The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

COVID-19 in Adults With Congenital Heart Disease.

BACKGROUND Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. OBJECTIVES This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. METHODS Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. RESULTS From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. CONCLUSIONS COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity

The Global Retinoblastoma Outcome Study: a prospective, cluster-based analysis of 4064 patients from 149 countries

Background Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. Methods We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1,2017, and Dec 31,2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. Findings The cohort included 4064 children from 149 countries. The median age at diagnosis was 23.2 months (IQR 11.0-36.5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0.8%) of 636 children from high-income countries, 55 (5.4%) of 1027 children from upper-middle-income countries, 342 (19. 7%) of 1738 children from lower-middle-income countries, and 196 (42.9%) of 457 children from low-income countries. Enudeation surgery was available for all children and intravenous chemotherapy was available for 4014 (98.8%) of 4064 children. The 3-year survival rate was 99.5% (95% CI 98.8-100.0) for children from high-income countries, 91.2% (89.5-93.0) for children from upper-middle-income countries, 80.3% (78.3-82.3) for children from lower-middle-income countries, and 57.3% (524-63-0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16.67; 95% CI 4.76-50.00), cT4 advanced tumour compared to cT1 (8.98; 4.44-18.18), and older age at diagnosis in children up to 3 years (1.38 per year; 1.23-1.56). For children aged 3-7 years, the mortality risk decreased slightly (p=0.0104 for the change in slope). Interpretation This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Y

Branching Fraction Measurements of the Rare Bs0→ϕμ+μ−B^0_s\rightarrow\phi\mu^+\mu^- and Bs0→f2′(1525)μ+μ−B^0_s\rightarrow f_2^\prime(1525)\mu^+\mu^-- Decays

International audienceThe branching fraction of the rare Bs0→ϕμ+μ- decay is measured using data collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to integrated luminosities of 1, 2, and 6  fb-1, respectively. The branching fraction is reported in intervals of q2, the square of the dimuon invariant mass. In the q2 region between 1.1 and 6.0  GeV2/c4, the measurement is found to lie 3.6 standard deviations below a standard model prediction based on a combination of light cone sum rule and lattice QCD calculations. In addition, the first observation of the rare Bs0→f2′(1525)μ+μ- decay is reported with a statistical significance of 9 standard deviations and its branching fraction is determined

Observation of excited Ωc0\Omega_c^0 baryons in Ωb−→Ξc+K−π−\Omega_b^- \to \Xi_c^+ K^-\pi^-decays

International audienceThe first observation of the Ωb-→Ξc+K-π- decay is reported using p p collision data at center of mass energies of 7, 8, and 13 TeV collected by the LHCb experiment, corresponding to an integrated luminosity of 9  fb-1. Four excited Ωc0 baryons are observed in the Ξc+ K- mass projection of the Ωb-→Ξc+K-π- decays with the significance of each exceeding five standard deviations. They coincide with the states previously observed in prompt pp and e+e- production. Relative production rates, masses, and natural widths of the states are measured, and a test of spin hypotheses is performed. Moreover, the branching ratio of Ωb-→Ξc+K-π- is measured relative to the Ωb-→Ωc0π- decay mode and a precise measurement of the Ωb- mass of 6044.3±1.2±1.1-0.22+0.19  MeV is obtained

Global Retinoblastoma Presentation and Analysis by National Income Level

This cross-sectional analysis reports the retinoblastoma stage at diagnosis across the world during a single year, investigates associations between clinical variables and national income level, and investigates risk factors for advanced disease at diagnosis. Key PointsQuestionIs the income level of a country of residence associated with the clinical stage of presentation of patients with retinoblastoma? FindingsIn this cross-sectional analysis that included 4351 patients with newly diagnosed retinoblastoma, approximately half of all new retinoblastoma cases worldwide in 2017, 49.1\% of patients from low-income countries had extraocular tumor at time of diagnosis compared with 1.5\% of patients from high-income countries. MeaningThe clinical stage of presentation of retinoblastoma, which has a major influence on survival, significantly differs among patients from low-income and high-income countries, which may warrant intervention on national and international levels. ImportanceEarly diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. ObjectivesTo report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and ParticipantsA total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and MeasuresAge at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. ResultsThe cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4\%) were female. Most patients (n=3685 {[}84.7\%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n=2638 {[}62.8\%]), followed by strabismus (n=429 {[}10.2\%]) and proptosis (n=309 {[}7.4\%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5\%) patients having intraocular retinoblastoma and 2 (0.3\%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1\%) having extraocular retinoblastoma and 94 of 498 (18.9\%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 {[}95\% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 {[}95\% CI, 4.30-7.68]). Conclusions and RelevanceThis study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Angular analysis of the rare decay Bs0 {B}_s^0 → ϕμ+^{+}μ−^{−}

