Impaired Group Research Articles

Spinal cord and brain atrophy patterns in neuromyelitis optica spectrum disorder and multiple sclerosis.

Spinal cord and brain atrophy are common in neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (RRMS) but harbor distinct patterns accounting for disability and cognitive impairment. This study included 209 NMOSD and 304 RRMS patients and 436 healthy controls. Non-negative matrix factorization was used to parse differences in spinal cord and brain atrophy at subject level into distinct patterns based on structural MRI. The weights of patterns were obtained using a linear regression model and associated with Expanded Disability Status Scale (EDSS) and cognitive scores. Additionally, patients were divided into cognitive impairment (CI) and cognitive preservation (CP) groups. Three patterns were observed in NMOSD: (1) Spinal Cord-Deep Grey Matter (SC-DGM) pattern was associated with high EDSS scores and decline of visuospatial memory function; (2) Frontal-Temporal pattern was associated with decline of language learning function; and (3) Cerebellum-Brainstem pattern had no observed association. Patients with CI had higher weights of SC-DGM pattern than CP group. Three patterns were observed in RRMS: (1) DGM pattern was associated with high EDSS scores, decreased information processing speed, and decreased language learning and visuospatial memory functions; (2) Frontal-Temporal pattern was associated with overall cognitive decline; and (3) Occipital pattern had no observed association. Patients with CI trended to have higher weights of DGM and Frontal-Temporal patterns than CP group. This study estimated the heterogeneity of spinal cord and brain atrophy patterns in NMOSD and RRMS patients at individual level, and evaluated the clinical relevance of these patterns, which may contribute to stratifying participants for targeted therapy.

Swallowing Function and Quality of Life in Patients Treated With Transoral Videolaryngoscopic Surgery for Pharyngolaryngeal Cancer.

It is controversial whether transoral resection for early pharyngolaryngeal cancer preserves swallowing function and quality of life. We investigated swallowing function and quality of life before and after transoral videolaryngoscopic surgery (TOVS). Seventy-three patients with pharyngolaryngeal cancer who underwent TOVS between July 2012 and July 2022 were enrolled in this prospective analysis. The Hyodo score and European Organization for Research and Treatment of Cancer Quality of Life Questionnaires were recorded preoperatively and at three, six, and 12 months postoperatively, in addition to the postoperative functional outcome swallowing scale (FOSS) at six months postoperatively. Although most patients could consume food orally without restrictions with a preferable FOSS score, 23 patients showed impaired Hyodo scores. Age ≥65 years significantly predicted impaired swallowing. Sub-scores of the impaired patient group showed worsening for the glottal closure reflex when the endoscope touchedthe epiglottis or arytenoid, as well as a reduction in the extent of pharyngeal clearance following the ingestion of blue-dyed water. After TOVS, swallowing function is generally well preserved. Elderly patients, especially those with laryngeal hypoesthesia and poor clearance, are at risk of swallowing dysfunction.

Risk factors and characteristics analysis of cognitive impairment in patients with cerebral infarction during recovery period

Objective To analyze the risk factors and characteristics of cognitive impairment in patients with cerebral infarction during the recovery period. Methods This retrospective case-control study included 183 patients with cerebral infarction in the recovery period. According to the MMSE score, they were divided into a cognitive impairment group of 79 cases and a cognitive normal group of 104 cases. Collect clinical data from all patients, including age, gender, body mass index, laboratory test results, past medical history, National Institute of Health Stroke Scale (NIHSS) score, modified Barthel index, Oxfordshire Community Stroke Project (OCSP) classification, and number of infarcted lesions. Multiple logistic regression analysis was used to identify risk factors related to cognitive impairment in patients with cerebral infarction. Result There were significant differences (p < 0.05) between the cognitive impairment group and the cognitive normal group in terms of age, body mass index, low-density lipoprotein level, NIHSS score, modified Barthel index, and number of infarcted lesions. Multivariate logistic regression analysis showed that age ≥ 65 years, stroke, carotid artery plaques, NIHSS score ≥ 5, anterior circulation infarction type, and multiple infarcted lesions were important risk factors for cognitive impairment. Conclusion Elderly age, presence of carotid artery plaques, high NIHSS score, multiple infarct lesions, and specific infarct types are important risk factors for cognitive dysfunction in patients during the recovery period of cerebral infarction.

