Significant Longitudinal Changes Research Articles

Patient-reported sexual adjustment after definitive chemoradiation and MR-guided brachytherapy for cervical cancer

PurposeThe treatment of locally advanced cervical cancer with definitive chemoradiation (CRT) is associated with vaginal toxicity and altered sexual satisfaction. This prospective study assessed patient-reported sexual adjustment, vaginal dosimetry, and physician-reported vaginal toxicity in patients with cervical cancer treated with CRT and MR-guided brachytherapy (BT). Materials and MethodsBetween 2008 and 2010, International Federation of Gynecologists and Obstetricians stage IB-IVA patients with cervical cancer receiving definitive CRT were enrolled in a feasibility study assessing MR-guided BT. Patients completed the validated sexual adjustment questionnaire (SAQ) before BT (baseline) and during followup. Physician-reported vaginal toxicity was recorded. The International Commission on Radiation Units and Measurements rectovaginal point, mean vaginal dose, and D2cm3 were calculated. Mean SAQ scores at baseline and followup assessments were calculated. Mean time effects were estimated using a linear mixed-effects model. A multivariable linear mixed-effects model was used to examine the association between total and individual scores (repeated measures) and covariates. ResultsSixty patients were approached to participate: 29 consented and 27 completed the SAQ at baseline and followup. The diagnosis of cervical cancer and treatment negatively impacted sexual relationships in 61% and 39%, respectively. There were no significant changes in sexual adjustment over time (p = 0.599). There were no associations between sexual adjustment and the International Commission on Radiation Units and Measurements rectovaginal point dose or clinical vaginal involvement. Patients with higher International Federation of Gynecologists and Obstetricians stages (≥IIB) had significantly worse sexual adjustment (p = 0.005). ConclusionCRT and MR-guided BT negatively impacted sexual relationships in patients with cervix cancer; however, there were no significant longitudinal changes in patient-reported sexual adjustment. Worse sexual adjustment may be associated with more advanced disease presentations.

Personalized pathology maps to quantify diffuse and focal brain damage

Background and objectivesQuantitative MRI (qMRI) permits the quantification of brain changes compatible with inflammation, degeneration and repair in multiple sclerosis (MS) patients. In this study, we propose a new method to provide personalized maps of tissue alterations and longitudinal brain changes based on different qMRI metrics, which provide complementary information about brain pathology.MethodsWe performed baseline and two-years follow-up on (i) 13 relapsing-remitting MS patients and (ii) four healthy controls. A group consisting of up to 65 healthy controls was used to compute the reference distribution of qMRI metrics in healthy tissue. All subjects underwent 3T MRI examinations including T1, T2, T2* relaxation and Magnetization Transfer Ratio (MTR) imaging. We used a recent partial volume estimation algorithm to estimate the concentration of different brain tissue types on T1 maps; then, we computed a deviation map (z-score map) for each contrast at both time-points. Finally, we subtracted those deviation maps only for voxels showing a significant difference with healthy tissue in one of the time points, to obtain a difference map for each subject.Results and conclusionControl subjects did not show any significant z-score deviations or longitudinal z-score changes. On the other hand, MS patients showed brain regions with cross-sectional and longitudinal concomitant increase in T1, T2, T2* z-scores and decrease of MTR z-scores, suggesting brain tissue degeneration/loss. In the lesion periphery, we observed areas with cross-sectional and longitudinal decreased T1/T2 and slight decrease in T2* most likely related to iron accumulation. Moreover, we measured longitudinal decrease in T1, T2 - and to a lesser extent in T2* - as well as a concomitant increase in MTR, suggesting remyelination/repair.In summary, we have developed a method that provides whole-brain personalized maps of cross-sectional and longitudinal changes in MS patients, which are computed in patient space. These maps may open new perspectives to complement and support radiological evaluation of brain damage for a given patient.

