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Shan, Guogen, Xinlin Lu, Zhigang Li, Jessica Z. K. Caldwell, Charles Bernick, and Jeffrey Cummings. "ADSS: A Composite Score to Detect Disease Progression in Alzheimer’s Disease." Journal of Alzheimer's Disease Reports 8, no. 1 (2024): 307–16. http://dx.doi.org/10.3233/adr-230043.
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Background: Composite scores have been increasingly used in trials for Alzheimer’s disease (AD) to detect disease progression, such as the AD Composite Score (ADCOMS) in the lecanemab trial. Objective: To develop a new composite score to improve the prediction of outcome change. Methods: We proposed to develop a new composite score based on the statistical model in the ADCOMS, by removing duplicated sub-scales and adding the model selection in the partial least squares (PLS) regression. Results: The new AD composite Score with variable Selection (ADSS) includes 7 cognitive sub-scales. ADSS can increase the sensitivity to detect disease progression as compared to the existing total scores, which leads to smaller sample sizes using the ADSS in trial designs. Conclusions: ADSS can be utilized in AD trials to improve the success rate of drug development with a high sensitivity to detect disease progression in early stages.
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Roussanov, Bisser V., Jeremy M. G. Taylor, and Janis V. Giorgi. "Calculation and use of an HIV-1 disease progression score." AIDS 14, no. 17 (2000): 2715–22. http://dx.doi.org/10.1097/00002030-200012010-00011.
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Pihlstrøm, Lasse, Kristina Rebekka Morset, Espen Grimstad, Valeria Vitelli, and Mathias Toft. "A cumulative genetic risk score predicts progression in Parkinson's disease." Movement Disorders 31, no. 4 (2016): 487–90. http://dx.doi.org/10.1002/mds.26505.
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Ungaro, R., R. Jordan, C. Yzet, et al. "P240 CDEIS score of 2 is optimal cut-off associated with lower risk of disease progression in early Crohn’s disease: Data from the CALM study." Journal of Crohn's and Colitis 14, Supplement_1 (2020): S264—S266. http://dx.doi.org/10.1093/ecco-jcc/jjz203.369.
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Abstract Background The optimal endoscopic target in early Crohn’s disease (CD) that limits long-term disease complications is unknown. Methods We analysed medical records from patients who had follow-up data since the end of CALM. Patients with Crohn’s disease endoscopic index of severity (CDEIS) scores at the end of CALM were included. The primary outcome was a composite of major adverse outcomes reflecting CD progression: new internal fistula/abscess, stricture, perianal fistula/abscess, CD hospitalisation, or CD surgery since the end of CALM. We compared median CDEIS and per cent improvement from baseline CDEIS. Youden index analysis was used to identify optimal CDEIS cut-off score associated with CD progression. Kaplan–Meier and Cox regression methods were used to compare rates of progression by different CDEIS targets. Multivariable models were adjusted for age, prior surgery, and stricturing behaviour. Results 110 patients with median age 28 (IQR 22–38) years, disease duration 0.2 (0.1–0.5) years, and median follow up of 3.1 (1.9–4.4) years were included. Eleven per cent had a history of stricture, 5.5% history of surgery, and 52% were originally in the tight control arm of the CALM study. Median CDEIS score at end of CALM was 3 (0–5.4) and 32 (29%) patients had disease progression. Baseline median CDEIS score was similar between those with and without progression [10.9 (7.5–15.5) vs. 11.9 (8–17.5)]. Median CDEIS score at the end of CALM was higher among those with progression [1.3 (0–5.1) vs. 4.9 (3–9.1), p < 0.001)]. Patients within higher quartiles of CDEIS score had higher rates of progression over time (Figure 1). Patients without disease progression had a greater median decrease in CDEIS score from baseline to end of CALM [90% (60–100%) vs. 50% (30–80%), p < 0.001]. The optimal CDEIS score cut-off was 2 with sensitivity 84%, specificity 60% and NPV 90% for progression. Patients with CDEIS ≤ 2 had less progression over time compared with patients with > 50% improvement from baseline CDEIS (not reaching CDEIS ≤ 2) and those not meeting either endpoint (Figure 2). On adjusted analysis, CDEIS score ≤ 2 was associated with a decreased risk of progression (aHR 0.23, 95% CI 0.09–0.56). Conclusion In early CD, a CDEIS score ≤ 2 is optimal cut-off associated with a lower risk of disease progression.
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Moore, Ursula, Marni Jacobs, Meredith K. James, et al. "Assessment of disease progression in dysferlinopathy." Neurology 92, no. 5 (2019): e461-e474. http://dx.doi.org/10.1212/wnl.0000000000006858.
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ObjectiveTo assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year.MethodsOne hundred ninety-three patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, and 1-year assessments included adapted North Star Ambulatory Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6-minute walk test (6MWT), Brooke scale, Jebsen test, manual muscle testing, and hand-held dynamometry. Patients also completed the ACTIVLIM questionnaire. Change in each measure over 6 months and 1 year was calculated and compared between disease severity (ambulant [mild, moderate, or severe based on a-NSAA score] or nonambulant [unable to complete a 10-meter walk]) and clinical diagnosis.ResultsThe functional a-NSAA test was the most sensitive to deterioration for ambulant patients overall. The a-NSAA score was the most sensitive test in the mild and moderate groups, while the 6MWT was most sensitive in the severe group. The 10-meter walk test was the only test showing significant change across all ambulant severity groups. In nonambulant patients, the MFM domain 3, wrist flexion strength, and pinch grip were most sensitive. Progression rates did not differ by clinical diagnosis. Power calculations determined that 46 moderately affected patients are required to determine clinical effectiveness for a hypothetical 1-year clinical trial based on the a-NSAA as a clinical endpoint.ConclusionCertain functional outcome measures can detect changes over 6 months and 1 year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials.ClinicalTrials.gov identifier:NCT01676077.
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Shi, Manman, Yan Ouyang, Mingxin Yang, et al. "IgA Nephropathy Susceptibility Loci and Disease Progression." Clinical Journal of the American Society of Nephrology 13, no. 9 (2018): 1330–38. http://dx.doi.org/10.2215/cjn.13701217.
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Background and objectivesAt least 20 susceptibility loci of IgA nephropathy have been identified by genome-wide association studies to date. Whether these loci were associated with disease progression is unclear.Design, setting, participants, & measurementsWe enrolled 613 adult patients with IgA nephropathy for a follow-up of ≥12 months. All 20 IgA nephropathy susceptibility loci were selected and their tag single nucleotide polymorphisms (SNPs) were genotyped. After strict quality control, 16 SNPs and 517 patients with IgA nephropathy were eligible for subsequent analysis. Progression was defined as ESKD or 50% decrease in eGFR. A stepwise Cox regression analysis of all SNPs on Akaike information criterion was performed to select the best model.ResultsA four-SNP model, rs11150612 (ITGAM-ITGAX), rs7634389 (ST6GAL1), rs2412971 (HORMAD2), and rs2856717 (HLA-DQ/DR), was selected as the best predictive model. The genetic risk score calculated on the basis of the four SNPs was independently associated with disease progression before (hazard ratio [HR], 1.65; 95% confidence interval [95% CI], 1.29 to 2.12) and after adjustment by a recently reported clinical model (HR, 1.29; 95% CI, 1.03 to 1.62) or clinical–pathologic model (HR, 1.35; 95% CI, 1.03 to 1.77). Compared with low genetic risk, patients with middle genetic risk had a 2.12-fold (95% CI, 1.33 to 3.40) increase of progression risk, whereas patients with high genetic risk had 3.61-fold (95% CI, 2.00 to 6.52) progression risk increase. In addition, incorporation of genetic risk score could potentially increase discrimination of the clinical model (c-statistic increase from 0.83 to 0.86) or the clinical–pathologic model (c-statistic increase from 0.82 to 0.85) in predicting 5-year progression risk.ConclusionsThe four-SNP genetic risk score was independently associated with IgA nephropathy progression and could enhance the performance of clinical and clinical–pathologic risk models.
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Jönsson, Linus, Milana Ivkovic, Ron Handels, et al. "OP142 Progression Analysis Versus Traditional Methods To Quantify Slowing Of Disease Progression In Alzheimer’s Disease." International Journal of Technology Assessment in Health Care 39, S1 (2023): S42. http://dx.doi.org/10.1017/s0266462323001435.
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IntroductionNew statistical methodology, known as progression models for repeated measures (PMRM), can estimate the slowing of progression (percentage slowing or time delay) of Alzheimer’s disease from trial data on disease-modifying therapies. We compared the PMRM methodology with mixed models for repeated measures (MMRM) and Cox time-to-event analysis on simulated trial data with respect to their power and interpretability of estimates.MethodsTwo novel models were included: PMRM (estimating slowing of progression and allowing different rates across visits) and proportional-slowing PMRM. Clinical Dementia Rating (CDR) Sum of Boxes score and progression to dementia as assessed by CDR global score were the primary outcomes for MMRM/PMRM and the Cox model, respectively. Subject-level placebo arm trajectories were jointly simulated based on estimated CDR mean trajectories and joint temporal correlation structure of 538 amyloid-positive patients with mild cognitive impairment who met typical disease-modifying trial inclusion criteria from the Alzheimer’s Disease Neuroimaging Initiative study. Active arm trajectories were simulated to show an average 20 percent slowing of disease progression, compared with placebo, at each visit. We conducted 1,000 simulations across multiple scenarios, varying the number of patients per arm (200 to 700) and clinical trial duration (18 to 36 months).ResultsThe power of PMRM models was greater than that of MMRM, and much greater than that of the Cox model whose power never exceeded 45 percent. PMRM models accurately estimated the underlying treatment effect (median 20% slowed progression, which translated to a delay in progression of 5 and 7 months at trial durations of 24 and 36 months, respectively), unlike quantifications of the MMRM (median estimated 25% reduction in decline), and the Cox model (median estimated hazard ratio of 0.9).ConclusionsFor disease-modifying therapies, PMRM estimates may have a more intuitive clinical interpretation in terms of delayed progression than MMRM or Cox models and enable a description of the amount of time spent in less severe disease stages. Among all the methods studied, PMRM offered the best combination of interpretability and power.
