PubMed, Scopus, Livivo, Web of Science, and Google Scholar. We adopted the following inclusion criteria: studies that evaluate tumor budding in oral cancer, that investigate survival, and presenting cohort design. We excluded reviews and studies without hazard-ratio (HR) data., Results: This systematic review included 22 studies and showed an association between TB and survival. High-grade TB is associated with a worse OS in univariate analysis (HR = 3.11; 95% CI: 2.06-4.69, p<0.01) and multivariate analysis (HR = 2.62; 95% CI: 1.64-4.20, p<0.01); with a poorer DSS in univariate (HR = 2.43; 95% CI: 1.94-3.03, p<0.01) and multivariate analysis (HR = 2.01; 95% CI: 1.43-2.83, p< 0.01); and with a worse DFS in univariate (HR = 1.94; 95% CI: 1.44-2.62, p<0.01) and multivariate analysis (HR = 2.15; 95% CI: 1.31-3.53, p< 0.01). Sensitivity analysis showed that the results are robust, and no significant publication bias was identified in univariate analysis for DFS (Egger's test: p = 0.94). The certainty of the evidence was graded as low or very low., Conclusion: Our findings indicate that TB is an independent prognostic factor of OS, DSS, and DFS in oral cancer. However, further studies are needed to increase the certainty of the evidence.

Objective: Class 3 semaphorins are reduced in the synovial tissue of RA patients and these proteins are involved in the pathogenesis of the disease. The aim of this study was to identify the transcription factors involved in the expression of class 3 semaphorins in the synovium of RA patients., Methods: Protein and mRNA expression in synovial tissue from RA and individuals at risk (IAR) patients, human umbilical vein endothelial cells (HUVEC) and RA fibroblast-like synoviocytes (FLS) was determined by ELISA, immunoblotting and quantitative PCR. TCF-3, EBF-1 and HOXA5 expression was knocked down using siRNA. Cell viability, migration and invasion were determined using MTT, calcein, wound closure and invasion assays, respectively., Results: mRNA expression of all class 3 semaphorins was significantly lower in the synovium of RA compared with IAR patients. In silico analysis suggested TCF-3, EBF-1 and HOXA5 as transcription factors involved in the expression of these semaphorins. TCF-3, EBF-1 and HOXA5 silencing significantly reduced the expression of several class 3 semaphorin members in FLS and HUVEC. Importantly, HOXA5 expression was significantly reduced in the synovium of RA compared with IAR patients and was negatively correlated with clinical disease parameters. Additionally, TNF-α down-regulated the HOXA5 expression in FLS and HUVEC. Finally, HOXA5 silencing enhanced the migratory and invasive capacities of FLS and the viability of HUVEC., Conclusion: HOXA5 expression is reduced during the progression of RA and could be a novel therapeutic strategy for modulating the hyperplasia of the synovium, through the regulation of class 3 semaphorins expression., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: Semaphorin 3B (Sema3B) decreases the migratory and invasive capacities of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) and suppresses expression of matrix metalloproteinases. We undertook this study to examine the role of Sema3B in a mouse model of arthritis and its expression in RA patients., Methods: Clinical responses, histologic features, and FLS function were examined in wild-type (WT) and Sema3B -/- mice in a K/BxN serum transfer model of arthritis. Protein and messenger RNA expression of Sema3B in mouse joints and murine FLS, as well as in serum and synovial tissue from patients with arthralgia and patients with RA, was determined using enzyme-linked immunosorbent assay, immunoblotting, quantitative polymerase chain reaction, and RNA sequencing. FLS migration was determined using a wound closure assay., Results: The clinical severity of serum-induced arthritis was significantly higher in Sema3B -/- mice compared to WT mice. This was associated with increased expression of inflammatory mediators and increased migratory capacity of murine FLS. Administration of recombinant mouse Sema3B reduced the clinical severity of serum-induced arthritis and the expression of inflammatory mediators. Sema3B expression was significantly lower in the synovial tissue and serum of patients with established RA compared to patients with arthralgia. Serum Sema3B levels were elevated in patients with arthralgia that later progressed to RA, but not in those who did not develop RA; however, these levels drastically decreased 1 and 2 years after RA development., Conclusion: Sema3B expression plays a protective role in a mouse model of arthritis. In RA patients, expression levels of Sema3B in the serum depend on the disease stage, suggesting different regulatory roles in disease onset and progression., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To assess survival and success rates of dental implants and the occurrence of peri-implant diseases (mucositis/peri-implantitis) in HIV-1-infected individuals., Material and Methods: In this prospective study, 13 HIV-1-infected individuals undergoing highly active antiretroviral therapy (with undetectable plasma HIV RNA levels, and CD4+ T cells > 350/mm 3 ) were followed after implant placement, as well as 13 non-HIV-1-infected matched controls. Patients enrolled in this study were followed up to 120 months (mean = 40.6 months; standard deviation = 22.2; range 18 -120 months). Twenty-five implants were placed in pristine healed sites for each group and bone augmentation procedures, when needed, were done only for contour augmentation. Patients were enrolled in a strict periodontal/peri-implant supportive therapy protocol with three recalls per year. The two groups were compared regarding subject-level characteristics (age, gender, smoking, diabetes) and implant-level characteristics (marginal bone level, peri-implant health status)., Results: All the implants healed uneventfully and reached 100% survival rates (after at least 18 months) in both groups. There were no significant differences between groups for peri-implant diseases (mucositis/peri-implantitis) and for all subject-level co-variables (p > .05). Only the variables dental implant prosthesis type (DIPT) (p = .021, d = .86) and follow up (p = .011, d = .77) showed statistically significant differences between groups., Conclusion: The findings suggest that well-controlled HIV-1-infected individuals are eligible to undergo implant therapy, achieving survival and success rates comparable to non-HIV-1-infected controls., (© 2021 Special Care Dentistry Association and Wiley Periodicals LLC.)

