Diffusion MRI Metrics and their Relation to Dementia Severity: Effects of Harmonization Approaches

Diffusion-weighted magnetic resonance imaging (dMRI) is sensitive to microstructural changes in the brain that occur with normal aging and Alzheimer's disease (AD). There is much interest in which dMRI measures are most strongly correlated with clinical measures of AD severity, such as the clinical dementia rating (CDR), and biological processes that may be disrupted in AD, such as brain amyloid load measured using PET. Of these processes, some can be targeted using novel drugs. Since 2016, the Alzheimer's Disease Neuroimaging Initiative (ADNI) has collected dMRI data from three scanner manufacturers across 58 sites using 7 different protocols that vary in angular resolution, scan duration, and in the number and distribution of diffusion-weighted gradients. Here, we assessed dMRI data from 730 of those individuals (447 cognitively normal controls, 214 with mild cognitive impairment, 69 with dementia; age: 74.1±7.9 years; 381 female/349 male). To harmonize data from different protocols, we applied ComBat, ComBat-GAM, and CovBat to dMRI metrics from 28 white matter regions of interest. We ranked all dMRI metrics in order of the strength of clinically relevant associations, and assessed how this depended on the harmonization methods employed. dMRI metrics were associated with age and clinical impairment, but also with amyloid positivity. All harmonization methods gave comparable results while enabling data integration across multiple scanners and protocols.

MR Imaging Biomarkers for Clinical Impairment and Disease Progression in Patients with Shoulder Adhesive Capsulitis: A Prospective Study

Background: MRI diagnostic criteria of shoulder adhesive capsulitis (AC) are nowadays widely used, but there is little information available on the association between MRI findings and clinical impairment. Purpose: To determine the correlation of MRI findings with the Constant–Murley Score (CMS), pain duration and symptoms at the one-year follow-up in AC patients. Materials and methods: This monocentric prospective study included 132 patients with a clinical diagnosis of shoulder AC who underwent shoulder MRI. Mean patient age was 54.1 ± 9.3 years, and there were 55 men and 77 women. A radiologist examined all patients and completed the CMS just prior to MRI. Pain duration was assessed along with the signal intensity and measured the maximal thickness of the inferior glenohumeral ligament (IGHL) by two radiologists. Medical record analysis was performed in a sub-group of 49 patients to assess prognosis approximately one year after the MRI examination. Linear regression analysis with the Pearson test and the Fisher exact test were used to determine the association between MRI findings and clinical impairment. Results: There was a significant difference in mean pain duration score (3.8 ± 1.2 versus 3.2 ± 0.9 and 3.8 ± 1.2 versus 3.2 ± 0.9, respectively, for readers 1 and 2) and in mean mobility scores (15.7 ± 8 points versus 19.6 ± 10.1 points and 15.8 ± 8.2 points versus 19.4 ± 10 points, respectively, for readers 1 and 2) in patients with a high IGHL signal compared to those with a low IGHL signal (p < 0.05). IGHL was thicker in patients with clinical improvement at one-year follow-up compared to those presenting clinical stability or worsening (p < 0.05). Conclusions: In patients with shoulder AC, the degree of signal intensity at the IGHL was inversely related to shoulder pain duration and range of motion, and a thickened IGHL indicated a favorable outcome at one-year follow-up.

Tissue damage detected by quantitative gradient echo MRI correlates with clinical progression in non-relapsing progressive MS

Background: Imaging biomarkers of progressive MS are needed. Quantitative gradient recalled echo (qGRE) MRI technique allows evaluation of tissue damage associated with microstructural damage in multiple sclerosis (MS). Objective: To evaluate qGRE-derived R2t* as an imaging biomarker of MS disease progression as compared to atrophy and lesion burden. Methods: Twenty-three non-relapsing progressive MS (PMS), twenty-two relapsing-remitting MS (RRMS) and eighteen healthy control participants were imaged with qGRE at 3T. PMS subjects were imaged and neurologically assessed every nine months over five sessions. In each imaging session, lesion burden, atrophy and R2t* in cortical grey matter (GM), deep GM, normal-appearing white matter (NAWM) were measured. Results: R2t* reductions correlated with neurological impairment cross-sectionally and longitudinally. PMS patients with clinically defined disease progression showed significantly faster decrease of R2t* in NAWM and deep GM compared with the clinically stable PMS group. Importantly, tissue damage measured by R2t* outperformed lesion burden and atrophy as a biomarker of progression during the study period. Conclusion: Clinical impairment and progression correlated with accumulating R2t*-defined microstructural tissue damage in deep GM and NAWM. qGRE-derived R2t* is a potential imaging biomarker of MS progression.

