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

Predictors; Macular edema; Non-infectious uveitisPredictors; Edema macular; Uveïtis no infecciosaPredictores; Edema macular; Uveítis no infecciosaAIMS: 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 μm 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 mm2 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 μm) 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

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

Supplemental material available at www.aaojournal.org. Supported by AbbVie, Inc., and the Fundamentals of Care for Uveitis Initiative National Faculty. This manuscript was developed subsequent to an AbbVie-sponsored literature review of noninfectious, nonanterior uveitis. The meeting was conducted to understand the available literature regarding the management of patients with noninfectious, nonanterior uveitis. The program involved a total of 139 experts from 28 countries, who were selected for participation by AbbVie. However, AbbVie was not involved in the development of the manuscript. The authors maintained complete control over the content and this manuscript reflects the opinions of the authors. AbbVie selected the discussion participants and reviewed the final manuscript draft for scientific accuracy, but the authors determined the final content. All authors made substantial contributions to the article or critically revised it for important intellectual content and approved the final manuscript. AbbVie provided funding to invited participants, including honoraria for their attendance at the meetings. Travel to and from the meetings was reimbursed. No payments were made to the authors for the development of this manuscript. Dhinakaran Sambandan, PhD, and Shula Sarner, PhD, of Lucid Partners, Burleighfield House, Buckinghamshire, United Kingdom, provided medical writing and editorial support to the authors in the development of this manuscript; financial support for these services was provided by AbbVie. AbbVie reviewed the manuscript, but was not involved in the methodology, data collection and analysis, or completion of this manuscript.Peer reviewedPublisher PD

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

CLUH regulates mitochondrial metabolism by controlling translation and decay of target mRNAs

Mitochondria are essential organelles that host crucial metabolic pathways and produce adenosine triphosphate. The mitochondrial proteome is heterogeneous among tissues and can dynamically change in response to different metabolic conditions. Although the transcriptional programs that govern mitochondrial biogenesis and respiratory function are well known, posttranscriptional regulatory mechanisms remain unclear. In this study, we show that the cytosolic RNA-binding protein clustered mitochondria homologue (CLUH) regulates the expression of a mitochondrial protein network supporting key metabolic programs required under nutrient deprivation. CLUH exerts its function by controlling the stability and translation of target messenger RNAs. In the absence of Cluh, mitochondria are severely depleted of crucial enzymes involved in catabolic energy-converting pathways. CLUH preserves oxidative mitochondrial function and glucose homeostasis, thus preventing death at the fetal–neonatal transition. In the adult liver, CLUH ensures maximal respiration capacity and the metabolic response to starvation. Our results shed new light on the posttranscriptional mechanisms controlling the expression of mitochondrial proteins and suggest novel strategies to tailor mitochondrial function to physiological and pathological conditions.Peer reviewe

Surgical treatment for colorectal cancer: Analysis of the influence of an enhanced recovery programme on long-term oncological outcomes-a study protocol for a prospective, multicentre, observational cohort study

Introduction The evidence currently available from enhanced recovery after surgery (ERAS) programmes concerns their benefits in the immediate postoperative period, but there is still very little evidence as to whether their correct implementation benefits patients in the long term. The working hypothesis here is that, due to the lower response to surgical aggression and lower rates of postoperative complications, ERAS protocols can reduce colorectal cancer-related mortality. The main objective of this study is to analyse the impact of an ERAS programme for colorectal cancer on 5-year survival. As secondary objectives, we propose to analyse the weight of each of the predefined items in the oncological results as well as the quality of life. Methods and analysis A multicentre prospective cohort study was conducted in patients older than 18 years of age who are scheduled to undergo surgery for colorectal cancer. The study involved 12 hospitals with an implemented enhanced recovery protocol according to the guidelines published by the Spanish National Health Service. The intervention group includes patients with a minimum implementation level of 70%, and the control group includes those who fail to reach this level. Compliance will be studied using 18 key performance indicators, and the results will be analysed using cancer survival indicators, including overall survival, cancer-specific survival and relapse-free survival. The time to recurrence, perioperative morbidity and mortality, hospital stay and quality of life will also be studied, the latter using the validated EuroQol Five questionnaire. The propensity index method will be used to create comparable treatment and control groups, and a multivariate regression will be used to study each variable. The Kaplan-Meier estimator will be used to estimate survival and the log-rank test to make comparisons. A p value of less than 0.05 (two-tailed) will be considered to be significant. Ethics and dissemination Ethical approval for this study was obtained from the Aragon Ethical Committee (C.P.-C.I. PI20/086) on 4 March 2020. The findings of this study will be submitted to peer-reviewed journals (BMJ Open, JAMA Surgery, Annals of Surgery, British Journal of Surgery). Abstracts will be submitted to relevant national and international meetings.The present research study was awarded a Ministerio de Ciencia e Innovación health research project grant (PI19/00291) from the Carlos III Institute of the Spanish National Health Service as part of the 2019 call for Strategic Action in Health

Measurement of charm production at central rapidity in proton-proton collisions at s=2.76\sqrt{s} = 2.76 TeV

The $p_{\rm T}$-differential production cross sections of the prompt (B feed-down subtracted) charmed mesons D$^0$, D$^+$, and D$^{*+}$ in the rapidity range $|y|<0.5$, and for transverse momentum $1< p_{\rm T} <12$ GeV/$c$, were measured in proton-proton collisions at $\sqrt{s} = 2.76$ TeV with the ALICE detector at the Large Hadron Collider. The analysis exploited the hadronic decays D$^0 \rightarrow$K$\pi$, D$^+ \rightarrow$K$\pi\pi$, D$^{*+} \rightarrow$D$^0\pi$, and their charge conjugates, and was performed on a $L_{\rm int} = 1.1$ nb$^{-1}$ event sample collected in 2011 with a minimum-bias trigger. The total charm production cross section at $\sqrt{s} = 2.76$ TeV and at 7 TeV was evaluated by extrapolating to the full phase space the $p_{\rm T}$-differential production cross sections at $\sqrt{s} = 2.76$ TeV and our previous measurements at $\sqrt{s} = 7$ TeV. The results were compared to existing measurements and to perturbative-QCD calculations. The fraction of cdbar D mesons produced in a vector state was also determined.Comment: 20 pages, 5 captioned figures, 4 tables, authors from page 15, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/307

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry