Longitudinal Progression Research Articles

Approaches to optimize analyses of multidimensional ordinal MRI data in osteoarthritis research: A perspective

ObjectiveKnee osteoarthritis (OA) is a disease of the whole joint involving multiple tissue types. MRI-based semi-quantitative (SQ) scoring of knee OA is a method to perform multi-tissue joint assessment and has been shown to be a valid and reliable way to measure structural multi-tissue involvement and progression of the disease. While recent work has described how SQ scoring may be used for clinical trial enrichment and disease phenotyping in OA, less guidance is available for how these parameters may be used to assess study outcomes. DesignHere we present recommendations for summarizing disease progression within specific tissue types. We illustrate how various methods may be used to quantify longitudinal change using SQ scoring and review examples from the literature. ResultsApproaches to quantify longitudinal change across subregions include the count of number of subregions, delta-subregion, delta-sum, and maximum grade changes. Careful attention should be paid to features that may fluctuate, such as bone marrow lesions, or with certain interventions, for example pharmacologic interventions with anticipated cartilage anabolic effects. The statistical approach must align with the nature of the outcome. ConclusionsSQ scoring presents a way to understand disease progression across the whole joint. As OA is increasingly recognized as a heterogeneous disease with different phenotypes a better understanding of longitudinal progression across tissue types may present an opportunity to match study outcome to patient phenotype or to treatment mechanism of action.

Association of Filifactor alocis and its RTX toxin gene ftxA with periodontal attachment loss, and in synergy with Aggregatibacter actinomycetemcomitans.

The Gram-positive bacterium, Filifactor alocis is an oral pathogen, and approximately 50% of known strains encode a recently identified repeat-in-toxin (RTX) protein, FtxA. By assessing a longitudinal Ghanaian study population of adolescents (10-19 years of age; mean age 13.2 years), we recently discovered a possible correlation between deep periodontal pockets measured at the two-year follow-up, presence of the ftxA gene, and a high quantity of F. alocis. To further understand the contribution of F. alocis and FtxA in periodontal disease, we used qPCR in the present study to assess the carriage loads of F. alocis and the prevalence of its ftxA gene in subgingival plaque specimens, sampled at baseline from the Ghanaian cohort (n=500). Comparing these results with the recorded clinical attachment loss (CAL) longitudinal progression data from the two-year follow up, we concluded that carriers of ftxA-positive F. alocis typically exhibited higher loads of the bacterium. Moreover, high carriage loads of F. alocis and concomitant presence of the ftxA gene were two factors that were both associated with an enhanced prevalence of CAL progression. Interestingly, CAL progression appeared to be further promoted upon the simultaneous presence of F. alocis and the non-JP2 genotype of Aggregatibacter actinomycetemcomitans. Taken together, our present findings are consistent with the notion that F. alocis and its ftxA gene promotes CAL during periodontal disease.

Abstract 1307: Community-driven support platform BlueHQ: An innovative solution to address the needs of patients with colorectal cancer

Abstract Background: Colorectal cancer (CRC) is the third-most commonly diagnosed cancer and the second-leading cause of cancer death in men and women combined in the United States. To manage the disease, patients and caregivers turn to various tools and resources for financial assistance, information dissemination, emotional and peer support, and treatment planning, among other critical issues and needs they face. The Colorectal Cancer Alliance (the Alliance) created BlueHQ to provide patients and caregivers with a resource solution encompassing all potential areas of need. Methods: A survey aimed at understanding needs, barriers, and quality improvement opportunities was disseminated via the Alliance's Blue Hope Nation community for two weeks and by email. One hundred sixty-seven colorectal cancer patients and forty caregivers of colorectal cancer patients completed the survey. Results: Patients and caregiver respondents report reliance on external tools and resources to manage disease and support information. Of the support methods, patient respondents reported using social media (46.11%); notebooks, journals, and planners (45.41%); online articles (44.91%); the Blue Hope Nation Facebook group (41.32%); cancer discussion boards (35.33%); and spiritual or religious advice (29.94%). Patients sought financial assistance, local peer support and groups, and mental health help to minimize diagnosis-related stressors. To provide more efficient care and limit stress, the community suggested financial help, communication and support from other patients and caregivers, and informational resources. Conclusions: These survey results are consistent with other published learnings about patient and caregiver reliance on support tools and highlight the myriad resources that patients and caregivers currently use for managing CRC. BlueHQ is a support solution that provides patients and caregivers with access to information and resources tailored to users’ specified profiles, including molecular characteristics of the tumor. Users can also store documents and information from healthcare encounters, creating a longitudinal record and tracking disease progression. In the age of precision oncology, BlueHQ ensures patients and users are presented with personalized educational materials and multimedia resources to help manage their disease and bridge the gaps in patient support. BlueHQ was explicitly designed to connect the CRC community to the latest therapeutic and clinical research resources to improve outcomes and quality of life for all CRC patients. Citation Format: Kimberly Lynn Newcomer. Community-driven support platform BlueHQ: An innovative solution to address the needs of patients with colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1307.