Psychological adjustment of young subjects with Möbius sequence and their primary caregivers’ strain and life satisfaction: First longitudinal data

Aims/MethodsAt present, there is no information about the course of psychological adjustment in young subjects with Möbius sequence (MS) and their parents' strain and life satisfaction. To fill this gap, we performed a four-year follow-up study. Parents were anonymously asked to fill out the Child Behavior Checklist 4-18 [CBCL/ 4-18] or the Young Adult Behavior Checklist 18-30 [YABCL/ 18-30] and the Freiburger Personality Inventory-Revised [FPI-R], subscales strain and life satisfaction. Results12 males and 14 females (mean: 15.20 years, standard deviation: 3.48 years) could be included in the follow-up (response rate: 83.9%).Compared to the general population, subjects with MS showed significantly higher scores on almost all CBCL scales (exception: externalizing problems) at T1 and T2. At both study times, parental strain and life satisfaction were not significantly different from findings in the general population. No significant longitudinal changes could be found for CBLC scales, parental strain and life satisfaction. ConclusionsProblems with psychological adjustment seem to be frequent among younger subjects with MS. Therefore, careful monitoring as well as early and adequate interventions, if indicated, are crucial for subjects with MS, not only with regard to somatic complaints but also to aspects of adjustment.

Predicting and understanding the response to short-term intensive insulin therapy in people with early type 2 diabetes

ObjectiveShort-term intensive insulin therapy (IIT) early in the course of type 2 diabetes acutely improves beta-cell function with long-lasting effects on glycemic control. However, conventional measures cannot determine which patients are better suited for IIT, and little is known about the molecular mechanisms determining response. Therefore, this study aimed to develop a model that could accurately predict the response to IIT and provide insight into molecular mechanisms driving such response in humans. MethodsTwenty-four patients with early type 2 diabetes were assessed at baseline and four weeks after IIT, consisting of basal detemir and premeal insulin aspart. Twelve individuals had a beneficial beta-cell response to IIT (responders) and 12 did not (nonresponders). Beta-cell function was assessed by multiple methods, including Insulin Secretion-Sensitivity Index-2. MicroRNAs (miRNAs) were profiled in plasma samples before and after IIT. The response to IIT was modeled using a machine learning algorithm and potential miRNA-mediated regulatory mechanisms assessed by differential expression, correlation, and functional network analyses (FNA). ResultsBaseline levels of circulating miR-145-5p, miR-29c-3p, and HbA1c accurately (91.7%) predicted the response to IIT (OR = 121 [95% CI: 6.7, 2188.3]). Mechanistically, a previously described regulatory loop between miR-145-5p and miR-483-3p/5p, which controls TP53-mediated apoptosis, appears to also occur in our study population of humans with early type 2 diabetes. In addition, significant (fold change > 2, P < 0.05) longitudinal changes due to IIT in the circulating levels of miR-138-5p, miR-192-5p, miR-195-5p, miR-320b, and let-7a-5p further characterized the responder group and significantly correlated (|r| > 0.4, P < 0.05) with the changes in measures of beta-cell function and insulin sensitivity. FNA identified a network of coordinately/cooperatively regulated miRNA-targeted genes that potentially drives the IIT response through negative regulation of apoptotic processes that underlie beta cell dysfunction and concomitant positive regulation of proliferation. ConclusionsResponses to IIT in people with early type 2 diabetes are associated with characteristic miRNA signatures. This study represents a first step to identify potential responders to IIT (a current limitation in the field) and provides important insight into the pathophysiologic determinants of the reversibility of beta-cell dysfunction.ClinicalTrial.gov identifier: NCT01270789.

Repeatability of dynamic contrast enhanced vp parameter in healthy subjects and patients with brain tumors.

To study the repeatability of plasma volume (vp) extracted from dynamic-contrast-enhanced (DCE) MRI in order to define threshold values for significant longitudinal changes, and to assess changes in patients with high-grade-glioma (HGG). Twenty eight healthy subjects, of which eleven scanned twice, were used to assess the repeatability of vp within the normal-appearing brain tissue and to define threshold values for significant changes based on least-detected-differences (LDD) of mean vp values and histogram comparisons using earth-mover's-distance (EMD). Sixteen patients with HGG were scanned longitudinally with eight patients scanned before and following bevacizumab therapy. Longitudinal changes were assessed based on defined threshold values in comparison to RANO criteria. The threshold values for significant changes were: LDD = 0.0024 (ml/100ml, 21%) for mean vp and EMD = 4.14. In patients, in 20/24 comparisons, no significant longitudinal changes were detected for vp within the normal-appearing brain tissue. Concurring results were obtained between changes in lesion volume (RANO criteria) and LDD or EMD values in cases diagnosed with progressive-disease, yet in about 50% of cases diagnosed with partial-response preliminary results demonstrated significant increase in vp despite significant reductions in lesion volume. In two patients, these changes preceded progression detected at follow-up scans. In general, a good concordance was obtained between LDD and EMD. This study shows high repeatability of vp and provides threshold values for significant changes in longitudinal assessment of patients with brain tumors. Preliminary results suggest the use of vp-DCE parameter to improve assessment of therapy response in patients with high-grade-glioma.

