Detecting microstructural changes due to chronic ischemia potentially enables early identification of patients at risk of cognitive impairment. In this study, diffusional kurtosis imaging and ...diffusion tensor imaging were used to investigate whether the former provides additional information regarding microstructural changes in the gray and white matter of adult patients with Moyamoya disease.
MR imaging (diffusional kurtosis imaging and DTI) was performed in 23 adult patients with Moyamoya disease and 23 age-matched controls. Three parameters were extracted from diffusional kurtosis imaging (mean kurtosis, axial kurtosis, and radial kurtosis), and 4, from DTI (fractional anisotropy, radial diffusivity, mean diffusivity, and axial diffusivity). Voxelwise analysis for these parameters was performed in the normal-appearing brain parenchyma. The association of these parameters with neuropsychological performance was also evaluated.
Voxelwise analysis revealed the greatest differences in fractional anisotropy, followed, in order, by radial diffusivity, mean diffusivity, and mean kurtosis. In patients, diffusional kurtosis imaging parameters were decreased in the dorsal deep white matter such as the corona radiata and superior longitudinal fasciculus (P < .01), including areas without DTI abnormality. Superior longitudinal fasciculus fiber-crossing areas showed weak correlations between diffusional kurtosis imaging and DTI parameters compared with tissues with a single-fiber direction (eg, the corpus callosum). Diffusional kurtosis imaging parameters were associated with general intelligence and frontal lobe performance.
Although DTI revealed extensive white matter changes, diffusional kurtosis imaging additionally demonstrated microstructural changes in ischemia-prone deep white matter with abundant fiber crossings. Thus, diffusional kurtosis imaging may be a useful adjunct for detecting subtle chronic ischemic injuries.
The usefulness of low-dose oral immunotherapy (OIT) for the treatment of egg allergy has been unclear.
To evaluate the efficacy and safety of OIT with low allergen cookies (LACs) containing a low ...dose of hen's egg.
Thirty-three patients with severe hen's egg allergy were randomly administered either OIT with LACs (n = 21) or placebo (n = 12). Two patients in the LACs group withdrew before completing OIT. The primary endpoint was the number of good responders (G-R), patients with negative results in the oral food challenge (OFC) with a final dose of 2 g hard-boiled egg whites after 4 months of OIT, in each group. Total OFC Aichi score for anaphylaxis/cumulative protein dose (TS/Pro) as the marker of severity of food allergy was also compared. Adverse events during OIT were evaluated using patients' diaries.
The proportion of G-R in the LACs group was higher than in the placebo group (7/19 37% vs. 1/12 8%, χ2 test; p = 0.077). The TS/Pro after OIT in the LACs group was lower than in the placebo group (median score, 44.2 vs. 104.1, p = 0.059; Mann-Whitney U test). The threshold and TS/Pro before and after OIT significantly improved in the LACs group (p = 0.015, p = 0.027, respectively; Wilcoxon signed-rank test). There were 99 recorded incidences of symptoms of 1,938 intake events in the LACs group during OIT. Of these, 90 were mild; no severe symptoms occurred.
OIT with LACs potentially increases the OFC threshold and decreases allergy severity and is a relatively safe treatment modality.
