The Influence of Sonographer Experience on Skeletal Muscle Image Acquisition and Analysis

The amount of experience with ultrasonography may influence measurement outcomes while images are acquired or analyzed. The purpose of this study was to identify the interrater reliability of ultrasound image acquisition and image analysis between experienced and novice sonographers and image analysts, respectively. Following a brief hands-on training session (2 h), the experienced and novice sonographers and analysts independently performed image acquisition and analyses on the biceps brachii, vastus lateralis, and medial gastrocnemius in a sample of healthy participants (n = 17). Test–retest reliability statistics were computed for muscle thickness (transverse and sagittal planes), muscle cross-sectional area, echo intensity and subcutaneous adipose tissue thickness. The results show that image analysis experience generally has a greater impact on measurement outcomes than image acquisition experience. Interrater reliability for measurements of muscle size during image acquisition was generally good–excellent (ICC2,1: 0.82–0.98), but poor–moderate for echo intensity (ICC2,1: 0.43–0.77). For image analyses, interrater reliability for measurements of muscle size for the vastus lateralis and biceps brachii was poor–moderate (ICC2,1: 0.48–0.70), but excellent for echo intensity (ICC2,1: 0.90–0.98). Our findings have important implications for laboratories and clinics where members possess varying levels of ultrasound experience

Acute kidney injury in patients treated with immune checkpoint inhibitors

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery

The Influence of Sonographer Experience on Skeletal Muscle Image Acquisition and Analysis

The amount of experience with ultrasonography may influence measurement outcomes while images are acquired or analyzed. The purpose of this study was to identify the interrater reliability of ultrasound image acquisition and image analysis between experienced and novice sonographers and image analysts, respectively. Following a brief hands-on training session (2 h), the experienced and novice sonographers and analysts independently performed image acquisition and analyses on the biceps brachii, vastus lateralis, and medial gastrocnemius in a sample of healthy participants (n = 17). Test–retest reliability statistics were computed for muscle thickness (transverse and sagittal planes), muscle cross-sectional area, echo intensity and subcutaneous adipose tissue thickness. The results show that image analysis experience generally has a greater impact on measurement outcomes than image acquisition experience. Interrater reliability for measurements of muscle size during image acquisition was generally good–excellent (ICC2,1: 0.82–0.98), but poor–moderate for echo intensity (ICC2,1: 0.43–0.77). For image analyses, interrater reliability for measurements of muscle size for the vastus lateralis and biceps brachii was poor–moderate (ICC2,1: 0.48–0.70), but excellent for echo intensity (ICC2,1: 0.90–0.98). Our findings have important implications for laboratories and clinics where members possess varying levels of ultrasound experience

The effects of resistance training to near failure on strength, hypertrophy, and motor unit adaptations in previously trained adults

Abstract Limited research exists examining how resistance training to failure affects applied outcomes and single motor unit characteristics in previously trained individuals. Herein, resistance‐trained adults (24 ± 3 years old, self‐reported resistance training experience was 6 ± 4 years, 11 men and 8 women) were randomly assigned to either a low‐repetitions‐in‐reserve (RIR; i.e., training near failure, n = 10) or high‐RIR (i.e., not training near failure, n = 9) group. All participants implemented progressive overload during 5 weeks where low‐RIR performed squat, bench press, and deadlift twice weekly and were instructed to end each training set with 0–1 RIR. high‐RIR performed identical training except for being instructed to maintain 4–6 RIR after each set. During week 6, participants performed a reduced volume‐load. The following were assessed prior to and following the intervention: (i) vastus lateralis (VL) muscle cross‐sectional area (mCSA) at multiple sites; (ii) squat, bench press, and deadlift one‐repetition maximums (1RMs); and (iii) maximal isometric knee extensor torque and VL motor unit firing rates during an 80% maximal voluntary contraction. Although RIR was lower in the low‐ versus high‐RIR group during the intervention (p < 0.001), total training volume did not significantly differ between groups (p = 0.222). There were main effects of time for squat, bench press, and deadlift 1RMs (all p‐values < 0.05), but no significant condition × time interactions existed for these or proximal/middle/distal VL mCSA data. There were significant interactions for the slope and y‐intercept of the motor unit mean firing rate versus recruitment threshold relationship. Post hoc analyses indicated low‐RIR group slope values decreased and y‐intercept values increased after training suggesting low‐RIR training increased lower‐threshold motor unit firing rates. This study provides insight into how resistance training in proximity to failure affects strength, hypertrophy, and single motor unit characteristics, and may inform those who aim to program for resistance‐trained individuals

