Serum Tau-A and Tau-C Levels and Their Association with Cognitive Impairment and Dementia Progression in a Memory Clinic Derived Cohort.

BACKGROUND: Serum-measured fragments of Tau cleaved by ADAM-10 (Tau-A) and Caspase-3 (Tau-C) have been found linked to change in cognitive function and risk of dementia. OBJECTIVES: 1) To determine the discriminatory abilities of Tau-A, and Tau-C in subjects with either mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or AD dementia compared to a control group. 2) To determine if there is a relation between Tau-A, and Tau-C and established cerebrospinal fluid (CSF) markers of AD- ß-Amyloid1-42 (AB42), Phosphorylated-tau-181 (p-tau), and total-tau. 3) To determine if Tau-A and Tau-C are associated with progression rate from MCI due to AD to AD dementia. DESIGN: Cross-sectional and a substudy using a retrospective cohort design. SETTING: Memory clinic derived subjects contributing to the Danish Dementia Biobank. PARTICIPANTS: Cognitively unimpaired subjects (n=49), patients with mild cognitive impairment (MCI) due to AD (n=45), and Alzheimer's dementia (n=52). MEASUREMENTS: Competitive enzyme-linked immunosorbent assay (ELISA)-measured serum levels of Tau-A, and Tau-C. RESULTS: The ratio between Tau-A and Tau-C differed between the three groups (p=0.015). Age- and sex-adjusted Tau-A differed between groups with lower ratios being associated with more severe disease (p=0.023). Tau-C was trending towards significant correlation to CSF-levels of AB42 (Pearson correlation coefficient 0.164, p=0.051). Those with Tau-C-levels in the 2nd quartile had a hazard ratio (HR) of 2.91 (95% CI 1.01 - 8.44, p=0.04) of progression compared to those in the 1st quartile. Those in the 3rd quartile was found to have a borderline significant (p=0.055) HR of 2.63 (95% CI 0.98 - 7.05) when compared to those in the lowest quartile. CONCLUSIONS: Tau-A and the ratio between Tau-A and Tau-C showed significant differences between groups and were correlated to CSF-AB42. Tau-C values in the middle range were associated with faster progression from MCI to dementia. This pilot study adds to the mounting data suggesting serum-measured Tau-A and Tau-C as biomarkers useful in relation to diagnosis and progression rate in AD but need further validation.

A Potential Role of Interleukin-5 in the Pathogenesis and Progression of Amyotrophic Lateral Sclerosis: A New Molecular Perspective.

Cumulative data suggest that neuroinflammation plays a prominent role in amyotrophic lateral sclerosis (ALS) pathogenesis. The purpose of this work was to assess if patients with ALS present a specific peripheral cytokine profile and if it correlates with neurological disability assessed by ALSFRS-R, the rate of disease progression, and the pattern of disease progression (horizontal spreading [HSP] versus vertical spreading [VSP]). We determined the levels of 15 cytokines in the blood of 59 patients with ALS and 40 controls. We identified a positive correlation between levels of pro-inflammatory cytokines (interleukin [IL]-17F, IL-33, IL-31) and the age of ALS patients, as well as a positive correlation between IL-12p/70 and survival from ALS onset and ALS diagnosis. Additionally, there was a positive correlation between the ALSFRS-R score in the upper limb and respiratory domain and IL-5 levels. In our ALS cohort, the spreading pattern was 42% horizontal and 58% vertical, with patients with VSP showing a faster rate of ALS progression. Furthermore, we identified a negative correlation between IL-5 levels and the rate of disease progression, as well as a positive correlation between IL-5 and HSP of ALS. To the best of our knowledge, this is the first study reporting a "protective" role of IL-5 in ALS.

Analysis of risk factors related to the progression rate of hemifacial spasm.