Abstract 4177: High-throughput in vivo monitoring of splenomegaly and tumor burden in a murine breast cancer model

Abstract Splenomegaly is a valuable parameter in mouse model cancer studies, as it can reflect the magnitude of cancer burden, hematopoietic activity, immune status, and can provide an indirect measure of cancer treatment efficacy. In liquid cancer models specifically (leukemia/lymphoma), spleen sizing is important as it is usually the only measure of in vivo tumor burden that can be assessed noninvasively without genetic labeling of tumor cells. Magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CT) are highly effective at evaluating spleen size in small animals. However, these techniques can impose limitations on large-cohort study designs due to high cost, long scan time, and ionizing radiation. Ultrasound is an alternative method with lower cost, high frame rate, and no ionization, but can suffer from poor inter-user variability, limited 2D field-of-view, and low throughput due to manual operation. In this work, we evaluated a novel 3D automated ultrasound scanner (Vega, Revvity, Inc.) for rapid assessment of splenomegaly in a murine cancer model. Female BALB/c mice (n=10) were implanted with 5e5 4T1 (ATCC) cells on the right flank. Mice were imaged at five timepoints over 25 days to track longitudinal progression of both spleen and tumor enlargement. Images were segmented manually in 3D using the “Slice Draw” and “Fill Between Slices” effects in SonoEQ v2.0.1 (Revvity, Inc.) to quantify tissue volume. After the final timepoint, mice were euthanized, and spleen weight was measured ex vivo. An additional cohort of age-matched mice without tumors (n=7) were imaged at the final timepoint to serve as controls. Imaging revealed a substantial enlargement of the spleen over time, from 30 ± 3 mm3 to 545 ± 105 mm3, representing an 18-fold increase. In the same time span, tumor volume grew to 1966 ± 87 mm3. Correlation analysis demonstrated good agreement between ultrasound volumes and ex vivo spleen weights (R² = 0.90). The results in this study demonstrate that noninvasive, nonlabelled quantification of murine spleen size with automated ultrasound is feasible, robust, and fast. The average time to acquire the spleen image for each mouse was less than 30 seconds. Future studies will apply this workflow in liquid cancer models, as well as explore using machine learning approaches to automatically segment spleen borders for faster data analysis. Citation Format: Craig McMannus, Tomek J. Czernuszewicz, Ryan C. Gessner, Jeffrey D. Peterson. High-throughput in vivo monitoring of splenomegaly and tumor burden in a murine breast cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4177.

Abstract 1467: Contribution of estrogen metabolites to never-smoking lung cancer

Abstract There has been a consistent rise in the incidence of non-small cell lung cancer (NSCLC) among individuals who have never smoked. Remarkably, over 50% of diagnosed female cases and 15-20% of male cases are never-smokers. Notably, NSCLC in never-smokers exhibits distinctive clinical and pathological features, notably a higher incidence of tumors with EGFR mutations, setting it apart from its counterpart in smokers. Despite the improved disease-free survival observed with EGFR-tyrosine kinase inhibitors, eventual relapse and limited responsiveness to immunotherapy are common, underscoring the urgency to comprehend the molecular mechanisms driving the escalating prevalence of NSCLC in never-smokers and develop targeted preventive and interceptive therapeutic strategies. The preponderance of females among NSCLC patients who never smoked has prompted an exploration into the potential contribution of estrogen to lung tumorigenesis. In contrast to prevailing research focused on estrogen receptor-mediated signaling, our investigations have yielded compelling evidence supporting the involvement of estrogen metabolism in lung carcinogenesis among never-smokers. This group is the first to report that estrogen is metabolized extensively in both mouse and human lungs, resulting in the generation of various derivatives, including the potential carcinogen 4-hydroxyestrogen (4-OHE). Notably, recent findings from our laboratory indicate that prolonged exposure of nonneoplastic human bronchial epithelial cells to 17β estradiol or 4-OHE, at concentrations approximating physiological levels, induces the accumulation of double-strand DNA breaks and cellular transformation. A comprehensive analysis was performed to further elucidate the mechanisms underlying the transformation process. Isolated transformed clones obtained after 9, 18, and 22 wks of exposure to 4-OHE were subjected to karyotyping, F.I.S.H., and RNA and exome sequencing. A longitudinal progression of aberrant chromosomal rearrangements and copy number alterations was observed, that increased with time of 4-OHE exposure. In addition, RNA-Seq analyses revealed the epithelial-mesenchymal transition pathway was highly enriched at the early timepoint (9 wks), while replicative stress-related signaling pathways were induced at all timepoints. To determine if the differentially expressed genes were also dysregulated in clinical lung cancer cases, TCGA lung adenocarcinoma (LUAD) data were examined. Interestingly, many of the genes upregulated after estrogen exposure were similarly overexpressed in the LUAD samples and often associated with a worse prognosis. In conclusion, our data support the role of estrogen metabolites in promoting lung cancer among never-smokers. (Supported by CA217161 and generous contributions from the Hellendall Family Foundation, Gregory G. Lawton and the Timothy and Aurora Hughes Cancer Research Fund.) Citation Format: Mitchell Cheung, Lisa A. Vanderveer, Daniel Krzizike, J. Nicholas Bodor, Joseph Treat, Joseph R. Testa, Margie L. Clapper. Contribution of estrogen metabolites to never-smoking lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1467.