International audienceAn angular analysis of the rare decay ${B}_s^0$→ ϕμ$^{+}$μ$^{−}$ is presented, using proton-proton collision data collected by the LHCb experiment at centre-of-mass energies of 7, 8 and 13 TeV, corresponding to an integrated luminosity of 8.4 fb$^{−1}$. The observables describing the angular distributions of the decay ${B}_s^0$→ ϕμ$^{+}$μ$^{−}$ are determined in regions of q$^{2}$, the square of the dimuon invariant mass. The results are consistent with Standard Model predictions.[graphic not available: see fulltext

Transverse polarisation measurement of Λ\Lambda hyperons in ppNe collisions at sNN\sqrt{s_{NN}}=68.4 GeV with the LHCb detector

A measurement of the transverse polarization of the $\Lambda$ and $\bar{\Lambda}$hyperons in $p$Ne fixed-target collisions at $\sqrt{s_{NN}}$=68.4 GeV is presented using data collected by the LHCb detector. The polarization is studied using the decay $\Lambda \rightarrow p \pi^-$ together with its charge conjugated process, the integrated values measured are $$P_{\Lambda} = 0.029 \pm 0.019 \, (\rm{stat}) \pm 0.012 \, (\rm{syst}) \, ,$$ $$P_{\bar{\Lambda}} = 0.003 \pm 0.023 \, (\rm{stat}) \pm 0.014 \,(\rm{syst}) \,$$ Furthermore, the results are shown as a function of the Feynman $x$ variable, transverse momentum, pseudorapidity and rapidity of the hyperons, and are compared with previous measurements.A measurement of the transverse polarization of the $\Lambda$ and $\bar{\Lambda}$ hyperons in $p$Ne fixed-target collisions at $\sqrt{s_{NN}}$ = 68.4 GeV is presented using data collected by the LHCb detector. The polarization is studied using the decay $\Lambda \rightarrow p \pi^-$ together with its charge conjugated process, the integrated values measured are $$P_{\Lambda} = 0.029 \pm 0.019 \, (\rm{stat}) \pm 0.012 \, (\rm{syst}) \, ,$$ $$P_{\bar{\Lambda}} = 0.003 \pm 0.023 \, (\rm{stat}) \pm 0.014 \,(\rm{syst}) \,.$$ Furthermore, the results are shown as a function of the Feynman~$x$~variable, transverse momentum, pseudorapidity and rapidity of the hyperons, and are compared with previous measurements

Measurement of the Branching Fraction of B0→J/ψπ0B^{0} \rightarrow J/\psi \pi^{0} Decays

International audienceThe ratio of branching fractions between $B^{0} \rightarrow J/\psi \pi^{0}$ and $B^{+} \rightarrow J/\psi K^{*+}$ decays is measured with proton-proton collision data collected by the LHCb experiment, corresponding to an integrated luminosity of 9 fb$^{-1}$. The measured value is $\frac{\mathcal{B}_{B^{0} \rightarrow J/\psi \pi^{0}}}{\mathcal{B}_{B^{+} \rightarrow J/\psi K^{*+}}} = (1.153 \pm 0.053 \pm 0.048 ) \times 10^{-2}$, where the first uncertainty is statistical and the second is systematic. The branching fraction for $B^{0} \rightarrow J/\psi \pi^{0}$ decays is determined using the branching fraction of the normalisation channel, resulting in $\mathcal{B}_{B^{0} \rightarrow J/\psi \pi^{0}} = (1.670 \pm 0.077 \pm 0.069 \pm 0.095) \times 10^{-5}$, where the last uncertainty corresponds to that of the external input. This result is consistent with the current world average value and competitive with the most precise single measurement to date