Prospective comparative study on enhancing geometrical mental representation and anatomical learning in medical students through modeling clay as an assessment tool.

While traditional anatomy education often emphasizes passive learning and rote memorization, it seldom employs constructivist theories that focus on active, hands-on experiences for effective learning. This study tests the hypothesis that tactile experiences with modeling clay enhance geometric mental representation more effectively than verbal descriptions. We examine the potential of clay modeling to reflect and evaluate students' mental representation of anatomical structures. Utilizing a prospective randomized, open, blind endpoint (PROBE) design, we engaged 36 participants divided into three groups: blind, visually impaired, and a control group. The primary outcome measure was the difference between post-touch score and pre-touch score, which gauged the efficacy of tactile intervention in enhancing the participants' capacity to mentally reconstruct a well-designed anatomical fiction structure. Scoring was executed using a double-blind double-evaluation methodology, positioning clay model reconstruction as both an objective reliable assessment and a pedagogical tool. The analysis demonstrated a pronounced improvement in mental representation of anatomical structures, particularly in spatial comprehension and detailed textural discernment, with the mean score soaring from 47.81 pre-touch to 85.09 post-touch. Distinct cognitive processing adaptations were evident across groups, with the blind group excelling in tactile acuity and the visually impaired group showing the most significant gains in spatial understanding post-intervention (Cohen's d = 2.74). The application of modeling clay as a tactile intervention tool can significantly improve the learning of anatomy among medical students. The study underscores the value of active, multisensory engagement and customized teaching strategies for effective anatomy education among this demographic.

Use of Digitalisation and Machine Learning Techniques in Therapeutic Intervention at Early Ages: Supervised and Unsupervised Analysis.

Advances in technology and artificial intelligence (smart healthcare) open up a range of possibilities for precision intervention in the field of health sciences. The objectives of this study were to analyse the functionality of using supervised (prediction and classification) and unsupervised (clustering) machine learning techniques to analyse results related to the development of functional skills in patients at developmental ages of 0-6 years. We worked with a sample of 113 patients, of whom 49 were cared for in a specific centre for people with motor impairments (Group 1) and 64 were cared for in a specific early care programme for patients with different impairments (Group 2). The results indicated that in Group 1, chronological age predicted the development of functional skills at 85% and in Group 2 at 65%. The classification variable detected was functional development in the upper extremities. Two clusters were detected within each group that allowed us to determine the patterns of functional development in each patient with respect to functional skills. The use of smart healthcare resources has a promising future in the field of early care. However, data recording in web applications needs to be planned, and the automation of results through machine learning techniques is required.

Abstract P260: Association of Hearing Impairment and Physical Functioning Among Chinese Adults Aged 60 Years or Older: Evidence From the China Health and Retirement Longitudinal Study (CHARLS)