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Viticchi, Giovanna, Lorenzo Falsetti, Laura Buratti, et al. "Framingham risk score can predict cognitive decline progression in Alzheimer's disease." Neurobiology of Aging 36, no. 11 (2015): 2940–45. http://dx.doi.org/10.1016/j.neurobiolaging.2015.07.023.
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Ravindran, J., C. Cavill, C. Balakrishnan, S. M. Jones, E. Korendowych, and N. J. McHugh. "A modified sharp score demonstrates disease progression in established psoriatic arthritis." Arthritis Care & Research 62, no. 1 (2010): 86–91. http://dx.doi.org/10.1002/acr.20018.
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Kataoka, Hiroshi, and Kazuma Sugie. "Association between Fatigue and Hoehn-Yahr Staging in Parkinson’s Disease: Eight-Year Follow-Up Study." Neurology International 13, no. 2 (2021): 224–31. http://dx.doi.org/10.3390/neurolint13020023.
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The severity of Parkinson’s disease (PD) is developed by multifactorial factors. Falls can worsen disease severity. We previously found that frontal assessment battery (FAB) score was associated with a higher risk of future falls. This eight-year follow-up study aimed to verify whether factors including low FAB score can be the risk of PD progression based on the Hoehn and Yahr scale. In total, 95 patients were initially enrolled in this research and 45 were included in the final follow-up. Then, the cohort was classified into patients with and without disease progression, defined by upgrade of Hoehn-Yahr stage. Differences in clinical characteristics between patients with disease progression and those without were evaluated using the Mann–Whitney U test. Eighteen independent variables were evaluated via a univariate logistic regression analysis. Of the 45 patients enrolled, 32 had disease progression and 13 had no progression. Age (p = 0.033), BFI score (p = 0.003), Zung self-rating depression (p = 0.011), and anxiety scale (p = 0.026) were significantly increased in patients who had disease progression than those with no disease progression. On multivariate logistic regression analysis, brief fatigue inventory (BFI) score (OR = 1.048, p = 0.045, 95% CI = 1.001–1.098) was significantly related to disease progression. All BFI subscores related to general fatigue. Fatigue could predict the progression of motor dysfunction severity over a longitudinal duration in patients with PD with disease progression, having declining physical and mental fatigue.
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Preziosa, Paolo, Elisabetta Pagani, Alessandro Meani, et al. "Slowly Expanding Lesions Predict 9-Year Multiple Sclerosis Disease Progression." Neurology - Neuroimmunology Neuroinflammation 9, no. 2 (2022): e1139. http://dx.doi.org/10.1212/nxi.0000000000001139.
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Background and ObjectivesChronic active lesions contribute to multiple sclerosis (MS) severity, but their association with long-term disease progression has not been evaluated yet. White matter (WM) lesions showing linear expansion over time on serial T1- and T2-weighted scans (i.e., slowly expanding lesions [SELs]) have been proposed as a marker of chronic inflammation. In this study, we assessed whether SEL burden and microstructural abnormalities were associated with Expanded Disability Status Scale (EDSS) score worsening and secondary progressive (SP) conversion at 9.1-year follow-up in patients with relapsing-remitting (RR) MS.MethodsIn 52 patients with RRMS, SELs were identified among WM lesions by linearly fitting the Jacobian of the nonlinear deformation field between time points obtained combining 3T brain T1- and T2-weighted scans acquired at baseline and months 6, 12, and 24. Logistic regression analysis was applied to investigate the associations of SEL number, volume, magnetization transfer ratio (MTR), and T1-weighted signal intensity with disability worsening (i.e., EDSS score increase) and SP conversion after a median follow-up of 9.1 years.ResultsAt follow-up, 20/52 (38%) patients with MS showed EDSS score worsening; 13/52 (25%) showed SP conversion. A higher baseline EDSS score (for each point higher: OR = 3.15 [95% CI = 1.61; 8.38], p = 0.003), a higher proportion of SELs among baseline lesions (for each % increase: OR = 1.22 [1.04; 1.58], p = 0.04), and lower baseline MTR values of SELs (for each % higher: OR = 0.66 [0.41; 0.92], p = 0.033) were significant independent predictors of EDSS score worsening at follow-up (C-index = 0.892). A higher baseline EDSS score (for each point higher: OR = 6.37 [1.98; 20.53], p = 0.002) and lower baseline MTR values of SELs (for each % higher: OR = 0.48 [0.25; 0.89], p = 0.02) independently predicted SPMS conversion (C-index = 0.947).DiscussionThe proportion of SELs is associated with MS progression after 9 years. More severe SEL microstructural abnormalities independently predict EDSS score worsening and SPMS conversion. The quantification of SEL burden and damage using T1-, T2-weighted, and MTR sequences may identify patients with RRMS at a higher risk of long-term disability progression and SPMS conversion.Classification of EvidenceThis study provides Class III evidence that in patients with RRMS starting treatment with natalizumab or fingolimod, the proportion of SELs on brain MRI was associated with EDSS score worsening and SPMS conversion at 9-year follow-up.
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Wang, Linbo, Wei Cheng, Edmund T. Rolls, et al. "Association of specific biotypes in patients with Parkinson disease and disease progression." Neurology 95, no. 11 (2020): e1445-e1460. http://dx.doi.org/10.1212/wnl.0000000000010498.
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ObjectiveTo identify biotypes in patients with newly diagnosed Parkinson disease (PD) and to test whether these biotypes could explain interindividual differences in longitudinal progression.MethodsIn this longitudinal analysis, we use a data-driven approach clustering PD patients from the Parkinson's Progression Markers Initiative (n = 314, age 61.0 ± 9.5, years 34.1% female, 5 years of follow-up). Voxel-level neuroanatomic features were estimated with deformation-based morphometry (DBM) of T1-weighted MRI. Voxels with deformation values that were significantly correlated (p < 0.01) with clinical scores (Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale Parts I–III and total score, tremor score, and postural instability and gait difficulty score) at baseline were selected. Then, these neuroanatomic features were subjected to hierarchical cluster analysis. Changes in the longitudinal progression and neuroanatomic pattern were compared between different biotypes.ResultsTwo neuroanatomic biotypes were identified: biotype 1 (n = 114) with subcortical brain volumes smaller than heathy controls and biotype 2 (n = 200) with subcortical brain volumes larger than heathy controls. Biotype 1 had more severe motor impairment, autonomic dysfunction, and much worse REM sleep behavior disorder than biotype 2 at baseline. Although disease durations at the initial visit and follow-up were similar between biotypes, patients with PD with smaller subcortical brain volume had poorer prognosis, with more rapid decline in several clinical domains and in dopamine functional neuroimaging over an average of 5 years.ConclusionRobust neuroanatomic biotypes exist in PD with distinct clinical and neuroanatomic patterns. These biotypes can be detected at diagnosis and predict the course of longitudinal progression, which should benefit trial design and evaluation.
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Swanson, Gregory P., Steven Stone, Lauren Lenz, and Todd Cohen. "Ability of cell-cycle progression score to predict risk for progression to metastatic disease and disease-specific mortality in prostate cancer patients after prostatectomy." Journal of Clinical Oncology 38, no. 15_suppl (2020): 5524. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.5524.
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5524 Background: Prostate cancer treatment aims to prevent metastatic disease (METS) and disease-specific mortality (DSM). A major challenge is to identify those at highest risk so additional intervention can be initiated earlier when it has a better chance of success. Pathologic parameters alone have limited ability to predict METS and DSM, but data suggests biomarkers can improve risk discrimination. Methods: Eligible patients had: (1) prostate cancer treated with radical prostatectomy (RP; 1988-1995); (2) available tissue for cell-cycle progression (CCP) testing that resulted in a valid score; (3) preoperative prostate-specific antigen (PSA); (4) no neoadjuvant therapy; and (5) clinical follow-up (N = 360). Cancer of the prostate risk assessment post-surgical (CAPRA-S) was combined with CCP into a combined cell-cycle risk score (CCR = 0.38 × CAPRA-S + 0.57 × CCP). Results: Median follow-up was 23.5 years for patients alive at last follow-up. Overall, 11% (41/360) developed METS and 9% (33/360) had DSM. CCP score added significant information to CAPRA-S when predicting METS (p = 0.001) and DSM (p = 0.001). CCR score was also a significant predictor of METS and DSM (p-values < 1×10−8). CCP and CCR scores were prognostic of METS in patients with rising post-RP PSA. Of patients with biochemical recurrence (BCR), 25% (41/163) developed METS. CAPRA-S alone was predictive of these events (p = 0.01) but was significantly improved with the addition of CCP (Hazard Ratio [HR] = 1.69 [95% Confidence Interval (CI) 1.13, 2.52], p = 0.014). CCR was also highly prognostic (HR = 1.56 [95% CI 1.20, 2.03], p = 0.001). CCR score discriminated risk of METS both post-RP and after post-RP BCR (Table). Conclusions: Overall, the CCR score significantly predicted METS and DSM in prostate cancer post-RP and was also highly prognostic in those with a post-RP rising PSA. It is therefore a useful tool for determining who is at greatest risk of treatment failure and may benefit from earlier intervention. [Table: see text]
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Koc, G. H., M. R. Kok, J. Luime, et al. "OP0065 THE DETERMINANTS OF RADIOGRAPHIC PROGRESSION IN EARLY PSA PATIENTS." Annals of the Rheumatic Diseases 82, Suppl 1 (2023): 44.2–45. http://dx.doi.org/10.1136/annrheumdis-2023-eular.5638.