Introduction: Although there have been many researches on the etiology and risk factors with the onset of hemifacial spasm, researches on the risk factors related to progression rate are limited. This study aims to analyze the risk factors related to the progression rate of hemifacial spasm. Methods: The study enrolled 142 patients who underwent microvascular decompression for hemifacial spasm. Based on the duration and severity of symptoms, patients were classified into rapid progression group and slow progression group. To analyze risk factors, univariate and multivariate logistic regression analyses were conducted. Of 142 patients with hemifacial spasm, 90(63.3%) were classified as rapid progression group, 52(36.7%) were classified as slow progression group. Results: In the univariate analysis, there were significant statistical differences between the two groups in terms of age of onset (P = 0.021), facial nerve angle (P < 0.01), hypertension (P = 0.01), presence of APOE ε4 expression (P < 0.01) and different degrees of brainstem compression in the Root Entry Zone (P < 0.01). In the multivariable analyses, there were significant statistical differences between the two groups in terms of age of symptom onset (P < 0.01 OR = 6.591), APOE ε4 (P < 0.01 OR = 5.691), brainstem compression (P = 0.006 OR = 5.620), and facial nerve angle (P < 0.01 OR = 5.758). Furthermore, we found no significant correlation between the severity of facial spasms and the progression rate of the disease (t = 2.47, P = 0.12>0.05). Conclusion: According to our study, patients with facial nerve angle ≤ 96.5°, severer compression of the brainstem by offending vessels, an onset age > 45 years and positive expression of APOE ε4, may experience faster progression of hemifacial spasm.

Revisiting distinct nerve excitability patterns in patients with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease, characterized by loss of central and peripheral motor neurones. Although the disease is clinically and genetically heterogeneous, axonal hyperexcitability is a commonly observed feature that has been suggested to reflect an early pathophysiological step linked to the neurodegenerative cascade. Therefore, it is important to clarify the mechanisms causing axonal hyperexcitability and how these relate to the clinical characteristics of patients. Measures derived directly from a nerve excitability recording are frequently used as study endpoints, even though their biophysical basis is difficult to deduce. Mathematical models can aid in the interpretation, but are only reliable when applied to group-averaged recordings. Consequently, model estimates of membrane properties cannot be compared to clinical characteristics or treatment effects in individual patients, posing a considerable limitation in heterogeneous diseases such as amyotrophic lateral sclerosis. To address these challenges, we revisited nerve excitability using a novel pattern-analysis-based approach (principal component analysis). We evaluated disease-specific patterns of excitability changes and established their biophysical origins. Based on the observed patterns, we developed novel compound measures of excitability that facilitate the implementation of this approach in clinical settings We found that excitability changes in amyotrophic lateral sclerosis patients (n = 161, median disease duration = 11 months) were characterized by four unique patterns compared to controls (n = 50, age-gender matched). These four patterns were best explained by changes in resting membrane potential (modulated by Na+/K + -currents), slow potassium- and sodium-currents (modulated by their gating kinetics) and refractory properties of the nerve. Consequently, we were able to show that altered gating of slow potassium-channels was associated with, and predictive of, the disease's progression rate on the amyotrophic lateral sclerosis functional rating scale. Based on these findings, we designed four composite measures that capture these properties to facilitate implementation outside of this study. Our findings demonstrate that nerve excitability changes in patients with amyotrophic lateral sclerosis are dominated by four distinct patterns, each with a distinct biophysical origin. Based on this new approach, we provide evidence that altered slow potassium-channel function may play a role in the rate of disease progression. The magnitudes of these patterns, quantified using either a similar approach or our novel composite measures, have potential as efficient measures to study membrane properties directly in amyotrophic lateral sclerosis patients, and thus aid prognostic stratification and trial design.

Analysis of the progression rate of idiopathic macular holes and the optimal cut-off for baseline minimum linear diameter and base diameter.