Spondyloarthritis (SpA) is a family of chronic inflammatory diseases, being the most prevalent ankylosing spondylitis (AS) and psoriatic arthritis (PsA). These diseases share genetic, clinical and immunological features, such as the implication of human leukocyte antigen (HLA) class I molecule 27 (HLA-B27), the inflammation of peripheral, spine and sacroiliac joints and the presence of extra-articular manifestations (psoriasis, anterior uveitis, enthesitis and inflammatory bowel disease). Monocytes and macrophages are essential cells of the innate immune system and are the first line of defence against external agents. In rheumatic diseases including SpA, the frequency and phenotypic and functional characteristics of both cell types are deregulated and are involved in the pathogenesis of these diseases. In fact, monocytes and macrophages play key roles in the inflammatory processes characteristics of SpA. The aim of this review is analysing the characteristics and functional roles of monocytes and macrophages in these diseases, as well as the impact of different current therapies on these cell types.

Aim: To assess intraocular pressure (IOP) during the daily curve of intraocular pressure (DCPo) in keratoconic eyes and compare Goldmann applanation tonometer (GAT), without and with astigmatism correction (nGAT and cGAT) and Tono-Pen AVIA (TPA) assessment methods., Methods: Thirty-nine keratoconic eyes of 24 patients were assessed. DCPo was evaluated with five IOP measurements; four were performed with a GAT (nGAT and cGAT), and a Tono-Pen AVIA (TPA) at various times throughout the day., Results: Mean IOP DCPo values (mm Hg) were: nGAT, 9.9±2.6; cGAT, 11.3±2.6; TPA 12.3±3.1. Mean IOP DCPo differences (mm Hg) and Spearman's correlation coefficients were as follows: cGATc-nGAT, 1.32±1.31, r s =0.879 ( P <0.01); cGAT-TPA, -1.02±2.08, r s =0.723 ( P <0.01); and nGAT-TPA, -2.35±2.23, r s =0.730 ( P <0.01). Bland-Altman analysis for agreement between cGAT-TPA and nGAT-TPA mean IOP DCPo measurements revealed a mean difference of 1.02 (95%CI, 0.35-1.70) and 2.35 (95%CI, 1.62-3.07) mm Hg, respectively. Regression analysis yielded the following equation: TPA IOP=5.49+0.775×cGAT-0.015×ACD-0.299×corneal astig matism, which allowed us to infer TPA IOP values from other parameters., Conclusion: In keratoconic eyes, IOP peaks of DCPo measurements are identified at 6 a.m. , independent of the tonometer. The mean DCPo values are: TPA>cGAT>nGAT. IOP TPA measures are predictive of cGAT values, adjusted according to anterior chamber depth and corneal astigmatism., (International Journal of Ophthalmology Press.)

