Effectiveness of management strategies for uninvestigated dyspepsia: systematic review and network meta-analysis

Objective To determine the effectiveness of management strategies for uninvestigated dyspepsia. Design Systematic review and network meta-analysis. Data sources Medline, Embase, Embase Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov from inception to September 2019, with no language restrictions. Conference proceedings between 2001 and 2019. Eligibility criteria for selecting studies Randomised controlled trials that assessed the effectiveness of management strategies for uninvestigated dyspepsia in adult participants (age ≥18 years). Strategies of interest were prompt endoscopy; test for Helicobacter pylori and perform endoscopy in participants who test positive; test for H pylori and eradication treatment in those who test positive (“test and treat”); empirical acid suppression; or symptom based management. Trials reported dichotomous assessment of symptom status at final follow-up (≥12 months). Results The review identified 15 eligible randomised controlled trials that comprised 6162 adult participants. Data were pooled using a random effects model. Strategies were ranked according to P score, which is the mean extent of certainty that one management strategy is better than another, averaged over all competing strategies. “Test and treat” ranked first (relative risk of remaining symptomatic 0.89, 95% confidence interval 0.78 to 1.02, P score 0.79) and prompt endoscopy ranked second, but performed similarly (0.90, 0.80 to 1.02, P score 0.71). However, no strategy was significantly less effective than “test and treat.” Participants assigned to “test and treat” were significantly less likely to receive endoscopy (relative risk v prompt endoscopy 0.23, 95% confidence interval 0.17 to 0.31, P score 0.98) than all other strategies, except symptom based management (relative risk v symptom based management 0.60, 0.30 to 1.18). Dissatisfaction with management was significantly lower with prompt endoscopy (P score 0.95) than with “test and treat” (relative risk v “test and treat” 0.67, 0.46 to 0.98), and empirical acid suppression (relative risk v empirical acid suppression 0.58, 0.37 to 0.91). Upper gastrointestinal cancer rates were low in all trials. Results remained stable in sensitivity analyses, with minimal inconsistencies between direct and indirect results. Risk of bias of individual trials was high; blinding was not possible because of the pragmatic trial design. Conclusions “Test and treat” was ranked first, although it performed similarly to prompt endoscopy and was not superior to any of the other strategies. “Test and treat” led to fewer endoscopies than all other approaches, except symptom based management. However, participants showed a preference for prompt endoscopy as a management strategy for their symptoms. Systematic review registration PROSPERO registration number CRD42019132528

Endoscopic ultrasound-guided fine-needle aspiration vs fine-needle biopsy for the diagnosis of pancreatic neuroendocrine tumors

Background and study aims Endoscopic ultrasoundguided fine-needle aspiration (EUS-FNA) as a method of obtaining preoperative diagnosis of pancreatic neuroendocrine tumors (PanNETs) has been reported in several series. Fine-needle biopsies (FNB) are increasingly employed to obtain core specimens during EUS. However, the differences in efficacy between these sampling methods in the diagnosis of PanNETs still needs to be defined. Patients and methods Over a 13-year period, all patients who underwent EUS-guided tissue sampling of suspicious pancreatic lesions with clinical, endoscopic and pathologic details were entered into an electronic database. Lesions underwent EUS-FNA or FNB sampling, or a combination of the two. The accuracy and safety of different EUS-guided sampling methods for confirmed PanNETs were investigated. Results A total of 91 patients (M/F: 42/49, median age: 57 years), who underwent 102 EUS procedures had a final diagnosis of PanNET. Both EUS-guided sampling modalities were used in 28 procedures, EUS-FNA alone was used in 61 cases, while EUS-FNB alone in 13 cases. Diagnostic yield of EUS-FNA and EUS-FNB alone, including the inadequate specimens, was 77.5 % (95 %CI: 68.9 – 86.2%) and 85.4 % (95 % CI: 74.6 – 96.2 %), respectively. The combination of both sampling modalities established the diagnosis in 96.4 % of cases (27/28) (95 %CI: 89.6 – 100%), significantly superior to EUS-FNA alone (P = 0.023). Diagnostic sensitivity among the adequate samples for EUS-FNA, EUS-FNB and for the combination of the two methods was 88.4 % (95 %CI: 80.9 – 96.0 %), 94.3% (95 %CI: 86.6 – 100%) and 100% (95% CI: 100 – 100 %). There was one reported complication, a post-FNA bleeding, treated conservatively. Conclusions EUS-FNB improves diagnostic sensitivity and confers additional information to cytological assessment of PanNETs

Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype

BACKGROUND: We aimed to clarify the incidence and the clinicopathological value of non-muscle myoglobin (Mb) in a large cohort of non-invasive and invasive breast cancer cases. METHODS: Matched pairs of breast tissues from 10 patients plus 17 breast cell lines were screened by quantitative PCR for Mb mRNA. In addition, 917 invasive and 155 non-invasive breast cancer cases were analysed by immunohistochemistry for Mb expression and correlated to clinicopathological parameters and basal molecular characteristics including oestrogen receptor-alpha (ERalpha)/progesteron receptor (PR)/HER2, fatty acid synthase (FASN), hypoxia-inducible factor-1alpha (HIF-1alpha), HIF-2alpha, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX). The spatial relationship of Mb and ERalpha or FASN was followed up by double immunofluorescence. Finally, the effects of estradiol treatment and FASN inhibition on Mb expression in breast cancer cells were analysed. RESULTS: Myoglobin mRNA was found in a subset of breast cancer cell lines; in microdissected tumours Mb transcript was markedly upregulated. In all, 71% of tumours displayed Mb protein expression in significant correlation with a positive hormone receptor status and better prognosis. In silico data mining confirmed higher Mb levels in luminal-type breast cancer. Myoglobin was also correlated to FASN, HIF-2alpha and CAIX, but not to HIF-1alpha or GLUT1, suggesting hypoxia to participate in its regulation. Double immunofluorescence showed a cellular co-expression of ERalpha or FASN and Mb. In addition, Mb levels were modulated on estradiol treatment and FASN inhibition in a cell model. CONCLUSION: We conclude that in breast cancer, Mb is co-expressed with ERalpha and co-regulated by oestrogen signalling and can be considered a hallmark of luminal breast cancer phenotype. This and its possible new role in fatty acid metabolism may have fundamental implications for our understanding of Mb in solid tumours

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Association between Helicobacter pylori genotypes and severity of chronic gastritis, peptic ulcer disease and gastric mucosal interleukin-8 levels: evidence from a study in the Middle East

Background: The varied clinical presentations of Helicobacter pylori (H. pylori) infection are most likely due to differences in the virulence of individual strains, which determines its ability to induce production of interleukin-8 (IL-8) in the gastric mucosa. The aim of this study was to examine association between cagA, vacA-s1 and vacA-s2 genotypes of H. pylori and severity of chronic gastritis and presence of peptic ulcer disease (PUD), and to correlate these with IL-8 levels in the gastric mucosa. Methods: Gastric mucosal biopsies were obtained from patients during esophagogastroduodenoscopy. The severity of chronic gastritis was documented using the updated Sydney system. H. pylori cagA and vacA genotypes were detected by PCR. The IL-8 levels in the gastric mucosa were measured by ELISA. Results: H. pylori cagA and/or vacA genotypes were detected in 99 patients (mean age 38.4±12.9; 72 males), of whom 52.5% were positive for cagA, 44.4% for vacA-s1 and 39.4% for vacA-s2; and 70.7% patients had PUD. The severity of inflammation in gastric mucosa was increased with vacA-s1 (p=0.017) and decreased with vacA-s2 (p=0.025), while cagA had no association. The degree of neutrophil activity was not associated with either cagA or vacA-s1, while vacA-s2 was significantly associated with decreased neutrophil activity (p=0.027). PUD was significantly increased in patients with cagA (p=0.002) and vacA-s1 (p=0.031), and decreased in those with vacA-s2 (p=0.011). The level of IL-8 was significantly increased in patients with cagA (p=0.011) and vacA-s1 (p=0.024), and lower with vacA-s2 (p=0.004). Higher levels of IL-8 were also found in patients with a more severe chronic inflammation (p=0.001), neutrophil activity (p=0.007) and those with PUD (p=0.001). Conclusions: Presence of vacA-s1 genotype of H. pylori is associated with more severe chronic inflammation and higher levels of IL-8 in the gastric mucosa, as well as higher frequency of PUD. Patients with vacA-s2 have less severe gastritis, lower levels of IL-8, and lower rates of PUD. The presence of cagA genotype is not associated with the severity of gastritis or IL-8 induction in the gastric mucosa. The association of cagA with PUD may be a reflection of its presence with vacA-s1 genotype

