Hepatic encephalopathy (HE) is a major cause of morbidity in cirrhosis. However, its severity assessment is often subjective, which needs to be studied systematically. The aim was to determine how accurately trainee and nontrainee practitioners grade and manage HE patients throughout its severity. We performed a survey study using standardized simulated patient videos at 4 US and 3 Canadian centers. Participants were trainees (gastroenterology/hepatology fellows) and nontrainees (faculty, nurse practitioners, physician assistants). We determined the accuracy of HE severity identification and management options between grades <2 or ≥2 HE and trainees/nontrainees. In total, 108 respondents (62 trainees, 46 nontrainees) were included. For patients with grades <2 versus ≥2 HE, a higher percentage of respondents were better at correctly diagnosing grades ≥2 compared with grades <2 (91% versus 64%; P < 0.001). Specialized cognitive testing was checked significantly more often in grades <2, whereas more aggressive investigation for precipitating factors was ordered in HE grades >2. Serum ammonia levels were ordered in almost a third of grade ≥2 patients. For trainees and nontrainees, HE grades were identified similarly between groups. Trainees were less likely to order serum ammonia and low-protein diets, more likely to order rifaximin, and more likely to perform a more thorough workup for precipitating factors compared with nontrainee respondents. There was excellent concordance in the classification of grade ≥2 HE between nontrainees versus trainees, but lower grades showed discordance. Important differences were seen regarding blood ammonia, specialized testing, and nutritional management between trainees and nontrainees. These results have important implications at the patient level, interpreting multicenter clinical trials, and in the education of practitioners. Liver Transplantation 24 587-594 2018 AASLD.

Main objective

Systematically review and synthesize preoperative and intraoperative factors associated with pain after total knee arthroplasty (TKA) in patients with osteoarthritis.

Methods

Based on a peer-reviewed protocol, we searched Medline, Embase, CINAHL, Cochrane Library, and PEDro for prospective observational studies (January 2000 to February 2023) investigating factors associated with pain after TKA. The primary outcome was pain twelve months after TKA. Pain at three and six months were secondary outcomes. Multivariate random-effects meta-analyses were used to estimate mean correlation (95% CIs) between factors and pain. Sensitivity analysis was performed for each risk of bias domain and certainty of evidence was assessed.

Results

Of 13,640 studies, 29 reports of 10,360 patients and 61 factors were analysed. The mean correlation between preoperative factors and more severe pain at twelve months was estimated to be 0.36 (95% CI, 0.24, 0.47; P < .000; moderate-certainty evidence) for more catastrophizing, 0.15 (95% CI; 0.08, 0.23; P < .001; moderate-certainty evidence) for more symptomatic joints, 0.13 (95% CI, 0.06, 0.19; P < .001; very low-certainty evidence) for more preoperative pain. Mean correlation between more severe radiographic osteoarthritis and less pain was -0.15 (95% CI; -0.23, -0.08; P < .001; low-certainty evidence). In sensitivity analysis, the estimated correlation coefficient for pain catastrophizing factor increased to 0.38 (95% CI 0.04, 0.64). At six and three months, more severe preoperative pain was associated with more pain. Better preoperative mental health was associated with less pain at six months.

Conclusion and relevance

More pain catastrophizing, more symptomatic joints and more pain preoperatively were correlated with more pain, while more severe osteoarthritis was correlated with less pain one year after TKA. More preoperative pain was correlated with more pain, and better mental health with less pain at six and three months. These findings should be further tested in predictive models to gain knowledge which may improve TKA outcomes.

Introduction

One in five patients undergoing total knee arthroplasty (TKA) experience unchanged or worse pain and physical function 1 year after surgery. Identifying risk factors for unfavourable outcomes is necessary to develop tailored interventions to minimise risk. There is a need to review more current literature with updated methodology that addresses the limitations of earlier systematic reviews and meta-analyses. We present a Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols compliant protocol for a systematic review and meta-analysis of predictors of chronic pain and impaired function after TKA.

Methods and analysis

This review will include prospective longitudinal observational studies, or randomised trials (including cluster and crossover designs) that report arm-wise predictors of chronic postsurgical pain or impaired physical function at 3 months, 6 months or 12 months. A comprehensive literature search of studies published between 2000 and 2019 will be performed in Medline, Embase, CINAHL, Cochrane Library and PEDro. Blinded assessment with consensus agreement will be applied for inclusion of studies, data extraction and assessment of bias risk (Quality in Prognosis Studies tool). The co-primary outcomes, pain and impaired function, at 12 months after TKA will be analysed separately. Estimates of association between each outcome and any preoperative or intraoperative factor that may predict chronic pain or impaired physical function will be extracted from the included studies, where possible. For randomised studies, results will only be extracted from TKA arms (or the first period of crossover trials). Estimates of association from the primary evidence will be synthesised narratively, and quantitatively using multivariate meta-analysis to provide 'pooled' estimates of association. Subgroup and sensitivity analyses will be performed. Certainty of evidence for each predictor will be derived from the Grading of Recommendations Assessment, Development and Evaluation framework.

Ethics and dissemination

No ethical issues are associated with this project. The results from this review will be published in peer-reviewed journals and presented at international conferences.

Prospero registration number

CRD42018079069.

The assembly status of the V. cholerae flagellum regulates biofilm formation, suggesting that the bacterium senses a lack of movement to commit to a sessile lifestyle. Motility and biofilm formation are inversely regulated by the second messenger molecule cyclic dimeric guanosine monophosphate (c-di-GMP). Therefore, we sought to define the flagellum-associated c-di-GMP-mediated signaling pathways that regulate the transition from a motile to a sessile state. Here we report that elimination of the flagellum, via loss of the FlaA flagellin, results in a flagellum-dependent biofilm regulatory (FDBR) response, which elevates cellular c-di-GMP levels, increases biofilm gene expression, and enhances biofilm formation. The strength of the FDBR response is linked with status of the flagellar stator: it can be reversed by deletion of the T ring component MotX, and reduced by mutations altering either the Na+ binding ability of the stator or the Na+ motive force. Absence of the stator also results in reduction of mannose-sensitive hemagglutinin (MSHA) pilus levels on the cell surface, suggesting interconnectivity of signal transduction pathways involved in biofilm formation. Strains lacking flagellar rotor components similarly launched an FDBR response, however this was independent of the status of assembly of the flagellar stator. We found that the FDBR response requires at least three specific diguanylate cyclases that contribute to increased c-di-GMP levels, and propose that activation of biofilm formation during this response relies on c-di-GMP-dependent activation of positive regulators of biofilm production. Together our results dissect how flagellum assembly activates c-di-GMP signaling circuits, and how V. cholerae utilizes these signals to transition from a motile to a sessile state.

Analyzing proteins from single cells by tandem mass spectrometry (MS) has recently become technically feasible. While such analysis has the potential to accurately quantify thousands of proteins across thousands of single cells, the accuracy and reproducibility of the results may be undermined by numerous factors affecting experimental design, sample preparation, data acquisition and data analysis. We expect that broadly accepted community guidelines and standardized metrics will enhance rigor, data quality and alignment between laboratories. Here we propose best practices, quality controls and data-reporting recommendations to assist in the broad adoption of reliable quantitative workflows for single-cell proteomics. Resources and discussion forums are available at https://single-cell.net/guidelines .