Improved measurement of disease progression in people living with early Parkinson’s disease using digital health technologies

BackgroundDigital health technologies show promise for improving the measurement of Parkinson’s disease in clinical research and trials. However, it is not clear whether digital measures demonstrate enhanced sensitivity to disease progression compared to traditional measurement approaches.MethodsTo this end, we develop a wearable sensor-based digital algorithm for deriving features of upper and lower-body bradykinesia and evaluate the sensitivity of digital measures to 1-year longitudinal progression using data from the WATCH-PD study, a multicenter, observational digital assessment study in participants with early, untreated Parkinson’s disease. In total, 82 early, untreated Parkinson’s disease participants and 50 age-matched controls were recruited and took part in a variety of motor tasks over the course of a 12-month period while wearing body-worn inertial sensors. We establish clinical validity of sensor-based digital measures by investigating convergent validity with appropriate clinical constructs, known groups validity by distinguishing patients from healthy volunteers, and test-retest reliability by comparing measurements between visits.ResultsWe demonstrate clinical validity of the digital measures, and importantly, superior sensitivity of digital measures for distinguishing 1-year longitudinal change in early-stage PD relative to corresponding clinical constructs.ConclusionsOur results demonstrate the potential of digital health technologies to enhance sensitivity to disease progression relative to existing measurement standards and may constitute the basis for use as drug development tools in clinical research.

Fasting plasma glucose level and longitudinal motor and cognitive outcomes in Parkinson's disease.

Hyperglycemia and diabetes mellitus have been recognized as poor prognostic factors for motor and nonmotor outcomes in patients with Parkinson's disease (PD), although there is some controversy. In the present study, we investigated the effects of fasting plasma glucose (FPG) level on longitudinal motor and cognitive outcomes in PD patients. We included a total of 201 patients diagnosed with PD between January 2015 and January 2020. The patients were categorized based on FPG level: euglycemia (70< FPG <100 mg/dL), intermediate glycemia (100≤ FPG <126 mg/dL), and hyperglycemia (FPG ≥126 mg/dL), and longitudinal FPG trajectories were analyzed using group-based trajectory modeling. Survival analysis was conducted to determine the time until motor outcome (Hoehn and Yahr stage≥2) and the conversion from normal cognition to mild cognitive impairment. Among the patients studied, 82 had euglycemia, 93 had intermediate glycemia, and 26 had hyperglycemia. Intermediate glycemia (HR 1.75, 95% CI 1.08-2.81, p=0.022) and hyperglycemia (HR 3.86, 95% CI 2.00-7.48, p<0.01) emerged as significant predictors of worsening motor symptoms. However, neither intermediate glycemia (HR 1.245, 95% CI 0.764-2.029, p=0.3789) nor hyperglycemia (HR 1.602, 95% CI 0.763-3.362, p=0.2129) demonstrated associations with longitudinal progression of cognitive impairment. Diabetes mellitus defined by self-reported medical history was not related to poor motor or cognitive impairment outcomes. Our results support that both impaired glucose tolerance and hyperglycemia could be associated with motor progression in PD.

