Immunohistochemical, functional, and anatomical evaluation of patients with idiopathic epiretinal membrane.

PURPOSE: The main purpose of this study was to perform an immunohistochemical, functional, and anatomical evaluation of patients with idiopathic epiretinal membrane (ERM). METHODS: Twenty-four specimens of idiopathic ERM from 24 consecutive patients who underwent 23 G pars plana vitrectomy for ERM and internal limiting membrane (ILM) peeling at the San Juan University Hospital in Alicante (Spain) in 2019 were analyzed. All patients underwent a complete ophthalmological examination including measurement of best corrected visual acuity (BCVA) and macular analysis by spectral-domain optical coherence tomography (SD-OCT) at the time of diagnosis and 3 months after surgery. Specific glial fibrillar acid protein antibodies (GFAP) and S100 calcium-binding protein ß (S100ß) immunostaining markers were used to identify the macroglial component of the ERM, Müller cells, and astrocytes. Ionized calcium-binding adapter molecule 1 protein (Iba1) antibodies were used as specific markers for inflammatory cells, such as microglia and macrophages. RESULTS: Mean preoperative BCVA measured with Snellen chart was 0.3 and 0.6 preoperatively and at 3 months after surgery, respectively. SD-OCT identified 15 patients (62.5%) with a disruption of the outer retinal hyperreflective bands. The immunohistochemical study showed the presence of Müller cells in almost all cases (91.6%), as well of abundant microglia and macrophages. Microglia and macrophages were more frequently present in earlier stages of ERM. Microglia were present in ERM independently of the outer retinal hyperreflective bands integrity as measured by SD-OCT. A greater presence of macrophages was found in those ERMs with no outer retinal hyperreflective band disruption. CONCLUSIONS: Müller cells seem to be the most frequent cell group in ERMs, with also presence of microglia cells and macrophages. Astrocytes were more frequently found in early stages of ERMs. Microglia and macrophages were most frequent in ERMs with early stage (1, 2, or 3) than in advanced stages (4).

Visual manifestations in giant cell arteritis: identification of risk factors from the ARTESER Registry.

OBJECTIVE: To determine the prevalence and predictive factors of visual manifestations in a large registry of patients with GCA. METHODS: ARTESER is a large Spanish multicentre registry supported by the Spanish Society of Rheumatology. It includes patients with GCA from across the entire country diagnosed between June 2013 and March 2019. The variables collected at diagnosis were demographics, clinical manifestations (including all visual manifestations), laboratory, temporal artery biopsy, and imaging findings (ultrasound, FDG-PET/CT, MRI angiography, CT angiography). Patients with and without visual involvement were compared in a bivariate analysis. Multivariate logistic regression was performed to determine potential predictive factors of visual manifestations. RESULTS: The study population comprised 1636 GCA patients, of whom 599 (36.6%) presented visual manifestations. Anterior ischemic optic neuropathy was the most frequent (n = 274 of 599; 45.7%) ocular complication. The independent predictors that increased the risk (OR; 95% confidence interval) of visual involvement were older age (1.027; 1.009-1.045) and jaw claudication (1.724; 1.325-2.243). The variables associated with a reduced risk were polymyalgia rheumatica (0.541; 0.414-0.708), fever (0.373; 0.264-0.527), longer symptom duration (0.946; 0.909-0.985), and higher erythrocyte sedimentation rate (ESR) (0.992; 0.988-0.997), common features of patients with large vessel-GCA. CONCLUSION: One-third of GCA patients present visual manifestations at diagnosis. Older age and jaw claudication are independent predictors of visual manifestations, whereas polymyalgia rheumatica, fever, longer symptom duration, and high ESR reduce the risk of visual involvement.

Latinx LGBTQ Youth, COVID-19, and Psychological Well-Being: A Systematic Review.

