Improvement of the Prediction Power of the CoMFA and CoMSIA Models on Histamine H3 Antagonists by Different Variable Selection Methods

The aim of this study is to enhance the predictivity power of CoMFA and CoMSIA models by means of different variable selection algorithms. The genetic algorithm (GA), successive projection algorithm (SPA), stepwise multiple linear regression (SW-MLR), and the enhanced replacement method (ERM) were used and tested as variable selection algorithms. Then, the selected variables were used to generate a simple and predictive model by the multilinear regression algorithm. A set of 74 histamine H₃ antagonists were split into 40 compounds as a training set, and 17 compounds as a test set, by the Kennard-Stone algorithm. Before splitting the data, 17 compounds were randomly selected from the pool of the whole data set as an evaluation set without any supervision, pretreatment, or visual inspection. Among applied variable selection algorithms, ERM had noticeable improvement on the statistical parameters. The r² values of training, test, and evaluation sets for the ERM-MLR model using CoMFA fields were 0.9560, 0.8630, and 0.8460 and using the CoMSIA fields were 0.9800, 0.8521, and 0.9080, respectively. In this study, the principles of organization for economic cooperation and development (OECD) for regulatory acceptability of QSARs are considered.     

Transvenous embolization of a dural arteriovenous fistula of the cavernous sinus through the contralateral pterygoid plexus

We report a new transvenous endovascular route for treatment of dural arteriovenous fistulas of the cavernous sinus. The cavernous sinus was approached from the contralateral pterygoid plexus and embolization of a dural fistula was performed successfully with Guglielmi detachable coils. Received: 16 June 1997 Accepted: 6 August 1997     

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.     

Embolization of arteriovenous malformations with Onyx: clinicopathological experience in 23 patients

OBJECTIVE: To report our experience in treatment of arteriovenous malformations (AVMs) using a new liquid embolic agent, Onyx (Micro Therapeutics, Inc., Irvine, CA). METHODS: Between January 1998 and May 1999, 23 patients (8 men and 15 women) were treated. The patients' average age was 40 years, with seizure being the most common presenting symptom (39%). The average Spetzler-Martin grade on presentation was 3. The average AVM volume before embolization was 14.5 cm3. RESULTS: We observed an average 63% reduction in AVM volume after 129 arterial feeders were embolized. There were four adverse events. Two patients experienced ischemia because of inadvertent occlusion of an arterial feeder. One of these patients made a full recovery, but the other patient had a permanent deficit. Two other patients experienced transient neurological deficits that resolved within 1 week of embolization. Permanent morbidity was thus 4% (1 of 23 patients). There were no deaths. Twelve patients underwent subsequent radiosurgery, and 11 patients had surgery that resulted in complete resection of their AVMs. Histopathological examinations showed mild acute inflammation in specimens resected 1 day after embolization. Chronic inflammatory changes were observed in specimens resected more than 4 days after embolization. In two patients, angionecrosis of the embolized vessels was noted. No evidence of parenchymal hemorrhage was observed in these patients, and vessel wall integrity was maintained as well. CONCLUSION: Onyx is a new nonadhesive liquid embolic agent that has been used to treat 23 patients at our institution with good results. Its nonadhesive nature and ease of use make it a promising agent in the future treatment of AVMs.     

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.