Predictors Of Clinical Progression Research Articles

Do Tau Deposition and Glucose Metabolism Dissociate in Alzheimer's Disease Trajectory?

Tau aggregation demonstrates close associations with hypometabolism in Alzheimer's disease (AD), although differing pathophysiological processes may underlie their development. To establish whether tau deposition and glucose metabolism have different trajectories in AD progression and evaluate the utility of global measures of these pathological hallmarks in predicting cognitive deficits. 279 participants with amyloid-β (Aβ) status, and T1-weighted MRI scans, were selected from the Alzheimer's Disease Neuroimaging Initiative (http://adni.loni.usc.edu). We created the standard uptake value ratio images using Statistical Parametric Mapping 12 for [18F]AV1451-PET (tau) and [18F]FDG-PET (glucose metabolism) scans. Voxel-wise group and single-subject level SPM analysis evaluated the relationship between global [18F]FDG-PET and [18F]AV1451-PET depending on the Aβ status. Linear models assessed whether tau deposition or glucose metabolism better predicted clinical progression. There was a dissociation between global cerebral glucose hypometabolism and global tau load in amyloid-positive AD and amyloid-negative mild cognitive impairment (MCI) (p > 0.05). Global hypometabolism was only associated with global cortical tau in amyloid-positive MCI. Voxel-level single subject tau load better predicted neuropsychological performance, Alzheimer's disease assessment scale-cognitive (ADAS-Cog) 13 score, and one-year change compared with regional and global hypometabolism. A dissociation between tau pathology and glucose metabolism at a global level in AD could imply that other pathological processes influence glucose metabolism. Furthermore, as tau is a better predictor of clinical progression, these processes may have independent trajectories and require independent consideration in the context of therapeutic interventions.

Long-term functional outcomes in patients undergoing radical nephrectomy for renal cell carcinoma and tumor thrombus.

Up to 15% of patients with locally advanced renal cell carcinoma (RCC) harbors tumor thrombus (TT). In those cases, radical nephrectomy (RN) and thrombectomy represents the standard of care. We assessed the impact of TT on long-term functional and oncological outcomes in a large contemporary cohort. Within a prospective maintained database, 1207 patients undergoing RN for non-metastatic RCC between 2000 and 2021 at a single tertiary centre were identified. Of these, 172 (14%) harbored TT. Multivariable logistic regression analyses evaluated the impact of TT on the risk of postoperative acute kidney injury (AKI). Multivariable Poisson regression analyses estimated the risk of long-term chronic kidney disease (CKD). Kaplan Meier plots estimated disease-free survival and cancer specific survival. Multivariable Cox regression models assessed the main predictors of clinical progression (CP) and cancer specific mortality (CSM). Patients with TT showed lower BMI (24 vs. 26kg/m2) and preoperative Hb (11 vs. 14g/mL; all-p < 0.05). Clinical tumor size was higher in patients with TT (9.6 vs. 6.5cm; p < 0.001). After adjusting for potential confounders, the presence of TT was significantly associated with a higher risk of postoperative AKI (OR 2.03, 95% CI 1.49-3.6; p < 0.001) and long-term CKD (OR: 1.32, 95% CI 1.10-1.58; p < 0.01). Notably, patients with TT showed worse long-term oncological outcomes and TT was a predictor for CP (2.02, CI 95% 1.49-2.73, p < 0.001) and CSM (HR 1.61, CI 95% 1.04-2.49, p < 0.03). The presence of TT in RCC patients represents a key risk factor for worse perioperative, as well as long-term renal function. Specifically, patients with TT harbor a significant and early estimated glomerular filtration rate (eGFR) decrease. However, despite TT patients show a greater eGFR decline after surgery, they retain acceptable renal function, which remains stable over time.