PURPOSE: To determine the cut-off points of minimum linear diameter (MLD) and base diameter (BD) at which the progression rate of idiopathic full-thickness macular holes (MHs) decreases before vitrectomy. STUDY DESIGN: A retrospective study. METHODS: We investigated the differences in MLD and BD between baseline and operation days in patients with stages 2, 3, and 4 MHs using optical coherence tomography (OCT). Each difference in OCT parameters was divided by the time interval to calculate the MH progression rates and the cut-off points of MLD and BD. RESULTS: Overall, 269 patients (282 eyes) were included. It took an average of 36.02 ± 24.69 (7-197) days from baseline to operation. MLD and BD progressed faster in stages 2 and 3 without posterior vitreous detachment (PVD) than in stage 4 with PVD (MLD: p < 0.001 and p = 0.007; BD: p < 0.001 and p = 0.019, respectively). Simple linear regression showed the relationship between baseline MLD and BD, and the progression rate; the progression rate decreased as baseline MLD (p = 0.004) and BD increased ( p < 0.001). For baseline MLD and BD, the cut-off points where the progression rate decreased were 306.0 and 470.0 µm, respectively. CONCLUSION: The group without PVD progressed faster than the group with PVD. Moreover, the progression rates were faster in MHs with MLD < 306.0 µm and BD < 470.0 µm. In these patients, vitrectomy without delay is expected to improve the visual prognosis.

Clinical factors and vascular endothelial growth factor as determinants of disease progression in Indian patients with amyotrophic lateral sclerosis.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder. Prognostication remains sub-optimally defined. We aimed to assess clinical determinants of disease progression rates in Indian patients with ALS and to assess the role of vascular endothelial growth factor (VEGF) in disease progression. METHODS: In this cross-sectional study, consecutive patients with clinically definite/probable ALS according to the revised El Escorial criteria and controls were included. Patients were classified into fast or slow progressors based on disease progression rate (DPR). Serum and CSF VEGF level was assessed for patients and controls. RESULTS: Of 142 patients recruited, 93 (65.5%) were male. Mean age at enrollment was 49.37 ± 12.65 years. Mean duration of symptoms was 20.53 ± 20.88 months. Mean DPR was 1.14 ± 0.94. Based on DPR, 81 (57%) patients were slow progressors and 61 (43%) were fast progressors. Univariate analysis demonstrated a statistically significant association of DPR with age at onset, symptom duration, time to spread, wasting of small muscles of the hand, frontal release signs, and neurophysiologic bulbar abnormalities. On multivariate analysis, age at onset and symptom duration had a significant association with disease progression. The CSF VEGF levels of ALS patients (46.18 ± 27.8) were significantly elevated compared to controls (25.95 ± 25.64 pg/ml) (p = 0.001), but not serum VEGF. CONCLUSION: Age at symptom onset and duration of disease had a significant impact on disease progression in Indian patients with ALS. CSF VEGF levels were significantly elevated in ALS compared to controls, indicating the role of CSF VEGF as a potential biomarker.

Assessment of Cerebral White Matter Involvement in Amyotrophic Lateral Sclerosis Patients With Disease Progression and Cognitive Impairment by Fixel-Based Analysis and Neurite Orientation Dispersion and Density Imaging.