Immune system CD4 T-cells with high cell-surface CD26 expression show anti-tumoral properties. When engineered with a chimeric antigen receptor (CAR), they incite strong responses against solid cancers. This subset was originally associated to human CD4 T helper cells bearing the CD45R0 effector/memory phenotype and later to Th17 cells. CD26 is also found in soluble form (sCD26) in several biological fluids, and its serum levels correlate with specific T cell subsets. However, the relationship between glycoprotein sCD26 and its dipeptidyl peptidase 4 (DPP4) enzymatic activity, and cell-surface CD26 expression is not well understood. We have studied ex vivo cell-surface CD26 and in vitro surface and intracellular CD26 expression and secretome's sCD26 in cultured CD4 T cells under different polarization conditions. We show that most human CD26negative CD4 T cells in circulating lymphocytes are central memory (T CM ) cells while CD26high expression is present in effector Th1, Th2, Th17, and T EM (effector memory) cells. However, there are significant percentages of Th1, Th2, Th17, and Th22 CD26 negative cells. This information may help to refine the research on CAR-Ts. The cell surface CD45R0 and CD26 levels in the different T helper subsets after in vitro polarization resemble those found ex vivo. In the secretomes of these cultures there was a significant amount of sCD26. However, in all polarizations, including Th1, the levels of sCD26 were lower (although not significantly) compared to the Th0 condition (activation without polarization). These differences could have an impact on the various physiological functions proposed for sCD26/DPP4.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a broad spectrum of clinical presentations that can affect almost all organ systems. Lupus nephritis (LN) is a severe complication that affects approximately half of the systemic erythematosus lupus (SLE) patients, which significantly increases the morbidity and the mortality risk. LN is characterized by the accumulation of immune complexes, ultimately leading to renal failure. Aberrant activation of T cells plays a critical role in the pathogenesis of both SLE and LN and is involved in the production of inflammatory cytokines, the recruitment of inflammatory cells to the affected tissues and the co-stimulation of B cells. Calcineurin is a serine-threonine phosphatase that, as a consequence of the T cell hyperactivation, induces the production of inflammatory mediators. Moreover, calcineurin is also involved in the alterations of the podocyte phenotype, which contribute to proteinuria and kidney damage observed in LN patients. Therefore, calcineurin inhibitors have been postulated as a potential treatment strategy in LN, since they reduce T cell activation and promote podocyte cytoskeleton stabilization, both being key aspects in the development of LN. Here, we review the role of calcineurin in SLE and the latest findings about calcineurin inhibitors and their mechanisms of action in the treatment of LN., Competing Interests: The authors declare no conflict of interest.

Angiopoietin-2 (Ang-2), a ligand of the tyrosine kinase receptor Tie2, is essential for vascular development and blood vessel stability and is also involved in monocyte activation. Here, we examined the role of Ang-2 on monocyte activation in patients with systemic sclerosis (SSc). Ang-2 levels were measured in serum and skin of healthy controls (HCs) and SSc patients by ELISA and array profiling, respectively. mRNA expression of ANG2 was analyzed in monocytes, dermal fibroblasts, and human pulmonary arterial endothelial cells (HPAECs) by quantitative PCR. Monocytes were stimulated with Ang-2, or with serum from SSc patients in the presence of a Tie2 inhibitor or an anti-Ang2 neutralizing antibody. Interleukin (IL)-6 and IL-8 production was analyzed by ELISA. Ang-2 levels were elevated in the serum and skin of SSc patients compared to HCs. Importantly, serum Ang-2 levels correlated with clinical disease parameters, such as skin involvement. Lipopolysaccharide (LPS) LPS, R848, and interferon alpha2a (IFN-α) stimulation up-regulated the mRNA expression of ANG2 in monocytes, dermal fibroblasts, and HPAECs. Finally, Ang-2 induced the production of IL-6 and IL-8 in monocytes of SSc patients, while the inhibition of Tie2 or the neutralization of Ang-2 reduced the production of both cytokines in HC monocytes stimulated with the serum of SSc patients. Therefore, Ang-2 induces inflammatory activation of SSc monocytes and neutralization of Ang-2 might be a promising therapeutic target in the treatment of SSc.

Systemic rheumatic diseases are a heterogeneous group of autoimmune disorders that affect the connective tissue, characterized by the involvement of multiple organs, leading to disability, organ failure and premature mortality. Despite the advances in recent years, the therapeutic options for these diseases are still limited and some patients do not respond to the current treatments. Interleukin-17 (IL-17) is a cytokine essential in the defense against extracellular bacteria and fungi. Disruption of IL-17 homeostasis has been associated with the development and progression of rheumatic diseases, and the approval of different biological therapies targeting IL-17 for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) has highlighted the key role of this cytokine. IL-17 has been also implicated in the pathogenesis of systemic rheumatic diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome (SS) and systemic sclerosis (SSc). The aim of this review is to summarize and discuss the most recent findings about the pathogenic role of IL-17 in systemic rheumatic and its potential use as a therapeutic option.