Expanding HIV clinical monitoring: the role of CD4, CD8, and CD4/CD8 ratio in predicting non-AIDS events

While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio <0.3 predicted an increased risk of SNAEs during the next five years (OR 1.63, 95% CI 1.03-2.58). The effect was stronger at a CD4/CD8 ratio cut-off of <0.2 (OR 3.09, 95% CI 1.57-6.07). Additionally, low CD4 count at cut-offs of <500cells/μL predicted an increased risk of clinical events. Among participants with a CD4 count ≥500cells/μL, a CD8 count ≥1500cells/μL or a CD4/CD8 ratio <0.4 predicted increased SNAE risk. Our results support the use of the CD4/CD8 ratio and CD8 count as predictors of clinical progression. Patients with CD4/CD8 ratio <0.3 or CD8 count ≥1500/μL, regardless of their CD4 count, may benefit from closer monitoring and targeted preventive interventions. This work was supported by CIBER (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU; by the Spanish AIDS Research Network (RIS) RD16/0025/0001 project as part of the Plan Nacional R+D+I, and cofinanced by Instituto de Salud Carlos III (ISCIII)- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), ISCIII projects PI18/00154, PI21/00141, and ERDF, "A way to make Europe", ICI20/00058.

#4613 PREVALENCE OF DKD RAPID PROGRESSION IN TYPE 2 DIABETES IN A DEVELOPING COUNTRY AND ITS CLINICAL PREDICTORS: A SINGLE CENTERED RETROSPECTIVE STUDY

Abstract Background and Aims A significant proportion of diabetic kidney patients experience a rapid decline in GFR, leading to ESRD within months. Although there is a large number of studies on DKD, at present, there is a lack of well-controlled long follow-up studies to assess the burden of rapid progression, distinguishing the clinical profile of rapid progressors from non-progressors and its predictors. Identifying independent risk factors that contribute specifically to rapid progression is essential to prevent end-stage renal disease. Here we conducted a retrospective, hospital-based cohort study aimed to assess the prevalence, clinical profile, and clinical predictors for the rapid progression of DKD in type 2 DM. Method Type 2 DKD patients attending tertiary care hospital in South India were involved between January 2018 and 2022. CKD5 and those without minimum 6 months follow-up were excluded. Patients were followed up for 3.5 years. A sustained decline of eGFR &amp;gt;10 mL/1.73 m2/year was defined as rapid progressors. Patients were categorized into rapid and non-rapid progressors. Clinical profiles, micro-macrovascular complications, cardiovascular events, and other risk factors for rapid progression were studied. Data were analyzed using SPSS22 Results In a median follow-up of 3.5 years, 220(61.3%) were rapidly progressed with median eGFR decline 12ml/1.73 m2/year(IQR 8.5-19.3), and 139(38.7%) were non-rapid progressors with median eGFR decline 1.6ml/1.73 m2(IQR-0-3.3).The baseline characteristics were given in Table 1. The presence of hypertension, proteinuria, diabetic retinopathy, and cardiovascular events (p-0.01) was higher in rapid progressors than non-progressors.On logistic regression analysis, independent predictors of rapid progression were proteinuria (OR4.7;95%CI(2.24-9.88); P = .001), diabetic retinopathy(OR 0.24; 95% CI(0.11-0.52); P = .001), and AKI episodes(OR 2.18;95% CI (1.28-3.71); P = .003) (Table 2). Conclusion The majority of type 2 DKD patients in our setting are rapid progressors. The higher degree of baseline proteinuria, presence of diabetic retinopathy, and AKI episodes were found independently associated with clinical predictors of progression.

Boston Remote Assessment for Neurocognitive Health in preclinical AD

AbstractBackgroundThere is a need for cognitive assessments that can be completed remotely on personal devices which are sensitive to the earliest cognitive changes in AD. The Boston Remote Assessment for Neurocognitive Health (BRANCH) is a web‐based assessment including measures which tap into cognitive domains/processes known to decline early in the AD trajectory (e.g., associative memory, pattern separation). Tasks were designed to be intuitive and use stimuli relevant to everyday life. While BRANCH can characterize cognition at a single timepoint, learning curves (collected over 7 daily assessments) provide a unique cognitive variable that may to capture subtle but meaningful AD‐related memory decrements.MethodsParticipants completed three BRANCH tasks (memory for pairs of face‐names, grocery‐prices, and street signs‐digits) daily over 7 days (approximately 12 minutes/day) repeating the same stimuli to capture multi‐day‐learning‐curves (MDLC). Participants included 192 clinically normal older adults enrolled in the Harvard Aging Brain and related studies (mean age = 74.0, 63% female, 87% Caucasian, mean education = 16.6). Participants underwent PET imaging to assess global amyloid‐Aβ (PiB) and entorhinal cortex tau (FTP). Separate mixed models were used to determine whether differences in MDLC (composite performance across the 3 tasks) were associated with Aβ and tau.ResultsControlling for age, sex and education, there was no association between amyloid and BRANCH performance on Day 1 (t = 1.07, p = 0.286). However, higher amyloid was associated with a diminished MDLC (t = ‐4.22, p&lt;0.001; medium effect size between Aβ+/Aβ‐, Cohen’s d = 0.5). Higher entorhinal tau was similarly associated with diminished MDLC (t = ‐3.67, p&lt;0.001); however, those with higher entorhinal tau also exhibited lower Day 1 performance (t = ‐1.99, p = 0.048).ConclusionsRemote, digital testing provides the opportunity to deploy memory paradigms that mimic everyday life by exposing participants to repeated stimuli, such as the same face‐name pairs, over more frequent intervals. Results indicate that diminished MDLCs provide unique information about Aβ and tau‐related cognitive decrements, otherwise unable to be observed with a single timepoint (e.g., Day 1) assessment. We discuss how diminished MDLCs may serve as screening tool, a clinically meaningful outcomes over short timescales, and as a predictor for clinical progression.