Test of lepton flavour universality using B0→D∗−τ+ντB^0 \to D^{*-}\tau^+\nu_{\tau} decays with hadronic τ\tau channels

The branching fraction $\mathcal{B}(B^0 \to D^{*-}\tau^+\nu_\tau)$ is measured relative to that of the normalisation mode $B^0 \to D^{*-}\pi^+\pi^-\pi^+$ using hadronic $\tau^+ \to \pi^+\pi^-\pi^+(\pi^0)\bar{\nu}_\tau$ decays in proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the LHCb experiment, corresponding to an integrated luminosity of 2 fb$^{-1}$. The measured ratio is $\mathcal{B}(B^0 \to D^{*-}\tau^+\nu_\tau)/\mathcal{B}(B^0 \to D^{*-}\pi^+\pi^-\pi^+)= 1.70 \pm 0.10^{+0.11}_{-0.10}$, where the first uncertainty is statistical and the second is related to systematic effects. Using established branching fractions for the $B^0 \to D^{*-}\pi^+\pi^-\pi^+$ and $B^0 \to D^{*-} \mu^+\nu_\mu$ modes, the lepton universality test, $\mathcal{R}(D^{*-}) \equiv \mathcal{B}(B^0 \to D^{*-}\tau^+\nu_\tau)/\mathcal{B}(B^0 \to D^{*-} \mu^+\nu_\mu)$ is calculated, $$\mathcal{R}(D^{*-}) = 0.247 \pm 0.015 \pm 0.015 \pm 0.012\, ,$$ where the third uncertainty is due to the uncertainties on the external branching fractions. This result is consistent with the Standard Model prediction and with previous measurements.The branching fraction B(B0→D*-τ+ντ) is measured relative to that of the normalization mode B0→D*-π+π-π+ using hadronic τ+→π+π-π+(π0)ν¯τ decays in proton-proton collision data at a center-of-mass energy of 13 TeV collected by the LHCb experiment, corresponding to an integrated luminosity of 2  fb-1. The measured ratio is B(B0→D*-τ+ντ)/B(B0→D*-π+π-π+)=1.70±0.10-0.10+0.11, where the first uncertainty is statistical and the second is related to systematic effects. Using established branching fractions for the B0→D*-π+π-π+ and B0→D*-μ+νμ modes, the lepton universality test R(D*-)≡B(B0→D*-τ+ντ)/B(B0→D*-μ+νμ) is calculated, R(D*-)=0.247±0.015±0.015±0.012, where the third uncertainty is due to the uncertainties on the external branching fractions. This result is consistent with the Standard Model prediction and with previous measurements.The branching fraction $\mathcal{B}(B^0 \to D^{*-}\tau^+\nu_{\tau})$ is measured relative to that of the normalisation mode $B^0 \to D^{*-}\pi^+\pi^-\pi^+$ using hadronic $\tau^+ \to \pi^+\pi^-\pi^+(\pi^0)\bar{\nu}_{\tau}$ decays in proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the LHCb experiment, corresponding to an integrated luminosity of 2 fb$^{-1}$. The measured ratio is $\mathcal{B}(B^0 \to D^{*-}\tau^+\nu_{\tau})/\mathcal{B}(B^0 \to D^{*-}\pi^+\pi^-\pi^+)= 1.70 \pm 0.10^{+0.11}_{-0.10}$, where the first uncertainty is statistical and the second is related to systematic effects. Using established branching fractions for the $B^0 \to D^{*-}\pi^+\pi^-\pi^+$ and $B^0 \to D^{*-} \mu^+\nu_\mu$ modes, the lepton universality test, $\mathcal{R}(D^{*-}) \equiv \mathcal{B}(B^0 \to D^{*-}\tau^+\nu_{\tau})/\mathcal{B}(B^0 \to D^{*-} \mu^+\nu_\mu)$ is calculated, $$\mathcal{R}(D^{*-}) = 0.247 \pm 0.015 \pm 0.015 \pm 0.012\, ,$$ where the third uncertainty is due to the uncertainties on the external branching fractions. This result is consistent with the Standard Model prediction and with previous measurements