Bristol Hospital

The neutrophil-to-lymphocyte ratio (NLR) is a novel inflammatory marker predicting cardiovascular mortality (CVM) and all-cause mortality (ACM). To investigate the association between the NLR and CVM and ACM in patients with peritoneal dialysis (PD). We reviewed articles from PubMed, Google Scholar, and Scopus until May 2024 for the association of ACM and CVM in patients with NLR following PD. We used a fixed effects model and I 2 statistics to pool hazard ratio (HR) and measure heterogeneity. Leave-one-out sensitivity analysis assessed the robustness of our study. Multivariate meta-regression (MMR) was utilized to identify influencing confounding factors. Joanna Briggs Institute (JBI) tool was used for quality assessment. Out of 160 articles screened, seven studies from 2011 to 2024 with 4350 patients, a mean age of 49.9 years ± 15 years, and a median follow-up of 4 years were included. We found that higher NLR (> 3) was significantly associated with ACM [adjusted HR (aHR): 1.18, 95%CI: 1.03-1.36, P = 0.016]. However, there was no significant association of NLR (> 3) with CVM (aHR: 1.16, 95%CI: 0.68-1.98, P = 0.59) in patients following PD. Sensitivity analysis showed no variations. JBI tool revealed low bias among the studies. MMR revealed a significant relationship between age and ACM (coefficient: 0.14, P = 0.04). Our meta-analysis identifies a significant association between NLR (> 3) and ACM outcome, which can help prevent deaths in the elderly and optimize resource use. Caution is needed when predicting mortality in this group as age significantly confounds ACM in patients undergoing PD.

SummaryTeenage and young adult (TYA) patients undergoing allogeneic stem cell transplant have distinct psychosocial needs, yet they are poorly represented in research and their outcomes are not well understood. This study uses prospectively collected data from the British Society of Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT) registry to explore UK transplant practice and outcomes for TYA patients (aged 16–24) in this healthcare setting, alongside children (aged 1–15) and adults (aged 25–39), transplanted for acute leukaemia (including lymphoblastic, acute lymphoblastic leukaemia [ALL], and myeloid, acute myeloid leukaemia [AML]). Nine hundred and forty TYA patients, transplanted between 1999 and 2018, are included, representing 87% of all UK activity during the study period. On adjusted analyses, overall survival after transplant for ALL worsened from children, through TYA, to adults; survival for patients with AML was similar across age groups. Non‐relapse mortality was not significantly worse in TYA patients compared with children (p = 0.117 in ALL, p = 0.379 in AML). The risk of chronic graft‐versus‐host disease (GvHD) was strongly correlated with age, with rates in the TYA group much closer to those seen in adults. While a graft‐versus‐leukaemia effect may be suppressing relapse, the high rate of GvHD represents an unmet need in this group, who are at a crucial juncture in their personal, educational and social development.

Background International guidelines for S aureus bacteraemia often recommend screening echocardiography irrespective clinical factors that influence the likelihood of endocarditis, but this is not the case for enterococci or streptoccoci that are also high risk organism. Time to blood culture positivity (TTP) reflects bacterial load and has the potential to identify patients at higher risk of endocarditis. Methods We performed a retrospective analysis of clinical data that have been performed in a tertiary hospital in England. We investigate time to positivity (TTP) as a predictor variable in our S. aureus , enterococci and streptococci in logistic regression models and assess non-linearity of this affect using generalised additive models. We calculate NPV for TTP beyond the median value. Results The odds ratio for endocarditis from S. aureus bacteria was 0.92 (95%CI 0.85-0.99, p = 0.02) for each hour increase in TTP, with a negative predictive value of TTP greater than the median being 90% (95% CI 85-95%). For streptococci the OR was 1.02 (95%CI 0.98-1.06, p:0.31) and enterococci 1.08 (95% CI 0.99-1.18, p = 0.1) for every increase in hour of TTP. Conclusion Longer TTP is associated with lower risk of endocarditis in S. aureus bacteraemia, at 8% reduction per hour, giving an NPV of 90% beyond 13 hours. There was no evidence of association with enterococci or streptococci.

