Predictors for functional and anatomic outcomes in macular edema secondary to non-infectious uveitis

Aims We aimed to investigate predictive factors for visual and anatomic outcomes in patients with macular edema secondary to non-infectious uveitis. Material and methods We conducted a multicenter, prospective, observational, 12-month follow-up study. Participants included in the study were adults with non-infectious uveitic macular edema (UME), defined as central subfoveal thickness (CST) of > 300 mu m as measured by spectral domain optical coherence tomography (SD-OCT) and fluid in the macula. Demographic, clinical and tomographic data was recorded at baseline, 1, 3, 6 and 12 months. Foveal-centered SD-OCT exploration was set as the gold-standard determination of UME using a standard Macular Cube 512x128 A-scan, within a 6 x 6 mm(2) area, and the Enhanced High Definition Single-Line Raster. To assess favorable prognosis, the main outcomes analyzed were the best-corrected visual acuity (BCVA) and the CST. Favorable prognosis was defined as sustained improvement of BCVA (2 lines of gain of the Snellen scale) and CST (decrease of 20% of the initial value or < 300 mu m) within a 12 month period. Results Fifty-six eyes were analyzed. The number of eyes with sustained improvement in the CST was 48 (86.2%), against 23 (41.1%) eyes with sustained improvement in BCVA. Favorable prognosis, as defined above, was observed in 18 (32.1%) eyes. UME prognosis was negatively correlated with baseline foveal thickening, alteration in the vitreo-macular interface and cystoid macular edema. In contrast, bilaterally, systemic disease and the presence of anterior chamber cells were predictive of favorable prognosis. Conclusion Available treatment modalities in UME may avoid chronic UME and improve anatomic outcome. However, the proportion of functional amelioration observed during 12 months of follow-up is lower. Thicker CST, alteration in the vitreo-macular interface and cystoid macular edema may denote less favorable prognosis. Conversely, bilaterally, systemic disease and anterior chamber cells may be associated with favorable prognosis in UME.This work was supported by grants from: Spanish Ministry of Economy, Industry and Competitivity, Carlos III Health Institute, cofinanced by the European Regional Development Fund, identification number: PI13/02148, Principal Investigator: AA; http://www.eng.isciii.es/ISCIII/es/contenidos/fd-investigacion/financiacion.shtml.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Comparison of CMS measurements with predictions at NLO applying the Parton Branching Method and PYTHIA

In August 2023, more than 30 students joined the Special Remote DESY summer-school to work on projects of importance for LHC experiments. In a dedicated initiative, analyses that had not been incorporated into the RIVET package were implemented and verified. Here, a brief description of the accomplished work is given, and a comparison of the measurements with predictions obtained from matched standard parton shower Monte Carlo event generators as well as with those obtained from Parton-Branching TMDs with corresponding parton showers are presented

Long-term follow-up of certolizumab pegol in uveitis due to immune-mediated inflammatory diseases : multicentre study of 80 patients

Objectives To evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID). Methods Multicentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis. These variables were compared between the baseline, and first week, first, third, sixth months, first and second year. Results We studied 80 (33 men/47 women) patients (111 affected eyes) with a mean age of 41.6±11.7 years. The IMID included were: spondyloarthritis (n=43), Behçet's disease (n=10), psoriatic arthritis (n=8), Crohn's disease (n=4), sarcoidosis (n=2), juvenile idiopathic arthritis (n=1), reactive arthritis (n=1), rheumatoid arthritis (n=1), relapsing polychondritis (n=1), Conclusions CZP seems to be effective and safe in uveitis related to different IMID, even in patients refractory to previous biological drugs

Overexpression of S100A4 in human cancer cell lines resistant to methotrexate

Methotrexate is a chemotherapeutic drug that is used in therapy of a wide variety of cancers. The efficiency of treatment with this drug is compromised by the appearance of resistance. Combination treatments of MTX with other drugs that could modulate the expression of genes involved in MTX resistance would be an adequate strategy to prevent the development of this resistance. Methods: The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. A global comparison of all the studied cell lines was performed in order to find out differentially expressed genes in the majority of the MTX-resistant cells. S100A4 mRNA and protein levels were determined by RT-Real-Time PCR and Western blot, respectively. Functional validations of S100A4 were performed either by transfection of an expression vector for S100A4 or a siRNA against S100A4. Transfection of an expression vector encoding for β-catenin was used to inquire for the possible transcriptional regulation of S100A4 through the Wnt pathway. Results: S100A4 is overexpressed in five out of the seven MTX-resistant cell lines studied. Ectopic overexpression of this gene in HT29 sensitive cells augmented both the intracellular and extracellular S100A4 protein levels and caused desensitization toward MTX. siRNA against S100A4 decreased the levels of this protein and caused a chemosensitization in combined treatments with MTX. β-catenin overexpression experiments support a possible involvement of the Wnt signaling pathway in S100A4 transcriptional regulation in HT29 cells. Conclusions: S100A4 is overexpressed in many MTX-resistant cells. S100A4 overexpression decreases the sensitivity of HT29 colon cancer human cells to MTX, whereas its knockdown causes chemosensitization toward MTX. Both approaches highlight a role for S100A4 in MTX resistanc

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Pileup mitigation at CMS in 13 TeV data

With increasing instantaneous luminosity at the LHC come additional reconstruction challenges. At high luminosity, many collisions occur simultaneously within one proton-proton bunch crossing. The isolation of an interesting collision from the additional "pileup" collisions is needed for effective physics performance. In the CMS Collaboration, several techniques capable of mitigating the impact of these pileup collisions have been developed. Such methods include charged-hadron subtraction, pileup jet identification, isospin-based neutral particle "delta beta" correction, and, most recently, pileup per particle identification. This paper surveys the performance of these techniques for jet and missing transverse momentum reconstruction, as well as muon isolation. The analysis makes use of data corresponding to 35.9 fb(-1) collected with the CMS experiment in 2016 at a center-of-mass energy of 13 TeV. The performance of each algorithm is discussed for up to 70 simultaneous collisions per bunch crossing. Significant improvements are found in the identification of pileup jets, the jet energy, mass, and angular resolution, missing transverse momentum resolution, and muon isolation when using pileup per particle identification.Peer reviewe