Mean glucose during ICU admission is related to mortality by a U-shaped curve in surgical and medical patients: a retrospective cohort study

Lowering of hyperglycemia in the intensive care unit (ICU) is widely practiced. We investigated in which way glucose regulation, defined as mean glucose concentration during admission, is associated with ICU mortality in a medical and a surgical cohort. Retrospective database cohort study including patients admitted between January 2004 and December 2007 in a 20-bed medical/surgical ICU in a teaching hospital. Hyperglycemia was treated using a computerized algorithm targeting for glucose levels of 4.0-7.0 mmol/l. Five thousand eight hundred twenty-eight patients were eligible for analyses, of whom 1,339 patients had a medical and 4,489 had a surgical admission diagnosis. The cohorts were subdivided in quintiles of increasing mean glucose. We examined the relation between these mean glucose strata and mortality. In both cohorts we observed the highest mortality in the lowest and highest strata. Logistic regression analysis adjusted for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, admission duration and occurrence of severe hypoglycemia showed that in the medical cohort mean glucose levels 8.4 mmol/l and in the surgical cohort mean glucose levels 9.4 mmol/l were associated with significantly increased ICU mortality (OR 2.4-3.0 and 4.9-6.2, respectively). Limitations of the study were its retrospective design and possible incomplete correction for severity of disease. Mean overall glucose during ICU admission is related to mortality by a U-shaped curve in medical and surgical patients. In this cohort of patients a 'safe range' of mean glucose regulation might be defined approximately between 7.0 and 9.0 mmol/

Neurofilaments in spinocerebellar ataxia type 3: blood biomarkers at the preataxic and ataxic stage in humans and mice

With molecular treatments coming into reach for spinocerebellar ataxia type 3 (SCA3), easily accessible, cross-species validated biomarkers for human and preclinical trials are warranted, particularly for the preataxic disease stage. We assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in ataxic and preataxic subjects of two independent multicentric SCA3 cohorts and in a SCA3 knock-in mouse model. Ataxic SCA3 subjects showed increased levels of both NfL and pNfH. In preataxic subjects, NfL levels increased with proximity to the individual expected onset of ataxia, with significant NfL elevations already 7.5 years before onset. Cross-sectional NfL levels correlated with both disease severity and longitudinal disease progression. Blood NfL and pNfH increases in human SCA3 were each paralleled by similar changes in SCA3 knock-in mice, here also starting already at the presymptomatic stage, closely following ataxin-3 aggregation and preceding Purkinje cell loss in the brain. Blood neurofilaments, particularly NfL, might thus provide easily accessible, cross-species validated biomarkers in both ataxic and preataxic SCA3, associated with earliest neuropathological changes, and serve as progression, proximity-to-onset and, potentially, treatment-response markers in both human and preclinical SCA3 trials.Acknowledgements: This work was supported by the Horizon 2020 research and innovation programme (grant 779257 Solve-RD to MS and RS), the National Ataxia Foundation (grant to CW and MS), the Wilhelm Vaillant Stiftung (grant to CW), the EU Joint Programme—Neurodegenerative Disease Research (JPND) through participating national funding agencies, and the European Union’s Horizon 2020 research and innovation programme under grant agreement No 643417. BM was supported in part from the grant NKFIH 119540. HJ was funded by the Medical Faculty of the University of Heidelberg. CB was funded by the University of Basel (PhD Program in Health Sciences). The funding sources had no role in the study design, data collection, data analysis, data interpretation or writing of the manuscript

Otolith shape and size: The importance of age when determining indices for fish-stock separation

Stock-separation of highly mobile Clupeids (sprat – Sprattus sprattus and herring – Clupea harengus) using otolith morphometrics was explored. Analysis focused on three stock discrimination problems with the aim of reassigning individual otoliths to source populations using experiments undertaken using a machine learning environment known as \{WEKA\} (Waikato Environment for Knowledge Analysis). Six feature sets encoding combinations of size and shape together with nine learning algorithms were explored. To assess saliency of size/shape features half of the feature sets included size indices, the remainder encoded only shape. Otolith sample sets were partitioned by age so that the impact of age on classification accuracy could be assessed for each method. In total we performed 540 experiments, representing a comprehensive evaluation of otolith morphometrics and learning algorithms. Results show that for juveniles, methods encoding only shape performed well, but those that included size indices held more classification potential. However as fish age, shape encoding methods were more robust than those including size information. This study suggests that methods of stock discrimination based on early incremental growth are likely to be effective, and that automated classification techniques will show little benefit in supplementing early growth information with shape indices derived from mature outlines

Which acetabular measurements most accurately differentiate between patients and controls? A comparative study