Longitudinal Analysis of Superficial Midfacial Fat Volumes Over a 10-Year Period.

Volumetric changes to facial fat that occur with aging remain poorly understood. The aim of this study was to evaluate for longitudinal changes to midfacial fat volumes in a group of individuals. We conducted a retrospective longitudinal study of adult subjects who underwent multiple facial computed tomographic (CT) scans timed at least 8years apart. Subjects who underwent facial surgery or suffered facial trauma were excluded. Facial CT scans were analyzed, and superficial cheek fat volumes were measured and compared to track changes that occurred with aging. Fourteen subjects were included in our analysis of facial aging (5 male, 9 female; mean initial age 50.9years; mean final age 60.4years). In the right superficial cheek there was an increase in mean (SD) superficial fat volume from 10.33 (2.01) to 10.50 (1.80)cc, which was not statistically significant (P = 0.75). Similar results were observed in the left cheek. There were no statistically significant longitudinal changes to caudal, middle, or cephalad subdivisions of bilateral superficial cheek fat. A simple linear regression was performed to predict superficial cheek fat pad volume based on age which did not reach statistical significance (P = 0.31), with an R2 of 0.039. This study is the first to quantitatively assess for longitudinal changes to midfacial fat in a group of individuals. Superficial cheek fat remained stable as subjects aged from approximately 50 to 60years old, with no change in total volume or redistribution within a radiographically defined compartment. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The impact of a hospital electronic prescribing and medication administration system on medication administration safety: an observational study

BackgroundThe aim of the study was to explore the impact of the implementation of an electronic prescribing and medication administration system (ePA) on the safety of medication administration in an inpatient hospital setting. Objectives were to compare the prevalence and types of: 1) medication administration errors, and 2) documentation discrepancies, between a paper and an ePA system. Additionally, we wanted to describe any observed changes to medication administration practices.MethodsThe study was based on an elderly medicine ward in an English hospital. From December 2014 to June 2015, nurses’ medication administration rounds were observed every 5 days before and after ePA implementation using an interrupted time-series approach. Medication administration error and documentation discrepancy rates pre- versus post-ePA were analysed descriptively and chi-squared tests used to test for any difference; segmented regression analysis was used to determine changes in longitudinal trend.ResultsObservations were made at 15 pre- and 15 post-ePA implementation time-points. Pre-ePA on paper, there were 18 medication administration errors in 428 opportunities for error (4.2%; 95% confidence interval 2.3–6.1%), and with ePA there were 18 in 528 (3.4%; 95% confidence interval 1.9–5.0%; p = 0.64). Regarding documentation, pre-ePA on paper there were 5 discrepancies in 460 observed documentations (1.1%; 95% confidence interval 0.1–2.0%); with ePA there were 18 in 557 (3.2%; 95% confidence interval 1.8–4.7%; p = 0.04). The most common electronic documentation discrepancy was documentation that a dose had been administered when it had not. Segmented regression analysis was unable to detect any significant longitudinal changes. Changes to working practices post-ePA were observed, such as nurses demonstrating less-consistent self-checking when preparing and administering medications.ConclusionsFindings suggest no change in medication error rate, although ePA encourages certain types of errors and mitigates others. There was a statistically significant increase in documentation discrepancies which is likely to be due to adoption of new working practices with ePA.

MRI findings of knee abnormalities in adolescent and adult volleyball players

BackgroundTo longitudinally and cross-sectionally evaluate knee abnormalities by sex and age in adolescent and adult volleyball athletes over 2 years using magnetic resonance imaging (MRI).MethodsThirty-six high-level volleyball athletes (18 adolescents: 56% female, mean age 16.0 ± 0.8 years; and 18 adults: 50% female, mean age 46.8 ± 5.1 years) were imaged by MRI at BL and at 2-year follow-up (FU). Prevalence and severity of cartilage lesions, subarticular bone marrow lesions (BMLs), subarticular cysts, osteophytes, and ligament and meniscus integrity were evaluated by sex and by age cohort (adolescents and adults) using the whole-organ MRI score (WORMS).ResultsThere were no significant longitudinal changes in any of the features within any of the sex or age groups. No significant differences were found in overall prevalence or severity of any of the features between males and females, although at FU, males had a significantly higher prevalence of osteophytes in the medial femorotibial joint (MFTJ) than females (p=0.044). Compared to adolescents, adult volleyball players had a significantly greater prevalence and severity of cartilage lesions (p<0.001 for both), BMLs (p=0.0153 and p=0.005), and osteophytes (p≤0.003 and p<0.001), and more severe meniscal lesions (p≤0.021).ConclusionWe found significant differences in the prevalence and severity of knee abnormalities between adolescent and adult volleyball players, but no overall differences by sex. These findings lay the groundwork for further investigations with larger cohorts and longer FU times to determine whether or not these knee abnormalities are associated with the development of OA.