BACKGROUND: Previous studies using emerging diffusion MRI techniques have revealed damage to the white matter (WM) microstructure in amyotrophic lateral sclerosis (ALS), particularly the influence of crossed fibers, but there is a lack of subgroup analyses. PURPOSE: To detect WM microstructural changes in ALS patients using fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI) MRI. STUDY TYPE: Prospective. POPULATION: Thirty-six ALS patients (aged 60.50 ± 9.5 years) and 25 healthy controls (HCs) (aged 58.90 ± 8.1 years). FIELD STRENGTH/SEQUENCE: 3 T; NODDI and FBA (b-values = 0, 1000, and 2500 seconds/mm2 ). ASSESSMENT: Subgroups were performed according to progression rate and cognition, including fast and slow progression (FP/SP), ALS with and without cognitive impairment (ALS-ci/ALS-nci). Fiber density (FD), fiber-bundle cross-section (FC), combined fiber density and cross-section (FDC), neurite density index (NDI), orientation dispersion index (ODI), isotropic volume fraction (ISO), and fractional anisotropy (FA) were calculated and their correlation with clinical variables examined. STATISTICAL TESTING: Chi-square test, Mann-Whitney U test, two-sample t test, partial correlation analysis, and false discovery rate (FDR) corrected. A P-value <0.05 was considered significant. RESULTS: ALS patients had lower FD and FDC values predominantly in the corticospinal tract (CST) and corpus callosum (CC) regions, as well as lower NDI value in the CC, radial crown, and internal capsule compared to HCs. Subgroup analysis based on progression rate and cognitive function showed significant differences in FBA results. The FC in the right CST region was significantly lower in the FP than SP, and the FD in the CC region was significantly lower in the ALS-ci than ALS-nci. Furthermore, a negative correlation was found between the mean FC value and the rate of progression in ALS patients (r = -0.408). DATA CONCLUSION: FBA is a powerful tool for detecting complex cerebral WM microstructural damage for evaluating ALS cognition and disease progression.

Scoliosis in osteogenesis imperfecta: identifying the genetic and non-genetic factors affecting severity and progression from longitudinal data of 290 patients.

BACKGROUND: Scoliosis is widely prevalent among osteogenesis imperfecta (OI) patients, and is progressive with age. However, factors affecting scoliosis in OI are not well known. METHODS: We retrospectively retrieved longitudinal radiographic and clinical records of consecutive OI patients seeking treatments at our hospital from 2014 to 2022, graded their pre-operative spinal conditions into four outcome groups, estimated their progression rates, and descriptively and inferentially analyzed the genetic and non-genetic factors that may affect the outcomes and progression rates. RESULTS: In all, 290 OI patients met the inclusion criteria, where 221 had genetic records. Of these 221, about 2/3 had mutations in COL1A1 or COL1A2, followed by mutations in WNT1 (9.0%), IFITM5 (9.0%) and other OI risk genes. With an average age of 12.0 years (interquartile range [IQR] 6.9-16.1), 70.7% of the cohort had scoliosis (Cobb angle > 10°), including 106 (36.5%) mild (10°-25°), 40 (13.8%) moderate (25°-50°), and 59 (20.3%) severe (> 50°) scoliosis patients. Patients with either COL1A1 and COL1A2 were strongly biased toward having mild or no scoliosis, whereas patients with mutations in IFITM5, WNT1 and other recessive genes were more evenly distributed among the four outcome grades. Lower-limb discrepancy, bone mineral density (BMD) and age of first drug used were all significantly correlated with severity outcomes. Using multivariate logistic regression, we estimated that each year older adds an odds ratio of 1.13 (95% confidence interval [CI] 1.07-1.2) in progression into advanced stages of scoliosis. We estimated a cohort-wide progression rate of 2.7 degrees per year (95% CI 2.4-3.0). Early-onset patients experienced fast progressions during both infantile and adolescent stages. Twenty-five of the 59 (42.8%) patients with severe scoliosis underwent spinal surgeries, enjoying an average Cobb angle reduction of 33° (IQR 23-40) postoperatively. CONCLUSION: The severity and progression of scoliosis in osteogenesis imperfecta were affected by genetic factors including genotypes and mutation types, and non-genetic factors including age and BMD. As compared with COL1A1, mutations in COL1A2 were less damaging while those on IFITM5 and other recessive genes conferred damaging effects. Progression rates were the fastest in the adolescent adult age-group.

Inter- and intra-variability in tooth wear progression at surface-, tooth- and patient-level over a period of three years: A cohort study: Inter- and intra-variation in tooth wear progression.