Semaphorin (Sema)4A is a transmembrane glycoprotein that is elevated in several autoimmune diseases such as systemic sclerosis, rheumatoid arthritis and multiple sclerosis. Sema4A has a key role in the regulation of Thelper Th1 and Th2 differentiation and we recently demonstrated that CD4 + T cell activation induces the expression of Sema4A. However, the autocrine role of Sema4A on Th cell differentiation remains unknown. Naïve Th cells from healthy controls were cell sorted and differentiated into Th1, Th2 and Th17 in the presence or absence of a neutralizing antibody against the Sema4A receptor PlexinD1. Gene expression was determined by quantitative PCR and protein expression by ELISA and flow cytometry. We found that the expression of Sema4A is induced during Th1, Th2 and Th17 differentiation. PlexinD1 neutralization induced the differentiation of Th1 cells, while reduced the Th2 and Th17 skewing. These effects were associated with an upregulation of the transcription factor T-bet by Th1 cells, and to downregulation of GATA3 and RORγt in Th2 cells and Th17 cells, respectively. Finally, PlexinD1 neutralization regulates the systemic sclerosis patients serum-induced cytokine production by CD4 + T cells. Therefore, the autocrine Sema4A-PlexinD1 signaling acts as a negative regulator of Th1 skewing but is a key mediator on Th2 and Th17 differentiation, suggesting that dysregulation of this axis might be implicated in the pathogenesis of CD4 + T cell-mediated diseases.

Aims: The prognostic impact of heart rate (HR) in acute heart failure (AHF) patients is not well known especially in atrial fibrillation (AF) patients. The aim of the study was to evaluate the impact of admission HR, discharge HR, HR difference (admission-discharge) in AHF patients with sinus rhythm (SR) or AF on long- term outcomes., Methods: We included 1398 patients consecutively admitted with AHF between October 2013 and December 2014 from a national multicentre, prospective registry. Logistic regression models were used to estimate the association between admission HR, discharge HR and HR difference and one- year all-cause mortality and HF readmission., Results: The mean age of the study population was 72 ± 12 years. Of these, 594 (42.4%) were female, 655 (77.8%) were hypertensive and 655 (46.8%) had diabetes. Among all included patients, 745 (53.2%) had sinus rhythm and 653 (46.7%) had atrial fibrillation. Only discharge HR was associated with one year all-cause mortality (Relative risk (RR) = 1.182, confidence interval (CI) 95% 1.024-1.366, p = 0.022) in SR. In AF patients discharge HR was associated with one year all cause mortality (RR = 1.276, CI 95% 1.115-1.459, p ≤ 0.001). We did not observe a prognostic effect of admission HR or HRD on long-term outcomes in both groups. This relationship is not dependent on left ventricular ejection fraction., Conclusions: In AHF patients lower discharge HR, neither the admission nor the difference, is associated with better long-term outcomes especially in AF patients., Competing Interests: We declare that we have no conflict of interest., (© 2019 The Authors.)

Introduction: The aim of this study was to evaluate the effectiveness of peracetic acid (PAA) in cleaning root canals contaminated with Enterococcus faecalis., Methods: Sixty first and second mandibular molars were used. Their mesiobuccal canals were prepared with the Reciproc System (VDW, Munich, Germany). The canals were irrigated with 10 mL saline during instrumentation. The teeth were randomly divided into 3 groups (n = 20), according to the irrigation solution to be used after instrumentation: group PAA (5 mL 1% PAA), group EDTA/sodium hypochlorite (NaOCl) (5 mL 17% EDTA followed by 5 mL 2.5% sodium hypochlorite), and group S (5 mL saline). Microbiological samples were collected before instrumentation and after final irrigation. Bacterial quantification was performed by counting the number of colony-forming units (CFUs/mL). The results were analyzed by the nonparametric Wilcoxon and Kruskal-Wallis tests., Results: The 3 groups showed a significant reduction (P < .05) in CFUs/mL after final irrigation. PAA and NaOCl associated with EDTA produced a significantly higher reduction in CFUs/mL (P < .05) compared with saline. There was no statistically significant difference between PAA and EDTA + 2.5% NaOCl (P > .05)., Conclusions: According to the results of the present study, the effectiveness of 1% PAA was similar to that of 17% EDTA + 2.5% NaOCl in cleaning curved root canals contaminated with E. faecalis., (Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare, clinically and biometrically, affected and fellow acute primary angle-closure (APAC) eyes and glaucomatous eyes with narrow angle (NA)., Methods: Comparative case series; 30 patients with APAC and 27 glaucomatous patients with NA were evaluated. Keratometry (K), central corneal thickness (CCT), lens thickness (LT), axial length (AL) and anterior chamber depth (ACD) were measured. Parameters defined as lens posisiton (LP) and relative lens position (RLP) were calculated., Results: Biometric difference between APAC-affected and fellow eyes was found only in LP (P=0.046). When fellow eyes were compared to glaucomatous eyes with NA, differences were found in ACD (P=0.009), AL (P=0.010), and LT/AL (P=0.005). The comparison between APAC-affected and glaucomatous eyes with NA showed significant differences in almost all biometric parameters, except for LT (P=0.148) and RLP (P=0.374). We found that the logistic regression model (LRM), built with three parameters (K, CCT and LT/AL), higher than 0.334 could be a reasonable instrument to differentiate APAC eyes from glaucomatous eyes with NA., Conclusions: This study showed that APAC-affected and fellow eyes have similar biometric features, and glaucomatous eyes with NA have a less crowded anterior segment. The LRM built showed promising results in distinguishing APAC from glaucomatous eyes with NA.

