Novel immunotherapeutic options for BCG‐unresponsive high‐risk non‐muscle‐invasive bladder cancer

Abstract Background High‐risk non‐muscle‐invasive bladder cancer (HR‐NMIBC) presents a challenge to many physicians due to its ability to resist Bacillus Calmette–Guérin (BCG) intravesical therapy and the substantial rate of progression into muscle‐invasive bladder cancer (MIBC). Patients who are BCG‐unresponsive have worse prognosis and thus require further management including radical cystectomy (RC), which significantly impacts quality of life. Moreover, the ongoing worldwide shortage of BCG warrants the need for policies that prioritize drug use and utilize alternative treatment strategies. Hence, there is a significant unmet need for bladder preserving therapy in this subset of patients. Methods To address this issue, we searched the relevant literature in PUBMED for articles published from 2019 through May of 2023 using appropriate keywords. All clinical trials of patients with HR‐NMIBC treated with immune‐related agents were retrieved from clinicaltrials.gov. Findings and Future Perspectives Exploratory treatments for BCG‐Unresponsive HR‐NMIBC included immune checkpoint inhibitors (ICI), oncolytic viral therapy, cytokine agonists, and other immunomodulators targeting TLR, EpCaM, FGFR, MetAP2, and IDO1. Some combination therapies have been found to work synergistically and are preferred therapeutically over monotherapy. Three drugs—pembrolizumab, valrubicin, and most recently, nadofaragene firadenovec‐vncg—have been FDA approved for the treatment of BCG‐unresponsive NMIBC in patients who are ineligible for or decline RC. However, all explored treatment options tend to postpone RC rather than provide long‐term disease control. Additional combination strategies need to be studied to enhance the effects of immunotherapy. Despite the challenges faced in finding effective therapies, many potential treatments are currently under investigation. Addressing the landscape of biomarkers, mechanisms of progression, BCG resistance, and trial design challenges in HR‐NMIBC is essential for the discovery of new targets and the development of effective treatments

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

Two-particle Bose-Einstein correlations and their Lévy parameters in PbPb collisions at sNN\sqrt{s_\mathrm{NN}} = 5.02 TeV

Two-particle Bose-Einstein momentum correlation functions are studied for charged-hadron pairs in lead-lead collisions at a center-of-mass energy per nucleon pair of $\sqrt{s_\mathrm{NN}}$ = 5.02 TeV. The data sample, containing 4.27$\times10^{9}$ minimum bias events corresponding to an integrated luminosity of 0.607 nb$^{-1}$, was collected by the CMS experiment in 2018. The experimental results are discussed in terms of a L\'evy-type source distribution. The parameters of this distribution are extracted as functions of particle pair average transverse mass and collision centrality. These parameters include the L\'evy index or shape parameter ($\alpha$), the L\'evy scale parameter ($R$), and the correlation strength parameter ($\lambda$). The source shape, characterized by $\alpha$, is found to be neither Cauchy nor Gaussian, implying the need for a full L\'evy analysis. Similarly to what was previously found for systems characterized by Gaussian source radii, a hydrodynamical scaling is observed for the L\'evy $R$ parameter. The $\lambda$ parameter is studied in terms of the core-halo model.Comment: Submitted to Physical Review C. All figures and tables can be found at http://cms-results.web.cern.ch/cms-results/public-results/publications/HIN-21-011 (CMS Public Pages

Two-particle Bose-Einstein correlations and their Lévy parameters in PbPb collisions at sNN\sqrt{s_\mathrm{NN}} = 5.02 TeV

International audienceTwo-particle Bose-Einstein momentum correlation functions are studied for charged-hadron pairs in lead-lead collisions at a center-of-mass energy per nucleon pair of $\sqrt{s_\mathrm{NN}}$ = 5.02 TeV. The data sample, containing 4.27$\times10^{9}$ minimum bias events corresponding to an integrated luminosity of 0.607 nb$^{-1}$, was collected by the CMS experiment in 2018. The experimental results are discussed in terms of a Lévy-type source distribution. The parameters of this distribution are extracted as functions of particle pair average transverse mass and collision centrality. These parameters include the Lévy index or shape parameter ($\alpha$), the Lévy scale parameter ($R$), and the correlation strength parameter ($\lambda$). The source shape, characterized by $\alpha$, is found to be neither Cauchy nor Gaussian, implying the need for a full Lévy analysis. Similarly to what was previously found for systems characterized by Gaussian source radii, a hydrodynamical scaling is observed for the Lévy $R$ parameter. The $\lambda$ parameter is studied in terms of the core-halo model