Introduction: Hearing impairment is a common treatable condition and a risk factor for various adverse health outcomes. Prior evidence associated hearing impairment with physical functioning declines in older adults of Western countries, but longitudinal evidence on such association is limited among Chinese older adults. Method: We pooled the first three waves of CHARLS (2011, 2013, and 2015) together as a longitudinal dataset with repeated measurements. For each participant, self-reported hearing status was collected at each wave and categorized as normal hearing or impaired hearing (reported fair or poor hearing). Physical functioning was assessed by Short Physical Performance Battery (SPPB), including gait speed, duration to complete five chair stands and balance test. Each SPPB component was assigned a score from 1 to 4 corresponding from the lowest to highest quartile. The SPPB score ranged from 1 to 12, with higher scores representing better physical functioning. We used a series of linear mixed-effects models with participant-level random intercepts and slopes to assess the association of hearing impairment with physical functioning, adjusting for demographics, socioeconomics, and comorbidities. Results: A total of 8,894 participants aged 60 or above at baseline were included, with a median age of 68 years. At baseline, the impaired hearing group were estimated to be 0.21 (0.11, 0.31) lower in average SPPB score, 0.02 (0.01, 0.03) lower in average gait speed, and 1.04 (1.02, 1.05) times longer in average duration to complete the chair stand test as compared to the normal hearing group ( Table ). Statistically significant differences in average rate of longitudinal changes were not observed for either outcome. Conclusion: Baseline hearing impairment was associated with poorer physical functioning among Chinese older adults, but no significant association with longitudinal changes was observed. This finding emphasizes the necessity of monitoring hearing status among the Chinese elderly population.

Measures of Awareness in Alzheimer's Disease and Clinical Differences Between Groups with Preserved, Impaired, and Absent Awareness.

Awareness is a heterogeneous construct that requires accurate assessment. There is no consensus on the best methodology for capturing the phenomenon, thus leading to inconsistent results in this area. We aim to evaluate the reliability of clinicians' ratings and a discrepancy assessment method, examining groups of people with Alzheimer's disease (PwAD) according to their degree of awareness and demographic and clinical aspects. We cross-sectionally assessed 134 PwAD and their caregivers. Individuals' level of awareness was assessed with two methods: clinicians' ratings identified three groups (preserved awareness, impaired awareness, and absent awareness), while discrepancy assessment identified four groups (preserved awareness, mildly impaired awareness, moderately impaired awareness, and absent awareness). Clinicians' ratings showed significant differences between PwAD with preserved, impaired, and absent awareness groups in cognition, functionality, and neuropsychiatric symptoms. There was a significant difference in caregivers' anxiety between the impaired and absent awareness groups. Discrepancy assessment showed no clinical differences between the preserved and mildly impaired awareness groups or between the absent and moderately impaired awareness groups. A significant difference in functionality was observed between the other groups. Clinical aspects of each measure tended to differ between the chosen methods. Impairments in awareness fluctuate despite disease progression. Cognition and severity of disease cannot explain deficits in awareness.

Go out or stress out? Exploring nature connectedness and cumulative stressors as resilience and vulnerability factors in different manifestations of climate anxiety

Given the increasing severity of the climate crisis and, with it, rising climate anxiety, it is imperative to understand what climate anxiety is, how it functions, and how people can cope with it constructively. Nevertheless, research has often mixed different conceptualizations and operationalizations of climate anxiety, yielding sometimes seemingly contradictory findings. This study contributes with a more nuanced and structured approach by 1) exploring systematically how climate anxiety manifests (i.e., investigating the existence of subgroups), and 2) investigating vulnerability and resilience factors that might explain belonging to these different subgroups. We analyzed answers of N = 2052 German-speaking survey respondents, stratified for age, gender, and education, who provided information on different facets of their climate anxiety (namely climate-anxious appraisal, affect, and potentially related impairment). Using latent profile analysis, we identified four subgroups with different manifestations of climate anxiety: climate-anxious impaired (8.5%), climate-anxious less impaired (17.5%), climate-anxious functioning (41%), and non-climate anxious (33%). Subsequent multinomial logistic regression revealed that high nature connectedness, male gender, and young age but not exposure to cumulative stressors (i.e., combination of stressors such as unemployment and low presence of high-quality nature in one's living environment) were potential vulnerability factors to belong to the climate-anxious impaired group compared to all other groups. Our person-centered approach nuances the study of climate anxiety and advances possibilities to study constructive coping with climate anxiety.

Incremental Value of Biventricular Strain in Patients with Severe Aortic Stenosis.