Purpose: To investigate, through ultrasound biomicroscopy images, the presence of plateau iris configuration in eyes with narrow-angle from patients with open-angle glaucoma and in eyes with previous acute primary angle-closure and compare the biometric features of eyes with plateau iris configuration with those of normal eyes., Methods: Ultrasound biomicroscopic images from 196 patients with open-angle glaucoma and narrow-angle and 32 patients with acute primary angle-closure were retrospectively analyzed. The inclusion and specific criteria for the diagnosis of plateau iris configuration was the presence of an anterior positioning of the ciliary processes, supporting the peripheral iris so that it was parallel to the trabecular meshwork; the iris root had a steep rise from its insertion point, followed by a downward angulation from the corneoscleral wall; presence of a central flat iris plane; an absent (complete plateau iris configuration) or partially absent (incomplete plateau iris configuration) ciliary sulcus. The ultrasound biomicroscopic parameters were compared between complete and incomplete plateau iris configuration. The same parameters of both groups were compared with those of normal eyes. The following measurements were performed: anterior chamber depth; angle opening distance at 500 microm from the scleral spur; peripheral iris thickness at 500 microm from the scleral spur; iris-ciliary process distance; trabecular-ciliary process distance and angle recess area., Results: Plateau iris configuration was found in 33 eyes of 20 (10.2%) out of 196 patients with open-angle glaucoma and narrow-angle and in 4 eyes of 2 (6.3%) out of 32 patients with acute primary angleclosure. Seventeen (77.3%) patients with plateau iris configuration were female and 5 (22.7%) male. Twenty-three (62.2%) out of 37 eyes had complete plateau iris configuration, and 14 (37.8%) had incomplete plateau iris configuration. Complete and incomplete plateau iris configuration presented similar biometric features with the exception of the iris-ciliary process distance. All plateau iris configuration eyes showed biometric parameters completely different from those of normal eyes except for peripheral iris thickness at 500 microm from the scleral spur., Conclusions: Plateau iris configuration was present in 10.2% of patients with open-angle glaucoma and narrow-angle and in 6.3% of patients with acute primary angle-closure. Biometric features were similar in eyes with complete and incomplete plateau iris configuration with the exception of iris-ciliary process distance. Compared to normal eyes, all plateau iris configuration eyes showed biometric parameters completely different except for peripheral iris thickness at 500 microm from the scleral spur.

Purpose: To study the mechanisms of pupillary block in eyes with occludable angle by ultrasound biomicroscopy., Methods: Initially, a pilot study of 13 eyes with acute primary angle-closure without medication was executed. Ultrasound biomicroscopy measurements of the angle, posterior chamber depth and iris thickness were performed in the temporal quadrant under light and dark conditions. Afterwards, ultrasound biomicroscopy measurements of iris-lens contact distance and iris-lens angle in the temporal quadrant and central anterior chamber depth were made in 32 eyes with acute primary angle-closure or intermittent primary angle-closure without medication, under light and dark conditions before and after laser peripheral iridectomy., Results: In the pilot study, a significant decrease in the angle as well as a significant increase in the iris thickness occurred when comparing light to dark conditions. Before and after laser peripheral iridectomy (second study), significant differences were found in iris-lens contact distance (P<0.001) and iris-lens angle (P<0.001) under light and dark conditions. Also, significant differences were found in light and dark conditions, before laser peripheral iridectomy, in iris-lens angle (P=0.005), and after laser peripheral iridectomy, in iris-lens contact distance (P<0.001). No significant change occurred with anterior chamber depth., Conclusions: A decreased angle was correlated to an increase in iris thickness. After laser peripheral iridectomy, acute primary angle-closure or primary angle-closure eyes had an increased iris-lens contact distance and a decreased iris-lens angle. The anterior chamber depth did not change. These findings contradict the theory that pupillary block is the mechanism of acute primary angle-closure.