Abstract A029: Development of a new iPSC-derived organoid platform to model FTE-derived HGSOC onset and progression

Abstract A029: Development of a new iPSC-derived organoid platform to model FTE-derived HGSOC onset and progression

Contemporaneous and temporal network analysis of complex Posttraumatic stress disorder among Chinese college students with Childhood adversity: A longitudinal study

ObjectiveTo enhance understanding of the longitudinal progression of complex posttraumatic stress disorder (CPTSD) symptoms, this longitudinal study examined how CPTSD symptoms interact over time in Chinese college students with childhood trauma. MethodsFrom 18,933 college students who took part in two surveys 12 months apart, 4,006 participants who reported adverse childhood experiences were screened. Cross-sectional network comparisons and cross-lagged panel network (CLPN) analysis characterized interactions among CPTSD symptoms. ResultsIn the cross-sectional networks, feeling like a failure and avoid activities reminiscent of the trauma were the central symptoms. Takes long time to calm down and exaggerated startle are important bridge symptoms in the two networks respectively. The comparison of cross-sectional networks indicates that the global network strength was stable. The findings of the CLPN model reveal that feel worthless and feel like a failure had the highest "out" expected influence; exaggerated startle and avoid thoughts and feelings about the trauma had the highest "in" expected influence. ConclusionsBy conducting cross-sectional network analyses, the study illuminated the attributes of CPTSD networks across various time points. Additionally, the CLPN analysis uncovered the longitudinal patterns of CPTSD symptoms.

Evaluation of ATNPD Framework and Biofluid Markers to Predict Cognitive Decline in Early Parkinson Disease.

In Parkinson disease (PD), Alzheimer disease (AD) copathology is common and clinically relevant. However, the longitudinal progression of AD CSF biomarkers-β-amyloid 1-42 (Aβ42), phosphorylated tau 181 (p-tau181), and total tau (t-tau)-in PD is poorly understood and may be distinct from clinical AD. Moreover, it is unclear whether CSF p-tau181 and serum neurofilament light (NfL) have added prognostic utility in PD, when combined with CSF Aβ42. First, we describe longitudinal trajectories of biofluid markers in PD. Second, we modified the AD β-amyloid/tau/neurodegeneration (ATN) framework for application in PD (ATNPD) using CSF Aβ42 (A), p-tau181 (T), and serum NfL (N) and tested ATNPD prediction of longitudinal cognitive decline in PD. Participants were selected from the Parkinson's Progression Markers Initiative cohort, clinically diagnosed with sporadic PD or as controls, and followed up annually for 5 years. Linear mixed-effects models (LMEMs) tested the interaction of diagnosis with longitudinal trajectories of analytes (log transformed, false discovery rate [FDR] corrected). In patients with PD, LMEMs tested how baseline ATNPD status (AD [A+T+N±] vs not) predicted clinical outcomes, including Montreal Cognitive Assessment (MoCA; rank transformed, FDR corrected). Participants were 364 patients with PD and 168 controls, with comparable baseline mean (±SD) age (patients with PD = 62 ± 10 years; controls = 61 ± 11 years]; Mann-Whitney Wilcoxon: p = 0.4) and sex distribution (patients with PD = 231 male individuals [63%]; controls = 107 male individuals [64%]; χ2: p = 1). Patients with PD had overall lower CSF p-tau181 (β = -0.16, 95% CI -0.23 to -0.092, p = 2.2e-05) and t-tau than controls (β = -0.13, 95% CI -0.19 to -0.065, p = 4e-04), but not Aβ42 (p = 0.061) or NfL (p = 0.32). Over time, patients with PD had greater increases in serum NfL than controls (β = 0.035, 95% CI 0.022 to 0.048, p = 9.8e-07); slopes of patients with PD did not differ from those of controls for CSF Aβ42 (p = 0.18), p-tau181 (p = 1), or t-tau (p = 0.96). Using ATNPD, PD classified as A+T+N± (n = 32; 9%) had worse cognitive decline on global MoCA (β = -73, 95% CI -110 to -37, p = 0.00077) than all other ATNPD statuses including A+ alone (A+T-N-; n = 75; 21%). In patients with early PD, CSF p-tau181 and t-tau were low compared with those in controls and did not increase over 5 years of follow-up. Our study shows that classification using modified ATNPD (incorporating CSF Aβ42, CSF p-tau181, and serum NfL) can identify biologically relevant subgroups of PD to improve prediction of cognitive decline in early PD.

Longitudinal progression trajectory of estimated glomerular filtration rate in children with chronic kidney disease: results from the KNOW-Ped CKD (KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease).