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BackgroundPsoriatic arthritis (PsA) is inflammatory arthritis associated with a progressive erosive disease which had been reported in more than one-half of patients with PsA and is often associated with functional impairment [1]. Despite advances in diagnosis and therapy, radiographic structural damage is still prevalent in PsA. To shed light on this topic, we studied which clinical characteristics determine radiographic progression using conventional radiography.ObjectivesOur aim is to assess baseline clinical parameters as determinants for radiographic progression in early PsA patients at 2-year follow-up.MethodsThe study population consisted of 358 PsA patients from the DEPAR study which consists of PsA patients who were newly diagnosed from 11 centers in the Netherlands. Radiographic progression was measured with the modified Total Sharp Score(mTSS). The proportion of patients with radiographic progression was defined as a change in(ΔmTSS)>1.97(the smallest detectable change) over 2 years of follow-up. Baseline clinical parameters comparisons between groups at diagnosis were made by Student’s t-test, chi-squared test, ANCOVA(age, gender baseline CRP and baseline mTSS were used as confounders). All clinical data are observed, without imputation; except for the mTSS values, which were imputed using the linear interpolation approach.ResultsOf the 358 early PsA patients, change in mTSS(mean(S.D.) was found 1.23(5.21), and 42 were in the radiographic progression group at follow-up 2-year(12%). At diagnosis, the mean age of the progression group was older than the non-progression group(57 ± 14 vs 50 ± 14). Patients who had a radiographic progression in 2 years had significantly higher median scores in mTSS(22, IQR =4-48 vs 0, IQR =0-2) and in joint space narrowing score(JSN)(13, IQR =1-23 vs 0, IQR = 0-1) at diagnosis. The erosion score in progressors followed poorer results compared to non-progressors but there was no significance. In addition, the patients with progressive mTSS had a significantly higher prevalence of erosive disease at baseline(57% versus 18%). The progression group had higher swollen joint counts (median(IQR)) but was no difference in statistics. However, the percentage of the presence of swollen joints was significantly greater in the progression group at baseline(93% vs 78%)(Figure 1). Baseline CRP levels were higher in progressions than non-progressions, but there was no difference between groups as a continuous measure(12.3(18.4) vs 8.5(13.6)). Furthermore, the progression group had a significantly higher percentage of patients with CRP levels of more than 1 mg/dl(88% vs. 74%). Meanwhile, DAPSA, ESR, and the baseline presence of dactylitis/enthesitis did not differ between the groups. We also observed a difference in initial treatments between progressors and non-progressors.ConclusionAccording to this real-world longitudinal cohort, early PsA patients have low radiographic progressions with the current treatment protocols. Baseline clinical determinants for radiographic progression at follow-up 2 years are older age, swollen joints, erosive disease, JSN score, and baseline CRP levels (>1 mg/dl).Reference[1]Gladman DD, Brockbank J: Psoriatic arthritis. Expert Opin Investig Drugs 2000, 9:1511-1522.Table 1.Baseline clinical parameters for radiographic progressionNon-progression(n=316)Progression(n=42)Agea50 (14)57 (11)Gender (Female)(%)50%52%Symptom durationb10 (4-27)11 (4-35)Swollen joint countb2 (1-5)3 (2-5)Swollen joint count (y/n)(%)78%93%Tender joint countb4 (2-8)4 (1-8)Tender joint count (y/n) (%)89%83%CRPa8.50 (13.61)12.28 (18.4)CRP* (%)74%88%ESRb10 (5-26)16 (8-40)DAPSAa19.3 (10.57)18.81 (9.55)Enthesitis (y/n)(%)44%50%ΔmTSSb0 (0-0)3 (2-5)mTSSb0 (0-2)22 (4-48)JSNb0 (0-1)13 (1-23)Erosion scoreb0 (0-1)11 (1-21)Erosive disease (y/n) ° (%)18%57%amean (S.D)bmedian(IQR)*CRP level >1mg/dl at baseline°Erosion score >1 in three separate jointsFigure 1.Cumulative probability plots for radiographic progressionA: All study populationB: Stratified according to the presence of SJCAcknowledgements:NIL.Disclosure of InterestsNone Declared.
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Markusse, Iris M., Linda Dirven, Marianne van den Broek, et al. "A Multibiomarker Disease Activity Score for Rheumatoid Arthritis Predicts Radiographic Joint Damage in the BeSt Study." Journal of Rheumatology 41, no. 11 (2014): 2114–19. http://dx.doi.org/10.3899/jrheum.131412.
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Objective.To determine whether a multibiomarker disease activity (MBDA) score predicts radiographic damage progression in the subsequent year in patients with early rheumatoid arthritis.Methods.There were 180 serum samples available in the BeSt study (trial numbers NTR262, NTR 265): 91 at baseline (84 with radiographs available) and 89 at 1-year followup (81 with radiographs available). Radiographs were assessed using the Sharp/van der Heijde Score (SvdH). Twelve serum biomarkers were measured to determine MBDA scores using a validated algorithm. Receiver-operating curves and Poisson regression analyses were performed, with Disease Activity Score (DAS) and MBDA score as independent variables, and radiographic progression as dependent variable.Results.At baseline, MBDA scores discriminated more between patients who developed radiographic progression (increase in SvdH ≥ 5 points) and patients who did not [area under the curve (AUC) 0.767, 95% CI 0.639–0.896] than did DAS (AUC 0.521, 95% CI 0.358–0.684). At 1 year, MBDA score had an AUC of 0.691 (95% CI 0.453–0.929) and DAS had an AUC of 0.649 (95% CI 0.417–0.880). Adjusted for anticitrullinated protein antibody status and DAS, higher MBDA scores were associated with an increased risk for SvdH progression [relative risk (RR) 1.039, 95% CI 1.018–1.059 for baseline MBDA score; 1.037, 95% CI 1.009–1.065 for Year 1 MBDA score]. Categorized high MBDA scores were also correlated with SvdH progression (RR for high MBDA score at baseline 3.7; low or moderate MBDA score as reference). At 1 year, high MBDA score gave a RR of 4.6 compared to low MBDA score.Conclusion.MBDA scores predict radiographic damage progression at baseline and during disease course.
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Lipshitz, Jay, Sewanti Limaye, and Dilip Patel. "Leukocyte Alkaline Phosphatase Score as a Marker of Severity and Progression of Myelodysplastic Syndrome." Blood 110, no. 11 (2007): 4625. http://dx.doi.org/10.1182/blood.v110.11.4625.4625.
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Abstract Leukocyte Alkaline Phosphatase (LAP) Score is valuable in the work-up of certain hematological diseases. Most notably, the score is decreased in Chronic Myelogenous Leukemia and Paraoxysmal Nocturnal Hemaglobinurea but increased in leukemoid reaction to infection and Polycythemia Vera. Last year we reported the LAP scores of 14 patients with Myelodysplastic Syndrome (MDS). Our results showed that patients with less than 5% bone marrow blasts had significantly higher LAP scores than patients with 5–19% bone marrow blasts. We raised the possibility that LAP scores decrease as MDS progresses (Blood, Nov 2006; 108: 4865). In the present study we attempt to further evaluate the utility of LAP in MDS. In addition to our original cohort, bone marrow aspirate results and LAP scores were reviewed from 14 more patients with MDS, for a total of 28 patients. We again assessed the relationship of LAP to bone marrow blast percentage. Furthermore, we recorded a second LAP score, taken at a later date, from 16 of the 28 patients. For those patients with two LAP scores we compared the trend of LAP score to the interval activity of MDS, using transfusion requirement, complete blood cell count (CBC) and clinical assessment as markers of disease activity. In our analysis of LAP score relative to bone marrow blast percentage we again found a significant difference between patients with less than 5% blasts (n=8) and those with 5% to19% blasts (n=20). Patients with less than 5% blasts had significantly higher LAP scores (90.25 ± 18.27) than those with 5 to19% blasts (44.35 ± 52.09) (p<0.0048) (see charts 1 and 2). In our analysis of LAP score in relation to disease progression we found that among patients for whom LAP score decreased, 42.9% (3/7) had disease progression. In patients whose LAP score increased, 11.1% (1/9) had disease progression (p<0.2615) (chart 3). Overall, our results confirm that LAP scores do tend to be lower in patients with more severe disease, as assessed by bone marrow blast percentage. However, although a trend was observed toward change in LAP score correlating with disease activity this was not statistically significant, and larger prospective studies are necessary to assess whether LAP is an accurate marker of MDS progression. Chart 1: LAP scores of patients 1 through 8 with bone marrow blasts less than 5% (mean 90.25, median 96) Chart 2: LAP scores for patients 1 through 20 with bone marrow blasts of 5% to 19% (mean 44.35, median 30) Chart 1: LAP scores of patients 1 through 8 with bone marrow blasts less than 5% (mean 90.25, median 96) . / Chart 2: LAP scores for patients 1 through 20 with bone marrow blasts of 5% to 19% (mean 44.35, median 30) Chart 3: Percent of patients with disease progression among those with decrease in LAP score (white) and those with increase in LAP score (gray) (p<0.2615). Chart 3: Percent of patients with disease progression among those with decrease in LAP score (white) and those with increase in LAP score (gray) (p<0.2615).