Purpose: To investigate biometrically the differences between plateau iris configuration (PIC) eyes and primary open angle glaucoma with narrow angle eyes., Methods: A comparative study involving a case series with 20 eyes of 11 plateau iris configuration patients and 45 eyes of 27 primary open angle glaucoma with narrow angle eyes patients was done. The following measurements were taken: corneal curvature, central corneal thickness, anterior chamber depth, lens thickness (LT), axial length (AL), lens thickness and axial length ratio, lens position (LP) and relative lens position (RLP)., Results: The plateau iris configuration eyes presented a higher corneal cuvature value than primary open angle glaucoma with narrow angle eyes eyes but not with clinical and statistical difference (P=0.090). The plateau iris configuration eyes demonstrated a higher central corneal thickness, with statistical significance, when compared to primary open angle glaucoma with narrow angle eyes (P=0.010). Statistical significant difference between plateau iris configuration and primary open angle glaucoma with narrow angle eyes was found in axial length (21.69 +/- 0.98 vs. 22.42 +/- 0.89; P=0.003). No significant difference was found when anterior chamber depth (2.62 +/- 0.23 vs. 2.71 +/- 0.31; P=0.078), LT (4.67 +/- 0.36 vs. 4.69 +/- 0.45; P=0.975), LT/AL (2.16 +/- 0.17 vs. 2.10 +/- 0.21; P=0.569), LP (4.95 +/- 0.25 vs. 5.06 +/- 0.34; P=0.164) and RLP (0.23 +/- 0.01 vs. 0.22 +/- 0.14; P=0.348) were evaluated., Conclusion: The eyes with plateau iris configuration presented statistical significantly shorter axial length and higher central corneal thickness than primary open angle glaucoma with narrow angle eyes.

Purpose: To compare morphometric features between fellow acute primary angle-closure (APAC) eyes and glaucomatous or suspect eyes with narrow angle (NA)., Methods: Fellow eyes of 30 patients with unilateral APAC and 30 with NA were evaluated by ultrasound biomicroscopy (UBM) under light and dark conditions. UBM parameters such as anterior chamber depth (ACD), angle opening distance at 250 microm/500 microm from the scleral spur (AOD250/AOD500), trabecular ciliary process distance (TCPD) and iris-lens contact distance (ILCD) were measured in the superior (SQ) and inferior (IQ) quadrants., Results: Significant differences between APAC fellow and NA eyes were found in ACD, P<0.001; AOD250 at SQ and IQ, P<0.001; AOD500 at SQ and IQ, P<0.001; TCPD light, P=0.010 and TCPD dark at SQ, P=0.031; and TCPD light at IQ, P=0.010. Significant differences between light and dark examinations of APAC fellow eyes were found in ILCD (P=0.009) at SQ and ILCD at IQ (P=0.006), and of NA eyes in ILCD at SQ (P=0.047) and ILCD at IQ (P<0.001)., Conclusions: APAC fellow eyes have a more crowded anterior segment and shallower ACD than NA eyes. ILCD decreases in both groups when the illumination conditions change from light to dark.

The term plateau iris was first coined in 1958 to describe the iris configuration of a patient. Two years later the concept of plateau iris was published. In 1977, the plateau iris configuration was classically defined as presurgical changes of an eye with a relative normal central anterior chamber depth, flat iris by conventional biomicroscopy, but displaying an extremely narrow or closed angle on gonioscopic examination. On the other hand, the plateau iris syndrome was defined as an acute glaucoma crisis in one eye with a relative normal central anterior chamber depth and patent iridotomy on direct examination, presenting angle closure confirmed by gonioscopic examination after mydriasis. In 1992, the anatomic aspects of plateau iris were studied using ultrasound biomicroscopy. Finally, plateau iris has been considered an anatomic variant of iris structure in which the iris periphery angulates sharply forward from its insertion point and then again angulates sharply and centrally backward, along with an anterior positioning of the ciliary processes seen on ultrasound biomicroscopy. The clinical treatment of plateau iris syndrome is carried out with topical use of pilocarpine. However, the definitive treatment should be fulfilled by performing an argon laser peripheral iridoplasty.

Purpose: To determine the incidence of the primary angle-closure glaucoma at the Glaucoma Service of São Geraldo Hospital, to establish the profile of these patients and to identify the possible risk factors., Methods: Transversal study. Period of assessment: from September/2005 to August/2006., Inclusion Criteria: diagnosis of primary angle-closure glaucoma., Exclusion Criteria: presence of cataracts that cause low visual acuity or index-myopia, secondary glaucoma, plateau iris. Number of visits, incidence of primary angle-closure glaucoma, age, gender, race, family history of glaucoma, keratometric, and biometric data were assessed., Results: Of 879 attended patients, 20 (2.3%) had the diagnosis of primary angle-closure glaucoma, therefore, the incidence of the primary angle-closure glaucoma was 22.7 cases per 1000 attended. Of those patients with primary angle-closure glaucoma: 6 (30.0%) were men and 14 (70.0%) women; the age varied from 40 to 73 years (average: 60.4 +/- 8.1 years); 12 (60.0%) were leukodermics and 8 (40.0%) pheodermics; 5 (25.0%) with positive familiar history of glaucoma. The relative risk for women was 1.44 (95% IC). Eleven (55.0%) patients had primary angle-closure glaucoma of the right eye and 9 (45.0%) of the left. When biometric data and keratometry were compared between the affected and contralateral eye, no statistical significant difference was observed., Conclusions: The incidence of the primary angle-closure glaucoma at the Glaucoma Service of São Geraldo Hospital was 22.7 cases per 1000 attended. It was more frequent in leukodermic women, without family history of glaucoma and with an average age of 60.4 years. The affected and contralateral eyes were biometrically similar.