Gastrostomies Preserve But Do Not Increase Quality of Life forPatients and Caregivers.

Gastrostomies are widely used to provide long-term enteral nutrition to patients with neurologic conditions that affect swallowing (eg, following a cerebrovascular accident or for patients with motor neuron disease) or with oropharyngeal malignancies. The benefits derived from this intervention are uncertain for patients and caregivers. We conducted a prospective, multicenter cohort study to determine how gastrostomies affect health-related quality of life (HRQoL) in recipients and caregivers. We performed a study of 100 patients who received gastrostomies (55% percutaneous endoscopic gastrostomy, 45% radiologically inserted) at 5 centers in the United Kingdom, 100 caregivers, and 200 population control subjects. We used the EuroQol-5D (comprising a questionnaire, index, visual analogue scale) to assess HRQoL for patients and caregivers before the gastrostomy insertion and then 3 months afterward; findings were compared with those from control subjects. Ten patients and 10 caregivers were also interviewed after the procedure to explore quantitative findings. Findings from the EuroQol-5D and semi-structured interviews were integrated using a mixed-methods matrix. Six patients died before the 3-month HRQoL reassessments. We observed no significant longitudinal changes in mean EuroQol-5D index scores for patients (0.70 before vs 0.710 after; P=.83) or caregivers (0.95 before vs 0.95 after; P= .32) following gastrostomy insertion. The semi-structured interviews revealed problems in managing gastrostomy tubes, social isolation, and psychological and emotional consequences that reduced HRQoL. We performed a mixed-methods prospective study of the effects of gastrostomy feeding on HRQoL. HRQoL did not significantly improve after gastrostomy insertion for patients or caregivers. The lack of significant decrease in HRQoL after the procedure indicates that gastrostomies may help maintain HRQoL. Findings have relevance to those involved in gastrostomy insertion decisions and indicate the importance of carefully selecting patients for this intervention, despite the relative ease of insertion.

Composite metric R2 - R1ρ (1/T2 - 1/T1ρ ) as a potential MR imaging biomarker associated with changes in pain after ACL reconstruction: A six-month follow-up.

This study looked to investigate a new quantitative metric, R2 - R1ρ (1/T2 - 1/T1ρ ), using magnetic resonance (MR) images and voxel-based relaxometry (VBR) for detecting early cartilage degeneration and explore the association with patient-reported outcomes measures (PROMs) in patients 6 months after ACL reconstruction. Sixty-four patients from three sites were bilaterally scanned on a 3T MR with a combined T1ρ /T2 protocol to calculate R1ρ (1/T1ρ ) and R2 (1/T2 ) values at baseline and 6 months after reconstructive surgery. Non-rigid registration was applied to align images onto a template, allowing VBR to determine VBR rate differences and explore cross-sectional and longitudinal differences between injured and uninjured knees, generating Statistical Parametric Maps (SPMs). Baseline R2 - R1ρ differences were further correlated with change in PROMs from the Knee Injury and Osteoarthritis Outcome Score (KOOS) from baseline to 6 months. Cross-sectional results demonstrated low relaxation rate differences in the injured patella (baseline: 21%, p = 0.01; 6-months: 18%, p = 0.02), lateral tibia (baseline: 25%, p = 0.01; 6-months: 24%, p = 0.01), and weight-bearing regions of the tibia and femur. The uninjured patella showed significant longitudinal changes (17%, p = 0.02). R2 - R1ρ differences showed significant correlations with KOOS PROMs, particularly in the lateral tibia, patella, and trochlea. R2 - R1ρ difference VBR analyses provide new and highly sensitive parameters for assessing early cartilage degeneration in patients after ACL injury by integrating findings from both T1ρ and T2 , commonly used relaxation time parameters, into a single metric. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:718-729, 2017.