(1) Background: Left ventricular global longitudinal (LVGLS) and right ventricular free wall strain (RVFWS) demonstrated separate prognostic values in patients with severe aortic stenosis (AS). However, studies evaluating the combined assessment of LVGLS and RVFWS have shown contradictory results. This study explored the prognostic value of combining LVGLS and RVFWS in a large group of severe AS patients referred for transcatheter aortic valve implantation. (2) Methods: Patients were classified into three groups: preserved (LVGLS ≥ 15% AND RVFWS > 20%), single-ventricle impaired (LVGLS < 15% OR RVFWS ≤ 20%), or biventricular-impaired strain group (LVGLS < 15% AND RVFWS ≤ 20%). The cut-off values were based on previously published data and spline analyses. The endpoint was all-cause mortality. (3) Results: Of the 712 patients included (age 80 ± 7 years, 53% men), 248 (35%) died. The single-ventricle impaired and biventricular-impaired (vs. preserved) strain groups showed significantly lower 5-year survival rates (68% and 55% vs. 77%, respectively, p < 0.001). Through multivariable analysis, single-ventricle impaired (HR 1.762; 95% CI: 1.114-2.788; p = 0.015) and biventricular-impaired strain groups (HR 1.920; 95% CI: 1.134-3.250; p = 0.015) were independently associated with all-cause mortality. These findings were confirmed with a sensitivity analysis in patients with preserved LV ejection fraction. (4) Conclusions: In patients with severe AS, biventricular strain allows better risk stratification, even if LV ejection fraction is preserved.

Directed Functional Connectivity Changes of Triple Networks for Stable and Progressive Mild Cognitive Impairment

Mild cognitive impairment includes two distinct subtypes, namely progressive mild cognitive impairment and stable mild cognitive impairment. While alterations in extensive functional connectivity have been observed in both subtypes, limited attention has been given to directed functional connectivity. A triple network, composed of the central executive network, default mode network, and salience network, is considered to be the core cognitive network. We evaluated the alterations in directed functional connectivity within and between the triple network in progressive and stable mild cognitive impairment groups and investigated its role in predicting disease conversion. Resting-state functional magnetic resonance imaging was used to analyze directed functional connectivity within the triple networks. A correlation analysis was performed to investigate potential associations between altered directed functional connectivity within the triple networks and the neurocognitive performance of the participants. Our study revealed significant differences in directed functional connectivity within and between the triple network in the progressive and stable mild cognitive impairment groups. Altered directed functional connectivity within the triple network was involved in episodic memory and executive function. Thus, the directed functional connectivity of the triple network may be used as an imaging marker of mild cognitive impairment.

Clinical phenotypes of nontuberculous mycobacterial disease by cluster analysis based on pulmonary function

BackgroundNontuberculous mycobacterial pulmonary disease (NTM-PD) often exhibits pulmonary function impairment, such as obstructive or restrictive pattern, with variation among patients according to the damaged lesions in the lung. MethodsPatients with NTM-PD were consecutively enrolled between September 2019 and December 2020 at the Respiratory Infection Clinic of our hospital. Patients’ data were comprehensively collected through laboratory examinations, PFT, chest computed tomography, and questionnaires for the assessment of subjective symptoms and health-related quality of life (HRQOL). Hierarchical cluster analysis was performed using PFT parameters to compare the clinical findings among clusters. ResultsData of 104 patients were analyzed and classified into four clusters. The restrictive pattern with decreased forced expiratory volume in 1 s (FEV1) group showed high serum C-reactive protein and low albumin levels, severe radiological findings, and low HRQOL. In the restrictive pattern with preserved FEV1 group, HRQOL was as low as that in the restrictive pattern with decreased FEV1 group, and bacterial exacerbation was observed relatively frequently. HRQOL in the obstructive impairment group was maintained in comparison with that in the normal group. ConclusionNTM-PD phenotypes were identified using cluster analysis based on PFT. Two different severe phenotypes were also observed. In the early stages of NTM-PD, PFT may be useful in recognizing disease progression.