Search for the lepton flavor violating τ ⁣→ ⁣3μ \tau \!\to\! 3\mu decay in proton-proton collisions at s= \sqrt{s} = 13 TeV

A search for the lepton flavor violating $\tau \!\to\! 3\mu$ decay is performed using proton-proton collision events at a center-of-mass energy of 13 TeV collected by the CMS experiment at the LHC in 2017--2018, corresponding to an integrated luminosity of 97.7 fb$^{-1}$. Tau leptons produced in both heavy-flavor hadron and W boson decays are exploited in the analysis. No evidence for the decay is observed. The results of this search are combined with an earlier null result based on data collected in 2016 to obtain a total integrated luminosity of 131 fb$^{-1}$. The observed (expected) upper limits on the branching fraction $\mathcal{B}(\tau \!\to\! 3\mu)$ at confidence levels of 90 and 95% are 2.9 $\times$ 10$^{-8}$ (2.4 $\times$ 10$^{-8}$) and 3.6 $\times$ 10$^{-8}$ (3.0 $\times$ 10$^{-8}$), respectively.A search for the lepton flavor violating $\tau \to$ 3$\mu$ decay is performed using proton-proton collision events at a center-of-mass energy of 13 TeV collected by the CMS experiment at the LHC in 2017-2018, corresponding to an integrated luminosity of 97.7 fb$^{-1}$. Tau leptons produced in both heavy-flavor hadron and W boson decays are exploited in the analysis. No evidence for the decay is observed. The results of this search are combined with an earlier null result based on data collected in 2016 to obtain a total integrated luminosity of 131 fb$^{-1}$. The observed (expected) upper limits on the branching fraction $\mathcal{B}$($\tau \to$ 3$\mu$) at confidence levels of 90 and 95% are 2.9$\times$10$^{-8}$ (2.4$\times$10$^{-8}$) and 3.6$\times$10$^{-8}$ (3.0$\times$10$^{-8}$), respectively

Search for exotic Higgs boson decays H →\toAA\mathcal{A}\mathcal{A}→\to 4γ\gamma with events containing two merged diphotons in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceWe present the first direct search for exotic Higgs boson decays H $\to$$\mathcal{A}\mathcal{A}$, $\mathcal{A}$$\to$$\gamma\gamma$ in events with two photonlike objects. The hypothetical particle $\mathcal{A}$ is a low-mass spin-0 particle decaying promptly to a merged diphoton reconstructed as a single photonlike object. We analyze the data collected by the CMS experiment at $\sqrt{s}$ = 13 TeV corresponding to an integrated luminosity of 136 fb$^{-1}$. No excess above the estimated background is found. We set upper limits on the branching fraction $\mathcal{B}$(H $\to$$\mathcal{A}\mathcal{A}$$\to$ 4$\gamma$) of (0.9-3.3) $\times$ 10$^{-3}$ at 95% confidence level for masses of $\mathcal{A}$ in the range 0.1-1.2 GeV

Luminosity determination using Z boson production at the CMS experiment

International audienceThe measurement of Z boson production is presented as a method to determine the integrated luminosity of CMS data sets. The analysis uses proton-proton collision data, recorded by the CMS experiment at the CERN LHC in 2017 at a center-of-mass energy of 13 TeV. Events with Z bosons decaying into a pair of muons are selected. The total number of Z bosons produced in a fiducial volume is determined, together with the identification efficiencies and correlations from the same dataset, in small intervals of 2 pb$^{-1}$ of integrated luminosity, thus facilitating the efficiency and rate measurement as a function of time and instantaneous luminosity. Using the ratio of the efficiency-corrected numbers of Z bosons, the precisely measured integrated luminosity of one data set is used to determine the luminosity of another. For the first time, a full quantitative uncertainty analysis of the use of Z bosons for the integrated luminosity measurement is performed. The uncertainty in the extrapolation between two data sets, recorded in 2017 at low and high instantaneous luminosity, is less than 0.5%. We show that the Z boson rate measurement constitutes a precise method, complementary to traditional methods, with the potential to improve the measurement of the integrated luminosity