Dose-Escalated Stereotactic Body Radiation Therapy for Prostate Cancer: Quality-of-Life Comparison of Two Prospective Trials.

The optimal prostate stereotactic body radiation therapy (SBRT) dose-fractionation scheme is controversial. This study compares long-term quality of life (QOL) from two prospective trials of prostate SBRT to investigate the effect of increasing dose (NCT01578902 and NCT01146340). Patients with localized prostate cancer received SBRT 35 or 40 Gy delivered in five fractions, once per week. QOL was measured using the Expanded Prostate Cancer Index Composite at baseline and every 6 months. Fisher's exact test and generalized estimating equations were used to analyze proportions of patients with clinically significant change and longitudinal changes in QOL. One hundred fourteen patients were included, 84 treated with 35 Gy and 30 treated with 40 Gy. Median QOL follow-up was 56 months [interquartile range (IQR) 46-60] and 38 months (IQR 32-42), respectively. The proportion of patients reporting clinically significant declines in average urinary, bowel, and sexual scores were not significantly different between dose levels, and were 20.5 vs. 24.1% (p = 0.60), 26.8 vs. 41.4% (p = 0.16), and 42.9 vs. 38.5% (p = 0.82), respectively. Similarly, longitudinal analysis did not identify significant differences in QOL between treatment groups. Dose-escalated prostate SBRT from 35 to 40 Gy in five fractions was not associated with significant decline in long-term QOL.

Thin-plate spline analysis of mandibular shape changes induced by functional appliances in Class II malocclusion : A long-term evaluation.

The purpose of this work was to evaluate the long-term morphological mandibular changes induced by functional treatment of Class II malocclusion with mandibular retrusion. Forty patients (20 females, 20 males) with Class II malocclusion consecutively treated with either a Bionator or an Activator followed by fixed appliances were compared with a control group of 40 subjects (19 females, 21 males) with untreated Class II malocclusion. Lateral cephalograms were available at the start of treatment (T1, mean age 9.9years), at the end of treatment with functional appliances (T2, mean age 12.2years), and for long-term follow-up (T3, mean age 18.3years). Mandibular shape changes were analyzed on lateral cephalograms of the subjects in both groups via thin-plate spline (TPS) analysis. Shape differences were statistically analyzed by conducting permutation tests on Goodall F statistics. In the long term, both the treated and control groups exhibited significant longitudinal mandibular shape changes characterized by upward and forward dislocation of point Co associated with a vertical extension in the gonial region and backward dislocation of point B. Functional appliances induced mandible's significant posterior morphogenetic rotation over the short term. The treated and control groups demonstrated similar mandibular shape over the long term.

Diffusion tensor imaging study of pediatric patients with congenital hydrocephalus: 1-year postsurgical outcomes.

OBJECTIVE The purpose of this study was to investigate white matter (WM) structural abnormalities using diffusion tensor imaging (DTI) in children with hydrocephalus before CSF diversionary surgery (including ventriculoperitoneal shunt insertion and endoscopic third ventriculostomy) and during the course of recovery after surgery in association with neuropsychological and behavioral outcome. METHODS This prospective study included 54 pediatric patients with congenital hydrocephalus (21 female, 33 male; age range 0.03-194.5 months) who underwent surgery and 64 normal controls (30 female, 34 male; age range 0.30-197.75 months). DTI and neurodevelopmental outcome data were collected once in the control group and 3 times (preoperatively and at 3 and 12 months postoperatively) in the patients with hydrocephalus. DTI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were extracted from the genu of the corpus callosum (gCC) and the posterior limb of internal capsule (PLIC). Group analysis was performed first cross-sectionally to quantify DTI abnormalities at 3 time points by comparing the data obtained in the hydrocephalus group for each of the 3 time points to data obtained in the controls. Longitudinal comparisons were conducted pairwise between different time points in patients whose data were acquired at multiple time points. Neurodevelopmental data were collected and analyzed using the Adaptive Behavior Assessment System, Second Edition, and the Bayley Scales of Infant Development, Third Edition. Correlation analyses were performed between DTI and behavioral measures. RESULTS Significant DTI abnormalities were found in the hydrocephalus patients in both the gCC (lower FA and higher MD, AD, and RD) and the PLIC (higher FA, lower AD and RD) before surgery. The DTI measures in the gCC remained mostly abnormal at 3 and 12 months after surgery. The DTI abnormalities in the PLIC were significant in FA and AD at 3 months after surgery but did not persist when tested at 12 months after surgery. Significant longitudinal DTI changes in the patients with hydrocephalus were found in the gCC when findings at 3 and 12 months after surgery were compared. In the PLIC, trend-level longitudinal changes were observed between preoperative findings and 3-month postoperative findings, as well as between 3- and 12-month postoperative findings. Significant correlation between DTI and developmental outcome was found at all 3 time points. Notably, a significant correlation was found between DTI in the PLIC at 3 months after surgery and developmental outcome at 12 months after surgery. CONCLUSIONS The data showed significant WM abnormality based on DTI in both the gCC and the PLIC in patients with congenital hydrocephalus before surgery, and the abnormalities persisted in both the gCC and the PLIC at 3 months after surgery. The DTI values remained significantly abnormal in the gCC at 12 months after surgery. Longitudinal analysis showed signs of recovery in both WM structures between different time points. Combined with the significant correlation found between DTI and neuropsychological measures, the findings of this study suggest that DTI can serve as a sensitive imaging biomarker for underlying neuroanatomical changes and postsurgical developmental outcome and even as a predictor for future outcomes.