The natural course of chronic kidney disease (CKD) progression in children varies according to their underlying conditions. This study aims to identify different patterns of subsequent decline in kidney function and investigate factors associated with different patterns of estimated glomerular filtration rate (eGFR) trajectories. We analyzed data from the KNOW-Ped CKD (KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease), which is a longitudinal, prospective cohort study. A latent class linear mixed model was applied to identify the trajectory groups. In a total of 287 patients, the median baseline eGFR (mL/min/1.73 m2) was 63.3, and the median age was 11.5 years. The eGFR decline rate was -1.54 during a 6.0-year follow-up. The eGFR trajectory over time was classified into four groups. Classes 1 (n = 103) and 2 (n = 11) had a slightly reduced eGFR at enrollment with a stable trend (ΔeGFR, 0.2/year) and a rapid decline eGFR over time (ΔeGFR, -10.5/year), respectively. Class 3 had a normal eGFR (n = 16), and class 4 had a moderately reduced eGFR (n = 157); both these chasses showed a linear decline in eGFR over time (ΔeGFR, -4.1 and -2.4/year). In comparison with classes 1 and 2, after adjusting for age, causes of primary renal disease, and baseline eGFR, nephrotic-range proteinuria was associated with a rapid decline in eGFR (odds ratio, 8.13). We identified four clinically relevant subgroups of kidney function trajectories in children with CKD. Most children showed a linear decline in eGFR; however, there are different patterns of eGFR trajectories.

Long-term Radiological and Pulmonary Function Abnormalities at 3-year post COVID-19 Hospitalization: A Longitudinal Cohort Study.

This study aimed to evaluate the longitudinal progression of residual lung abnormalities (ground-glass opacities, reticulations, and fibrotic-like changes) and pulmonary function, three years following coronavirus disease 2019(COVID-19). This prospective, longitudinal cohort study enrolled COVID-19 survivors who exhibited residual lung abnormalities upon discharge from two hospitals. Follow-up assessments were conducted at 6 months, 12 months, 2 years, and 3 years post-discharge, and included pulmonary function tests, 6-minute walk distance (6MWD), chest CT scans, and symptom questionnaires. Non-COVID-19 controls were retrospectively recruited for comparative analysis. 728 COVID-19 survivors and 792 controls were included. From 6 months to 3 years, there was a gradual improvement in reduced diffusing capacity of the lungs for carbon monoxide (DLCO＜80% predicted, 49% versus 38%, p=0.001), 6MWD (496 m versus 510 m, p=0.002) and residual lung abnormalities(46% versus 36%, p<0.001), regardless of the disease severity. Patients with residual lung abnormalities at 3 years more commonly had respiratory symptoms (32% versus 16%, p<0.001), lower 6MWD (494 m versus 510 m, p=0.003), and abnormal DLCO (57% versus 27%, p<0.001) compared to those with complete resolution. Compared to the controls, the proportion of DLCO impairment (38% versus 17%, p<0.001) and respiratory symptoms (23% versus 2.2%, p<0.001) were significantly higher in the matched COVID-19 survivors at the 3-year follow-up. Most patients exhibited improvement in radiological abnormalities and pulmonary function over time following COVID-19. However, more than one-third continued to have persistent lung abnormalities at the 3-year mark, which were associated with respiratory symptoms and reduced diffusion capacity.

Clinical Significance of Optic Disc Hemorrhage Size in Visual Field Progression in Glaucoma

PurposeTo investigate the correlation between optic disc hemorrhage (DH) size and glaucoma progression. DesignA retrospective observational cohort study MethodsXXXX SettingA single tertiary hospital in South Korea Study PopulationTwo hundred and fifty (250) open-angle glaucoma (OAG) patients with DH. Participants were followed for 5 years or longer, with a minimum of 5 visual field (VF) tests. Observation ProcedureThe DH area was calculated by comparing the pixel numbers of the DH area with the disc area based on optical coherence tomography (OCT). For recurrent DH cases, we calculated the average DH area. DH size was classified as large or small based on the median value. Rates of mean deviation (MD) loss were determined using Guided Progression Analysis (GPA). Univariable and multivariable regression analyses were performed to identify significant predictors of MD loss. Main outcome measuresDH size and longitudinal VF progression ResultsThe mean follow-up period was 11.1 ± 3.6 years. The group with large DH showed faster global MD loss relative to the group with small DH (-0.51±0.48 dB/y vs. -0.36±0.42 dB/y, p = 0.01). In the multivariable model, mean DH size, maximum DH size, and initial MD were all significantly associated with the overall rate of MD loss (all p < 0.05). ConclusionsDH size was associated with the rate of VF deterioration. Eyes with larger DH showed more pronounced VF progression.