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Scelsi, Marzia A., Raiyan R. Khan, Marco Lorenzi, et al. "Genetic study of multimodal imaging Alzheimer’s disease progression score implicates novel loci." Brain 141, no. 7 (2018): 2167–80. http://dx.doi.org/10.1093/brain/awy141.
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EPSTEIN, JONATHAN I., CHARLES R. POUND, ALAN W. PARTIN, and PATRICK C. WALSH. "DISEASE PROGRESSION FOLLOWING RADICAL PROSTATECTOMY IN MEN WITH GLEASON SCORE 7 TUMOR." Journal of Urology 160, no. 1 (1998): 97–101. http://dx.doi.org/10.1016/s0022-5347(01)63045-3.
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Rossetti, Heidi C., C. Munro Cullum, Linda S. Hynan, and Laura H. Lacritz. "The CERAD Neuropsychologic Battery Total Score and the Progression of Alzheimer Disease." Alzheimer Disease & Associated Disorders 24, no. 2 (2010): 138–42. http://dx.doi.org/10.1097/wad.0b013e3181b76415.
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Migliorelli, Carolina, Meritxell Gómez-Martinez, Paula Subías-Beltrán, et al. "Multidimensional Biomechanics-Based Score to Assess Disease Progression in Duchenne Muscular Dystrophy." Sensors 23, no. 2 (2023): 831. http://dx.doi.org/10.3390/s23020831.
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(1) Background: Duchenne (DMD) is a rare neuromuscular disease that progressively weakens muscles, which severely impairs gait capacity. The Six Minute-Walk Test (6MWT), which is commonly used to evaluate and monitor the disease’s evolution, presents significant variability due to extrinsic factors such as patient motivation, fatigue, and learning effects. Therefore, there is a clear need for the establishment of precise clinical endpoints to measure patient mobility. (2) Methods: A novel score (6M+ and 2M+) is proposed, which is derived from the use of a new portable monitoring system capable of carrying out a complete gait analysis. The system includes several biomechanical sensors: a heart rate band, inertial measurement units, electromyography shorts, and plantar pressure insoles. The scores were obtained by processing the sensor signals and via gaussian-mixture clustering. (3) Results: The 6M+ and 2M+ scores were evaluated against the North Star Ambulatory Assessment (NSAA), the gold-standard for measuring DMD, and six- and two-minute distances. The 6M+ and 2M+ tests led to superior distances when tested against the NSAA. The 6M+ test and the 2M+ test in particular were the most correlated with age, suggesting that these scores better characterize the gait regressions in DMD. Additionally, the 2M+ test demonstrated an accuracy and stability similar to the 6M+ test. (4) Conclusions: The novel monitoring system described herein exhibited good usability with respect to functional testing in a clinical environment and demonstrated an improvement in the objectivity and reliability of monitoring the evolution of neuromuscular diseases.
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Bergamaschi, Roberto, Silvana Quaglini, Eleonora Tavazzi, et al. "Immunomodulatory therapies delay disease progression in multiple sclerosis." Multiple Sclerosis Journal 22, no. 13 (2016): 1732–40. http://dx.doi.org/10.1177/1352458512445941.
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Background: Few studies have analysed long-term effects of immunomodulatory disease modifying drugs (DMDs). Objective: Assessment of the efficacy of DMDs on long-term evolution of multiple sclerosis, using a Bayesian approach to overcome methodological problems related to open-label studies. Methods: MS patients from three different Italian multiple sclerosis centres were divided into subgroups according to the presence of treatment in their disease history before the endpoint, which was represented by secondary progression. Patients were stratified on the basis of the risk score BREMS (Bayesian risk estimate for multiple sclerosis), which is able to predict the unfavourable long-term evolution of MS at an early stage. Results: We analysed data from 1178 patients with a relapsing form of multiple sclerosis at onset and at least 10 years of disease duration, treated (59%) or untreated with DMDs. The risk of secondary progression was significantly lower in patients treated with DMDs, regardless of the initial prognosis predicted by BREMS. Conclusions: DMDs significantly reduce the risk of multiple sclerosis progression both in patients with initial high-risk and patients with initial low-risk. These findings reinforce the role of DMDs in modifying the natural course of the disease, suggesting that they have a positive effect not only on the inflammatory but also on the neurodegenerative process. The study also confirms the capability of the BREMS score to predict MS evolution.
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Ham, Young Rok, Eu Jin Lee, Hae Ri Kim, et al. "Ultrasound Renal Score to Predict the Renal Disease Prognosis in Patients with Diabetic Kidney Disease: An Investigative Study." Diagnostics 13, no. 3 (2023): 515. http://dx.doi.org/10.3390/diagnostics13030515.
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Renal disease associated with type 2 diabetes mellitus (T2DM) has become the leading cause of chronic kidney disease (CKD). Renal ultrasonography is an imaging examination required in the work-up of renal disease. This study aimed to identify the differences in renal ultrasonographic findings between patients with and without DM, and to evaluate the relationship between renal ultrasound findings and renal prognosis in patients with DM. A total of 252 patients who underwent renal ultrasonography at Chungnam National University Hospital were included. Kidney disease progression was defined as a ≥10% decline in the annual estimated glomerular filtration rate (eGFR), which, in this paper, is referred to as ΔeGFR/year, or the initiation of renal replacement therapy after follow-up. The renal scoring system was evaluated by summing up the following items: the value of renal parenchymal echogenicity (0: normal; 1: mildly increased; and 2: increased) and the shape of the cortical margin (0: normal and 1: irregular; right kidney length/height (RH—0 or 1), mean cortical thickness/renal length/height (CKH—0 or 1), and cortical thickness/parenchymal thickness (CK/PK—0 or 1) based on the median: 0—above median, and 1—below median). Patients with DM had thicker renal PKH than those without, despite having lower eGFRs (0.91 ± 0.15, 0.86 ± 0.14, p = 0.006). In the progression group, the renal scores were significantly higher than those from the non-progression group. In the multivariate logistic regression analysis, the higher renal scores, presence of DM, and younger age were independently predicted for renal disease progression after adjusting for confounding variables, such as the presence of hypertension, serum hemoglobin and albumin levels, and UPCR. In conclusion, patients with high renal scores were significantly associated with renal disease progression. Our results suggest that renal ultrasonography at the time of diagnosis provides useful prognostic information in patients with kidney disease.
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Jehn, Lutz B., Ulrich Costabel, Eda Boerner, et al. "Serum KL-6 as a Biomarker of Progression at Any Time in Fibrotic Interstitial Lung Disease." Journal of Clinical Medicine 12, no. 3 (2023): 1173. http://dx.doi.org/10.3390/jcm12031173.
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The development of a progressive phenotype of interstitial lung disease (ILD) is still unpredictable. Whereas tools to predict mortality in ILD exist, scores to predict disease progression are missing. The aim of this study was to investigate whether baseline serum KL-6 as an established marker to assess disease activity in ILD, alone or in combination with clinical variables, could improve stratification of ILD patients according to progression risk at any time. Consecutive patients with fibrotic ILD, followed at our institution between 2008 and 2015, were investigated. Disease progression was defined as relative decline of ≥10% in forced vital capacity (FVC) or ≥15% in diffusing capacity of the lung for carbon monoxide (DLco)% from baseline at any time. Serum KL-6 was measured using an automated immunoassay (Fujirebio Europe, Gent, Belgium). A stepwise logistic regression was performed to select variables to be included in the score. A total of 205 patients (49% idiopathic pulmonary fibrosis (IPF), 51% fibrotic nonspecific interstitial pneumonia (NSIP)) were included, of them 113 (55%) developed disease progression during follow up. Male gender (G) and serum KL-6 strata (K) were significant predictors of progression at regression analysis and were included in the GK score. A threshold of 2 GK score points was best for discriminating patients at high risk versus low risk to develop disease progression at any time. Serum KL-6 concentration, alone or combined in a simple score with gender, allows an effective stratification of ILD patients for risk of disease progression at any time.
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Kang, Min Kyoung, Jung Hwan Shin, Tae Jung Kim, Ji Sung Lee, Byung-Woo Yoon, and Sang-Bae Ko. "Use of proton pump inhibitor may be associated with progression of cerebral small vessel disease." PLOS ONE 17, no. 12 (2022): e0279257. http://dx.doi.org/10.1371/journal.pone.0279257.