OBJECTIVE: To explore the variability of tooth wear progression at the surface-, tooth- and patient-level over a period of three years three years using in vivo 3D-measurements of full dentitions amongst patients with moderate to severe tooth wear and without demand for restorative rehabilitation. METHODS: Fifty-five eligible patients with moderate to severe tooth wear had intra-oral scans taken using either the 3 M True Definition Intraoral Scanner or the 3 M Lava Chairside Oral Scanner. The maximum height loss (µm) per cusp/incisal/palatal surface at unrestored surfaces was measured using the 3D Wear Analysis (3DWA)-protocol with Geomagic Qualify, resulting in sixty-four measurements per dentition. Data was visualized using box plots. Correlation was calculated between tooth wear progression rates of different tooth types and surfaces. RESULTS: Thirty patients with scans at intake and after three years were included (38 ± 8 years, 77% M, 23% F). Mean observation time was 3.1 ± 0.2 years. Surface measurements (N = 1,615) showed a high deviation and a high number of outliers at all surfaces, indicating large variability amongst the surfaces, tooth types and patients with tooth wear progression rates. Correlations between regions were very low: anterior-molar region -0.219, anterior-premolar region 0.116 and premolar-molar region 0.113. Correlations between the surfaces of molars were also low (between 0.190 and 0.565). CONCLUSIONS: In a group of patients with moderate to severe tooth wear, large differences in wear progression were found within and amongst patients. Tooth wear progression is therefore highly individualized and can be very localized. CLINICAL SIGNIFICANCE: This study confirms the necessity of individual management of patients with moderate to severe tooth wear. Effective monitoring of tooth wear is important when deciding the timing and need for restorative intervention. CLINICAL TRIAL REGISTRATION NUMBER: NCT04790110.

Prognostic Usefulness of Motor Unit Number Index (MUNIX) in Patients Newly Diagnosed with Amyotrophic Lateral Sclerosis.

The MUNIX technique allows us to estimate the number and size of surviving motor units (MUs). Previous studies on ALS found correlations between MUNIX and several clinical measures, but its potential role as a predictor of disease progression rate (DPR) has not been thoroughly evaluated to date. We aimed to investigate MUNIX's ability to predict DPR at a six-month follow up. METHODS: 24 ALS patients with short disease duration (<24 months from symptoms' onset) were enrolled and divided according to their baseline DPR into two groups (normal [DPR-N] and fast [DPR-F] progressors). MUNIX values were obtained from five muscles (TA, APB, ADM, FDI, Trapezius) and averaged for each subject. RESULTS: MUNIX was found to predict DPR at follow up in a multivariable linear regression model; namely, patients with lower MUNIX values were at risk of showing greater DPR scores at follow up. The result was replicated in a simple logistic regression analysis, with the dichotomic category "MUNIX-Low" as the independent variable and the outcome "DPR-F" as the dependent variable. CONCLUSIONS: our results pave the way for the use of the MUNIX method as a prognostic tool in early ALS, enabling patients' stratification according to their rates of future decline.

Comparison of spinal magnetic resonance imaging and classical clinical factors in predicting motor capacity in amyotrophic lateral sclerosis.

BACKGROUND: Motor capacity is crucial in amyotrophic lateral sclerosis (ALS) clinical trial design and patient care. However, few studies have explored the potential of multimodal MRI to predict motor capacity in ALS. This study aims to evaluate the predictive value of cervical spinal cord MRI parameters for motor capacity in ALS compared to clinical prognostic factors. METHODS: Spinal multimodal MRI was performed shortly after diagnosis in 41 ALS patients and 12 healthy participants as part of a prospective multicenter cohort study, the PULSE study (NCT00002013-A00969-36). Motor capacity was assessed using ALSFRS-R scores. Multiple stepwise linear regression models were constructed to predict motor capacity at 3 and 6 months from diagnosis, based on clinical variables, structural MRI measurements, including spinal cord cross-sectional area (CSA), anterior-posterior, and left-to-right cross-section diameters at vertebral levels from C1 to T4, and diffusion parameters in the lateral corticospinal tracts (LCSTs) and dorsal columns. RESULTS: Structural MRI measurements were significantly correlated with the ALSFRS-R score and its sub-scores. And as early as 3 months from diagnosis, structural MRI measurements fit the best multiple linear regression model to predict the total ALSFRS-R (R2 = 0.70, p value = 0.0001) and arm sub-score (R2 = 0.69, p value = 0.0002), and combined with DTI metric in the LCST and clinical factors fit the best multiple linear regression model to predict leg sub-score (R2 = 0.73, p value = 0.0002). CONCLUSIONS: Spinal multimodal MRI could be promising as a tool to enhance prognostic accuracy and serve as a motor function proxy in ALS.

