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Urinary biomarkers indicative of recovery from spinal cord injury: A pilot study

IBRO Neurosci Rep. 2021 Feb 18;10:178-185. doi: 10.1016/j.ibneur.2021.02.007. eCollection 2021 Jun.

ABSTRACT

Current assessments of recovery following spinal cord injury (SCI) focus on clinical outcome measures. These assessments bear an inherent risk of bias, emphasizing the need for more reliable prognostic biomarkers to measure SCI severity. This study evaluated fluid biomarkers as an objective tool to aid with prognosticating outcomes following SCI. Using a 1H nuclear magnetic resonance (NMR)-based quantitative metabolomics approach of urine samples, the objectives were to determine (a) if alterations in metabolic profiles reflect the extent of recovery of individual SCI patients, (b) whether changes in urine metabolites correlate to patient outcomes, and (c) whether biological pathway analysis reflects mechanisms of neural damage and repair. An inception cohort exploratory pilot study collected morning urine samples from male SCI patients (n=6) following injury and again at 6-months post-injury. A 700 MHz Bruker Avance III HD NMR spectrometer was used to acquire the metabolic signatures of urine samples, which were used to derive metabolic pathways. Multivariate statistical analyses were used to identify changes in metabolic signatures, which were correlated to clinical outcomes in the Spinal Cord Independence Measure (SCIM). Among SCI-induced metabolic changes, biomarkers which significantly correlated to patient SCIM scores included caffeine (R = -0.76, p < 0.01), 3-hydroxymandelic acid (R= -0.85, p < 0.001), L-valine (R = 0.90, p < 0.001; R = -0.64, p < 0.05), and N-methylhydantoin (R = -0.90, p < 0.001). The most affected pathway was purine metabolism. These findings indicate that urinary metabolites reflect SCI lesion severity and recovery and provide potentially prognostic biomarkers of SCI outcome in precision medicine approaches.

PMID:33842921 | PMC:PMC8020035 | DOI:10.1016/j.ibneur.2021.02.007

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Functional analysis of XRCC4 mutations in reported microcephaly and growth defect patients in terms of radiosensitivity

J Radiat Res. 2021 Apr 12:rrab016. doi: 10.1093/jrr/rrab016. Online ahead of print.

ABSTRACT

Non-homologous end joining is one of the main pathways for DNA double-strand break (DSB) repair and is also implicated in V(D)J recombination in immune system. Therefore, mutations in non-homologous end-joining (NHEJ) proteins were found to be associated with immunodeficiency in human as well as in model animals. Several human patients with mutations in XRCC4 were reported to exhibit microcephaly and growth defects, but unexpectedly showed normal immune function. Here, to evaluate the functionality of these disease-associated mutations of XRCC4 in terms of radiosensitivity, we generated stable transfectants expressing these mutants in XRCC4-deficient murine M10 cells and measured their radiosensitivity by colony formation assay. V83_S105del, R225X and D254Mfs*68 were expressed at a similar level to wild-type XRCC4, while W43R, R161Q and R275X were expressed at even higher level than wild-type XRCC4. The expression levels of DNA ligase IV in the transfectants with these mutants were comparable to that in the wild-type XRCC4 transfectant. The V83S_S105del transfectant and, to a lesser extent, D254Mfs*68 transfectant, showed substantially increased radiosensitivity compared to the wild-type XRCC4 transfectant. The W43R, R161Q, R225X and R275X transfectants showed a slight but statistically significant increase in radiosensitivity compared to the wild-type XRCC4 transfectant. When expressed as fusion proteins with Green fluorescent protein (GFP), R225X, R275X and D254Mfs*68 localized to the cytoplasm, whereas other mutants localized to the nucleus. These results collectively indicated that the defects of XRCC4 in patients might be mainly due to insufficiency in protein quantity and impaired functionality, underscoring the importance of XRCC4’s DSB repair function in normal development.

PMID:33842963 | DOI:10.1093/jrr/rrab016

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Flexor digitorum superficialis muscular activity is more reliable than mentalis muscular activity for rapid eye movement sleep without atonia quantification

Sleep. 2021 Apr 12:zsab094. doi: 10.1093/sleep/zsab094. Online ahead of print.

ABSTRACT

STUDY OBJECTIVES: To evaluate interrater reliability for artefact correction in the context of semi-automated quantification of rapid eye movement (REM) sleep without atonia (RWA) in the mentalis and flexor digitorum superficialis (FDS) muscles.