Longitudinal Changes in the Motor Learning-Related Brain Activation Response in Presymptomatic Huntington's Disease.

Neurocognitive decline, including deficits in motor learning, occurs in the presymptomatic phase of Huntington’s disease (HD) and precedes the onset of motor symptoms. Findings from recent neuroimaging studies have linked these deficits to alterations in fronto-striatal and fronto-parietal brain networks. However, little is known about the temporal dynamics of these networks when subjects approach phenoconversion. Here, 10 subjects with presymptomatic HD were scanned with 15O-labeled water at baseline and again 1.5 years later while performing a motor sequence learning task and a kinematically matched control task. Spatial covariance analysis was utilized to characterize patterns of change in learning-related neural activation occurring over time in these individuals. Pattern expression was compared to corresponding values in 10 age-matched healthy control subjects. Spatial covariance analysis revealed significant longitudinal changes in the expression of a specific learning-related activation pattern characterized by increasing activity in the right orbitofrontal cortex, with concurrent reductions in the right medial prefrontal and posterior cingulate regions, the left insula, left precuneus, and left cerebellum. Changes in the expression of this pattern over time correlated with baseline measurements of disease burden and learning performance. The network changes were accompanied by modest improvement in learning performance that took place concurrently in the gene carriers. The presence of increased network activity in the setting of stable task performance is consistent with a discrete compensatory mechanism. The findings suggest that this effect is most pronounced in the late presymptomatic phase of HD, as subjects approach clinical onset.

Serum Biomarkers Indicate Long-term Reduction in Liver Fibrosis in Patients With Sustained Virological Response toTreatment for HCV Infection.

Sustained virological response (SVR) to antiviral therapy for hepatitis C virus (HCV) correlates with changes in biochemical measures of liver function. However, little is known about the long-term effects of SVR on liver fibrosis. We investigated the effects of HCV therapy on fibrosis, based on the Fibrosis-4 (FIB4) score, over a 10-year period. We collected data from participants in the Chronic Hepatitis Cohort Study-a large observational multicenter study of patients with hepatitis at 4 US health systems-from January 1, 2006, through December 31, 2013. We calculated patients' FIB4 score and the aminotransferase-to-platelet ratio index (APRI) score over a 10-year period. Of 4731 patients with HCV infection, 1657 (35%) were treated and 755 (46%) of these patients achieved SVR. In propensity score-adjusted analyses, we observed significant longitudinal changes in FIB4 score that varied with treatment and response to treatment. In patients achieving SVR, FIB4 scores decreased sharply, remaining significantly lower over the 10-year period than in untreated patients or patients with treatment failure (P < .001). In independent analyses, men and patients with HCV genotype 1 or 3 infections had higher FIB4 scores than women or patients with HCV genotype 2 infections (P < .01 for both). Findings were similar in a sensitivity analysis that substituted the APRI as the marker of fibrosis instead of the FIB4 score. SVR to HCV treatment appears to induce long-term regression of fibrosis based on FIB4 scores collected over 10 years from a large observational study of US hepatitis patients. Patients receiving no treatment or with treatment failure had progressive increases in FIB4 scores.

No progressive brain changes during a 1-year follow-up of patients with first-episode psychosis.