A Multi-Isotope Investigation of Human and Dog Mobility and Diet in the Pre-Colonial Antilles

The complex relationships between humans and dogs (Canis lupus familiaris) have a very deep and unique history. Dogs have accompanied humans as they colonised much of the world, and were introduced via human agency into the insular Caribbean where they became widespread throughout the Ceramic Age. It is likely that the dynamic interactions between humans, dogs, and their environments in the Caribbean were spatially, chronologically, and socially variable. However, almost no research has specifically addressed the nature, or potential variability, of human/dog interactions in this region. This study presents isotopic (strontium and carbon) evidence bearing on human and dog paleomobility and paleodietary patterns in the pre-colonial Caribbean. The isotope results illustrate a generally high degree of correspondence between human and dog dietary practices at all analysed sites but also slight differences in the relative importance of different dietary inputs. Striking parallels are also observed between the human and dog mobility patterns and shed light on broader networks of social interaction and exchange. Lastly, the paper addresses the possible utility and relevance of canine isotope data as proxies for inferring past human behaviours.Seventh Framework Programme (FP7)Archaeology of the America

Shorter versus longer corticosteroid duration and recurrent immune checkpoint inhibitor-associated AKI

Background Corticosteroids are the mainstay of treatment for immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI), but the optimal duration of therapy has not been established. Prolonged use of corticosteroids can cause numerous adverse effects and may decrease progression-free survival among patients treated with ICPis. We sought to determine whether a shorter duration of corticosteroids was equally efficacious and safe as compared with a longer duration.Methods We used data from an international multicenter cohort study of patients diagnosed with ICPi-AKI from 29 centers across nine countries. We examined whether a shorter duration of corticosteroids (28 days or less) was associated with a higher rate of recurrent ICPi-AKI or death within 30 days following completion of corticosteroid treatment as compared with a longer duration (29–84 days).Results Of 165 patients treated with corticosteroids, 56 (34%) received a shorter duration of treatment and 109 (66%) received a longer duration. Patients in the shorter versus longer duration groups were similar with respect to baseline and ICPi-AKI characteristics. Five of 56 patients (8.9%) in the shorter duration group and 12 of 109 (11%) in the longer duration group developed recurrent ICPi-AKI or died (p=0.90). Nadir serum creatinine in the first 14, 28, and 90 days following completion of corticosteroid treatment was similar between groups (p=0.40, p=0.56, and p=0.89, respectively).Conclusion A shorter duration of corticosteroids (28 days or less) may be safe for patients with ICPi-AKI. However, the findings may be susceptible to unmeasured confounding and further research from randomized clinical trials is needed

NOTCH3 p.Arg1231Cys is markedly enriched in South Asians and associated with stroke

Acknowledgements: Supported by Regeneron Pharmaceuticals, Inc. This research has been conducted using the UK Biobank Resource (project 26041). The authors thank everyone who made this work possible, particularly the UK Biobank team, their funders, the professionals from the member institutions who contributed to and supported this work, and most especially the UK Biobank participants, without whom this research would not be possible. The exome sequencing was funded by the UK Biobank Exome Sequencing Consortium (Bristol Myers Squibb, Regeneron, Biogen, Takeda, Abbvie, Alnylam, AstraZeneca and Pfizer). Ethical approval for the UK Biobank was previously obtained from the North West Center for Research Ethics Committee (11/NW/0382). Disclosure forms provided by the authors are available with the full text of this article.The genetic factors of stroke in South Asians are largely unexplored. Exome-wide sequencing and association analysis (ExWAS) in 75 K Pakistanis identified NM_000435.3(NOTCH3):c.3691 C > T, encoding the missense amino acid substitution p.Arg1231Cys, enriched in South Asians (alternate allele frequency = 0.58% compared to 0.019% in Western Europeans), and associated with subcortical hemorrhagic stroke [odds ratio (OR) = 3.39, 95% confidence interval (CI) = [2.26, 5.10], p = 3.87 × 10−9), and all strokes (OR [CI] = 2.30 [1.77, 3.01], p = 7.79 × 10−10). NOTCH3 p.Arg231Cys was strongly associated with white matter hyperintensity on MRI in United Kingdom Biobank (UKB) participants (effect [95% CI] in SD units = 1.1 [0.61, 1.5], p = 3.0 × 10−6). The variant is attributable for approximately 2.0% of hemorrhagic strokes and 1.1% of all strokes in South Asians. These findings highlight the value of diversity in genetic studies and have major implications for genomic medicine and therapeutic development in South Asian populations