METHODS: We included video-polysomnographies of 14 subjects with apnea-hypopnea-index in REM sleep (AHIREM)<15/h and 11 subjects with AHIREM≥15/h. Eight subjects had isolated REM sleep behavior disorder. A validated algorithm (www.osg.be) automatically scored phasic and “any” EMG activity in the mentalis muscle, and phasic EMG activity in the FDS muscles. Four independent expert scorers performed artefact correction according to the SINBAR (Sleep Innsbruck Barcelona) recommendations. Interrater reliability for artefact correction was computed with B-statistics. The variability across scorers of four RWA indices (phasic mentalis, “any” mentalis, phasic FDS and SINBAR – i.e. “any” mentalis and/or phasic FDS – EMG activity indices) was computed. With Friedman tests we compared B-statistics obtained for mentalis and FDS muscles, and the variability of the RWA indices. Influence of AHIREM and RBD diagnosis on the RWA indices variability was evaluated with linear regressions.

RESULTS: Interrater reliability for artefact correction was higher in the FDS than in the mentalis muscle (p<0.001). Phasic FDS activity was minimally affected by artefacts. Accordingly, the phasic FDS EMG activity index had the lowest variability across scorers (p<0.001). Variability across scorers of the RWA indices including the mentalis muscle increased with AHIREM and was independent from RBD diagnosis.

CONCLUSIONS: Due to the consistently found low number of artefacts, phasic FDS activity is a reliable measure of RWA.

PMID:33842971 | DOI:10.1093/sleep/zsab094

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Surgical management of displaced femoral neck fractures in patients with dementia: a comparison in mortality between hemiarthroplasty and pins/screws

Eur J Trauma Emerg Surg. 2021 Apr 11. doi: 10.1007/s00068-021-01640-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Dementia is common in patients with hip fractures and is strongly associated with increased postoperative mortality. The choice of surgical intervention for displaced femoral neck fractures (dFNF) in patients with dementia has been a matter of debate. This study aims to investigate how short- and long-term mortality differs between those who have been operated with hemiarthroplasty or pins/screws.

METHODS: All patients with dementia and dFNF, i.e., Garden III and IV, who underwent primary emergency hip fracture surgery, with either hemiarthroplasty or pins/screws, in Sweden between Jan 1, 2008 and Dec 31, 2017 were eligible for inclusion in the current study. Patients were divided into two groups based on the surgical intervention: hemiarthroplasty and pins/screws. The primary outcome of interest was 30-day postoperative mortality, and the secondary outcome was 1-year postoperative mortality. Poisson and Cox regression analyses were performed both before and after propensity score matching.

RESULTS: A total of 9394 cases met the inclusion criteria; 84% received hemiarthroplasty and 16% received pins/screws. In the unmatched analysis, the adjusted incidence rate ratio (IRR) for 30-day postoperative mortality was not affected by the chosen surgical method (adj. IRR 0.96, CI 95% 0.83-1.12, p = 0.629). After propensity score matching, similar results were observed with no difference in 30-day postoperative mortality (adj. IRR 0.89, CI 95% 0.74-1.09, p = 0.286). There was a statistically significant decrease in the risk of 1-year postoperative mortality in the hemiarthroplasty group compared to the pins/screws group, both before and after propensity score matching.

CONCLUSION: This study could not demonstrate any difference in 30-day mortality in patients with dementia and dFNFs when comparing hemiarthroplasty with pins/screws. Patients that received hemiarthroplasties did, however, have a lower risk of 1-year postoperative mortality.

PMID:33842982 | DOI:10.1007/s00068-021-01640-0

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Fpemlocal: Estimating family planning indicators in R for a single population of interest

Gates Open Res. 2021 Feb 24;5:24. doi: 10.12688/gatesopenres.13211.1. eCollection 2021.

ABSTRACT

The global Family Planning Estimation model (FPEM) combines a Bayesian hierarchical model with country-specific time trends to yield estimates of contraceptive prevalence and unmet need for family planning for countries worldwide. In this paper, we introduce the R package fpemlocal that carries out the estimation of family planning indicators for a single population, for example, for a single country or smaller area. In this implementation of FPEM, all non-population-specific parameters are fixed at outcomes obtained in a prior global FPEM run. The development of this model was motivated by the demand for computational efficiency, without loss of model accuracy, when estimates and projections from FPEM were needed only for a single country. We present use cases to produce estimates for a single population of women by union status or all women based on package-provided data bases and user-specified data. We also explain how to aggregate estimates across multiple populations. The R package forms the basis of the Track20 Family Planning Estimation Tool to monitor trends in family planning indicators for the FP2020 initiative. Fpemlocal is available from: https://github.com/AlkemaLab/fpemlocal.

PMID:33842844 | PMC:PMC8008158 | DOI:10.12688/gatesopenres.13211.1

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Integrating Eye Tracking and Speech Recognition Accurately Annotates MR Brain Images for Deep Learning: Proof of Principle

Radiol Artif Intell. 2020 Nov 11;3(1):e200047. doi: 10.1148/ryai.2020200047. eCollection 2021 Jan.