Relationship of Mild to Moderate Impairment of Left Ventricular Ejection Fraction With Fatal Ventricular Arrhythmic Events in Cardiac Sarcoidosis.

Current guidelines recommend placing an implantable cardiac defibrillator for patients with cardiac sarcoidosis and a severely impaired left ventricular ejection fraction (LVEF) of ≤35%. In this study, we determined the association between mild or moderate LVEF impairment and fatal ventricular arrhythmic event (FVAE). We retrospectively analyzed 401 patients with cardiac sarcoidosis without sustained ventricular arrhythmia at diagnosis. The primary end point was an FVAE, defined as the combined endpoint of documented ventricular tachycardia or ventricular fibrillation and sudden cardiac death. Two cutoff points for LVEF were used:a sex-specific lower threshold of normal range of LVEF (52% for men and 54% for women) and an LVEF of 35%, which is used in the current guidelines. During a median follow-up of 3.2 years, 58 FVAEs were observed, and the 5- and 10-year estimated incidences of FVAEs were 16.8% and 23.0%, respectively. All patients were classified into 3 groups according to LVEF: impaired LVEF group, mild to moderate impairment of LVEF group, and maintained LVEF group. Multivariable competing risk analysis showed that both the impaired LVEF group (hazard ratio [HR], 3.24 [95% CI, 1.49-7.04]) and the mild to moderate impairment of LVEF group (HR, 2.16 [95% CI, 1.04-4.46]) were associated with a higher incidence of FVAEs than the maintained LVEF group after adjustment for covariates. Patients with cardiac sarcoidosis are at a high risk of FVAEs, regardless of documented ventricular arrhythmia at the time of diagnosis. In patients with cardiac sarcoidosis, mild to moderate impairment of LVEF is associated with FVAEs.

The Association Between Impaired Dyadic Coping and Frailty in Elderly Patients With Hypertension: A Latent Profile Analysis.

Lifelong hypertension highlights the importance of dyadic engagement in coping with the disease. Although dyadic coping is heterogeneous in patients with other diseases, little is known about it in elderly patients with hypertension. In addition, whether impaired dyadic coping is associated with frailty has yet to be elucidated. The aim of this study was to investigate the latent profiles and characteristics of dyadic coping and the potential association between impaired dyadic coping and frailty in elderly patients with hypertension. We recruited a total of 741 elderly patients with hypertension. Latent profile analysis was then used to identify the best-fitting model. Then, we used regression analysis to determine profile predictors and identify the association between impaired dyadic coping and frailty. The 5-profile model was considered to be the best-fitting model, as follows: profile 1, severely impaired dyadic coping; profile 2, mildly impaired dyadic coping; profile 3, normal dyadic coping; profile 4, better dyadic coping; and profile 5, the highest dyadic coping. In the fully adjusted model, the probability of frailty was 1.94-fold higher in the mildly impaired dyadic coping group (odds ratio, 1.94; 95% confidence interval, 1.09-3.47) and 2.66-fold higher in the severely impaired dyadic coping group (odds ratio, 2.66; 95% confidence interval, 1.11-6.39). We identified heterogeneity in dyadic coping and demonstrated that impaired dyadic coping was associated with frailty. Those at risk of dyadic coping impairment need to be identified early, followed by dyadic coping-based interventions to prevent or delay frailty.

Examining interrater agreement between self-report and proxy-report responses for the quality of life-aged care consumers (QOL-ACC) instrument

