The prognostic value of elevated neutrophil–lymphocyte ratio for cardiac surgery-associated acute kidney injury: A systematic review and meta-analysis

Background

Patients undergoing cardiac surgery are at significant risk of developing postoperative acute kidney injury (AKI). Neutrophil–lymphocyte ratio (NLR) is a widely available inflammatory biomarker which may be of prognostic value in this setting.

Methods

We conducted a systematic review and meta-analysis of studies reporting associations between perioperative NLR with postoperative AKI. We searched Medline, Embase and the Cochrane Library, without language restriction, from inception to May 2022 for relevant studies. We meta-analysed the reported odds ratios (ORs) with 95% confidence intervals (CIs) for both elevated preoperative and postoperative NLR with risk of postoperative AKI and need for renal replacement therapy (RRT). We conducted a meta-regression to explore inter-study statistical heterogeneity.

Results

Twelve studies involving 10,724 participants undergoing cardiac surgery were included, with eight studies being deemed at high risk of bias using PROBAST modelling. We found statistically significant associations between elevated preoperative NLR and postoperative AKI (OR 1.45, 95% CI 1.18–1.77), as well as postoperative need for RRT (OR 2.37, 95% CI 1.50–3.72). Postoperative NLR measurements were not of prognostic significance.

Conclusions

Elevated preoperative NLR is a reliable inflammatory biomarker for predicting AKI following cardiac surgery.     

Moderate Colitis Not Requiring Intravenous Steroids Is Associated with Improved Survival in Stage IV Melanoma after Anti-CTLA4 Monotherapy,But Not Combination Therapy

BackgroundFor patients with melanoma, gastrointestinal immune-related adverse events are common after receipt of anti-CTLA4 therapy. These present difficult decision points regarding whether to discontinue therapy. Detailing the situations in which colitis might predict for improved survival and how this is affected by discontinuation or resumption of therapy can help guide clinical decision-making.Materials and MethodsPatients with stage IV melanoma receiving anti-CTLA4 therapy from 2008 to 2019 were analyzed. Immune-related colitis treated with ≥50 mg prednisone or equivalent daily or secondary immunosuppression was included. Moderate colitis was defined as receipt of oral glucocorticoids only; severe colitis was defined as requiring intravenous glucocorticoids or secondary immunosuppression. The primary outcome was overall survival (OS).ResultsIn total, 171 patients received monotherapy, and 91 received dual checkpoint therapy. In the monotherapy group, 25 patients developed colitis and a nonsignificant trend toward improved OS was observed in this group. Notably, when colitis was categorized as none, moderate or severe, OS was significantly improved for moderate colitis only. This survival difference was not present after dual checkpoint therapy. There were no differences in known prognostic variables between groups, and on multivariable analysis neither completion of all ipilimumab cycles nor resumption of immunotherapy correlated with OS, while the development of moderate colitis did significantly affect OS.ConclusionThis single-institution retrospective series suggests moderate colitis correlates with improved OS for patients with stage IV melanoma treated with single-agent anti-CTLA4, but not dual agent, and that this is true regardless of whether the immune-checkpoint blockade is permanently discontinued.     

Evaluation of MindMatters Buddy Support to Secondary Schools in South West Sydney

This study assessed the outcomes of a buddy support scheme designed to increase the capacity of secondary schools to adopt a whole school approach to improving the well-being of students and to enhance uptake of MindMatters. The scheme supported schools implementing MindMatters, forming partnerships, and creating links with health services, organisations and community groups. The results showed that intervention schools were significantly more likely to ensure internal support by assigning a person responsible for MindMatters (90% vs 38%), forming a core team (79% vs 21%), reporting changes (94% vs 26%) and connectedness (100% vs 21%) and continuing MindMatters implementation (90% vs 33%) than non-intervention schools. They also reported positive outcomes in student and community participation, policy development and implementation. The results indicated the usefulness of the scheme and a plausible contribution to a greater level of sustainable changes than standard delivery of MindMatters. To assess the impact, further investigation with a larger sample is needed.     