Background: Severe forms of alpha(1)-antitrypsin (AAT) deficiency require augmentation therapy by intravenous administration of purified preparations of AAT concentrate. Although standard AAT treatment schedules are widely available, pharmacokinetic studies characterizing AAT serum decay are scarce, and data on the variability of individual patients are almost nonexistent., Objective: To establish individual AAT pharmacokinetics and develop a predictive model based on simple pharmacokinetic characterization that can be used to optimize individual AAT dosing regimens., Methods: Seven patients with severe hereditary AAT deficiency (PI(*)ZZ phenotype) with serum AAT levels less than 0.50 g/L initially received AAT 180 mg/kg every 3 weeks. At 7, 14, and 21 days after AAT administration, serum samples were taken for quantitative AAT analysis and further one-compartment pharmacokinetic analysis. Subsequently, patients were rescheduled (dose and dosing interval) according to their individual responses. The influence of baseline AAT level, age, sex, body weight, and commercial AAT preparation was evaluated., Results: The mean +/- SD AAT pharmacokinetic profile was: volume of distribution 127.6 +/- 31.9 mL/kg, clearance 10.13 +/- 1.84 mL/kg/day, and half-life 8.7 +/- 1.0 days. Hence, the mean optimized final AAT dose was 123.1 mg/kg every 2 weeks (range 118.5-125.6). AAT concentrations differed by a mean (geometrical) value of 3.9% (range -4.2% to 6.7%) from the minimum desired AAT serum trough of 0.50 g/L. The impact of baseline AAT levels and commercial AAT preparation used was statistically significant (p = 0.033 and p = 0.035, respectively). Differences between estimated and actual values were slightly lower when baseline AAT levels were taken into consideration, with a mean value of 3.3% (range -4.2% to 6.1%)., Conclusions: AAT augmentation therapy can be effectively individualized on a pharmacokinetic basis with a simple, easily executed method.

Purpose: To establish the profile of patients with acute primary angle-closure glaucoma (APACG) and to assess comparatively clinical and morphometric parameters between eyes with APACG and contralateral eyes (CLEs)., Methods: Prospective study including patients attended from September 2005 to March 2007., Inclusion Criteria: diagnosis of APACG., Exclusion Criteria: presence of cataract (except for "glaukomflecken") that may cause low visual acuity or myopization, secondary glaucoma, previous APAGC or surgical procedure in the (CLE), no possibility to control the acute crisis of glaucoma clinically, plateau iris. The following were evaluated: incidence of APACG, age, gender, race, family history of glaucoma, corrected visual acuity (CVA) and uncorrected visual acuity (UVA), spherical equivalent (SE), cup/disc ratio (C/D), gonioscopy, keratometry (K), central corneal thickness (CCT), and echobiometric data [anterior central chamber depth (ACCD), axial length (AL), lens thickness (LT)] and relation between lens thickness and axial length (LT/AL)., Results: One thousand and three hundred and forty-three patients were examined from September 2005 to March 2006; 28 (2.1%) had the diagnosis of APACG. The incidence of the APACG was 20.8 cases per 1000 patients. The patients with APACG were manly white women with a negative familial history of glaucoma and with an average age of 59.6 years. When clinical aspects were compared between eyes with APACG and CLEs, statistical significance was observed: UVA (APACG: 0.27 +/- 0.32; CLE: 0.57 +/- 0.33, p=0.000); CVA (APACG: 0.53 +/- 0.44; CLE: 0.88 +/- 0.23, p=0.000); SE (APACG: +0.49 +/- 1.98; CLE: +1.21 +/- 2.03, p=0.007); C/D (APACG: 0.51 +/- 0.28; CLE: 0.42 +/- 0.20; p=0.031). Also, by gonioscopy, eyes with APACG demonstrated more frequently angle closure than CLEs. The eye of the crisis showed the following characteristics: average K of 45.21 +/- 1.96 D, average CCT of 534.46 +/- 34.15 mm, average ACCD of 2.43 +/- 0.28 mm, average AL of 21.68 +/- 0.96 mm, average LT 4.85 +/- 0.32 mm and average LT/AL of 2.24 +/- 0.16. The CLE presented average K of 44.92 +/- 1.86 D, average CCT of 533.18 +/- 31.41 microm, average ACCD of 2.51 +/- 0.29 mm, average AL of 21.82 +/- 0.92 mm, average LT 4.85 +/- 0.36 mm and average LT/AL of 2.23 +/- 0.18. There were statistically significant differences only in two parameters (K and ACCD) when affected and the CLE were compared., Conclusions: The incidence of the APACG was 20.8/1000. It was more frequent in white women, leu kodermics, without family history of glaucoma and with an age average of 59.6 years. The eyes with APACG showed, with statistical significance, worse visual acuity, higher C/D, lower hypermetropic SE, higher average K, and lower ACCD than CLEs.