BackgroundQuality of life is an important quality indicator for health and aged care sectors. However, self-reporting of quality of life is not always possible given the relatively high prevalence of cognitive impairment amongst older people, hence proxy reporting is often utilised as the default option. Internationally, there is little evidence on the impact of proxy perspective on interrater agreement between self and proxy report.ObjectivesTo assess the impacts of (i) cognition level and (ii) proxy perspective on interrater agreement using a utility instrument, the Quality of Life-Aged Care Consumers (QOL-ACC).MethodsA cross-sectional study was undertaken with aged care residents and family member proxies. Residents completed the self-report QOL-ACC, while proxies completed two proxy versions: proxy-proxy perspective (their own opinion), and proxy-person perspective (how they believe the resident would respond). Interrater agreement was assessed using quadratic weighted kappas for dimension-level data and concordance correlation coefficients and Bland-Altman plots for utility scores.ResultsSixty-three residents (22, no cognitive impairment; 41, mild-to-moderate cognitive impairment) and proxies participated. In the full sample and in the mild-to-moderate impairment group, the mean self-reported QOL-ACC utility score was significantly higher than the means reported by proxies, regardless of perspective (p < 0.01). Agreement with self-reported QOL-ACC utility scores was higher when proxies adopted a proxy-person perspective.ConclusionRegardless of cognition level and proxy perspective, proxies tend to rate quality of life lower than residents. Further research is needed to explore the impact of such divergences for quality assessment and economic evaluation in aged care.

The effects of dietary diversity on health status among the older adults: an empirical study from China

BackgroundDietary diversity is an indicator of nutrient intake among the elderly. Previous researches have primarily examined dietary diversity and the risks with chronic and infectious disease and cognitive impairment, limited evidence shows the association between dietary diversity and the overall health status of specific populations with a heterogeneity analysis. This study aimed to probe the effects of dietary diversity on health status among Chinese older adults.MethodsThere were 5740 sample participants aged 65 and above selected from the Chinese Longitudinal Healthy Longevity Survey, among which 3334 samples in 2018 wave and 2406 samples in 2011 wave. Dietary diversity was assessed by Dietary Diversity Score ranged from 0 to 9, the higher the score, the better dietary diversity. Health status was assessed into healthy, impaired and dysfunctional state by three indicators: Activities of Daily Living, Instrument Activities of Daily Living and Mini-Mental State Examination. Multinomial logistic regression was employed to assess the effects of dietary diversity on the health status among the elderly. Heterogeneity analysis between different groups by age was further discussed.ResultsOlder adults with better dietary diversity are in better health status, the mean dietary diversity score for healthy group was higher than that of impaired and dysfunctional groups (In 2018 wave, the scores were 6.54, 6.26 and 5.92, respectively; and in 2011 wave, they were 6.38, 5.93 and 5.71, respectively). Heterogeneity analysis shows that the younger groups tend to have more diversified dietary and be in better health status. Dietary diversity was more significantly associated with health status of the younger elderly (OR, 1.22, 95% CI, 1.04–1.44, p < 0.05) than the older elderly (OR, 1.01, 95% CI, 0.37–2.78, p > 0.05) in 2018 wave; and in 2011 wave, dietary diversity was more significantly related to health status among the younger elderly (OR, 1.62, 95% CI, 1.26–2.08, p < 0.001) than the older elderly (OR, 0.08, 95%CI, 0.31–1.94, p > 0.05).ConclusionsBetter dietary diversity has positive effects on health status and is more significantly related to the younger elderly than the older elderly. So interventions including available dietary diversity assessment, variety of dietary assistance services in daily life, keeping nutrient digestion and absorption capacity for the venerable age might benefit to ensure the effects of dietary diversity on health status among older adults especially in maintaining intrinsic ability and physical function. In addition, healthy lifestyle should also be recommended.

Year-round injury and illness surveillance in UK summer paralympic sport athletes: 2016–2019

ObjectiveTo identify the priority injuries and illnesses across UK summer Paralympic World Class Programmes (WCP).MethodsFour years (2016–2019) of electronic medical records from 360 athletes across 17 Paralympic WCP sports were...