Do Individualized Patient-Specific Situations Predict the Progression Rate and Fate of Knee Osteoarthritis? Prediction of Knee Osteoarthritis.

Factors affecting the progression rate and fate of osteoarthritis need to be analyzed when considering patient-specific situation. This study aimed to identify the rate of remarkable progression and fate of primary knee osteoarthritis based on patient-specific situations. Between May 2003 and May 2019, 83,280 patients with knee pain were recruited for this study from the clinical data warehouse. Finally, 2492 knees with pain that were followed up for more than one year were analyzed. For analyzing affecting factors, patient-specific information was categorized and classified as demographic, radiologic, social, comorbidity disorders, and surgical intervention data. The degree of contribution of factors to the progression rate and the fate of osteoarthritis was analyzed. Bone mineral density (BMD), Kellgren-Lawrence (K-L) grade, and physical occupational demands were major contributors to the progression rate of osteoarthritis. Hypertension, initial K-L grade, and physical occupational demands were major contributors to the outcome of osteoarthritis. The progression rate and fate of osteoarthritis were mostly affected by the initial K-L grade and physical occupational demands. Patients who underwent surgical intervention for less than five years had the highest proportion of initial K-L grade 2 (49.0%) and occupations with high physical demand (41.3%). In identifying several contributing factors, the initial K-L grade and physical occupational demands were the most important factors. BMD and hypertension were also major contributors to the progression and fate of osteoarthritis, and the degree of contribution was lower compared to the two major factors.

Partogram of Grandmultiparous Parturients: A Multicenter Cohort Study.

Sparse and conflicting data exist regarding the normal partogram of grand-multiparous (GMP, defined as parity of 6+) parturients. Customized partograms may potentially lower cesarean delivery rates for protraction disorders in this population. In this study, we aim to construct a normal labor curve of GMP women and compare it to the multiparous (MP, defined as parity of 2-5) partogram. We conducted a multicenter retrospective cohort analysis of deliveries between the years 2003 and 2019. Eligible parturients were the trials of labor of singletons ≥37 + 0 weeks in cephalic presentation with ≥2 documented cervical examinations during labor. Exclusion criteria were elective cesarean delivery without a trial of labor, preterm labor, major fetal anomalies, and fetal demise. GMP comprised the study group while the MP counterparts were the control group. A total of 78,292 deliveries met the inclusion criteria, comprising 10,532 GMP and 67,760 MP parturients. Our data revealed that during the first stage of labor, cervical dilation progressed at similar rates in MPs and GMPs, while head descent was a few minutes faster in GMPs compared to MPs, regardless of epidural anesthesia. The second stage of labor was faster in GMPs compared to MPs; the 95th percentile of the second stage duration of GMPs (48 min duration) was 43 min less than that of MPs (91 min duration). These findings remained similar among deliveries with and without epidural analgesia or labor induction. We conclude that GMPs' and MPs' cervical dilation progression in the active phase of labor was similar, and the second stage of labor was shorter in GMPs, regardless of epidural use. Thus, GMPs' uterus function during labor corresponds, and possibly surpasses, that of MPs. These findings indicate that health providers can use the standard partogram of the active phase of labor when caring for GMP parturients.

Endoscopic Surveillance for Premalignant Esophageal Lesions: A Community-Based Multicenter, Prospective Cohort Study.