OBJECTIVE: As a result of the COVID-19 pandemic, Latinx youth report high rates of negative mental health outcomes such as anxiety and depression. Similarly, research with lesbian, gay, bisexual, transgender, and queer (LGBTQ) youth have documented increased negative mental health outcomes such as depression and anxiety as a result of the COVID-19 pandemic. However, the current literature has yet to systematically uncover the intersectional experiences of Latinx LGBTQ youth during this time. METHOD: We conducted a systematic review to uncover the experiences of Latinx LGBTQ youth during the pandemic. Our systematic review resulted in 14 empirical studies that explored the challenges, stressors, and impact of the COVID-19 pandemic on Latinx LGBTQ youth. RESULTS: Findings revealed that most studies include cisgender, gender binary, heterosexual, Latinx youth. Findings across studies include: (a) impact from school closures, (b) pandemic stressors, (c) impact from online media, (d) family and Latinx cultural values as a source of support and stress, and (e) the implementation and evaluation of interventions during the COVID-19 pandemic. DISCUSSION: We provide recommendations for clinicians working with Latinx LGBTQ youth including expanding their knowledge about the impact of the COVID-19 pandemic on these communities, considering the experiences of Latinx LGBTQ youth as multifaceted, and considering the role of heterogeneity in the mental health of Latinx LGBTQ Youth.

Structure-Guided Design and Synthesis of a Pyridazinone Series of Trypanosoma cruzi Proteasome Inhibitors.

There is an urgent need for new treatments for Chagas disease, a parasitic infection which mostly impacts South and Central America. We previously reported on the discovery of GSK3494245/DDD01305143, a preclinical candidate for visceral leishmaniasis which acted through inhibition of the Leishmania proteasome. A related analogue, active against Trypanosoma cruzi, showed suboptimal efficacy in an animal model of Chagas disease, so alternative proteasome inhibitors were investigated. Screening a library of phenotypically active analogues against the T. cruzi proteasome identified an active, selective pyridazinone, the development of which is described herein. We obtained a cryo-EM co-structure of proteasome and a key inhibitor and used this to drive optimization of the compounds. Alongside this, optimization of the absorption, distribution, metabolism, and excretion (ADME) properties afforded a suitable compound for mouse efficacy studies. The outcome of these studies is discussed, alongside future plans to further understand the series and its potential to deliver a new treatment for Chagas disease.

Longitudinal findings of a U.S. preventive evidence-based family intervention tested among youth in Ecuador: Familias Unidas.

Interventions that address adolescent conduct problems are essential for decreasing negative risk behaviors and promoting positive protective factors among youth. Although interventions have been developed and tested in the United States, preventive evidence-based interventions (EBIs) are less available in Latin American countries such as Ecuador. Therefore, the purpose of this study was to evaluate the efficacy of an evidence-based, parent-centered intervention, Familias Unidas, in preventing/reducing conduct problems, across time, among youth in Guayaquil, Ecuador. Ecuadorian youth (ages 12 through 14) and their respective primary caregiver were recruited from two public schools and randomized to either Familias Unidas or Community Practice. A series of latent growth models were run to test for differences between Familias Unidas and Community Practice on conduct disorder symptoms across three timepoints covering 6 months. Ecuadorian mental health professionals were trained to deliver the evidence-based intervention. Findings indicate no direct relationship between condition and average change in conduct problems at 6 months post baseline. However, indirect effects favoring Familias Unidas over Community Practice were found through improvements in family functioning. Findings highlight that Familias Unidas was efficacious in an international setting and indicate the viability of successfully delivering preventive EBIs in Ecuador.

Optimisation of tocilizumab therapy in giant cell arteritis. A multicentre real-life study of 471 patients.