Purpose: To compare the cardiovascular and mydriatic effects of 2.5% and 10.0% phenylephrine., Methods: A case-control, randomized, crossover clinical trial study. We monitored heart rate (HR), blood pressure (BP) and mydriasis in healthy volunteers aged 18-45 years after the instillation of 2.5% and 10.0% phenylephrine in two different occasions., Results: The sample comprised 28 healthy volunteers, 17 male and 11 female, with a mean age of 26.5 years. No changes in heart rate and systolic blood pressure were observed. No significant variation of the mean diastolic blood pressure was found after 1, 5, 10 and 30- minute instillation of 2.5% phenylephrine. However, with 10.0% phenylephrine, there was an increase in mean diastolic blood pressure after five and ten minutes, followed by a drop after 30 minutes, which was not statistically significant. Mydriasis was more marked in both eyes with a statistically significant difference after instillation of 10.0% phenylephrine., Conclusions: The mydriatic effect was greater with 10.0% phenylephrine than with 2.5% phenylephrine and the difference was statistically significant. No statistically significant difference was found in relation to cardiovascular effects in both phenylephrine concentrations.

Purpose: To present the prevalence of iridociliary cysts in eyes of patients submitted to UBM examination., Methods: We analyzed retrospectively the UBM images of 1157 patients in the period from September 1995 to June 2004. The inclusion criterion was the UBM examination had been made on the four quadrants (superior, inferior, nasal and temporal) of the eyes. The cysts were assessed and classified in relation to their number in each quadrant; localization and morphology. Using the UBM Pro 2000 software we took the measurements of the largest diameter, wall thickness and area of the cysts besides the angle recession area (ARA)., Results: The prevalence of the cysts was 4.9%. No statistical difference was found between the prevalence of cysts regarding gender or between the right and left eyes. They were more prevalent in the inferior (39.8%) and temporal (29.1%) quadrants. The cysts with the largest diameter and area were located in the temporal and superior quadrants. No difference was found in relation to cysts' wall thickness in all quadrants., Conclusions: No statistical difference was found between the prevalence of cysts as concerns gender or between the right and left eyes. However, the cysts were more prevalent in the inferior and temporal quadrants. The locations of the largest cysts are preferentially the temporal and superior quadrants. The angle recession area was smaller in the temporal and superior quadrants. The cysts' wall thickness is practically the same in all quadrants. The diagnosis of iridociliary cysts was an occasional finding in 64.3% of the patients.

Pellucid marginal degeneration is characterized by a progressive stromal thinning of the inferior corneal segment, between 4 and 8 o'clock, with a crescentic shape. The area of corneal thinning has a width of about 1 to 2 mm, and it is separated from the corneoscleral limbus by an area of normal corneal tissue. The initial treatment consists of optical correction. However, when the disease progresses to advanced stages, surgical procedures are necessary such as wedge resection, lamellar crescentic resection, penetrating keratoplasty, lamellar keratoplasty, epikeratoplasty and, recently, intracorneal segments.

Purpose: To establish the frequency of infantile cataract in the Low Vision Service of São Geraldo Hospital (HSG-HCUFMG) and to analyze basis of history, ophthalmologic examination and optical prescription in these patients., Methods: Retrospective study of infantile cataract recorded in the Low Vision Service from January/1992 to December/2002. Age, sex, race, age at the first evidence of leukocoria and who noticed it, ages at diagnosis and phacectomy, family history of cataract, intraocular lens implantation, visual acuity (VA) and optic prescription were evaluated., Results: There were 44 patients. The age ranged from 0-15 years: 19 (43.0%) 0-3, 14 (32.0%) 4-10 and 11 (25.0%) from 11-15 years. Twenty-eight (63.6%) were female and 19 (43.2%) leukodermic. The first evidence of leukocoria was observed by the mother in 17 patients (38.6%). Leukocoria was observed in the first 2 months of life in 45.5% of the patients; phacectomy was performed in 43.2% of the patients with more than 1 year of age. Optic prescription was performed in 61.4% of the cases with 9.1% of the patients below 1 year of age. Intraocular lens was implanted in 13.6% and 4 patients (9.1%) had a family history of congenital cataract. In 20.4% VA was lower than 20/400 and secondary glaucoma was observed in 18.2% of the cases. Low vision aids included two glasses and one telescope., Conclusion: More information about congenital cataract should be provided for families and pediatricians, and early surgical treatment, optic correction and treatment of amblyopia should be performed promptly.