Abstract Background Context Controversy exists regarding the effects of multilevel facetectomy and screw density on deformity correction, especially thoracic kyphosis (TK) restoration in adolescent ...idiopathic scoliosis (AIS) surgery. Purpose This study aimed to evaluate the effects of multilevel facetectomy and screw density on sagittal plane correction in patients with main thoracic (MT) AIS curve. Study Design A retrospective correlation and comparative analysis of prospectively collected, consecutive, non-randomized series of patients at a single institution was undertaken. Patient Sample Sixty-four consecutive patients with Lenke type 1 AIS treated with posterior correction and fusion surgery using simultaneous double-rod rotation technique were included. Outcome Measures Patient demographics and preoperative and 2-year postoperative radiographic measurements were the outcome measures for this study. Methods Multiple stepwise linear regression analysis was conducted between change in TK (T5–T12) and the following factors: age at surgery, Risser sign, number of facetectomy level, screw density, preoperative main thoracic curve, flexibility in main thoracic curve, coronal correction rate, preoperative TK, and preoperative lumbar lordosis. Patients were classified into two groups: TK<15° group defined by preoperative TK below the mean degree of TK for the entire cohort (<15°) and the TK≥15° group, defined by preoperative TK above the mean degree of kyphosis (≥15°). Independent sample t tests were used to compare demographic data as well as radiographic outcomes between the two groups. There were no study-specific biases related to conflicts of interest. Results The average preoperative TK was 14.0°, which improved significantly to 23.1° (p<.0001) at the 2-year final follow-up. Greater change in TK was predicted by a low preoperative TK (p<.0001). The TK <15° group showed significant correlation between change in TK and number of facetectomy level (r=0.492, p=.002). Similarly, significant correlation was found between change in TK and screw density (r=0.333, p=.047). Conversely, in the TK ≥15° group, correlation was found neither between change in TK and number of facetectomy level (r=0.047, p=.812), nor with screw density (r=0.030, p=.880). Furthermore, in patients with preoperative TK<15°, change in TK was significantly correlated with screw density at the concave side (r=0.351, p=.036) but not at the convex side (r=0.144, p=.402). Conclusions In patients with hypokyphotic thoracic spine, significant positive correlation was found between change in TK and multilevel facetectomy or screw density at the concave side. This indicates that in patients with AIS who have thoracic hypokyphosis as part of their deformity, the abovementioned factors must be considered in preoperative planning to correct hypokyphosis.
Abstract Whereas the cerebellum contains 22 different types of neuropeptides as presently known, their expression is generally weak and diffusely dispersed in cerebellar tissues, which often makes ...their functional significance doubtful. Nevertheless, our knowledge about certain neuropeptides has advanced to the extent that we can figure out their unique functional roles in cerebellar circuits. Throughout the cerebellum, CRF is contained in climbing fibers and its spontaneous release is required for the induction of cerebellar long-term depression (LTD), a cellular mechanism of motor learning. Corticotropin-releasing factor (CRF) is also expressed in the paraventricular nucleus–pituitary system and amygdala–lower brainstem system, both of which are involved in coping responses to stress. In view that motor learning requires stressful efforts for correcting errors in repeated trials, CRF in climbing fibers may imply that the olivocerebellar system is part of a large CRF-operated functional system that acts to cope with various stressors. Orexin, on the other hand, is contained in beaded fibers, which, originating from the hypothalamus, project to various brainstem nuclei and also to the cerebellum, exclusively the flocculus. Currently available evidence suggests that, in fight-or-flight situations, orexinergic neurons switch the state of cardiovascular control systems including the flocculus to secure blood supply to working muscles. Considerable knowledge has also been accumulated about angiotensin II, galanin, and cerebellin, but there is still a gap in defining their unique functional roles in cerebellar circuits.
Quantum spin liquids, which are spin versions of quantum matter, have been sought after in systems with geometrical frustration. We show that disorder drives a classical magnet into a quantum spin ...liquid through conducting NMR experiments on an organic Mott insulator, κ-(ET)_{2}CuN(CN)_{2}Cl. Antiferromagnetic ordering in the pristine crystal, when irradiated by x rays, disappears. Spin freezing, spin gap, and critical slowing down are not observed, but gapless spin excitations emerge, suggesting a novel role of disorder that brings forth a quantum spin liquid from a classical ordered state.