First-episode psychosis (FEP) patients show structural brain abnormalities. Whether the changes are progressive or not remain under debate, and the results from longitudinal magnetic resonance imaging (MRI) studies are mixed. We investigated if FEP patients showed a different pattern of regional brain structural change over a 1-year period compared with healthy controls, and if putative changes correlated with clinical characteristics and outcome. MRIs of 79 FEP patients [SCID-I-verified diagnoses: schizophrenia, psychotic bipolar disorder, or other psychoses, mean age 27.6 (s.d. = 7.7) years, 66% male] and 82 healthy controls [age 29.3 (s.d. = 7.2) years, 66% male] were acquired from the same 1.5 T scanner at baseline and 1-year follow-up as part of the Thematically Organized Psychosis (TOP) study, Oslo, Norway. Scans were automatically processed with the longitudinal stream in FreeSurfer that creates an unbiased within-subject template image. General linear models were used to analyse longitudinal change in a wide range of subcortical volumes and detailed thickness and surface area estimates across the entire cortex, and associations with clinical characteristics. FEP patients and controls did not differ significantly in annual percentage change in cortical thickness or area in any cortical region, or in any of the subcortical structures after adjustment for multiple comparisons. Within the FEP group, duration of untreated psychosis, age at illness onset, antipsychotic medication use and remission at follow-up were not related to longitudinal brain change. We found no significant longitudinal brain changes over a 1-year period in FEP patients. Our results do not support early progressive brain changes in psychotic disorders.

A Longitudinal Assessment of Structural and Chemical Alterations in Mixed Martial Arts Fighters

Growing evidence suggests that temporally proximal acute concussions and repetitive subconcussive head injuries may lead to long-term neurological deficits. However, the underlying mechanisms of injury and their relative time-scales are not well documented in human injury models. The current study therefore investigated whether biomarkers of brain chemistry (magnetic resonance [MR] spectroscopy: N-acetylaspartate [NAA], combined glutamate and glutamine [Glx], total creatine [Cre], choline compounds [Cho], and myo-inositol [mI]) and structure (cortical thickness, white matter [WM]/subcortical volume) differed between mixed martial artists (MMA; n = 13) and matched healthy controls (HC) without a history of contact sport participation (HC; n = 14). A subset of participants (MMA = 9; HC = 10) returned for follow-up visits, with MMA (n = 3) with clinician-documented acute concussions also scanned serially. As expected, MMA self-reported a higher incidence of previous concussions and significantly more cognitive symptoms during prior concussion recovery. Fighters also exhibited reduced memory and processing speed relative to controls on neuropsychological testing coupled with cortical thinning in the left posterior cingulate gyrus and right occipital cortex at baseline assessment. Over a 1-year follow-up period, MMA experienced a significant decrease in both WM volume and NAA concentration, as well as relative thinning in the left middle and superior frontal gyri. These longitudinal changes did not correlate with self-reported metrics of injury (i.e., fight diary). In contrast, HC did not exhibit significant longitudinal changes over a 4-month follow-up period (p > 0.05). Collectively, current results provide preliminary evidence of progressive changes in brain chemistry and structure over a relatively short time period in individuals with high exposure to repetitive head hits. These findings require replication in independent samples.

Group-wise evaluation and comparison of white matter fiber strain and maximum principal strain in sports-related concussion.

Sports-related concussion is a major public health problem in the United States and yet its biomechanical mechanisms remain unclear. In vitro studies demonstrate axonal elongation as a potential injury mechanism; however, current response-based injury predictors (e.g., maximum principal strain, ε(ep)) typically do not incorporate axonal orientations. We investigated the significance of white matter (WM) fiber orientation in strain estimation and compared fiber strain (ε(n)) with ε(ep) for 11 athletes with a clinical diagnosis of concussion. Geometrically accurate subject-specific head models with high mesh quality were created based on the Dartmouth Head Injury Model (DHIM), which was successfully validated (performance categorized as "good" to "excellent"). For WM regions estimated to be exposed to high strains using a range of injury thresholds (0.09-0.28), substantial differences existed between ε(n) and ε(ep) in both distribution (Dice coefficient of 0.13-0.33) and extent (∼ 5-10-fold differences), especially at higher threshold levels and higher rotational acceleration magnitudes. For example, an average of 3.2% vs. 29.8% of WM was predicted above an optimal threshold of 0.18 established from an in vivo animal study using ε(n) and ε(ep), respectively, with an average Dice coefficient of 0.14. The distribution of WM regions with high ε(n) was consistent with typical heterogeneous patterns of WM disruptions in diffuse axonal injury, and the group-wise extent at the optimal threshold matched well with the percentage of WM voxels experiencing significant longitudinal changes of fractional anisotropy and mean diffusivity (3.2% and 3.44%, respectively) found from a separate independent study. These results suggest the significance of incorporating WM microstructural anisotropy in future brain injury studies.