ABSTRACT

PURPOSE: To generate and assess an algorithm combining eye tracking and speech recognition to extract brain lesion location labels automatically for deep learning (DL).

MATERIALS AND METHODS: In this retrospective study, 700 two-dimensional brain tumor MRI scans from the Brain Tumor Segmentation database were clinically interpreted. For each image, a single radiologist dictated a standard phrase describing the lesion into a microphone, simulating clinical interpretation. Eye-tracking data were recorded simultaneously. Using speech recognition, gaze points corresponding to each lesion were obtained. Lesion locations were used to train a keypoint detection convolutional neural network to find new lesions. A network was trained to localize lesions for an independent test set of 85 images. The statistical measure to evaluate our method was percent accuracy.

RESULTS: Eye tracking with speech recognition was 92% accurate in labeling lesion locations from the training dataset, thereby demonstrating that fully simulated interpretation can yield reliable tumor location labels. These labels became those that were used to train the DL network. The detection network trained on these labels predicted lesion location of a separate testing set with 85% accuracy.

CONCLUSION: The DL network was able to locate brain tumors on the basis of training data that were labeled automatically from simulated clinical image interpretation.© RSNA, 2020.

PMID:33842890 | PMC:PMC7845782 | DOI:10.1148/ryai.2020200047

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Predictive Risk Factors for Postoperative Complications and Its Impact on Survival in Laparoscopic Resection for Colon Cancer

Surg Laparosc Endosc Percutan Tech. 2021 Apr 1. doi: 10.1097/SLE.0000000000000936. Online ahead of print.

ABSTRACT

BACKGROUND: Laparoscopic resection is the ideal treatment of colon cancer. The aim of the study was to analyze the predictive factors for postoperative complications and their impact on oncologic outcomes in laparoscopic resections in colon cancer.

MATERIALS AND METHODS: In all patients undergoing elective laparoscopic surgery the number and degree of severity of postoperative complications were recorded and classified according to Clavien-Dindo. A univariate analysis was made of the demographic, surgical, and oncologic variables of patients with and without complications. The statistically significant variables were then entered into a multivariate model. In both groups overall and disease-free survival were analyzed using Kaplan-Meier estimates.

RESULTS: Of 524 patients, 138 (26.3%) experienced some type of complication, 110 less severe (79.7%) and 28 (20.4%) severe. Twenty-nine conversions to open surgery occurred (5.5%) and hospital mortality was 0.2%.In the multivariate analysis, use of corticosteroids [odds ratio (OR): 3.619], oral anticoagulants (OR: 3.49), blood transfusions (OR: 4.30), and conversion to open surgery (OR: 3.93) were significantly associated with the development of complications. However, sigmoid resections were associated with fewer complications (OR: 0.45).Overall 5-year and 10-year survival in both groups, was 83.3%, 74.1%, 76.0%, and 67.1%, respectively (P=0.18). Disease-free survival at 5 and 10 years, excluding stage IV tumors, was 88.6% and 90.4%, respectively (P=0.881).

CONCLUSIONS: The use of corticosteroids, oral anticoagulants, blood transfusions, and conversion to open surgery are all independent predictive factors of postoperative complications. Sigmoid resections are associated with fewer complications. In laparoscopic resections of the colon, complications do not negatively affect long-term oncologic outcomes.

PMID:33840737 | DOI:10.1097/SLE.0000000000000936

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Thermal Ablation as an Alternative for Surgical Resection of Small (≤ 2 cm) Breast Cancers: A Meta-Analysis

Clin Breast Cancer. 2021 Mar 17:S1526-8209(21)00059-8. doi: 10.1016/j.clbc.2021.03.004. Online ahead of print.

ABSTRACT

Women with early-stage breast cancer have an excellent prognosis with current therapy, but could presumably be treated less invasively, without the need for surgery. The primary goal of this meta-analysis was to examine whether thermal ablation is an effective method to treat early-stage breast cancer. Studies reporting on complete ablation rate after thermal ablation as a treatment of small breast cancers (≤ 2 cm) were included. Methodologic quality of included studies was assessed using MINORS criteria. Complete ablation rates are given as proportions, and meta-regression and subgroup analyses were performed. The overall complete ablation rate in 1266 patients was 86% and was highest after radiofrequency ablation (RFA) (92%). Local recurrence rates varied from 0% to 3%, with a median follow-up of 15 to 61 months. Overall, complication rates were low (5%-18% across techniques) and were highest after high-intensity focused ultrasound ablation and lowest after cryoablation. Cosmetic outcome was good to excellent in at least 85% of patients but was reported infrequently and long-term results of cosmetic outcome after thermal ablation and radiotherapy are still lacking. Thermal ablation techniques treating early-stage breast cancer (≤ 2 cm) are safe and effective based on complete ablation rate and short-term local recurrence rates. Especially, RFA, microwave ablation, and cryoablation are promising techniques as an alternative to surgical resection without jeopardizing current treatment effectiveness or safety. Owing to great heterogeneity in the included studies, a formal recommendation on the best technique is not possible. These findings warrant the design of large randomized controlled trials comparing thermal ablation and breast-conserving surgery in the treatment of T1 breast cancer.