To explore modifications of the 2021 European Resuscitation Council/European Society of Intensive Care Medicine (ERC/ESICM) guideline algorithm for neuroprognostication after cardiac arrest to improve its prognostic accuracy. Post-hoc analysis of four prospective multicentre studies (TTM, TTM2, KORHN and ProNeCA). We raised the Glasgow Coma Scale motor (GCS-M) inclusion threshold at 72h after cardiac arrest from the current GCS-M<4 to GCS-M<6 (all unconscious patients). Secondly, we included good outcome predictors (GCS-M 4-5, neuron-specific enolase<17µg/L, benign electroencephalography patterns≤72h post-arrest and normal magnetic resonance imaging at 72-168h post-arrest) in the algorithm. Functional outcome was assessed dichotomously at six months, including modified Rankin Scale 0-3, Cerebral Performance Category 1-2 or Glasgow Outcome Scale 4-5 (no symptoms to moderate disability) as good outcome. We analysed 3,388 patients, of whom 2,079 had GCS-M<4 at≥72h. Of the 874 patients identified by the 2021 ERC/ESICM poor outcome criteria, 870 had poor functional outcome (specificity: 99.6% [95%CI 99.0-99.9]). Using the GCS-M<6 threshold, 366 more patients entered the algorithm (N=2,445). Seven more patients with poor outcomes were identified, with close to identical specificity. Good outcome predictors thereafter identified 673 patients with potential recovery, of whom 411 (61%) had a good functional outcome at six months. With the updated algorithm, the number of prognosticated patients with an indeterminate prognosis decreased from 1,205/2,079 (58%) to 891/2,445 (36%). Raising the GCS-M inclusion threshold and adding favourable predictors to the 2021 ERC/ESICM prognostication algorithm reduced prognostic uncertainty without increasing falsely pessimistic predictions.

International audience

Astrophysical observations provide compelling evidence for gravitationally interacting dark matter in the universe that cannot be explained by the standard model of particle physics. The extraordinary amount of data from the CERN LHC presents a unique opportunity to shed light on the nature of dark matter at unprecedented collision energies. This Report comprehensively reviews the most recent searches with the CMS experiment for particles and interactions belonging to a dark sector and for dark-sector mediators. Models with invisible massive particles are probed by searches for signatures of missing transverse momentum recoiling against visible standard model particles. Searches for mediators are also conducted via fully visible final states. The results of these searches are compared with those obtained from direct-detection experiments. Searches for alternative scenarios predicting more complex dark sectors with multiple new particles and new forces are also presented. Many of these models include long-lived particles, which could manifest themselves with striking unconventional signatures with relatively small amounts of background. Searches for such particles are discussed and their impact on dark-sector scenarios is evaluated. Many results and interpretations have been newly obtained for this Report.

Abstract BackgroundBlood culture remains a vital diagnostic tool in the acutely unwell patient. The UK Standards for Microbiology Investigations (SMI) stipulate pre-analytical requirements that are aimed at increasing yield and reducing turnaround time. The requirement to load blood cultures onto incubators within 4 hours has shown to reduce turnaround time but limited evidence exists as to whether it improves yield.MethodsWe extracted blood culture results including organism growth, time to detection (TTD), location and time of sample collection from 4 hospitals in Southwest England. We then used mixed effects, Bayesian linear and logistic regression models to examine the effect of predictor variables like time to loading (TTL) on the response variable of growth or TTD. We used generalised additive models to explore non-linearity.Results449,191 culture sets were analysed, 398,077 of which had enough data to include in the final analysis. 37,255 sets flagged positive (9.36%) of which 21,330 were considered pathogens. Our primary analysis identified a small decrease in yield with each hour delay in loading, OR 0.997 (95% credible interval, CrI 0.994 - 1.001). This effect was largest inStreptococcus pneumoniae, agalactiaeandpyogenes. In our analysis on TTD, culture sets spend 10.98 (95% CrI 7.8 – 13.2) minutes less incubating for each hour delay. There was no convincing non-linearity in either of these effects.ConclusionThere is a marginal loss of growth for every hour a blood culture is left unincubated, with the loss of recovery ofStreptococcus pyogenesand other streptococci most common. There was no evidence of a reduction in Gram-negatives, anaerobes, or yeasts. There was a small decrease in TTD for delayed sets. This analysis suggests there is only marginal benefit in reducing time to load blood cultures on incubators.HighlightsThe UK SMI stipulates blood cultures be loaded within 4 hours of being takenThe effect on yield has not been determined for delayed loadingWe found overall that there was a marginal 0.3% loss of yield per hour delayThere was a significant loss ofStreptococcus pyogenesat 3.2% per hour delay