Evaluation of cognitive functions and dementia two years after COVID-19 infection

Background: The Coronavirus disease 2019 (COVID-19) causes high morbidity and mortality in the acute period. Some patients with COVID-19 continue to have symptoms for a long time. However, data on the long-term effects of COVID-19, particularly on cognitive disorders is scarce. We aimed to evaluate cognitive functions and dementia in patients who survived two years after discharge from hospital due to acute covid-19 infection. Methods: Two hundred and five patients who had neurological symptoms during index hospitalization for COVID-19 infection were evaluated two years after discharge, and 64 patients were included in the study. According to cognitive assessments, patients were grouped as having normal cognitive levels (48 patients) or impaired cognitive levels (16 patients). Results: The impaired cognitive level was found in 16 (25.0%) of patients who underwent cognitive tests. Age, the pre-existence of neurological comorbidity, mean intensive care unit day, and Beck’s Anxiety Inventory and Beck’s Depression Inventory scores in the impaired cognitive level group were significantly higher than the normal cognitive level group (p:0.001, p:0.013, p:0.015, p:0.004 and p:0.008). The frequency of cognitive impairment in patients who developed altered mental state during hospitalization was 36.0%, while it was 17.9% in patients with normal mental state. Age, the pre-existence of neurological comorbidity, and anxiety were determined as independent risk factors for impaired cognitive level. In addition, we detected new-onset dementia in 8 patients (12.5%). Conclusion: We found a high frequency of cognitive impairment and new-onset dementia among COVID-19 survivors who developed neurological manifestations during the acute infection phase.

Usefulness of cardiopulmonary exercise test combined with exercise stress echocardiography in mild chronic thromboembolic pulmonary disease.

Chronic thromboembolic pulmonary disease (CTEPD) can lead to exercise limitations even without right ventricular (RV) dysfunction or pulmonary hypertension at rest. Combining exercise stress echocardiography with cardiopulmonary exercise testing (ESE-CPET) for RV function and pressure changes combined measuring overall function may be useful for CTEPD evaluation. This study aims to investigate CPET and ESE results to elucidate the mechanisms of exercise limitation in mild CTEPD cases. Among our CTEPD registry, 50 patients who performed both right heart catheterization data of mild disease (less than 30mm Hg of mean pulmonary arterial pressure (mPAP)) and ESE-CPET were enrolled.Echocardiography and CPET-derived parameters were compared with hemodynamic parameters measured through right heart catheterization. Peak VO2 (maximal oxygen consumption) was decreased in overall population (71.3±16.3% of predictive value). Peak VO2 during exercise was negatively correlate with mPAP and pulmonary vascular resistance at rest. A substantial increase in RV systolic pressure (RVSP) was observed during exercise (RVSP: pre-exercise 37.2±11.8mm Hg, postexercise 64.3±24.9mm Hg, p-value<.001). Furthermore, RV function deteriorated during exercise when compared to the baseline (RV fractional area change: 31.5±10.0% to 37.8±7.0%, p-value<.001; RV global longitudinal strain: -17.1±4.2% to -17.7±3.3%, p-value<.001) even though basal RV function was normal. While an excessive increase in RVSP during exercise was noticed in both groups, dilated RV and RV dysfunction during exercise were demonstrated only in the impaired exercise capacity group. CTEPD patients with mild PH or without PH exhibited limited exercise capacity alongside an excessive increase in RVSP during exercise. Importantly, RV dysfunction during exercise was significantly associated with exercise capacity. ESE-CPET could aid in comprehending the primary cause of exercise limitation in these patients.

Synaptic density patterns in early Alzheimer's disease assessed by independent component analysis.