BACKGROUND & AIMS: Mild and moderate dysplasia are major premalignant lesions of esophageal squamous cell carcinoma (ESCC); however, evidence of the progression risk in patients with these conditions is extremely limited. We aimed to assess the incidence and risk factors for advanced neoplasia in patients with mild-moderate dysplasia. METHODS: This prospective cohort study included patients with mild-moderate dysplasia from 9 regions in rural China. These patients were identified from a community-based ESCC screening program conducted between 2010 and 2016 and were offered endoscopic surveillance until December 2021. We estimated the incidence of advanced esophageal neoplasia, including severe dysplasia, carcinoma in situ, or ESCC, and identified potential risk factors using the Cox regression model. RESULTS: The 1183 patients with mild-moderate dysplasia were followed up over a period of 6.95 years. During follow-up evaluation, 88 patients progressed to advanced neoplasia (7.44%), with an incidence rate of 10.44 per 1000 person-years. The median interval from the progression of mild-moderate dysplasia to advanced neoplasia was 2.39 years (interquartile range, 1.58-4.32 y). A total of 74.47% of patients with mild-moderate dysplasia experienced regression to nondysplasia, and 18.09% showed no lesion progression. Patients with mild-moderate dysplasia who had a family history of esophageal cancer and were age 55 years and older showed 97% higher advanced neoplasia yields than all patients with mild-moderate dysplasia. CONCLUSIONS: In a country with a high incidence of ESCC, patients with mild-moderate dysplasia showed an overall risk of advanced neoplasia progression of 1.04% per year. Patients with mild-moderate dysplasia would be recommended for endoscopic surveillance during the first 2 to 3 years.

Prediction of progression rate and fate of osteoarthritis: Comparison of machine learning algorithms.

Appropriate prediction models can assist healthcare systems in delaying or reversing osteoarthritis (OA) progression. We aimed to identify a reliable algorithm for predicting the progression rate and fate of OA based on patient-specific information. From May 2003 to 2019, 83,280 knees were collected. Age, sex, body mass index, bone mineral density, physical demands for occupation, comorbidities, and initial Kellgren-Lawrence (K-L) grade were used as variables for the prediction models. The prediction targets were divided into dichotomous groups for even distribution. We compared the performances of logistic regression (LR), random forest (RF), and extreme gradient boost (XGB) algorithms. Each algorithm had the best precision when the model used all variables. XGB showed the best results in accuracy, recall, F1 score, specificity, and error rates (progression rate/fate of OA: 0.710/0.877, 0.542/0.637, 0.637/0.758, 0.859/0.981, and 0.290/0.123, respectively). The feature importance of RF and XGB had the same order up to the top six for each prediction target. Age and initial K-L grade had the highest feature importance in RF and XGB for the progression rate and fate of OA, respectively. The XGB and RF machine learning algorithms showed better performance than conventional LR in predicting the progression rate and fate of OA. The best performance was obtained when all variables were combined using the XGB algorithm. For each algorithm, the initial K-L grade and physical demand for occupation were the greatest contributors with superior feature importance compared with the others.

Deep learning algorithm reveals probabilities of stage-specific time to conversion in individuals with neurodegenerative disease LATE.

Introduction: Limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE) is a recently defined neurodegenerative disease. Currently, there is no effective way to make a prognosis of time to stage-specific future conversions at an individual level. Methods: After using the Kaplan-Meier estimation and log-rank test to confirm the heterogeneity of LATE progression, we developed a deep learning-based approach to assess the stage-specific probabilities of time to LATE conversions for different subjects. Results: Our approach could accurately estimate the disease incidence and transition to next stages: the concordance index was at least 82% and the integrated Brier score was less than 0.14. Moreover, we identified the top 10 important predictors for each disease conversion scenario to help explain the estimation results, which were clinicopathologically meaningful and most were also statistically significant. Discussion: Our study has the potential to provide individualized assessment for future time courses of LATE conversions years before their actual occurrence.

Relationship between Dietary Total Antioxidant Capacity and the Prognosis of Amyotrophic Lateral Sclerosis.