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Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases. However, recent studies have shown that chronic PPI use is associated with the progression of endothelial senescence and cerebrovascular diseases. We hypothesized that PPI users might be vulnerable to fast progression of cerebral small vessel disease (SVD) with cumulative effects. Four hundred and eleven patients, who underwent brain magnetic resonance imaging, more than twice between January 2010 and December 2016 were screened. Patients aged < 50 years, and those who had concomitant diseases that might affect the progression of cerebral SVD were excluded. Baseline characteristics were collected. We evaluated the severity of SVD using the Fazekas score, the number of cerebral microbleeds (CMBs), and assessed the progression of SVD or CMBs based on the cumulative dose of PPIs. Among the included patients (N = 137), 39 were PPI ever-users. Univariate Cox regression analysis showed that PPI use was independently associated with the progression of Fazekas score only in the deep white matter hyperintensities (WMH) (hazard ratio [HR] 2.891, 95% confidence interval [CI] 1.210–6.906, P = 0.017). In multivariate Cox regression analysis, long-term PPI use was associated with a progression of Fazekas score in the deep WMH (HR 3.453, 95% CI 1.027–9.475, P = 0.045). However, PPI use was not associated with the progression of CMB. The present study results suggest that long-term use of PPIs is associated with the progression of deep cerebral WMH. Further research is needed using a large number of patients to validate this relationship.
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Pavicic, Mirko, Kirk Overmyer, Attiq ur Rehman, Piet Jones, Daniel Jacobson, and Kristiina Himanen. "Image-Based Methods to Score Fungal Pathogen Symptom Progression and Severity in Excised Arabidopsis Leaves." Plants 10, no. 1 (2021): 158. http://dx.doi.org/10.3390/plants10010158.
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Image-based symptom scoring of plant diseases is a powerful tool for associating disease resistance with plant genotypes. Advancements in technology have enabled new imaging and image processing strategies for statistical analysis of time-course experiments. There are several tools available for analyzing symptoms on leaves and fruits of crop plants, but only a few are available for the model plant Arabidopsis thaliana (Arabidopsis). Arabidopsis and the model fungus Botrytis cinerea (Botrytis) comprise a potent model pathosystem for the identification of signaling pathways conferring immunity against this broad host-range necrotrophic fungus. Here, we present two strategies to assess severity and symptom progression of Botrytis infection over time in Arabidopsis leaves. Thus, a pixel classification strategy using color hue values from red-green-blue (RGB) images and a random forest algorithm was used to establish necrotic, chlorotic, and healthy leaf areas. Secondly, using chlorophyll fluorescence (ChlFl) imaging, the maximum quantum yield of photosystem II (Fv/Fm) was determined to define diseased areas and their proportion per total leaf area. Both RGB and ChlFl imaging strategies were employed to track disease progression over time. This has provided a robust and sensitive method for detecting sensitive or resistant genetic backgrounds. A full methodological workflow, from plant culture to data analysis, is described.
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Chenniappan, Raghavi, Hanumanthappa Nandeesha, Shivanand Kattimani, and Nandakumar Dalavaikodihalli Nanjaiah. "Interleukin-17 and Interleukin-10 Association with Disease Progression in Schizophrenia." Annals of Neurosciences 27, no. 1 (2020): 24–28. http://dx.doi.org/10.1177/0972753120929565.
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Background: Alteration in cytokine levels are known to be involved in the pathogenesis of schizophrenia. Objectives: To estimate the serum levels of interleukin-17 (IL-17) and interleukin-10 (IL-10) and their association with disease progression in schizophrenia. Methods: A total of 67 schizophrenia cases were enrolled in the present study. IL-17 and IL-10 were estimated by enzyme-linked immunosorbent assay. Positive and Negative Syndrome Scale (PANSS) was used to evaluate disease severity. Results: IL-17 was positively correlated with positive symptom score ( r = 0.256, p = .036), general psychopathology score ( r = 0.255, p = .038) and total score ( r = 0.273, p = .025) in schizophrenia. IL-17 and IL-10 were significantly increased in schizophrenia cases with PANSS more than 85 compared to those with 71–85. Conclusion: IL-17 and IL-10 are associated with disease severity in schizophrenia but are not good markers for predicting the disease progression.
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Segala, Francesco Vladimiro, Emanuele Rando, Federica Salvati, et al. "Anakinra in hospitalized COVID-19 patients guided by baseline soluble urokinase plasminogen receptor plasma levels: A real world, retrospective cohort study." PLOS ONE 18, no. 4 (2023): e0273202. http://dx.doi.org/10.1371/journal.pone.0273202.
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Background In patients with COVID-19 and baseline soluble urokinase plasminogen receptor plasma (suPAR) levels ≥ 6ng/mL, early administration of anakinra, a recombinant interleukin-1 receptor antagonist, may prevent disease progression and death. In case of suPAR testing unavailability, the Severe COvid Prediction Estimate (SCOPE) score may be used as an alternative in guiding treatment decisions. Methods We conducted a monocenter, retrospective cohort study, including patients with SARS-CoV2 infection and respiratory failure. Patients treated with anakinra (anakinra group, AG) were compared to two control groups of patients who did not receive anakinra, respectively with ≥ 6 ng/mL (CG1) and < 6 ng/mL (CG2) baseline suPAR levels. Controls were manually paired by age, sex, date of admission and vaccination status and, for patients with high baseline suPAR, propensity score weighting for receiving anakinra was applied. Primary endpoint of the study was disease progression at day 14 from admission, as defined by patient distribution on a simplified version of the 11-point World Health Organization Clinical Progression Scale (WHO-CPS). Results Between July, 2021 and January, 2022, 153 patients were included, among which 56 were treated with off-label anakinra, 49 retrospectively fulfilled prescriptive criteria for anakinra and were assigned to CG1, and 48 presented with suPAR levels < 6ng/mL and were assigned to CG2. At day 14, when comparing to CG1, patients who received anakinra had significantly reduced odds of progressing towards worse clinical outcome both in ordinal regression analysis (OR 0.25, 95% CI 0.11–0.54, p<0.001) and in propensity-adjusted multiple logistic regression analysis (OR 0.32, 95% CI 0.12–0.82, p = 0.021) thus controlling for a wide number of covariates. Sensitivities of baseline suPAR and SCOPE score in predicting progression towards severe disease or death at day 14 were similar (83% vs 100%, p = 0.59). Conclusion This real-word, retrospective cohort study confirmed the safety and the efficacy of suPAR-guided, early use of anakinra in hospitalized COVID-19 patients with respiratory failure.
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Umemoto, George, Shinsuke Fujioka, Yasuyuki Iwasa, et al. "Impact of Progression of Parkinson’s Disease on Swallowing Ability and Oral Environment." Parkinson's Disease 2021 (April 23, 2021): 1–6. http://dx.doi.org/10.1155/2021/5571556.
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This study investigated the impact of the severity and treatment of Parkinson’s disease (PD) on the swallowing ability and oral environment of patients. Swallowing dysfunction increases the aspiration risk and may lead to poor oral health among patients with PD. We investigated the influences of PD progression and drug treatment on the swallowing ability and oral environment using simple noninvasive screening measurements. We recruited 87 patients with PD (mean age, 71.9 ± 8.0 years; mean Hoehn and Yahr score, 2.9 ± 0.9). The PD condition was assessed in each patient using the unified Parkinson’s disease rating scale (UPDRS) part III, diet type and oropharyngeal function using the swallowing disturbances questionnaire (SDQ), maximum bite force (MBF), tongue pressure (TP), and oral bacterial count (OBC). Levodopa equivalent daily dose (LEDD) was also calculated for 56 participants. Based on an SDQ score of ≥11, 29.5% of patients were dysphagic, but almost all were still on a regular diet. The SDQ score was positively correlated with disease duration (rho = 0.228, p = 0.047 ) and UPDRS part III score (rho = 0.307, p = 0.007 ) but was negatively correlated with OBC (rho = −0.289, p = 0.012 ). OBC was significantly higher among patients with an SDQ score of <11 (nondysphagic) ( p = 0.01 ), and the SDQ score was lower in patients with higher OBC requiring professional oral care ( p = 0.03 ). However, OBC was also negatively correlated with LEDD (rho = −0.411, p = 0.004 ). These results indicated low self-awareness of dysphagia among the participants and an association between dysphagia and PD progression. Moreover, the oral environment could have deteriorated with swallowing dysfunction. Patients and clinicians should be aware that higher LEDD can increase xerostomia and associated deficits in oral health.
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Xie, Linjun, Keke Hou, Huayan Xu, et al. "Chest CT features and progression of patients with coronavirus disease 2019." British Journal of Radiology 93, no. 1116 (2020): 20200219. http://dx.doi.org/10.1259/bjr.20200219.