Abstract: Background Acetabular morphology is an important determinant of hip biomechanics. To identify features of acetabular morphology that may be associated with the development of hip symptoms while accounting for spinopelvic characteristics, one needs to determine acetabular characteristics in a group of individuals older than 45 years without symptoms or signs of osteoarthritis. Previous studied have used patients with unknown physical status to define morphological thresholds to guide management. Questions/purposes (1) To determine acetabular morphological characteristics in males and females between 45 and 60 years old with a high Oxford hip score (OHS) and no signs of osteoarthritis; (2) to compare these characteristics with those of symptomatic hip patients treated with hip arthroscopy or periacetabular osteotomy (PAO) for various kinds of hip pathology (dysplasia, retroversion, and cam femoroacetabular impingement); and (3) to assess which radiographic or CT parameters most accurately differentiate between patients who had symptomatic hips and those who did not, and thus, define thresholds that can guide management. Methods Between January 2018 and December 2018, 1358 patients underwent an abdominopelvic CT scan in our institution for nonorthopaedic conditions. Of those, we considered 5% (73) of patients as potentially eligible as controls based on the absence of major hip osteoarthritis, trauma, or deformity. Patients were excluded if their OHS was 43 or less (2% [28]), if they had a PROMIS less than 50 (1% [18]), or their T\uf6nnis score was higher than 1 (0.4% [6]). Another eight patients were excluded because of insufficient datasets. After randomly selecting one side for each control, 40 hips were left for analysis (age 55 \ub1 5 years; 48% [19 of 40] were in females). In this comparative study, this asymptomatic group was compared with a group of patients treated with hip arthroscopy or PAO. Between January 2013 and December 2020, 221 hips underwent hip preservation surgery. Of those, eight were excluded because of previous pelvic surgery, and 102 because of insufficient CT scans. One side was randomly selected in patients who underwent bilateral procedure, leaving 48% (107 of 221) of hips for analysis (age 31 \ub1 8 years; 54% [58 of 107] were in females). Detailed radiographic and CT assessments (including segmentation) were performed to determine acetabular (depth, cartilage coverage, subtended angles, anteversion, and inclination) and spinopelvic (pelvic tilt and incidence) parameters. Receiver operating characteristics (ROC) analysis was used to assess diagnostic accuracy and determine which morphological parameters (and their threshold) differentiate most accurately between symptomatic patients and asymptomatic controls. Results Acetabular morphology in asymptomatic hips was characterized by a mean depth of 22 \ub1 2 mm, with an articular cartilage surface of 2619 \ub1 415 mm2, covering 70% \ub1 6% of the articular surface, a mean acetabular inclination of 48\ub0 \ub1 6\ub0, and a minimal difference between anatomical (24\ub0 \ub1 7\ub0) and functional (22\ub0 \ub1 6\ub0) anteversion. Patients with symptomatic hips generally had less acetabular depth (20 \ub1 4 mm versus 22 \ub1 2 mm, mean difference 3 mm [95% CI 1 to 4]; p < 0.001). Hips with dysplasia (67% \ub1 5% versus 70% \ub1 6%, mean difference 6% [95% CI 0% to 12%]; p = 0.03) or retroversion (67% \ub1 5% versus 70% \ub1 6%, mean difference 6% [95% CI 1% to 12%]; p = 0.04) had a slightly lower relative cartilage area compared with asymptomatic hips. There was no difference in acetabular inclination (48\ub0 \ub1 6\ub0 versus 47\ub0 \ub1 7\ub0, mean difference 0.5\ub0 [95% CI -2\ub0 to 3\ub0]; p = 0.35), but asymptomatic hips had higher anatomic anteversion (24\ub0 \ub1 7\ub0 versus 19\ub0 \ub1 8\ub0, mean difference 6\ub0 [95% CI 3\ub0 to 9\ub0]; p < 0.001) and functional anteversion (22\ub0 \ub1 6\ub0 versus 13\ub0\ub1 9\ub0, mean difference 9\ub0 [95% CI 6\ub0 to 12\ub0]; p < 0.001). Subtended angles were higher in asymptomatic at 105\ub0 (124\ub0 \ub1 7\ub0 versus 114\ub0 \ub1 12\ub0, mean difference 11\ub0 [95% CI 3\ub0 to 17\ub0]; p < 0.001), 135\ub0 (122\ub0 \ub1 9\ub0 versus 111\ub0 \ub1 12\ub0, mean difference 10\ub0 [95% CI 2\ub0 to 15\ub0]; p < 0.001), and 165\ub0 (112\ub0 \ub1 9\ub0 versus 102\ub0 \ub1 11\ub0, mean difference 10\ub0 [95% CI 2\ub0 to 14\ub0]; p < 0.001) around the acetabular clockface. Symptomatic hips had a lower pelvic tilt (8\ub0 \ub1 8\ub0 versus 11\ub0 \ub1 5\ub0, mean difference 3\ub0 [95% CI 1\ub0 to 5\ub0]; p = 0.007). The posterior wall index had the highest discriminatory ability of all measured parameters, with a cutoff value of less than 0.9 (area under the curve [AUC] 0.84 [95% CI 0.76 to 0.91]) for a symptomatic acetabulum (sensitivity 72%, specificity 78%). Diagnostically useful parameters on CT scan to differentiate between symptomatic and asymptomatic hips were acetabular depth less than 22 mm (AUC 0.74 [95% CI 0.66 to 0.83]) and functional anteversion less than 19\ub0 (AUC 0.79 [95% CI 0.72 to 0.87]). Subtended angles with the highest accuracy to differentiate between symptomatic and asymptomatic hips were those at 105\ub0 (AUC 0.76 [95% CI 0.65 to 0.88]), 135\ub0 (AUC 0.78 [95% CI 0.70 to 0.86]), and 165\ub0 (AUC 0.77 [95% CI 0.69 to 0.85]) of the acetabular clockface. Conclusion An anatomical and functional acetabular anteversion of 24\ub0 and 22\ub0, with a pelvic tilt of 10\ub0, increases the acetabular opening and allows for more impingement-free flexion while providing sufficient posterosuperior coverage for loading. Hips with lower anteversion or a larger difference between anatomic and functional anteversion were more likely to be symptomatic. The importance of sufficient posterior coverage was also illustrated by the posterior wall indices and subtended angles at 105\ub0, 135\ub0, and 165\ub0 of the acetabular clockface having a high discriminatory ability to differentiate between symptomatic and asymptomatic hips. Future research should confirm whether integrating these parameters when selecting patients for hip preservation procedures can improve postoperative outcomes