Estimating Need for Glasses and Hearing Aids in The Gambia: Results from a National Survey and Comparison of Clinical Impairment and Self-Report Assessment Approaches

Few estimates are available of the need for assistive devices (ADs) in African settings. This study aimed to estimate population-level need for glasses and hearing aids in The Gambia based on (1) clinical impairment assessment, and (2) self-reported AD awareness, and explore the relationship between the two methods. The Gambia 2019 National Eye Health Survey is a nationally representative population-based sample of 9188 adults aged 35+ years. Participants underwent standardised clinical vision assessments including the need for glasses (distance and near). Approximately 25% of the sample underwent clinical assessment of hearing and hearing aid need. Data were also collected on self-reported awareness, need and access barriers to vision and hearing ADs. Overall, 5.6% of the study population needed distance glasses (95% CI 5.0–6.3), 45.9% (95% CI 44.2–47.5) needed near glasses and 25.5% (95% CI 22.2–29.2) needed hearing aids. Coverage for each AD was very low (<4%). The agreement between self-report and clinical impairment assessment for AD need was poor. In conclusion, there is high prevalence and very low coverage for distance glasses, near glasses and hearing aids in The Gambia. Self-report measures alone will not provide an accurate estimate of AD need.

Temperament-Based Treatment for Young Adults with Eating Disorders: Acceptability and Initial Efficacy of an Intensive, Multi-Family, Parent-Involved Treatment.

Background: Adult eating disorder treatments are hampered by lack of access and limited efficacy. This open-trial study evaluated the acceptability and preliminary efficacy of a novel intervention for adults with eating disorders delivered to young adults and parent-supports in an intensive, multi-family format (Young Adult Temperament-Based Treatment with Supports; YA-TBT-S). Methods: 38 YA-TBT-S participants (m age = 19.58; SD 2.13) with anorexia nervosa (AN)-spectrum disorders, bulimia nervosa (BN)-spectrum disorders, and avoidant/restrictive food intake disorder (ARFID) completed self-report assessments at admission, discharge, and 12-month follow-up. Assessments measured program satisfaction, eating disorder psychopathology and impairment, body mass index (BMI), and trait anxiety. Outcomes were analyzed using linear mixed effects models to examine changes in outcome variables across diagnoses over time. Results: Treatment was rated as highly satisfactory. 53.33% were in partial or full remission at 12-month follow-up. Participants reported reductions in ED symptomatology (AN and BN), increases in BMI (AN and ARFID), and reductions in clinical impairment (AN and ARFID) at 12-month follow-up. Conclusions: YA-TBT-S is a feasible and acceptable treatment that may improve ED outcomes in young adults with a broad range of diagnoses. Further evaluation of efficacy is needed in larger samples, and to compare YA-TBT-S to other ED treatment approaches.

MO985EFFICACY AND SAFETY OF FERRIC CARBOXYMALTOSE IN THE MANAGEMENT OF EARLY POST-RENAL TRANSPLANT ANEMIA

Background and Aims The efficacy and safety of intravenous ferric carboxymaltose (FeCarb) has been demonstrated both in patients with chronic kidney disease and dialysis, but its effects have not been evaluated in kidney transplant (KT) recipients. Method Retrospective study (2016-2018) of KT recipients who received FeCarb during the first 30 days after kidney transplantation (KT). Early efficacy was analyzed by evaluating the first determination of ferrokinetics and hemoglobin levels after administration and late efficacy with the determination &gt;90 days post-administration. Safety parameters were also analyzed. Results Out of 283 KT performed, 77 recipients received one dose of FeCarb (52 received a 500mg dose and 25 a 1000mg dose) after a median of 6 days after the KT (IQR 3.5-9 days). 24 patients required transfusion after administration, 7 of them in the setting of concomitant event and 17 for non-response to FeCarb. Among the non-responders (n=17) there was a higher percentage of women, the initial hemoglobin was lower and they received a higher dose of FeCarb (Table). Responders (n=53) improved early and late ferrokinetic and anemia parameters (Figure). In the multivariate analysis adjusted by gender, controlled infection at the time of FeCarb administration, dose of FeCarb administered, immunosuppression, and previous treatment with erythropoietin, hemoglobin levels below 8 g/dL were associated with increased risk of transfusion after FeCarb administration (HR 11.30 [3.03-42.2]). Tolerability was excellent, with no immediate adverse reactions after FeCarb administration. 17 responders had a controlled infection at the time of FeCarb administration (median days under antibiotic treatment: 3, IQR 1-5). The infection did not worsen the response to FeCarb and no clinical impairment after FeCarb administration was observed. Conclusion: FeCarb administration in early post-transplant anemia is effective in patients with hemoglobin higher than 8g/dl and is not associated with increased risk of infection deterioration.