Patellar tendon complaints and shear wave velocity patterns in maturing alpine skiers

Introduction&#x0D; Patellar tendinopathy is frequent in adolescent athletes and particularly accentuated in competitive alpine skiers (Fröhlich et al., 2020). Tendinopathies are characterized by long disease histories, and whether they can be healed completely is an open question (Kettunen et al., 2002). Three-dimensional (3D) shear wave elastography (SWE) has proven valuable in the early detection of tendinopathies (Götschi et al., 2023). The aims of this study were to (1) describe the longitudinal progression of patellar tendon complaint prevalence in competitive alpine skiers during adolescence, (2) compare the SWV patterns of skiers that were symptomatic four years ago with those with no history of patellar tendon complaints and (3) analyse whether shear wave velocity (SWV) average values correlate with SWV coefficient of variation (CV).&#x0D; Methods&#x0D; Forty-seven subjects were analysed in this 4-year follow-up study regarding their patellar tendon complaints and SWV patterns. Symptomatic and asymptomatic skiers were identified by clinical examinations including the criteria of pain sensation under loading and palpation-induced pain. SWV was determined by ultrasound-based 3D SWE. Prevalence differences were assessed using Pearson’s χ2 tests. Group differences in the SWV patterns were analysed using unpaired sample t tests. Correlations between SWV average and CV values were analysed by means of Pearson’s correlation coefficient.&#x0D; Results&#x0D; With proceeding adolescence, the prevalence of patellar tendon complaints significantly decreased from 29.8% at baseline assessment (13-16 years) to 12.7% at follow-up assessment (Pearson’s χ2 = 9.429; p = 0.002). Those skiers who were symptomatic at baseline but asymptomatic at the follow-up still had lower average SWV values and higher CVs than asymptomatic skiers with no history of patellar tendon complaints (p = 0.054 and p = 0.011, respectively). Furthermore, there was a significant negative correlation between the tendon SWV average values and their CVs (R = -0.55; p &lt; 0.001).&#x0D; Discussion/Conclusion&#x0D; Despite the decreasing prevalence of patellar tendon complaints in youth competitive alpine skiers after their growth spurt, structural abnormalities appear to remain in asymptomatic subjects with a previous history of patellar tendinopathy, indicating potential long-term implications for mechanical tendon proprieties. The SWV average and CV values were negatively correlated, which underlines our hypothesis that a low SWV is associated with a high CV. This altogether may reflect the degenerative processes in patellar tendons affected by complaints in the early stages of a sports career.&#x0D; References&#x0D; Fröhlich, S., Peterhans, L., Stern, C., Frey, W. O., Sutter, R., &amp; Spörri, J. (2020). Remarkably high prevalence of overuse-related knee complaints and MRI abnormalities in youth competitive alpine skiers: A descriptive investigation in 108 athletes aged 13-15 years. BMJ Open Sport &amp; Exercice Medicine, 6(1), Aticle e000738. https://doi.org/10.1136/bmjsem-2020-000738&#x0D; Götschi, T., Franchi, M. V., Schulz, N., Fröhlich, S., Frey, W. O., Snedeker, J. G., &amp; Spörri, J. (2023). Altered regional 3D shear wave velocity patterns in youth competitive alpine skiers suffering from patellar tendon complaints – A prospective case–control study. European Journal of Sport Science, 23(6), 1068-1076. https://doi.org/10.1080/17461391.2022.2088404&#x0D; Kettunen, J. A., Kvist, M., Alanen, E., &amp; Kujala, U. M. (2002). Long-term prognosis for jumper’s knee in male athletes. A prospective follow-up study. The American Journal of Sports Medicine, 30(5), 689-692. https://doi.org/10.1177/03635465020300051001

Are Cognitive Symptoms Part of the Phenotypic Spectrum of Idiopathic Adult-Onset Dystonia? Summary of Evidence from Controlled Studies.