OBJECTIVES: Tocilizumab (TCZ) is the only biologic therapy approved for giant cell arteritis (GCA). There is general agreement on the initial/maintenance dose, duration of TCZ therapy is not well established. In GiACTA trial, after one year on TCZ, most patients had GCA relapse after withdrawal. The aim of this study is to assess the effectiveness and safety of TCZ therapy optimisation in a large unselected series of patients with GCA in a clinical practice scenario. METHODS: We carried out a multicentre study on 471 GCA patients treated with TCZ. Once prolonged remission was achieved (n=231) and based on a decision between patient and physician, TCZ was optimised (n=125). We compared optimised (TCZOPT) and not optimised (TCZNON-OPT) groups. Prolonged remission defined as normalisation of clinical and laboratory data for 6 months. Optimisation was carried out by decreasing TCZ dose and/or increasing dosing interval. RESULTS: We evaluated 231 GCA patients on TCZ in prolonged remission. At TCZ onset, no differences in demographic, clinical, or laboratory data were observed. First TCZ optimisation was performed after a median follow-up of 12[6-17] months. Intravenous TCZ was optimised from 8 to 4mg/kg/4weeks in 44% patients, while subcutaneous TCZ was optimised from 162mg/w to 162mg/every-other-week in 65% cases. At the end of follow-up, prolonged remission (78.2% vs. 84.2%; p=0.29) and relapses (5.6% vs. 10.4%, p=0.177) were similar in TCZOPT vs. TCZNON-OPT. Severe infections were more frequent in TCZNON-OPT (12.9% vs. 6.6%; p=0.009). CONCLUSIONS: TCZ optimisation may be done once complete remission is achieved by reducing dose or increasing dosing interval. This seems to be effective, safe and cost-effective therapeutic scheme.

Variation of Corrosion Rate, Vcorr, during the Carbonation-Induced Corrosion Propagation Period in Reinforced Concrete Elements.

The structural systems of residential buildings in many developed countries have widely utilized reinforced concrete as the most common solution in construction systems since the early 20th century. The durability of reinforced concrete columns and beams is compromised, in most cases, by pathologies caused by the corrosion of their reinforcements. This study analyses the corrosion processes induced by carbonation in 25 buildings with reinforced concrete structures. The models estimate the service life of reinforced concrete elements by differentiating between the initiation period and the propagation period of damage, considering two possible stages: the time of corrosion propagation until the cracking of the concrete cover, and the time of propagation until a loss of section is considered unacceptable for structural safety. However, the mathematical expressions that model the propagation periods consider the same corrosion rate in both cases. This research has found that the average corrosion rate in elements with an unacceptable loss of reinforcement section was in the order of 8 times higher than the corrosion rate in cracked columns and beams without a loss of reinforcement. This opens up a path to improve the definition of the different stages experienced by a reinforced concrete element suffering corrosion of its reinforcements due to carbonation, because once the concrete has cracked, the corrosion rate increases significantly.

Changes in the Hyperreflective Bands of Outer Retinal Layers after Idiopathic Epiretinal Membrane Surgical Removal.

Purpose: The purpose of this study was to describe the relationship between the outer retinal hyperreflective bands and visual acuity recovery after idiopathic epiretinal macular membrane (ERM) surgical removal.Methods: A prospective longitudinal non-comparative study was conducted that included a total of 68 patients with idiopathic ERM, who underwent consecutive 23 G pars plana vitrectomy (PPV) at San Juan University Hospital (Alicante, Spain) from January 2019 to January 2021. All patients underwent a complete preoperative standard ophthalmic examination, including measurement of best corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT) examination. This protocol was repeated at 1 and 3 months after surgery.Results: Mean preoperative decimal BCVA was 0.30 ± 0.13 and disruption of the first, second, third and fourth outer retinal hyperreflective bands was observed by SD-OCT in 9 (27.9%), 27 (39.7%), 33 (48.5%) and 17 patients (25%), respectively. BCVA improved after ERM peeling at 1 and 3 months in all patients, regardless of the presence of disruption in any hyperreflective band. Significantly larger improvement of BCVA was found at 3 months after surgery in patients not showing disruption of hyperreflective bands 1 and 4 (p = 0.048 and 0.001, respectively).Conclusions: The integrity of the outer retinal hyperreflective bands by SD-OCT in patients with idiopathic ERM is a valuable tool to determine the visual prognosis of the surgical treatment of this condition. A successful recovery of hyperreflective bands 1 and 4 with ERM surgery may be a potential biomarker of the visual improvement achieved due to their important anatomical relation with cone photoreceptors at the foveal level.

Tocilizumab in visual involvement of giant cell arteritis: a multicenter study of 471 patients.