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Objectives: Coronavirus disease 2019 (COVID-19) is a major public health emergency. It poses a grave threat to human life and health. The purpose of the study is to investigate the chest CT findings and progression of the disease observed in COVID-19 patients. Methods: Forty-nine confirmed cases of adult COVID-19 patients with common type, severe and critically severe type were included in this retrospective single-center study. The thin-section chest CT features and progress of the disease were evaluated. The clinical and chest imaging findings of COVID-19 patients with different severity types were compared. The CT severity score and MuLBSTA score (a prediction of mortality risk) were calculated in those patients. Results: Among the 49 patients, 35 patients (71%) were common type and 14 patients (28%) were severe and critically severe type. Nearly all patients (98%) had pure ground-glass opacities (GGO) in CT imaging. Of the severe and critically severe type patients, 86% exhibited GGO with consolidation, in comparison with 54% of the patients with common type. Fibrosis presented in 79% of the severe and critically severe type patients and 43% of the common type patients. The severe and critically severe type patients were significantly more prone to experience five-lobe involvement compared to the common type patients (p = 0.002). The severe and critically severe type patients also had higher CT severity and MuLBSTA scores than the common type patients (5.43 ± 2.38 vs 3.37 ± 2.40, p < 0.001;and 10.21 ± 3.83 vs 4.63 ± 3.43, p < 0.001, respectively). MuLBSTA score was positively correlated with admittance to the intensive care unit (p = 0.005, r = 0.351). Nineteen patients underwent three times CT scan. The interval between first and second CT scan was 4[4,8] days, second and third was 3[2,4] days. There were greater improvements in the third CT follow-up findings compared to the second (p = 0.002). Conclusions: The severe and critically severe type patients often experienced more severe lung lesions, including GGO with consolidation. The CT severity score and MuLBSTA score may be helpful for the assessment of COVID-19 severity and progression. Advances in knowledge: Chest CT has the value of evaluated radiographical features of COVID-19 and allow for dynamic observation of the disease progression. Considering coagulation disorder of COVID-19, MuLBSTA score may need to be updated to increase new understanding of COVID-19.
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Tsai, Tsung-Ying, Pai-Feng Hsu, Cheng-Hsueh Wu, et al. "Association between Coronary Artery Plaque Progression and Liver Fibrosis Biomarkers in Population with Low Calcium Scores." Nutrients 14, no. 15 (2022): 3163. http://dx.doi.org/10.3390/nu14153163.
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Background: The severity of nonalcoholic fatty liver disease (NAFLD) has been found to be associated with atherosclerosis burden. However, whether liver fibrosis scores can be used to predict atherosclerosis progression, especially for patients with low calcium scores, remains undetermined. Methods: A total of 165 subjects who underwent repeated coronary computed tomography angiography (CCTA) and had low calcium scores (<100) were enrolled. The segment stenosis score (SSS) from the CCTA was measured, and the association between SSS progression and biochemical parameters was analyzed in addition to liver fibrosis scores, including nonalcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), and Forns score. Results: When compared with those without plaque at baseline (SSS = 0), subjects with plaque had higher blood pressure, higher coronary artery calcium (CAC) scores, and higher liver fibrosis scores, including Forns score, Fib-4, and NFS. During the medium follow-up interval of 24.7 months, 60 (39.4%) patients displayed SSS progression, while the remaining 105 (63.6%) patients showed no CAD progression. In a multivariate analysis, being male having a high diastolic blood pressure (DBP), and having a high NFS liver fibrosis score were independently associated with the odds ratio for SSS progression. Conclusions: Higher baseline blood pressure and liver fibrosis markers are associated with the presence of coronary artery disease (CAD) plaques in subjects in early CAD stages. For disease progression, the male gender, DBP, and NFS appear to be independently associated with coronary atherosclerosis plaque progression in subjects with low calcium scores.
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Chen, Szu-Ju, Yu-Chiao Chi, Chang-Han Ho, Wei-Shiung Yang, and Chin-Hsien Lin. "Plasma Lipopolysaccharide-Binding Protein Reflects Risk and Progression of Parkinson’s Disease." Journal of Parkinson's Disease 11, no. 3 (2021): 1129–39. http://dx.doi.org/10.3233/jpd-212574.
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Background: Lipopolysaccharide-binding protein (LBP) presents bacterial endotoxin, lipopolysaccharides, to cellular surface pattern receptors for immune responses in the gut-brain axis of Parkinson’s disease (PD). Objective: We investigated whether plasma LBP levels were associated with PD severity and progression. Methods: This study included 397 participants (248 PD patients and 149 controls). We measured participants’ plasma levels of LBP and pro-inflammatory cytokines, including TNF-α, IL-6, andIL-17A. PD patients underwent motor and cognition evaluations at baseline and at a mean follow-up interval of 4.7±2.3 years. We assessed the progression of motor and cognition symptoms based on changes in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III motor score and Mini-Mental State Examination (MMSE) score, respectively. Results: Plasma LBP levels were lower in PD patients than controls (9.08±2.91 vs. 10.10±3.00μg/ml, p < 0.01). A multiple logistic regression model with adjustment for age, sex, and plasma cytokine levels revealed that reduced plasma LBP levels were associated with increased PD risk (odds ratio 0.816, [95% CI 0.717–0.929], p = 0.002). Among PD patients, LBP levels were correlated with MDS-UPDRS part III motor score after adjustment for confounders (coefficient = 0.636, p = 0.017), but not with MMSE score. Adjusted Cox regression analysis showed that higher plasma LBP levels associated with faster motor progression (adjusted hazard ratio 1.084 [95% CI 1.011–1.163], p = 0.024) during follow-up. Conclusion: Our results demonstrated that plasma LBP levels reflect risk, motor symptom severity and progression in patients with PD.
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Jedynak, Bruno M., Andrew Lang, Bo Liu, et al. "A computational neurodegenerative disease progression score: Method and results with the Alzheimer's disease neuroimaging initiative cohort." NeuroImage 63, no. 3 (2012): 1478–86. http://dx.doi.org/10.1016/j.neuroimage.2012.07.059.
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Yavuz, Yasemin. "Are the Beck depression inventory score, SF 36 score and progression of the disease changing with education in chronic kidney disease patients?" Annals of Medical Research 25, no. 4 (2018): 723. http://dx.doi.org/10.5455/annalsmedres.2018.05.091.
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Yang, Yongbo, Jian Wang, Qun Liang, et al. "PHACTR1 is associated with disease progression in Chinese Moyamoya disease." PeerJ 8 (May 5, 2020): e8841. http://dx.doi.org/10.7717/peerj.8841.
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Moyamoya disease (MMD) is a progressive stenosis at the terminal portion of internal carotid artery and frequently occurs in East Asian countries. The etiology of MMD is still largely unknown. We performed a case-control design with whole-exome sequencing analysis on 31 sporadic MMD patients and 10 normal controls with matched age and gender. Patients clinically diagnosed with MMD was determined by digital subtraction angiography (DSA). Twelve predisposing mutations on seven genes associated with the sporadic MMD patients of Chinese ancestry (CCER2, HLA-DRB1, NSD-1, PDGFRB, PHACTR1, POGLUT1, and RNF213) were identified, of which eight single nucleotide variants (SNVs) were deleterious with CADD PHRED scaled score > 15. Sanger sequencing of nine cases with disease progression and 22 stable MMD cases validated that SNV (c.13185159G>T, p.V265L) on PHACTR1 was highly associated with the disease progression of MMD. Finally, we knocked down the expression of PHACTR1 by transfection with siRNA and measured the cell survival of human coronary artery endothelial cell (HCAEC) cells. PHACTR1 silence reduced the cell survival of HCAEC cells under serum starvation cultural condition. Together, these data identify novel predisposing mutations associated with MMD and reveal a requirement for PHACTR1 in mediating cell survival of endothelial cells.
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Oefelein, Michael G. "RE: DISEASE PROGRESSION FOLLOWING RADICAL PROSTATECTOMY IN MEN WITH GLEASON SCORE 7 TUMOR." Journal of Urology 161, no. 1 (1999): 231. http://dx.doi.org/10.1016/s0022-5347(01)62114-1.
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Serednicka, K., A. E. Smyth, C. M. Black, and C. P. Denton. "Using a self-reported functional score to assess disease progression in systemic sclerosis." Rheumatology 46, no. 7 (2007): 1107–10. http://dx.doi.org/10.1093/rheumatology/kel432.
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Harrison, Madaline B., Scott A. Wylie, Robert C. Frysinger, et al. "UPDRS activity of daily living score as a marker of Parkinson's disease progression." Movement Disorders 24, no. 2 (2009): 224–30. http://dx.doi.org/10.1002/mds.22335.
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Rodríguez-Rodríguez, E., P. Sánchez-Juan, J. L. Vázquez-Higuera, et al. "Genetic risk score predicting accelerated progression from mild cognitive impairment to Alzheimer’s disease." Journal of Neural Transmission 120, no. 5 (2012): 807–12. http://dx.doi.org/10.1007/s00702-012-0920-x.
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Gao, Yang, Hong-Liang Zhang, Meiying Xin, et al. "Serum Folate Correlates with Severity of Guillain-Barré Syndrome and Predicts Disease Progression." BioMed Research International 2018 (June 14, 2018): 1–5. http://dx.doi.org/10.1155/2018/5703279.
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The aim of this study was to determine the associations between serum folate level and the clinical course and severity of Guillain-Barré syndrome (GBS). We retrospectively enrolled 112 pairs of GBS patients and age- and sex-matched healthy controls with measured serum folate levels. On admission, 21 (18.9%) GBS patients had folate deficiency, of which only two were female patients. Patients with normal folate levels had a shorter disease progression than those with folate deficiency (median progression duration: 6 versus 13 days, p < 0.001). Serum folate levels on admission were correlated with progression duration and Medical Research Council (MRC) sum score in the upper limbs at nadir (r = -0.261, p = 0.005; r = -0.208, p = 0.03) but not with the duration of hospital stay or GBS disability score (p > 0.05). Logistic regression analysis revealed that normal folate levels on admission were an independent predictor of faster GBS progression, along with younger age, intact deep sensation, and a lower MRC sum score on admission. These results show that serum folate levels are correlated with the progression duration and severity of GBS. Further studies are required to confirm the potential of folate level as a biomarker for GBS prognosis.