PMID:33840627 | DOI:10.1016/j.clbc.2021.03.004

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Live implant dosimetry may be an effective replacement for postimplant computed tomography in localized prostate cancer patients receiving low dose rate brachytherapy

Brachytherapy. 2021 Apr 8:S1538-4721(21)00045-3. doi: 10.1016/j.brachy.2021.02.008. Online ahead of print.

ABSTRACT

PURPOSE: To determine if Live Implant Dosimetry (LIDO) utilizing intraoperative transrectal ultrasound (TRUS) is equivalent to postimplant CT dosimetry (either day 0 or day 30) in patients with localized prostate cancer (PC) treated with low dose rate (LDR) prostate seed brachytherapy.

METHODS AND MATERIALS: The treated population consisted of 628 men with localized (T1-T2) PC. All d’Amico risk categories (low, intermediate, and high) were included, and 437 patients were treated with monotherapy (160 Gy) [low and low tier intermediate], and the remainder (191) [high tier intermediate and high risk] with an implant boost (106 Gy) post external beam radiation, to a volume including the prostate and seminal vesicles (46 Gy). LIDO with intraoperative TRUS, postimplant CT (day 0 and day 30) were performed in all cases. Prostate volumes (V), V100 (prostate) and dose (D) D90 (prostate), D30 (urethra), and Rectum D2cc, were recorded. No urinary catheter was used on Day 30 CT.

RESULTS: More than 91.33% of monotherapy patients reached the target D90 according to LIDO while only 82.99% of Day 0 CT and 92.82% of Day 30 CT achieved target D90. When considering V100, monotherapy patients recorded target dosimetry in 90.93%, 82.31%, and 92.02% of cases assessed by LIDO, Day 0 CT and Day 30 CT, respectively. Strong correlations are observed in D90, Rectum D2cc and Urethra D30 across imaging modalities but V100 and V150 were poorly correlated due to the relative quantification of this parameter and high degree of error in measurement. Of all monotherapy patients with satisfactory dosimetry on LIDO, 94.82% reached target D90 at day 30 CT and 94.19% reached target V100.

CONCLUSIONS: LIDO and CT are both effective tools for assessing postimplant dosimetry. Patients with satisfactory LIDO dosimetry are highly likely to have equivalent dosimetry on CT at follow-up, indicating that postimplant CT may be eliminated in PC a patients implanted with this technique.

PMID:33840634 | DOI:10.1016/j.brachy.2021.02.008

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Long-term color stability of light-polymerized resin luting agents in different beverages

J Prosthodont Res. 2021 Apr 9. doi: 10.2186/jpr.JPR_D_20_00306. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the long-term color stability of light-polymerized resin luting agents stored in different beverages.

METHODS: Eleven shades of two light-polymerized resin luting agents, Choice2 (A1, A2, B1, TRANSLUCENT, MILKY OPAQUE, and MILKY BRIGHT) and BeautiCem Veneer (H-Value, M-Value, L-Value, Ivory-D, Ivory-L) were selected in this study. Disk-shaped specimens were fabricated with 1.3 mm thickness and 15.0 mm diameter. A total of 198 specimens, 18 for each shade, were prepared and randomly divided into six storage conditions (purified water, coffee, cola, tea, red wine, and air). All shades of specimens were three times measured at three random locations (n = 9) at 24 h storage in air after specimen preparation and then measured after immersion at 1, 3, 6, 9, and 12 mos. using a colorimeter. Then, the color difference (ΔE) between the specimens at 24 h after preparation and after storage in each liquid for 12 mos. was calculated. Statistical analysis was performed using Steele-Dwass multiple comparison test of the ΔE values or one-way ANOVA and Tukey’s honest significant difference test.

RESULTS: For all immersion conditions, ΔE was significantly higher than air (control). The ΔE of the shades in the various storage conditions showed no significant difference between Purified Water-Cola and Coffee-Tea. Comparisons of the color components L*, a*, and b* for each shade showed different behaviors among the shades.

CONCLUSIONS: The results suggest that the color stability of light-polymerized resin luting agents may differ between different shades and beverages.

PMID:33840707 | DOI:10.2186/jpr.JPR_D_20_00306