Background: Visual involvement is the most feared complication of giant cell arteritis (GCA). Information on the efficacy of tocilizumab (TCZ) for this complication is scarce and controversial. Objective: We assessed a wide series of GCA treated with TCZ, to evaluate its role in the prevention of new visual complications and its efficacy when this manifestation was already present before the initiation of TCZ. Design: This is an observational multicenter study of patients with GCA treated with TCZ. Methods: Patients were divided into two subgroups according to the presence or absence of visual involvement before TCZ onset. Visual manifestations were classified into the following categories: transient visual loss (TVL), permanent visual loss (PVL), diplopia, and blurred vision. Results: Four hundred seventy-one GCA patients (mean age, 74 ± 9 years) were treated with TCZ. Visual manifestations were observed in 122 cases (26%), of which 81 were present at TCZ onset: PVL (n = 60; unilateral/bilateral: 48/12), TVL (n = 17; unilateral/bilateral: 11/6), diplopia (n = 2), and blurred vision (n = 2). None of the patients without previous visual involvement or with TVL had new episodes after initiation of TCZ, while only 11 out of 60 (18%) patients with PVL experienced some improvement. The two patients with diplopia and one of the two patients with blurred vision improved. Conclusion: TCZ may have a protective effect against the development of visual complications or new episodes of TVL in GCA. However, once PVL was established, only a few patients improved.

Bromodomain factor 5 is an essential regulator of transcription in Leishmania.

Leishmania are unicellular parasites that cause human and animal diseases. Like other kinetoplastids, they possess large transcriptional start regions (TSRs) which are defined by histone variants and histone lysine acetylation. Cellular interpretation of these chromatin marks is not well understood. Eight bromodomain factors, the reader modules for acetyl-lysine, are found across Leishmania genomes. Using L. mexicana, Cas9-driven gene deletions indicate that BDF1-5 are essential for promastigotes. Dimerisable, split Cre recombinase (DiCre)-inducible gene deletion of BDF5 show it is essential for both promastigotes and murine infection. ChIP-seq identifies BDF5 as enriched at TSRs. XL-BioID proximity proteomics shows the BDF5 landscape is enriched for BDFs, HAT2, proteins involved in transcriptional activity, and RNA processing; revealing a Conserved Regulators of Kinetoplastid Transcription (CRKT) Complex. Inducible deletion of BDF5 causes global reduction in RNA polymerase II transcription. Our results indicate the requirement of Leishmania to interpret histone acetylation marks through the bromodomain-enriched CRKT complex for normal gene expression and cellular viability.

Apolipoprotein C-III in patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) has been associated with atherosclerotic cardiovascular disease (CV) and an altered lipid profile. High levels of apolipoprotein C-III (ApoC3) are associated with elevated triglyceride levels and an increased risk of CV. In the present study, we aimed to study circulating ApoC3 in patients with SLE and describe its relationship with the manifestations of the disease. METHODS: This is a cross-sectional study that included 186 patients with SLE. Disease-related data, CV comorbidity, full lipid profile, and serum levels of ApoC3 were assessed. A multivariable regression analysis was performed to study how ApoC3 was related to SLE features. RESULTS: Classic CV risk factors were significantly and strongly associated with circulating ApoC3. After a fully multivariable analysis that included classic CV risk factors and lipid profile molecules, SLICC damage (beta coef. 0.10 [95% CI 0.02-0.19] mg/dl, 0.020) and Katz severity (beta coef. 0.11 [95% CI 0.03-0.19] mg/dl, p = 0.011) indices and SLEDAI activity score (beta coef. 0.05 [95% CI 0.05-0.08] mg/dl, p = 0.004) were all independently associated with higher levels of circulating ApoC3. CONCLUSION: Among SLE patients, disease activity, severity, and disease damage are independently associated with higher ApoC3 serum levels.

Essential Bromodomain TcBDF2 as a Drug Target against Chagas Disease.