Does Ulnar Variance Change With Age and What Is the Influence of Training and Biological Characteristics in This Change? A Short-term Longitudinal Study in Portuguese Artistic Gymnasts

To analyze the variability and longitudinal stress-related changes in ulnar variance (UV) in a group of immature artistic gymnasts. The relationship between UV and a group of biological and training variables was also investigated. Prospective cohort study. Portuguese Federation of Gymnastics. Twenty-five Portuguese skeletally immature gymnasts competing nationally. Skeletal age (Tanner-Whitehouse 3 method), stature, body mass and body mass index (BMI) (Seca stadiometer), fat-free mass and percentage of body fat mass (Tanita BC 418), handgrip strength (Takei dynamometer), and training data (interview). To determine UV stress-related changes over time, left UV was obtained using Hafner procedure. Ulnar variance values and biological characteristics were tested twice (at baseline and after 18 months of training). Analysis of covariance analysis presented a significant interaction between age and time effect in UV at baseline. Each category of UV reacted differently to the interaction between age and training time. Significant relationships between UV and biological and training variables (chronological and skeletal age, body mass, BMI, handgrip strength, hour per week, and years of training) were evident in at least one of the moments of data collection. The gymnasts showed significant longitudinal UV changes toward less negative UV over the training period. Nevertheless, we could not find a significant correlation between UV and the majority of the researched variables. Thus, although UV has been broadly studied, this phenomenon is complex because it depends on different intrinsic and extrinsic factors that are difficult to control, making necessary additional research on this topic. The gymnast's wrist has been associated with a high incidence of painful symptomatology and injuries, leading to the formulation of several hypotheses related to the UV ethiology. Knowledge about the possible intrinsic or extrinsic factors related to UV changes and/or different UV categories (negative, neutral, and positive), as well as their consequent specific injuries in gymnasts' wrists may contribute to a primary prevention or reduction in the occurrence, recurrence and severity of pain, functional disability, or injuries in radius-ulnocarpal joint, thereby improving gymnasts' performance.

Assessment of the healing process in distal radius fractures by high resolution peripheral quantitative computed tomography

In clinical practice, fracture healing is evaluated by clinical judgment in combination with conventional radiography. Due to limited resolution, radiographs don't provide detailed information regarding the bone micro-architecture and bone strength. Recently, assessment of in vivo bone density, architectural and mechanical properties at the microscale became possible using high resolution peripheral quantitative computed tomography (HR-pQCT) in combination with micro finite element analysis (μFEA). So far, such techniques have been used mainly to study intact bone. The aim of this study was to explore whether these techniques can also be used to assess changes in bone density, micro-architecture and bone stiffness during fracture healing. Therefore, the fracture region in eighteen women, aged 50years or older with a stable distal radius fracture, was scanned using HR-pQCT at 1–2 (baseline), 3–4, 6–8 and 12weeks post-fracture. At 1–2 and 12weeks post-fracture the distal radius at the contra-lateral side was also scanned as control. Standard bone density, micro-architectural and geometric parameters were calculated and bone stiffness in compression, torsion and bending was assessed using μFEA. A linear mixed effect model with time post-fracture as fixed effect was used to detect significant (p-value ≤0.05) changes from baseline. Wrist pain and function were scored using the patient-rated wrist evaluation (PRWE) questionnaire. Correlations between the bone parameters and the PRWE score were calculated by Spearman's correlation coefficient. At the fracture site, total and trabecular bone density increased by 11% and 20%, respectively, at 6–8weeks, whereas cortical density was decreased by 4%. Trabecular thickness increased by 23–31% at 6–8 and 12weeks and the intertrabecular area became blurred, indicating intertrabecular bone formation. Compared to baseline, calculated bone stiffness in compression, torsion and bending was increased by 31% after 12weeks. A moderate negative correlation was found between the stiffness and the PRWE score. No changes were observed at the contra-lateral side. The results demonstrate that it is feasible to assess clinically relevant and significant longitudinal changes in bone density, micro-architecture and mechanical properties at the fracture region during the healing process of stable distal radius fractures using HR-pQCT.