Antioxidant intake has been suggested to be associated with the prognosis of amyotrophic lateral sclerosis (ALS). This study aimed to investigate whether dietary total antioxidant capacity (DTAC) and that of major food groups are related to disease progression rate (ΔFS) and survival time in ALS patients. A total of 301 participants diagnosed with sporadic ALS according to the revised El Escorial criteria were recruited from March 2011 and followed up to the event occurrence, or the end of October 2021. Events included percutaneous endoscopic gastrostomy, tracheostomy, and death. DTAC was estimated using task automation and an algorithm based on 24 h dietary recall. ΔFS was negatively correlated with the vegetable and legume DTAC, and event-free survival was different among the tertiles of vegetables and legumes DTAC. Consistently, the risk of events was negatively associated with DTAC from vegetables and legumes. These results suggest that the intake of antioxidants, especially those derived from vegetables and legumes, has a beneficial effect on delaying disease progression and prolonging survival in patients with ALS. Further studies with large prospective cohorts and clinical trials are needed to determine whether the consumption of foods with high DTAC improves the prognosis of ALS.

A novel quantitative indicator for disease progression rate in amyotrophic lateral sclerosis.

OBJECTIVE: The current study sought to develop a new indicator for disease progression rate in amyotrophic lateral sclerosis (ALS). METHODS: We used a nonparametric method to score diverse patterns of decline in the percentage of predicted forced vital capacity (%FVC) in patients with ALS. This involved 6317 longitudinal %FVC data sets from 920 patients in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database volunteered by PRO-ACT Consortium members. To assess the utility of the derived scores as a disease indicator, we examined changes over time, the association with prognosis, and correlation with the Risk Profile of the Treatment Research Initiative to Cure ALS (TRICALS). Our local cohort (n = 92) was used for external validation. RESULTS: We derived scores ranging from 35 to 106 points to construct the FVC Decline Pattern scale (FVC-DiP). Individuals' FVC-DiP scores were determined from a single measurement of %FVC and disease duration at assessment. Although the %FVC declined over the disease course (p < 0.0001), the FVC-DiP remained relatively stable. Low FVC-DiP scores were associated with rapid disease progression. Using our cohort, we demonstrated an association between FVC-DiP and the survival prognosis, the stability of the FVC-DiP per individual, and a correlation between FVC-DiP scores and the TRICALS Risk Profile (r2 = 0.904, p < 0.0001). CONCLUSIONS: FVC-DiP scores reflected patterns of declining %FVC over the natural course of ALS and indicated the disease progression rate. The FVC-DiP may enable easy assessment of disease progression patterns and could be used for assessing treatment efficacy.

In-Brace versus Out-of-Brace Protocol for Radiographic Follow-Up of Patients with Idiopathic Scoliosis: A Retrospective Study.

The purpose of this retrospective study was to compare two standardized protocols for radiological follow-up (in-brace versus out-of-brace radiographs) to study the rate of curve progression over time in surgically treated idiopathic scoliosis (IS) patients after failed brace treatment. In-brace radiographs have the advantage that proper fit of the brace and in-brace correction can be evaluated. However, detection of progression might theoretically be more difficult. Fifty-one IS patients that underwent surgical treatment after failed brace treatment were included. For 25 patients, follow-up radiographs were taken in-brace. For the other 26 patients, brace treatment was temporarily stopped before out-of-brace follow-up radiographs were taken. Both groups showed significant curve progression compared to baseline after a mean follow-up period of 3.4 years. The protocol with in-brace radiographs was noninferior regarding curve progression rate over time. The estimated monthly Cobb angle progression based on the mixed-effect model was 0.5 degrees in both groups. No interaction effect was found for time, and patients' baseline Cobb angle (p = 0.98), and for time and patients' initial in-brace correction (p = 0.32). The results of this study indicate that with both in-brace and out-of-brace protocols for radiographic follow-up, a similar rate of curve progression can be expected over time in IS patients with failed brace treatment.