Cognitive dysfunction has been reported in idiopathic adult-onset dystonia (IAOD), but whether this is a primary or secondary component of the disorder remains uncertain. Here, we aimed to analyze the key domains of abnormal cognitive performance in IAOD and whether this is associated with motor or mood changes. Article selection for our critical review was guided by PRISMA guidelines (mesh terms "dystonia" and "cognitive," publication period: 2000-2022). Only peer-reviewed, English-language original case-control studies involving patients with IAOD who were not exposed to dopamine- or acetylcholine-modulating agents and validated cognitive assessments were included. Abstract screening ultimately yielded 22 articles for full-text review and data extraction. A greater proportion of studies (17 of 22, 82%) reported abnormal cognitive performance in IAOD. Most of these studies focused on blepharospasm (BSP) and cervical dystonia (10 and 14, respectively). Most studies reporting cognitive impairment (11 of 17) identified multidomain impairment in cognition. Executive functions were the domain most frequently explored (14 of 22 studies), 79% of which detected worse performance in people with dystonia. Results related to other domains were inconclusive. Cognitive abnormalities were independent of motor symptoms in most studies (7 of 12) that explored this relationship and independent of mood status in all 8 that investigated this. Within IAOD, cognitive dysfunction (in particular, executive dysfunction) has been documented mainly in BSP and cervical dystonia. More comprehensive testing is warranted to assess abnormalities in other domains and in other forms of IAOD, as well as to evaluate longitudinal progression of cognitive disturbances in this condition.

Mismatch between clinically defined classification of ALS stage and the burden of cerebral pathology.

This study aimed to investigate the clinical stratification of amyotrophic lateral sclerosis (ALS) patients in relation to in vivo cerebral degeneration. One hundred forty-nine ALS patients and one hundred forty-four healthy controls (HCs) were recruited from the Canadian ALS Neuroimaging Consortium (CALSNIC). Texture analysis was performed on T1-weighted scans to extract the texture feature "autocorrelation" (autoc), an imaging biomarker of cerebral degeneration. Patients were stratified at baseline into early and advanced disease stages based on criteria adapted from ALS clinical trials and the King's College staging system, as well as into slow and fast progressors (disease progression rates, DPR). Patients had increased autoc in the internal capsule. These changes extended beyond the internal capsule in early-stage patients (clinical trial-based criteria), fast progressors, and in advanced-stage patients (King's staging criteria). Longitudinal increases in autoc were observed in the postcentral gyrus, corticospinal tract, posterior cingulate cortex, and putamen; whereas decreases were observed in corpus callosum, caudate, central opercular cortex, and frontotemporal areas. Both longitudinal increases and decreases of autoc were observed in non-overlapping regions within insula and precentral gyrus. Within-criteria comparisons of autoc revealed more pronounced changes at baseline and longitudinally in early- (clinical trial-based criteria) and advanced-stage (King's staging criteria) patients and fast progressors. In summary, comparative patterns of baseline and longitudinal progression in cerebral degeneration are dependent on sub-group selection criteria, with clinical trial-based stratification insufficiently characterizing disease stage based on pathological cerebral burden.

Artificial intelligence in glaucoma progression: A systematic review

Aims/Purpose: Glaucoma is the leading cause of irreversible blindness worldwide. Effective assessment of glaucoma progression could facilitate timely interventions and improve prognosis. This systematic review aims to evaluate the use of machine learning (ML) in the detection and prediction of longitudinal glaucoma progression.Methods: An online search was conducted on 31.12.2022, and relevant studies were identified. Outcomes included ML maximum sensitivity, specificity and area under the curve (MSSAUC) (mean (range)).Results: Of the 577 records initially identified, 40 studies with over 156 000 eyes were included. Overall, 30 studies included traditional ML methods, and 13 studies included representational methods. 28 studies used supervised ML, whilst 12 studies used unsupervised ML. 27 studies performed classification, and 16 studies included regression analysis. 11 studies evaluated structural glaucoma data, such as retinal nerve fibre layer thickness. Six studies detected glaucoma progression, with pooled MSSAUC of 68.9% (36.9–86.0), 80.5% (49.0–94.0) and 0.80 (0.60–0.91). Five studies predicted glaucoma progression, with pooled MSSAUC of 84.9% (81.0–93.0), 73.5% (59.0–91.7) and 0.82 (0.71–0.90). 23 studies evaluated functional visual field data. 10 studies detected glaucoma progression, with pooled MSSAUC of 74.8% (3.8–95.0), 94.3% (90.0–98.1) and 0.89 (0.82–0.94). Four studies predicted glaucoma progression, with pooled MSSAUC of 52.2% (20.0–72.0), 72.3% (49.0–95.0) and 0.73 (0.44–0.86). Eight studies combined structural and functional data. Two studies detected glaucoma progression and six studies predicted glaucoma progression, with pooled MSSAUC of 66.6% (44.2–83.7), 90.0% (85.0–100%) and 0.79 (0.61–0.88).Conclusions: ML detection and prediction of longitudinal glaucoma progression is highly accurate. However, there is significant heterogeneity in ML methodologies. Standardization is needed for robust evidence of the clinical utility of ML.