Real-Time Monitoring of High-Intensity Focused Ultrasound Thermal Therapy Using the Manifold Learning Method

High-intensity focused ultrasound (HIFU) induces thermal lesions by increasing the tissue temperature in a tight focal region. The main ultrasound imaging techniques currently used to monitor HIFU treatment are standard pulse-echo B-mode ultrasound imaging, ultrasound temperature estimation and elastography-based methods. The present study was carried out on ex vivo animal tissue samples, in which backscattered radiofrequency (RF) signals were acquired in real time at time instances before, during and after HIFU treatment. The manifold learning algorithm, a non-linear dimensionality reduction method, was applied to RF signals which construct B-mode images to detect the HIFU-induced changes among the image frames obtained during HIFU treatment. In this approach, the embedded non-linear information in the region of interest of sequential images is represented in a 2-D manifold with the Isomap algorithm, and each image is depicted as a point on the reconstructed manifold. Four distinct regions are chosen in the manifold corresponding to the four phases of HIFU treatment (before HIFU treatment, during HIFU treatment, immediately after HIFU treatment and 10-min after HIFU treatment). It was found that disorganization of the points is achieved by increasing the acoustic power, and if the thermal lesion has been formed, the regions of points related to pre- and post-HIFU significantly differ. Moreover, the manifold embedding was repeated on 2-D moving windows in RF data envelopes related to pre- and post-HIFU exposure data frames. It was concluded that if mean values of the points related to pre- and post-exposure frames in the reconstructed manifold are estimated, and if the Euclidean distance between these two mean values is calculated and the sliding window is moved and this procedure is repeated for the whole image, a new image based on the Euclidean distance can be formed in which the HIFU thermal lesion is detectable.     

Conformational dynamics of superoxide dismutase (SOD1) in osmolytes: a molecular dynamics simulation study

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the misfolding of Cu, Zn superoxide dismutase (SOD1). Several earlier studies have shown that monomeric apo SOD1 undergoes significant local unfolding dynamics and is the predecessor for aggregation. Here, we have employed atomistic molecular dynamics (MD) simulations to study the structure and dynamics of monomeric apo and holo SOD1 in water, aqueous urea and aqueous urea–TMAO (trimethylamine oxide) solutions. Loop IV (zinc-binding loop) and loop VII (electrostatic loop) of holo SOD1 are considered as functionally important loops as they are responsible for the structural stability of holo SOD1. We found larger local unfolding of loop IV and VII of apo SOD1 as compared to holo SOD1 in water. Urea induced more unfolding in holo SOD1 than apo SOD1, whereas the stabilization of both the form of SOD1 was observed in ternary solution (i.e. water/urea/TMAO solution) but the extent of stabilization was higher in holo SOD1 than apo SOD1. The partially unfolded structures of apo SOD1 in water, urea and holo SOD1 in urea were identified by the exposure of the hydrophobic cores, which are highly dynamic and these may be the initial events of aggregation in SOD1. Our simulation studies support the formation of aggregates by means of the local unfolding of monomeric apo SOD1 as compared to holo SOD1 in water.

Change in conformations of apo and holo SOD1 in water and in osmolytes in terms of configurational entropy (S).     

Pre- and post-intervention study to assess the impact of a sedation protocol in critically ill surgical patients

Introduction

Sedation and pain management for mechanically ventilated critically ill surgical patients pose many challenges for the intensivist. Even though daily interruption of sedatives and opioids is appropriate in medical intensive care unit (ICU) patients, it may not be feasible in the surgical patients with pain from surgical incision or trauma. Therefore we developed an analgesia/sedation based protocol for the surgical ICU population.

Methods

We performed a two-phase prospective observational control study. We evaluated a prescriber driven analgesia/sedation protocol (ASP) in a 12-bed surgical ICU. The pre-ASP group was sedated as usual (n = 100) and the post-ASP group was managed with the new ASP (n = 100). Each phase of the study lasted for 5 mo. Comparisons between the two groups were performed by χ² or Fisher’s exact test for categorical variables and the Mann-Whitney test for nonparametric variables. A P value <0.05 was statistically significant.

Results

We found a significant reduction in the use of fentanyl (P < 0.001) and midazolam (P = 0.001). We achieved sedation goals of 86.8% in the post-ASP group compared to 74.4% in the pre-ASP (P < 0.001). Mean mechanical ventilations days in pre- and post-ASP group were 5.9 versus 3.8 (P = 0.033).

Conclusion

In our cohort of critically ill surgery patients implementation of an ASP resulted in reduced use of continuously infused benzodiazepines and opioids, a decline in cumulative benzodiazepine and analgesic dosages, and a greater percentage of Richmond Agitation Sedation Scale scores at goal. We also showed reduced mechanical ventilation days.