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Rossi, Silvia, Fabio Buttari, Valeria Studer, et al. "The (AAT)n repeat of the cannabinoid CB1 receptor gene influences disease progression in relapsing multiple sclerosis." Multiple Sclerosis Journal 17, no. 3 (2010): 281–88. http://dx.doi.org/10.1177/1352458510388680.
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Background: Genetic and pharmacological inactivation of cannabinoid CB1 receptors (CB1Rs) exacerbates disease course in experimental autoimmune encephalomyelitis, suggesting that CB1Rs might play a role in the neurodegenerative damage associated with multiple sclerosis (MS). Objectives: To see whether CNR1 gene polymorphism could influence disease progression in relapsing–remitting MS. Methods: The genotype of 350 patients for the number of AAT repeats was characterized and correlation studies were performed with measures of disease severity and progression. Results: MS patients with the homozygous genotype for long AAT repeats in the CNR1 gene had more severe disease and higher risk of progression. These subjects had significantly higher scores on both the progression index and the MS severity scale. Furthermore, the percentage of patients with MS functional composite score progression or Bayesian Risk Estimate for MS (BREMS) score ≥2 (considered at very high risk of secondary progression) was significantly higher in the AAT long group than in the short group, while the frequency of patients with BREMS score ≤−0.63 (very likely to remain progression-free) was not significantly different between the two groups, although lower in the long group. Finally, the frequency of patients prescribed a second-line treatment was significantly higher among subjects of the AAT long group, providing a further, indirect indication of higher disease severity. Conclusions: The results of the present investigation point to CB1R as an important modulator of disease severity in relapsing MS subjects.
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Hasimoglu, Yasemin G., Xiqun Chen, Rachit Bakshi, Michael A. Schwarzschild, and Eric A. Macklin. "Does Serum Urate Change as Parkinson’s Disease Progresses?" Journal of Parkinson's Disease 10, no. 4 (2020): 1571–76. http://dx.doi.org/10.3233/jpd-202064.
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Higher serum urate concentration is associated with decreased risk of Parkinson’s disease (PD) as well as slower disease progression, but its relationship with severity of PD remains unclear. This study investigated whether changes in serum urate concentration over 5 years were associated with disease progression assessed by MDS-UPDRS Part III score, Hoehn and Yahr stage, or DaTscan imaging. Average serum urate concentration was stable over time and change in serum urate concentration did not correlate with worsening of measures of PD progression. These results suggest that serum urate concentration is not a monitoring biomarker of PD progression in early stages.
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Stopsack, Konrad H., Charles A. Whittaker, Travis A. Gerke, et al. "Aneuploidy drives lethal progression in prostate cancer." Proceedings of the National Academy of Sciences 116, no. 23 (2019): 11390–95. http://dx.doi.org/10.1073/pnas.1902645116.
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Aneuploidy, defined as chromosome gains and losses, is a hallmark of cancer. However, compared with other tumor types, extensive aneuploidy is relatively rare in prostate cancer. Thus, whether numerical chromosome aberrations dictate disease progression in prostate cancer patients is not known. Here, we report the development of a method based on whole-transcriptome profiling that allowed us to identify chromosome-arm gains and losses in 333 primary prostate tumors. In two independent cohorts (n = 404) followed prospectively for metastases and prostate cancer-specific death for a median of 15 years, increasing extent of tumor aneuploidy as predicted from the tumor transcriptome was strongly associated with higher risk of lethal disease. The 23% of patients whose tumors had five or more predicted chromosome-arm alterations had 5.3 times higher odds of lethal cancer (95% confidence interval, 2.2 to 13.1) than those with the same Gleason score and no predicted aneuploidy. Aneuploidy was associated with lethality even among men with high-risk Gleason score 8-to-10 tumors. These results point to a key role of aneuploidy in driving aggressive disease in primary prostate cancer.
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Sharad, Shashwat, Zsã³fia Sztupinszki, Zoltan Szallasi, et al. "PMEPA1 gene isoforms to indicate disease progression in solid tumors." Journal of Clinical Oncology 37, no. 15_suppl (2019): e16580-e16580. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e16580.
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e16580 Background: Dysfuncitons of androgen and TGF-β signaling play important roles in prostate tumorigenesis. PMEPA1 gene has been defined as an androgen and TGF-β responsive gene which inhibits androgen and TGF-β signaling via negative feed-back loops. Our previous data has established that PMEPA1 distinct isoforms ( PMEPA1-a and PMEPA1-b) with disparities within N-terminus protein sequences navigate different androgen/TGF-β signaling regulations. In this study, the roles of PMEPA1 isoforms in disease progressions were investigated in solid tumors of prostate (CaP), breast, lung and colon. Methods: RNA seq data from total 2479 solid tumor samples in the TCGA dataset were used to study the correlation between expressions of PMEPA1 isoforms and disease progression including Gleason score, pathology stages, progression free survival rate (PFS) and overall survival rate (OS). The cohort is composed of 482 prostate, 1049 breast, 499 lung and 449 colon cancer patients. Results: In CaP, the TCGA data analysis showed that lower transcript level of PMEPA1-b isoform associated with higher Gleason scores and lower progression free survival rate (PFS) (P = 0.014) and worse overall survival rate (OS) (P < 0.01). The ratio of mRNA levels of PMEPA1-a versus PMEPA-b indicated higher Gleason score, lower PFS rate (P = 0.0063) and worse OS rate (P = 0.0042). In contrast, higher expression of both PMEPA1-a and PMEPA- b associated with lower PFS (P = 0.023 and 0.028, respectively) in breast cancer. And the enhanced ratio of PMEPA1-a/ b was also found to indicate lower PFS (P = 0.016) and worse OS (P = 0.016) in breast cancer. Similarly, the increased transcript levels of PMEPA1-a and PMEPA1-b isoforms significantly associated with lower PFS and worse OS rates in lung and colon cancer. The expression of PMEPA1 isoforms was not found to associate with pathology stages of diseases. Conclusions: Our data establish the biomarker potential of PMEPA1 gene isoforms ( a and b) indicating more aggressive disease progressions in 4 solid tumors, further underscoring the PMEPA1 isoform specific biological functions to differentiate regulation of androgen and TGF-β signaling in cancer cells.
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Kister, Ilya, and Orhun H. Kantarci. "Multiple Sclerosis Severity Score: Concept and applications." Multiple Sclerosis Journal 26, no. 5 (2020): 548–53. http://dx.doi.org/10.1177/1352458519880125.
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Severity score represents disease duration–adjusted mean rank of disability in multiple sclerosis (MS) patients from the reference population. This measure allows one to compare the relative rates of disease progression among patients, patient subgroups, and across epochs, which opens up new question of what accounts for the observed differences in severity, and can be used to assess correlation between disease severity and clinical, radiologic, immunologic, genetic, and environmental variables of interest. Severity score can also prove useful for developing prognostic tools in MS. This article discusses the diverse applications of severity score concept in MS research, and (re)introduces Herbert’s proposal of severity-based MS classification in the context of variability of MS severity.
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Gautam, Sachin, Rahul Kumar, Dharam Pal Bhadoria, et al. "Clinical profile of hospitalised moderate category COVID-19 patients: Short study from a Tertiary Care Centre in Delhi." Journal of Family Medicine and Primary Care 12, no. 8 (2023): 1644–53. http://dx.doi.org/10.4103/jfmpc.jfmpc_2245_22.
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Background: The clinical profile of hospitalized moderate-category COVID-19 patients has been understudied globally and in India. Aim: The present study was conducted to study the clinical profile and assess the proportions of patients who progressed to severe disease and its predictors among moderate COVID-19 patients. Materials and Methods: In this single-center observational study, 100 moderate-category COVID-19 patients as per Ministry of Health and Family Welfare (MoHFW) criteria of age ≥18 years of either sex, excluding pregnant females from February to November 2021, were studied by analyzing their clinical profiles and assessing Quick Sequential Organ Failure Assessment (qSOFA), National Early Warning Score 2 (NEWS-2), and chest computed-tomography severity score (CTSS) to predict progression to severe disease. Severe disease was defined as per MoHFW criteria. Results: Out of 100 moderate-category COVID-19 patients, progression to severe disease was seen in 11 patients (11%), among which eight patients had expired, three patients were discharged, and the rest of the 89 patients (89%) who did not progress to severe disease were discharged. A higher age (62.2± 19.5 vs 54.8 ± 14.6 years), along with multivariate analysis revealing male sex (1.25 times), chronic kidney disease (2.86 times), leukocytosis (6.10 times), thrombocytopenia (1.04 times), anemia (9.3 times), a higher qSOFA score (3.6 times), and a higher NEWS-2 score on admission (1.56 times) had higher odds of progression to severe disease. A significant correlation (P < .05) of qSOFA score with serum LDH, ferritin, and hs-CRP levels; CT severity score with the serum ferritin, IL-6, and LDH levels; and NEWS-2 with serum LDH, hs-CRP, and ferritin levels were found. Moreover, the NEWS-2 score was found slightly better than qSOFA on receiver operating characteristic (ROC) curve analysis, with an area under the curve of 85.8% and 83.2%, respectively, predicting progression to severe disease. Conclusion: Our study revealed male gender, chronic kidney disease, leukocytosis, anemia, thrombocytopenia, a higher qSOFA and NEWS-2 score on admission, and further, NEWS-2 score better than qSOFA on ROC curve analysis, with an area under the curve of 85.8% and 83.2%, respectively, in predicting severe disease among hospitalized moderate COVID-19 patients.
