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ant improvement in the AUC of postoperative pain scores compared with plain local anesthetic. Furthermore, this benefit was rendered nonsignificant after excluding an industry-sponsored trial, and liposomal bupivacaine was found to be not different from plain local anesthetics for postoperative pain and all other analgesic and functional outcomes. High-quality evidence does not support the use of perineural liposomal bupivacaine over nonliposomal bupivacaine for peripheral nerve blocks.
Several cancer-susceptibility syndromes are reported to underlie pediatric rhabdomyosarcoma (RMS); however, there have been no systematic efforts to characterize the heterogeneous genetic etiologies of this often-fatal malignancy.
We performed exome-sequencing on germline DNA from 615 patients with newly diagnosed RMS consented through the Children's Oncology Group. We compared the prevalence of cancer-predisposition variants in 63 autosomal dominant cancer-predisposition genes in these patients with population controls (n = 9,963). All statistical tests were two-sided.
We identified germline cancer-predisposition variants in 45 RMS patients (7.3%; all FOXO1 fusion-negative) across 15 autosomal dominant genes, which was statistically significantly enriched compared with controls (1.4%; p = 1.3 × 10-22). Specifically, 73.3% of the predisposition variants were found in predisposition syndrome genes previously associated with pediatric RMS risk, such as Li-Fraumeni syndrome (TP53) and neurofibromatosis typyndromes. Germline genetic testing for children with RMS should be informed by RMS subtypes and not be limited to only young patients.
The objective of this study is to provide normative data for a tablet-based dual-task assessment in older adults without cognitive deficits.
In total, 264 participants aged between 60 and 90years, French and English-speaking, were asked to perform two discrimination tasks, alone and concurrently. The participants had to answer as fast as possible to one or two images appearing in the center of the tablet by pressing to the corresponding buttons. Normative data are provided for reaction time (RT), coefficient of variation, and accuracy. Analyses of variance were performed by trial types (single-pure, single-mixed, dual-mixed), and linear regressions assessed the relationship between performance and sociodemographic characteristics.
The participants were highly educated and a large proportion of them were women (73.9%). The accuracy on the task was very high across all blocks. RT data revealed both a task-set cost and a dual-task cost between the blocks. Age was associated with slower RT and with higher coefficient of variability. Men were significantly slower on dual-mixed trials, but their coefficient of variability was lower on single-pure trials. Education was not associated with performance.
This study provides normative data for a tablet-based dual-task assessment in older adults without cognitive impairment, which was lacking. All participants completed the task with good accuracy in less than 15 minutes and thus, the task is transferable to clinical and research settings.
This study provides normative data for a tablet-based dual-task assessment in older adults without cognitive impairment, which was lacking. All participants completed the task with good accuracy in less than 15 minutes and thus, the task is transferable to clinical and research settings.Skin sensitization following the covalent modification of proteins by low molecular weight chemicals (haptenation) is mediated by cytotoxic T lymphocyte (CTL) recognition of human leukocyte antigen (HLA) molecules presented on the surface of almost all nucleated cells. There exist 3 nonmutually exclusive hypotheses for how haptens mediate CTL recognition direct stimulation by haptenated peptides, hapten modification of HLA leading to an altered HLA-peptide repertoire, or a hapten altered proteome leading to an altered HLA-peptide repertoire. To shed light on the mechanism underpinning skin sensitization, we set out to utilize proteomic analysis of keratinocyte presented antigens following exposure to 2,4-dinitrochlorobenzene (DNCB). We show that the following DNCB exposure, cultured keratinocytes present cysteine haptenated (dinitrophenylated) peptides in multiple HLA molecules. In addition, we find that one of the DNCB modified peptides derives from the active site of cytosolic glutathione-S transferase-ω. These results support the current view that a key mechanism of skin sensitization is stimulation of CTLs by haptenated peptides. Mocetinostat Data are available via ProteomeXchange with identifier PXD021373.The authors provide a comprehensive summary of all randomized, controlled trials (n = 76) involving the clinical administration of liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, USA) to control postoperative pain that are currently published. When infiltrated surgically and compared with unencapsulated bupivacaine or ropivacaine, only 11% of trials (4 of 36) reported a clinically relevant and statistically significant improvement in the primary outcome favoring liposomal bupivacaine. Ninety-two percent of trials (11 of 12) suggested a peripheral nerve block with unencapsulated bupivacaine provides superior analgesia to infiltrated liposomal bupivacaine. Results were mixed for the 16 trials comparing liposomal and unencapsulated bupivacaine, both within peripheral nerve blocks. Overall, of the trials deemed at high risk for bias, 84% (16 of 19) reported statistically significant differences for their primary outcome measure(s) compared with only 14% (4 of 28) of those with a low risk of bias. The preponderance of evidence fails to support the routine use of liposomal bupivacaine over standard local anesthetics.
We investigated the prospective association between a brief self-report measure of engagement in HIV care (the Index) and suboptimal retention and viral suppression (VS) outcomes.
The CNICS cohort study combines medical record data with patient-reported outcomes from eight HIV clinics in the United States, which from April 2016-March 2017 included the 10-item Index. Multivariable logistic regression (LR) was used to estimate the risk and odds ratios of mean Index score on two outcomes in the subsequent year 1) not keeping at least 75% of scheduled HIV care appointments, and; 2) for those with VS at Index, having viral load >200 copies/mL on at least one measurement. We also employed generalized linear mixed models (GLMM) to estimate the risk and odds ratios of appointment non-attendance or unsuppressed viral load at any given observation. We generated receiver-operator characteristic (ROC) curves for the full models overlaid with Index as a sole predictor.
Mean Index score was 4.5 (SD 0.6). Higher Index scores were associated with lower relative risk of suboptimal retention (N=2,576; LR aRR 0.