Trypanosoma cruzi is a unicellular parasite that causes Chagas disease, which is endemic in the American continent but also worldwide, distributed by migratory movements. A striking feature of trypanosomatids is the polycistronic transcription associated with post-transcriptional mechanisms that regulate the levels of translatable mRNA. In this context, epigenetic regulatory mechanisms have been revealed to be of great importance, since they are the only ones that would control the access of RNA polymerases to chromatin. Bromodomains are epigenetic protein readers that recognize and specifically bind to acetylated lysine residues, mostly at histone proteins. There are seven coding sequences for BD-containing proteins in trypanosomatids, named TcBDF1 to TcBDF7, and a putative new protein containing a bromodomain was recently described. Using the Tet-regulated overexpression plasmid pTcINDEX-GW and CRISPR/Cas9 genome editing, we were able to demonstrate the essentiality of TcBDF2 in T. cruzi. This bromodomain is located in the nucleus, through a bipartite nuclear localization signal. TcBDF2 was shown to be important for host cell invasion, amastigote replication, and differentiation from amastigotes to trypomastigotes. Overexpression of TcBDF2 diminished epimastigote replication. Also, some processes involved in pathogenesis were altered in these parasites, such as infection of mammalian cells, replication of amastigotes, and the number of trypomastigotes released from host cells. In in vitro studies, TcBDF2 was also able to bind inhibitors showing a specificity profile different from that of the previously characterized TcBDF3. These results point to TcBDF2 as a druggable target against T. cruzi.

Epidemiological and genetic features of anti-3­hydroxy-3-methylglutaryl-CoA reductase necrotizing myopathy: Single-center experience and literature review.

OBJECTIVE: To characterize the demographic, genetic, clinical, and serological features of patients with anti-3­hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotizing myopathy (IMNM) in a region of northern Spain. METHODS: Study of all patients diagnosed with anti-HMGCR IMNM during a 5-year period at a reference hospital in northern Spain. Besides clinical and laboratory data, we analyzed the genetic influence of HLA genes and the rs4149056 (c.521T>C) single nucleotide polymorphism (SNP) in the SLCO1B1 gene. RESULTS: 8 patients (5 women, 3 men) with a mean ± SD age of 64.9 ± 7.3 years, fulfilled the criteria for anti-HMGCR IMNM. The incidence rate was 0.6 per 100.000 person-years and the prevalence 3 per 100.000 population. All patients had been exposed to statins. All of them had predominant lower limb proximal and symmetric muscle weakness that was severe in 2 and had elevated serum CK levels with a median [IQR] of 4488 [2538-9194] IU/L. Serum 25­hydroxy vitamin D levels were decreased in all patients in whom it was determined. The 3 patients with a previous diagnosis of hypothyroidism had abnormal levels of TSH at the time of diagnosis. All patients experienced improvement with different schemes of immunosuppressive therapy. Noteworthy, 7 of 8 patients carried the HLA-DRB1*11 allele. The frequency of the rs4149056 C allele in the SLCO1B1 gene (12.5%) was similar to that of the general population. CONCLUSION: In northern Spain, anti-HMGCR IMNM preferentially affects people over 50 years of age who are carriers of the HLA-DRB1*11 allele and take statins. Both low vitamin D levels and hypothyroidism may play a potential predisposing role in the development of this disease.

Correction: Ferraz-Amaro et al. SCORE2 Assessment in The Calculation of Cardiovascular Risk in Patients with Rheumatoid Arthritis. Diagnostics 2021, 11, 2363.

In the original article [...].

Genomic and Phenotypic Characterization of Experimentally Selected Resistant Leishmania donovani Reveals a Role for Dynamin-1-Like Protein in the Mechanism of Resistance to a Novel Antileishmanial Compound.