Exacerbations are among the major factors that may affect the natural history of chronic obstructive pulmonary disease (COPD). The aim was to investigate the clinical characteristics and determinants ...of COPD exacerbations in our 5-year observational cohort study which had a very low exacerbation frequency. A total of 279 patients with COPD participated in the Hokkaido COPD cohort study, and 268 subjects who had clinical data for multiple visits were analysed. Exacerbation was defined in multiple ways: the patient's subjective complaint, symptom definition, requiring prescription change, requiring antibiotic treatment, or requiring hospital admission. Exacerbation frequency (events per person per year) was 0.78 ± 1.16, 0.24 ± 0.47, 0.20 ± 0.43, 0.13 ± 0.28 and 0.06 ± 0.19 for subjective complaint and symptom, prescription, antibiotic and hospital admission definitions, respectively. Exacerbation events did not significantly affect the annual decline in forced expiratory volume in 1 s. A high St George's Respiratory Questionnaire total score, especially activity score, and a low body mass index were strongly associated with exacerbation-free survival, exacerbation frequency and development of recurrent exacerbations. Despite the low exacerbation frequency in our cohort, impaired health-related quality of life and weight loss were found to be independent risk factors for COPD exacerbations.
Summary
Background
A predisposition to exacerbations is being recognized as a distinct phenotype with “previous exacerbations” representing the strongest clinical factor associated with future ...exacerbation. Thus, to identify additional novel biomarkers associated with asthma exacerbations, “past exacerbation status” must be included as a confounding factor.
Objective
This study aimed to characterize the clinical and biomarker features associated with asthma exacerbations in severe asthma.
Methods
We evaluated clinical parameters from 105 severe asthmatics yearly for 3 years, as well as their exacerbation status. We classified the subjects into 3 groups: (i) consistent non‐exacerbators (CNE, subjects who did not experience any exacerbation over the 3‐year period); (ii) consistent frequent exacerbators (CFE, subjects with frequent exacerbation, defined as those who had 2 or more exacerbations within 1 year, throughout the 3‐year period); and (iii) intermittent exacerbators (IE). We conducted multivariate analysis for comparisons among the groups for multiple factors, including several Th2‐related biomarkers, in addition to the “past exacerbation status.”
Results
Thirty‐nine subjects were classified as CNE, 15 as CFE, and 51 as IE. Frequent exacerbations in the previous year predicted exacerbations for the following year (P < .001). Among the several Th2‐related biomarkers, only FeNO was associated with exacerbation status. When we analysed the data after the second visit, the impact of FeNO on predicting future exacerbation remained significant, even after considering the exacerbation status during the first year (P < .05).
Conclusions and Clinical Relevance
Measurement of FeNO has a significant potential to predict future asthma exacerbation, which is independent of the “past exacerbation history.”
Although the rate of annual decline in FEV1 is one of the most important outcome measures in chronic obstructive pulmonary disease (COPD), little is known about intersubject variability based on ...clinical phenotypes.
To examine the intersubject variability in a 5-year observational cohort study, particularly focusing on emphysema severity.
A total of 279 eligible patients with COPD (stages I-IV: 26, 45, 24, and 5%) participated. We conducted a detailed assessment of pulmonary function and computed tomography (CT) at baseline, and performed spirometry every 6 months before and after inhalation of bronchodilator. Smoking status, exacerbation, and pharmacotherapy were carefully monitored. Emphysema severity was evaluated by CT and annual measurements of carbon monoxide transfer coefficient.
Using mixed effects model analysis, the annual decline in post-bronchodilator FEV1 was -32±24 (SD) ml/yr (n=261). We classified the subjects of less than the 25th percentile as Rapid decliners, the 25th to 75th percentile as Slow decliners, and greater than the 75th percentile as Sustainers (-63±2, -31±1, and -2±1 SE ml/yr). Emphysema severity, but not %FEV1, showed significant differences among the three groups. Multiple logistic regression analysis demonstrated that the Rapid decliners were independently associated with emphysema severity assessed either by CT or carbon monoxide transfer coefficient. The Sustainers displayed less emphysema and higher levels of circulating eosinophils.
Emphysema severity is independently associated with a rapid annual decline in FEV1 in COPD. Sustainers and Rapid decliners warrant specific attention in clinical practice.
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