Search for Higgs boson decays to a Z boson and a photon in proton-proton collisions at s \sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2204.12945v2 [hep-ex], https://arxiv.org/abs/2204.12945v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/HIG-19-014 (CMS Public Pages). Report number: CMS-HIG-19-014, CERN-EP-2022-019.Results are presented from a search for the Higgs boson decay H → Zγ, where Z → ℓ+ℓ− with ℓ = e or μ. The search is performed using a sample of proton-proton (pp) collision data at a center-of-mass energy of 13 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138 fb^{−1}. Events are assigned to mutually exclusive categories, which exploit differences in both event topology and kinematics of distinct Higgs production mechanisms to enhance signal sensitivity. The signal strength μ, defined as the product of the cross section and the branching fraction [σ(pp → H)B(H → Zγ)] relative to the standard model prediction, is extracted from a simultaneous fit to the ℓ+ℓ−γ invariant mass distributions in all categories and is found to be μ = 2.4 ± 0.9 for a Higgs boson mass of 125.38 GeV. The statistical significance of the observed excess of events is 2.7 standard deviations. This measurement corresponds to σ(pp → H)B(H → Zγ) = 0.21 ± 0.08 pb. The observed (expected) upper limit at 95% confidence level on μ is 4.1 (1.8). The ratio of branching fractions B(H → Zγ)/B(H → γγ) is measured to be 1.5 +0.7−0.6, which agrees with the standard model prediction of 0.69 ± 0.04 at the 1.5 standard deviation level.SCOAP3

Measurements of the Higgs boson production cross section and couplings in the W boson pair decay channel in proton-proton collisions at s\sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2206.09466v2 [hep-ex], https://arxiv.org/abs/2206.09466v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at httpS://cms-results.web.cern.ch/cms-results/public-results/publications/HIG-20-013 (CMS Public Pages). Report number: CMS-HIG-20-013, CERN-EP-2022-120.Production cross sections of the standard model Higgs boson decaying to a pair of W bosons are measured in proton-proton collisions at a center-of-mass energy of 13 TeV. The analysis targets Higgs bosons produced via gluon fusion, vector boson fusion, and in association with a W or Z boson. Candidate events are required to have at least two charged leptons and moderate missing transverse momentum, targeting events with at least one leptonically decaying W boson originating from the Higgs boson. Results are presented in the form of inclusive and differential cross sections in the simplified template cross section framework, as well as couplings of the Higgs boson to vector bosons and fermions. The data set collected by the CMS detector during 2016-2018 is used, corresponding to an integrated luminosity of 138 fb^−1. The signal strength modifier μ, defined as the ratio of the observed production rate in a given decay channel to the standard model expectation, is measured to be μ = 0.95 +0.10−0.09. All results are found to be compatible with the standard model within the uncertainties.SCOAP3

Search for direct production of GeV-scale resonances decaying to a pair of muons in proton-proton collisions at s\sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2309.16003v2 [hep-ex], https://arxiv.org/abs/2309.16003v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables, including additional supplementary figures, can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/EXO-21-005 (CMS Public Pages). Report number: CMS-EXO-21-005, CERN-EP-2023-165.A search for direct production of low-mass dimuon resonances is performed using s√ = 13 TeV proton-proton collision data collected by the CMS experiment during the 2017-2018 operation of the CERN LHC with an integrated luminosity of 96.6 fb−1. The search exploits a dedicated high-rate trigger stream that records events with two muons with transverse momenta as low as 3 GeV but does not include the full event information. The search is performed by looking for narrow peaks in the dimuon mass spectrum in the ranges of 1.1-2.6 GeV and 4.2-7.9 GeV. No significant excess of events above the expectation from the standard model background is observed. Model-independent limits on production rates of dimuon resonances within the experimental fiducial acceptance are set. Competitive or world's best limits are set at 90% confidence level for a minimal dark photon model and for a scenario with two Higgs doublets and an extra complex scalar singlet (2HDM+S). Values of the squared kinetic mixing coefficient ε2 in the dark photon model above 10−6 are excluded over most of the mass range of the search. In the 2HDM+S, values of the mixing angle sin(θH) above 0.08 are excluded over most of the mass range of the search with a fixed ratio of the Higgs doublets vacuum expectation tanβ = 0.5.SCOAP3