Dissociating Sensorimotor Recovery and Compensation During Exoskeleton Training Following Stroke

The quality of arm movements typically improves in the sub-acute phase of stroke affecting the upper extremity. Here, we used whole arm kinematic analysis during reaching movements to distinguish whether these improvements are due to true recovery or to compensation. Fifty-three participants with post-acute stroke performed ∼80 reaching movement tests during 4 weeks of training with the ArmeoSpring exoskeleton. All participants showed improvements in end-effector performance, as measured by movement smoothness. Four ArmeoSpring angles, shoulder horizontal (SH) rotation, shoulder elevation (SE), elbow rotation, and forearm rotation, were recorded and analyzed. We first characterized healthy joint coordination patterns by performing a sparse principal component analysis on these four joint velocities recorded during reaching tests performed by young control participants. We found that two dominant joint correlations [SH with elbow rotation and SE with forearm rotation] explained over 95% of variance of joint velocity data. We identified two clusters of stroke participants by comparing the evolution of these two correlations in all tests. In the “Recoverer” cluster (N = 19), both joint correlations converged toward the respective correlations for control participants. Thus, Recoverers relearned how to generate smooth end-effector movements while developing joint movement patterns similar to those of control participants. In the “Compensator” cluster (N = 34), at least one of the two joint correlations diverged from the corresponding correlation of control participants. Compensators relearned how to generate smooth end-effector movements by discovering various new compensatory movement patterns dissimilar to those of control participants. New compensatory patterns included atypical decoupling of the SE and forearm joints, and atypical coupling of the SH rotation and elbow joints. There was no difference in clinical impairment level between the two groups either at the onset or at the end of training as assessed with the Upper Extremity Fugl-Meyer scale. However, at the start of training, the Recoverers showed significantly faster improvements in end-effector movement smoothness than the Compensators. Our analysis can be used to inform neurorehabilitation clinicians on how to provide movement feedback during practice and suggest avenues for refining exoskeleton robot therapy to reduce compensatory patterns.

Retrospective Evaluation Of The Accuracy Of Five Different Severity Scores To Predict The Mortality In Burns Patients

Background Patients with great clinical impairment, due to extensive burns, need to be admitted to intensive care units, in these treatment sites, indices are used to classify the severity of patients. The aim of the study was to compare the accuracy of the FLAMES score in relation to the Acute Physiologic and Chronic Health Evaluation II (APACHE II), the Simplified Acute Physiologic Score II (SAPS II), the Logistic Organ Dysfunction System (LODS) and the Abbreviated Burn Severity Index (ABSI) applied to the severe burn patient facing mortality in an ICU of a reference center for burns in Brazil. Methods A retrospective study conducted in ICU comparing the accuracy the APACHE II, SAPS II, LODS, ABSI and FLAMES instruments were applied to all the selected medical records. To evaluate the accuracy of the SIs, the Receiver Operating Characteristic curve was calculated and the area under the curve (AUC). Results Among the 574 patients included in the study, male individuals (70.13%), with an average age of 44.01 ± 28.64 prevailed and the majority of the burns were caused by accidents (76.53%). The outcome accounted for 35.29% of deaths. It was observed that the FLAMES and ABSI presented the two largest areas under the ROC curves and the highest sensitivities (96% and 89%, respectively). The APACHE II, SAPS II and LODS presented sensitivities equal to or greater than 80%. Conclusions It has been demonstrated that indices specifically developed for burn patients, specifically the FLAMES and ABSI indices, presented better accuracies and prediction performances.