Longitudinal Evaluation of Biomechanical Indices in Fellow Eyes of Patients With Keratoconus Classified as Having Very Asymmetric Ectasia With Normal Topography.

To evaluate the biomechanical longitudinal variability and progression of tomographically normal fellow eyes of patients with keratoconus. Of 513 patients with keratoconus, 30 patients with tomographically normal fellow eyes were included in this study. Tomographic and biomechanical parameters of the Pentacam and Corvis ST (Oculus Optikgeräte GmbH) were analyzed in multiple follow-up examinations, including the ABCD grading, Belin/Ambrósio Enhanced Ectasia total deviation index (BAD-D), Corvis Biomechanical Index (CBI), Corvis Biomechanical Factor (CBiF), and Tomographic and Biomechanical Index (TBI). A mixed regression model was applied. The results were compared to a healthy control group (n = 17) and a keratoconus group (n = 20). Within a maximum observation period of 3.3 years, no fellow eye (0%) showed a progression to tomographically evident keratoconus. No significant change in tomographic or biomechanical parameters was detected over the study period. The indices BAD-D, CBI, CbiF, and TBI exhibited a certain variability over time, whereas the tomographic ABC parameters and maximum keratometry barely changed. This was also shown in the control group and for all parameters in the keratoconus group, except the TBI. During the observation period none of the normal fellow eyes progressed to tomographically detectable keratoconus. However, biomechanical parameters CBI, CbiF, and TBI showed pathological values in 43.3% of eyes and certain variability. Subsequent studies with a longer observation period are warranted to confirm the biomechanical trends seen in this study and to rate the ability of single measurements to diagnose early keratoconus. [J Refract Surg. 2024;40(1):e48-e56.].

Delayed Spontaneous Closure of a Full Thickness Myopic Macular Hole with Good Visual Recovery

Purpose: To present the longitudinal progression of a myopic macular hole with eventual closure and excellent visual recovery over a decade after initial full-thickness hole formation. Methods: The patient was monitored using time-domain and spectral-domain optical coherence tomography images over 16 years. Results: A 68-year-old man with high myopia was referred for surgical evaluation of a full-thickness macular hole and retinal detachment of his left eye, which were repaired. At initial presentation, the fellow eye demonstrated a lamellar hole, which eventually also progressed to become a full-thickness macular hole. The patient subsequently declined surgery and was observed semiannually over the course of 16 years. At 10 years following initial injury, the full-thickness macular hole closed spontaneously. The visual recovery was excellent with an acuity of 20/25. Conclusion: Although surgical intervention remains the mainstay of treatment for macular holes, patients who are not surgical candidates may still have good visual and anatomic outcomes even long after initial hole formation. Lamellar hole epiretinal proliferation material is frequently seen in myopic full-thickness macular holes and may be associated with eventual delayed hole closure due to their slow progression.

Progressive white matter degeneration in patients with spinocerebellar ataxia type 2.

Spinocerebellar ataxia type 2 (SCA2) is a progressive neurodegenerative disorder characterized by cerebellar atrophy. However, studies to elucidate the longitudinal progression of the neuropathology are limited. We sought to identify brain macrostructural and microstructural alterations in patients with SCA2 using fixel-based analysis (FBA) to better understand its distribution patterns and progression. We enrolled 9 patients with SCA2 and 16 age- and gender-matched controls. Longitudinal clinical and imaging data were collected at baseline, and 3.5 years later. Fiber density (FD), fiber-bundle cross-section (FC), and a combination of FD and FC (FDC) were calculated. The paired t-test was used to examine longitudinal differences. The associations between fixel-based metrics and clinical variables were explored in SCA2 patients. At baseline, patients with SCA2 displayed multiple white matter tracts with significantly decreased FD, FC, and FDC in the corticospinal tract, cerebellar peduncles, brainstem, corpus callosum, thalamus, striatum, and prefrontal cortex, compared to controls. Over time, many of these macrostructural and microstructural alterations progressed, manifesting lower FD, FC, and FDC in corticospinal tract, middle cerebellar peduncle, brainstem, striatum, fornix, and cingulum. No significant brain white matter alterations were found in the healthy controls over time. There was no association between the FBA-derived metrics and clinical variables in SCA2. This study provides evidence of brain macrostructural and microstructural alterations and of progression over time in SCA2. The FBA-derived metrics may serve as potential biomarkers of SCA2 progression.