Synaptic loss is a primary pathology in Alzheimer's disease and correlates best with cognitive impairment as found in post-mortem studies. Previously, we observed in vivo reductions of synaptic density with [11C]UCB-J PET (radiotracer for synaptic vesicle protein 2A) throughout the neocortex and medial temporal brain regions in early Alzheimer's disease. In this study, we applied independent component analysis to synaptic vesicle protein 2A-PET data to identify brain networks associated with cognitive deficits in Alzheimer's disease in a blinded data-driven manner. [11C]UCB-J binding to synaptic vesicle protein 2A was measured in 38 Alzheimer's disease (24 mild Alzheimer's disease dementia and 14 mild cognitive impairment) and 19 cognitively normal participants. [11C]UCB-J distribution volume ratio values were calculated with a whole cerebellum reference region. Principal components analysis was first used to extract 18 independent components to which independent component analysis was then applied. Subject loading weights per pattern were compared between groups using Kruskal-Wallis tests. Spearman's rank correlations were used to assess relationships between loading weights and measures of cognitive and functional performance: Logical Memory II, Rey Auditory Verbal Learning Test-long delay, Clinical Dementia Rating sum of boxes and Mini-Mental State Examination. We observed significant differences in loading weights among cognitively normal, mild cognitive impairment and mild Alzheimer's disease dementia groups in 5 of the 18 independent components, as determined by Kruskal-Wallis tests. Only Patterns 1 and 2 demonstrated significant differences in group loading weights after correction for multiple comparisons. Excluding the cognitively normal group, we observed significant correlations between the loading weights for Pattern 1 (left temporal cortex and the cingulate gyrus) and Clinical Dementia Rating sum of boxes (r = -0.54, P = 0.0019), Mini-Mental State Examination (r = 0.48, P = 0.0055) and Logical Memory II score (r = 0.44, P = 0.013). For Pattern 2 (temporal cortices), significant associations were demonstrated between its loading weights and Logical Memory II score (r = 0.34, P = 0.0384). Following false discovery rate correction, only the relationship between the Pattern 1 loading weights with Clinical Dementia Rating sum of boxes (r = -0.54, P = 0.0019) and Mini-Mental State Examination (r = 0.48, P = 0.0055) remained statistically significant. We demonstrated that independent component analysis could define coherent spatial patterns of synaptic density. Furthermore, commonly used measures of cognitive performance correlated significantly with loading weights for two patterns within only the mild cognitive impairment/mild Alzheimer's disease dementia group. This study leverages data-centric approaches to augment the conventional region-of-interest-based methods, revealing distinct patterns that differentiate between mild cognitive impairment and mild Alzheimer's disease dementia, marking a significant advancement in the field.

Renal function and lipid metabolism in Japanese HIV-1-positive individuals 288 weeks after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate: a single-center, retrospective cohort study

BackgroundContinued use of tenofovir disoproxil fumarate (TDF), an antiretroviral drug, causes renal function decline and tubular damage in individuals with HIV. While tenofovir alafenamide fumarate (TAF) may have less damaging effects, it causes weight gain and abnormal lipid metabolism.MethodsThis single-center, retrospective cohort study used medical records from the National Hospital Organization Sendai Medical Center to investigate renal function of Japanese HIV-1-positive individuals who switched from TDF to antiretroviral therapy including TAF by 2017. The endpoints were: estimated glomerular filtration rate (eGFR), urinary β2 microglobulin (Uβ2MG), weight, and lipid metabolism parameters at 288 weeks after switching. Possible correlation between eGFR and Uβ2MG and factors affecting eGFR decline were examined.ResultsSixty patients switched from TDF to TAF and continued therapy for 288 weeks. eGFR showed a significant decline after 144 weeks, although it was controlled from the time of change until 96 weeks. In the renal impairment group, the decline was suppressed until week 288. Uβ2MG continued to decrease significantly after 48 weeks. However, the suggested correlation between eGFR and Uβ2MG disappeared when patients switched from TDF to TAF. Weight and lipid metabolic parameters increased significantly at 48 weeks and were maintained. Factors associated with decreased eGFR were: history of acquired immune deficiency syndrome (AIDS) and Uβ2MG. However, considering the odds ratio, the switch from TDF to TAF suppressed the eGFR decline in the group with a history of AIDS, and Uβ2MG had no effect on the eGFR decline.ConclusionsSwitching from TDF to TAF for the long term slows eGFR decline, decreases Uβ2MG levels, and reduces worsening of renal function. Weight gain and abnormal lipid metabolism may occur in the short term but are controllable.