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Mills, James A., Jeffrey D. Long, Amrita Mohan, Jennifer J. Ware, and Cristina Sampaio. "Cognitive and Motor Norms for Huntington’s Disease." Archives of Clinical Neuropsychology 35, no. 6 (2020): 671–82. http://dx.doi.org/10.1093/arclin/acaa026.
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Abstract Background The progression of Huntington’s disease (HD) for gene-expanded carriers is well-studied. Natural aging effects, however, are not often considered in the evaluation of HD progression. Objective To examine the effects of natural aging for healthy controls and to develop normative curves by age, sex, and education from the distribution of observed scores for the Symbol Digit Modalities Test, Stroop Word Reading Test, Stroop Color Naming Test, Stroop Interference Test, Total Motor Score, and Total Functional Capacity (TFC) from the Unified Huntington’s Disease Rating Scale (UHDRS) along with a composite score. Methods After combining longitudinal REGISTRY and Enroll-HD data, we used quantile regression and natural cubic splines for age to fit models for healthy controls (N = 3,394; N observations = 8,619). Normative curves were estimated for the 0.05, 0.25, 0.50, 0.75, and 0.95 quantiles. Two types of reference curves were considered: unconditional curves were dependent on age alone, whereas conditional curves were dependent on age and other covariates, namely sex and education. Results Conditioning on education was necessary for the Symbol Digit, Stroop Word, Stroop Color, Stroop Interference, and composite UHDRS. Unconditional curves were sufficient for the Total Motor Score. TFC was unique in that the curve was constant over age with its intercept at the maximum score (TFC = 13). For all measures, sex effects were minimal, so conditioning on sex was unwarranted. Conclusions Extreme quantile estimates for each measure can be considered as boundaries for natural aging and scores falling beyond these thresholds are likely the result of disease progression. Normative curves and tables are developed and can serve as references for clinical characterization in HD.
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Brandt, L., H. Schulze-Koops, T. Hügle, M. J. Nissen, H. Paul, and R. Muller. "OP0185 RADIOGRAPHIC PROGRESSION DESPITE PERSISTENT LDA OR REMISSION IS INFLUENCED BY CURRENT SMOKING RATHER THAN THE RESPECTIVE DAS 28 LEVEL, RESULTS OF THE SWISS RHEUMATOID ARTHRITIS REGISTER (SCQM)." Annals of the Rheumatic Diseases 80, Suppl 1 (2021): 112.1–112. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2557.
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Background:The therapeutic aim for rheumatoid arthritis (RA) is to control disease activity and prevent radiographic progression. Various clinical scores are utilized to describe disease activity in RA patients. The DAS28 score can define states of low disease activity (LDA) and remission. Despite achieving LDA or remission, radiographic progression may nevertheless occur. However, the rates and frequency of this occurrence have not been analyzed in detail.Objectives:To describe the frequency and rate of radiographic progression in patients with persistent LDA or remission.Methods:Analysis of RA patients from the SCQM cohort. Persistent LDA or remission were defined as DAS 28 ≤3.2 or <2.6 respectively, at two subsequent follow up time points in the database. We included patients with at least two sets of radiographs within these intervals of LDA and/or remission. Radiographic progression was measured with the Ratingen-score (range 0-190), which describes joint erosions numerically. Repair was defined as an improvement in the Ratingen score >5 points/year and progression as >2 or >5 points change in the Ratingen score within one year.Results:Among 10’141 RA patients, 4’342 episodes of remission occurred in 3’927 patients with 1’776 sets of X rays available within these episodes. Similarly, 8’136 episodes of LDA in 6’765 patients and 2’358 sets of X rays were present within these intervals. For patients in LDA or remission, rates of repair were 5.5% and 4.8%, respectively, while for radiographic progression >5 points in the Ratingen score/year were 10.3% in both groups and for >2 points change of Ratingen score/year were 27.7 and 25.4%, respectively).No differences for demographic factors or measures of disease activity, rheumatoid factor or ACPA were found comparing patients with radiographic progression or non-progression despite LDA or remission at the beginning of the episode of LDA and/or remission.Interestingly, 42.9% of patients in LDA with progression of >5 points in the Ratingen score/year were current smokers vs 29.4% among the non-progressors (X2 = 6.55, p = 0.01). This significant difference vanished when the cut-off for radiographic progression was set at >2 points yearly change in Ratingen score or in patients in remission.Conclusion:Radiographic progression despite LDA or remission are more frequent than expected. No differences in radiographic progression were found comparing LDA and remission suggesting that the goal of LDA is appropriate. Smoking seems to be an independent risk factor for radiographic progression despite LDA. Why the effect of smoking could was not demonstrated in patients in remission, remains unclear.Disclosure of Interests:Lena Brandt: None declared, Hendrik Schulze-Koops: None declared, Thomas Hügle Consultant of: GSK, Abbvie, Pfizer, Jansen, Novartis, Eli Lilly., Michael J. Nissen Consultant of: Abbvie, Celgene, Eli-Lilly, Janssen, Novartis and Pfizer, Hasler paul Consultant of: Abbvie, Lilly, Rudiger Muller Consultant of: AbbVie, Novartis, Grant/research support from: Gebro
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Clancy, Una, Stephen D. J. Makin, Caroline A. McHutchison, et al. "Impact of Small Vessel Disease Progression on Long-term Cognitive and Functional Changes After Stroke." Neurology 98, no. 14 (2022): e1459-e1469. http://dx.doi.org/10.1212/wnl.0000000000200005.
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Background and ObjectivesThe severity of white matter hyperintensities (WMH) at presentation with stroke is associated with poststroke dementia and dependency. However, WMH can decrease or increase after stroke; prediction of cognitive decline is imprecise; and there are few data assessing longitudinal interrelationships among changing WMH, cognition, and function after stroke, despite the clinical importance.MethodsWe recruited patients within 3 months of a minor ischemic stroke, defined as NIH Stroke Scale (NIHSS) score <8 and not expected to result in a modified Rankin Scale (mRS) score >2. Participants repeated MRI at 1 year and cognitive and mRS assessments at 1 and 3 years. We ran longitudinal mixed-effects models assessing change in Addenbrooke’s Cognitive Examination–Revised (ACE-R) and mRS scores. For mRS score, we assessed longitudinal WMH volumes (cube root; percentage intracranial volume [ICV]), adjusting for age, NIHSS score, ACE-R, stroke subtype, and time to assessment. For ACE-R score, we additionally adjusted for ICV, mRS, premorbid IQ, and vascular risk factors. We then used a multivariate model to jointly assess changing cognition/mRS score, adjusted for prognostic variables, using all available data.ResultsWe recruited 264 patients; mean age was 66.9 (SD 11.8) years; 41.7% were female; and median mRS score was 1 (interquartile range 1–2). One year after stroke, normalized WMH volumes were associated more strongly with 1-year ACE-R score (β = −0.259, 95% CI −0.407 to −0.111 more WMH per 1-point ACE-R decrease, p = 0.001) compared to subacute WMH volumes and ACE-R score (β = 0.105, 95% CI −0.265 to 0.054, p = 0.195). Three-year mRS score was associated with 3-year ACE-R score (β = −0.272, 95% CI −0.429 to −0.115, p = 0.001). Combined change in baseline-1-year jointly assessed ACE-R/mRS scores was associated with fluctuating WMH volumes (F = 9.3, p = 0.03).DiscussionAfter stroke, fluctuating WMH mean that 1-year, but not baseline, WMH volumes are associated strongly with contemporaneous cognitive scores. Covarying longitudinal decline in cognition and independence after stroke, central to dementia diagnosis, is associated with increasing WMH volumes.
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Mello, Ricardo Andrade Fernandes de, Melissa Bosi Nonato Mello, Laís Bastos Pessanha, and Ana Paula Alves Fonseca. "Skeletal involvement in Gaucher disease: extent of bone disease, splenic volume, and quality of life." Radiologia Brasileira 54, no. 2 (2021): 71–76. http://dx.doi.org/10.1590/0100-3984.2020.0014.
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Abstract Objective: To investigate the correlations among the extent of bone involvement, splenic volume, and quality of life in patients with Gaucher disease. Materials and Methods: This was a descriptive, prospective cross-sectional study of 18 patients with Gaucher disease who underwent 3-T magnetic resonance imaging of both femurs and the lumbar spine. Semiquantitative analyses were performed on the basis of the bone marrow burden (BMB) score. We looked for linear relationships among the variables splenic volume, quality of life score, and BMB score. Results: We identified a linear relationship between the BMB scores and splenic volume. The quality of life score showed no statistically significant relationship with splenic volume or the BMB score. Conclusion: The linear relationship between the BMB score and the splenic volume indicates that the extent of bone disease is greater in individuals with splenomegaly. No correlation was found between the BMB and quality of life scores, illustrating the insidious and silent progression of Gaucher disease.
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Jedynak, Bruno, Zhou Ye, Andrew Lang, Runze Tang, Pierre Jedynak, and Jerry Prince. "P1-197: The Alzheimer's Disease Progression Score (ADPS) can predict the transition from MCI to Alzheimer's disease." Alzheimer's & Dementia 9 (July 2013): P223. http://dx.doi.org/10.1016/j.jalz.2013.05.420.
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