Search for inelastic dark matter in events with two displaced muons and missing transverse momentum in proton-proton collisions at s= \sqrt{s} = 13 TeV

A search for dark matter in events with a displaced muon pair and missing transverse momentum is presented. The analysis is performed using an integrated luminosity of 138 fb$^{-1}$ of proton-proton (pp) collision data at a center-of-mass energy of 13 TeV produced by the LHC in 2016-2018. No significant excess over the predicted backgrounds is observed. Upper limits are set on the product of the inelastic dark matter production cross section $\sigma(\mathrm{p}\mathrm{p}\to \mathrm{A}' \to \chi_1 \, \chi_2)$ and the decay branching fraction $\mathcal{B}(\chi_2 \to \chi_1 \, \mu^{+} \, \mu^{-})$, where A' is a dark photon and $\chi_1$ and $\chi_2$ are dark matter states with near mass degeneracy. This is the first dedicated collider search for inelastic dark matter.A search for dark matter in events with a displaced muon pair and missing transverse momentum is presented. The analysis is performed using an integrated luminosity of 138 fb$^{-1}$ of proton-proton (pp) collision data at a center-of-mass energy of 13 TeV produced by the LHC in 2016-2018. No significant excess over the predicted backgrounds is observed. Upper limits are set on the product of the inelastic dark matter production cross section $\sigma$(pp $\to$ A' $\to$$\chi_1$$\chi_2$) and the decay branching fraction $\mathcal{B}$($\chi_2$$\to$$\chi_1\mu^+\mu^-$), where A' is a dark photon and $\chi_1$ and $\chi_2$ are dark matter states with near mass degeneracy. This is the first dedicated collider search for inelastic dark matter

Search for W' bosons decaying to a top and a bottom quark in leptonic final states in proton-proton collisions at s= \sqrt{s} = 13 TeV

A search for W' bosons decaying to a top and a bottom quark in final states including an electron or a muon is performed with the CMS detector at the LHC. The analyzed data correspond to an integrated luminosity of 138 fb$^{-1}$ of proton-proton collisions at a center-of-mass energy of 13 TeV. Good agreement with the standard model expectation is observed and no evidence for the existence of the W' boson is found over the mass range examined. The largest observed deviation from the standard model expectation is found for a W' boson mass ($m_{\mathrm{W^{'}}}$) hypothesis of 3.8 TeV with a relative decay width of 1%, with a local (global) significance of 2.6 (2.0) standard deviations. Upper limits on the production cross sections of W' bosons decaying to a top and a bottom quark are set. Left- and right-handed W' bosons with $m_{\mathrm{W^{'}}}$ below 3.9 and 4.3 TeV, respectively, are excluded at the 95% confidence level, under the assumption that the new particle has a narrow decay width. Limits are also set for relative decay widths up to 30%. These are the most stringent limits to date on this W' boson decay channel.A search for W' bosons decaying to a top and a bottom quark in final states including an electron or a muon is performed with the CMS detector at the LHC. The analyzed data correspond to an integrated luminosity of 138 fb$^{-1}$ of proton-proton collisions at a center-of-mass energy of 13 Tev. Good agreement with the standard model expectation is observed and no evidence for the existence of the W' boson is found over the mass range examined. The largest observed deviation from the standard model expectation is found for a W' boson mass ($m_\mathrm{W'}$) hypothesis of 3.8 TeV with a relative decay width of 1%, with a local (global) significance of 2.6 (2.0) standard deviations. Upper limits on the production cross sections of W' bosons decaying to a top and a bottom quark are set. Left- and right-handed W' bosons with $m_\mathrm{W'}$ below 3.9 and 4.3 TeV, respectively, are excluded at the 95% confidence level, under the assumption that the new particle has a narrow decay width. Limits are also set for relative decay widths up to 30%. These are the most stringent limits to date on this W' boson decay channel