The implementation of prospective drug resistance (DR) studies in the research-and-development (R&D) pipeline is a common practice for many infectious diseases but not for neglected tropical diseases (NTDs). Here, we explored and demonstrated the importance of this approach using as paradigms Leishmania donovani, the etiological agent of visceral leishmaniasis (VL), and TCMDC-143345, a promising compound of the GlaxoSmithKline (GSK) "Leishbox" to treat VL. We experimentally selected resistance to TCMDC-143345 in vitro and characterized resistant parasites at the genomic and phenotypic levels. We found that it took more time to develop resistance to TCMDC-143345 than to other drugs in clinical use and that there was no cross-resistance to these drugs, suggesting a new and unique mechanism. By whole-genome sequencing, we found two mutations in the gene encoding the L. donovani dynamin-1-like protein (LdoDLP1) that were fixed at the highest drug pressure. Through phylogenetic analysis, we identified LdoDLP1 as a family member of the dynamin-related proteins, a group of proteins that impacts the shapes of biological membranes by mediating fusion and fission events, with a putative role in mitochondrial fission. We found that L. donovani lines genetically engineered to harbor the two identified LdoDLP1 mutations were resistant to TCMDC-143345 and displayed altered mitochondrial properties. By homology modeling, we showed how the two LdoDLP1 mutations may influence protein structure and function. Taken together, our data reveal a clear involvement of LdoDLP1 in the adaptation/reduced susceptibility of L. donovani to TCMDC-143345. IMPORTANCE Humans and their pathogens are continuously locked in a molecular arms race during which the eventual emergence of pathogen drug resistance (DR) seems inevitable. For neglected tropical diseases (NTDs), DR is generally studied retrospectively once it has already been established in clinical settings. We previously recommended to keep one step ahead in the host-pathogen arms race and implement prospective DR studies in the R&D pipeline, a common practice for many infectious diseases but not for NTDs. Here, using Leishmania donovani, the etiological agent of visceral leishmaniasis (VL), and TCMDC-143345, a promising compound of the GSK Leishbox to treat VL, as paradigms, we experimentally selected resistance to the compound and proceeded to genomic and phenotypic characterization of DR parasites. The results gathered in the present study suggest a new DR mechanism involving the L. donovani dynamin-1-like protein (LdoDLP1) and demonstrate the practical relevance of prospective DR studies.

Un caso de síndrome de crouzon con sintomatología psiquiátrica / A case of Crouzon syndrome with psychiatric symptoms

El síndrome de Crouzon es un trastornoautosómico dominante caracterizado por craneosinostosis (cierre prenatal de una o varias suturas craneales) que provoca alteraciones secundarias de los huesos craneales y de la estructura facial. Las características más frecuentes incluyen deformidadesde cráneo y cara: proptosis ocular, exoftalmos y estrabismo divergente, nariz en forma de pico de loro, labio superior corto, maxilar hipoplásico y prognatismo mandibular relativo. La presión intracraneal enalgunos casos puede producir trastornos neurológicos y discapacidad intelectual.Realizamos una breve revisión del concepto y planteamos un caso clínico quepresenta graves alteraciones de conducta con agresividad y escasa respuesta terapéutica. (AU)

Crouzon syndrome is an autosomal dominant disorder characterized by craniosynostosis (prenatal closure of one or morecranial sutures) that causes secondary alterations of the cranial bones and facial structure. The most frequent features include skull and facial deformities: ocular proptosis, divergent exophthalmos and strabismus,parrot beak-shaped nose, short upper lip, hypoplastic maxilla, and relative mandibular prognathism. Intracranial pressure in some cases can cause neurological disorders andintellectual disability.We carry out a brief review of the concept and we present a clinical case that presents serious behavior alterations with aggressiveness and little therapeutic response. (AU)

Quantification of Chlorides and Sulphates on Concrete Surfaces Using Portable X-ray Fluorescence. Optimization of the Measurement Method Using Monte Carlo Simulation.

A correct assessment of the pathologies that can affect a reinforced concrete structure is required in order to define the repair procedure. This work addresses the challenge of quantifying chlorides and sulphates directly on the surface of concrete. The quantification was carried out by means of X-ray fluorescence analysis on the surface of concrete specimens at different points with portable equipment. Concrete prisms were made with different amounts of NaCl and Na2SO4. To avoid the influence of coarse aggregate, a qualitative estimate of the amount of coarse aggregate analyzed has been made, although the results show that there is no significant influence. Monte Carlo simulations were carried out in order to establish the necessary number of random analyses of the mean value to be within an acceptable range of error. In the case of quantifying sulphates, it is necessary to carry out six random analyses on the surface, and eight measurements in the case of quantifying chlorides; in this way, it is ensured that errors are below 10% in 95% of the cases. The results of the study highlight that a portable XRF device can be used in situ to obtain concentrations of chlorides and sulphates of a concrete surface with good accuracy. There is no need to take samples and bring them to a laboratory, allowing lower overall costs in inspection and reparation works.

SCORE2 Assessment in the Calculation of Cardiovascular Risk in Patients with Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD). Risk chart algorithms, such as the Systematic Coronary Risk Assessment (SCORE), often underestimate the risk of CVD in patients with RA. In this sense, the use of noninvasive tools, such as the carotid ultrasound, has made it possible to identify RA patients at high risk of CVD who had subclinical atherosclerosis disease and who had been included in the low or moderate CVD risk categories when the SCORE risk tables were applied. The 2003 SCORE calculator was recently updated to a new prediction model: SCORE2. This new algorithm improves the identification of individuals from the general population at high risk of developing CVD in Europe. Our objective was to compare the predictive capacity between the original SCORE and the new SCORE2 to identify RA patients with subclinical atherosclerosis and, consequently, high risk of CVD. 1168 non-diabetic patients with RA and age > 40 years were recruited. Subclinical atherosclerosis was searched for by carotid ultrasound. The presence of carotid plaque and the carotid intima media wall thickness (cIMT) were evaluated. SCORE and SCORE2 were also calculated. The relationships of SCORE and SCORE2 to each other and to the presence of subclinical carotid atherosclerosis were studied. The correlation between SCORE and SCORE2 was found to be high in patients with RA (Spearman's Rho = 0.961, p < 0.001). Both SCORE (Spearman's Rho = 0.524) and SCORE2 (Spearman's Rho = 0.521) were similarly correlated with cIMT (p = 0.92). Likewise, both calculators showed significant and comparable discriminations for the presence of carotid plaque: SCORE AUC 0.781 (95%CI 0.755-0.807) and SCORE2 AUC 0.774 (95%CI 0.748-0.801). Using SCORE, 80% and 20% of the patients were in the low or moderate and high or very high CVD risk categories, respectively. However, when the same categories were evaluated using SCORE2, the percentages were different (58% and 42%, respectively). Consequently, the number of RA patients included in the high or very high CVD risk categories was significantly higher with SCORE2 compared to the original SCORE. (p < 0.001). In conclusion, although predictive capacity for the presence of carotid plaque is equivalent between SCORE and SCORE2, SCORE2 identifies a significantly higher proportion of patients with RA who are at high or very high risk of CVD.

Prophylactic effect of brimonidine to minimize the incidence of subconjunctival hemorrhage in the early postoperative period after 23G pars plana vitrectomy.

BACKGROUND: Several studies have investigated and demonstrated the prophylactic effect of brimonidine drops in preventing subconjunctival hemorrhage in some microincisional ophthalmic surgeries, such as intravitreal injections or cataract surgery. However, there are no previous studies investigating this prophylactic effect after 23G microincisional vitreoretinal surgery. AIM: The aim of the current study was to determine whether subconjunctival hemorrhage after 23G pars plana vitrectomy (PPV) could be prevented with the use of prophylactic topical brimonidine. METHODS: This was a phase III, prospective, interventional, randomized, controlled single-center clinical trial with a follow-up of 2 weeks. A total of 77 eyes (mean age: 68.4 ±â€„10.7 years) undergoing 23G PPV were included and randomized into two groups: group 1 including 41 patients receiving prophylactic preoperative treatment with brimonidine, and group 2 (control group) including 36 patients not receiving this prophylactic treatment. Differences in terms of number of conjunctival quadrants affected with subconjunctival hemorrhage were evaluated in each of the follow-up visits. RESULTS: The presence of subconjunctival hemorrhage was similar in both groups the first days after surgery (p > 0.05). At the last visit (10-14 days after surgery), this condition was significantly more frequent in control group where there was a significant difference, being more frequent in the control group (7.3% vs 28.6%, p = 0.022). The number of conjunctival quadrants affected was also similar in both groups, except for the last visit in which most of the patients treated with brimonidine (92.7%) showed no bleeding compared to 71.4% in control group. No effect on the efficacy of brimonidine treatment of the presence of blood hypertension, diabetes, and antiplatelet or anticoagulant treatment was observed. CONCLUSION: Brimonidine seems to be a useful option to decrease subconjunctival hemorrhage after microincisional vitreoretinal surgery or improve its resolution during the first postoperative week. This finding should be mainly due to the vasoconstrictor effect of brimonidine. TRIAL REGISTRATION: EudraCT, 2012-002895-15 (registered 19 December 2012); https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-002895-15.