Outcomes of a High-Volume Organ Procurement Organization in the Era of Increasing Donation After Circulatory Death.

Introduction: Donation after circulatory death (DCD) is rapidly increasing in the United States. Detailed data outlining the process from referral to organ transplantation is lacking. Project Aims: We sought to quantify differences at each stage along the referral to donation pathway by donor type. Additionally, we examined factors associated with successful DCD organ utilization. Design: This program evaluation analyzed data from a single organ procurement organization in 2018 to assess demographic and clinical predictors of progression through the donation process, including the role of first-person authorization in DCD. Descriptive statistics were examined by donation stage for demographic characteristics using chi-square; univariate and multivariate logistic regression was used to model predictors of utilization and authorization by organ type, respectively. Results: There were 2466 organ donation referrals during 2018, including 575 donations after brainstem death (DBD), 1890 controlled DCD referrals, and 1 uncontrolled DCD referral. Univariate and multivariate logistic regression models highlighted differences in authorization rates by donor type (DCD vs DBD) and by age, race, and ethnicity. Next-of-kin authorization was declined in 23% of first-person authorized potential DCD, highlighting issues related to the role of donor registration in DCD. Pre-mortem heparin administration was predictive of DCD organ utilization; donor age and warm ischemia time of less than 30 min was statistically significantly associated with DCD extra-renal organ utilization. Conclusion: These results provided insight into strategies for increasing authorization and transplantation of organs from DCD donors and identified areas of improvement for process standardization and policy development.

Distinct disease trajectories in frontotemporal dementia-motor neuron disease and behavioural variant frontotemporal dementia: A longitudinal study.

The heterogeneity of cognitive and behavioural disturbances in frontotemporal dementia-motor neuron disease (FTD-MND), and clinical differences between FTD-MND and FTD subtypes, have been illustrated cross-sectionally. This study aimed to examine the FTD-MND disease trajectory by comparing clinical features of FTD-MND and the behavioural variant FTD (bvFTD) longitudinally. Neuropsychological and disease severity assessments were conducted in a cohort of FTD-MND (baseline, n= 42; follow-up, n= 18) and bvFTD (baseline, n= 116; follow-up, n= 111) using a longitudinal, case-control design. Age-, sex-, and education-matched controls (n= 52) were recruited. Predictors of clinical progression were analyzed. Voxel-based morphometry analysis was undertaken to investigate the progression of brain atrophy. At baseline, FTD-MND was characterized by semantic and general cognition deficits, whereas bvFTD had greater behavioural disturbances. General cognition and language deteriorated in FTD-MND when followed longitudinally. Language deficits at baseline predicted cognitive deterioration and disease progression and correlated with progressive atrophy of language regions. Further deterioration in behaviour was evident in bvFTD over time. The rate of disease progression (i.e., general cognition, semantic association, and disease severity) was significantly faster in FTD-MND than in bvFTD. FTD-MND and bvFTD appear to have distinct disease trajectories, with more rapid progression in FTD-MND. Language impairments should be closely monitored in FTD-MND as potential predictors of cognitive deterioration and disease progression.

Neurofilament light levels predict clinical progression and death in multiple system atrophy.

Disease-modifying treatments are currently being trialled in multiple system atrophy. Approaches based solely on clinical measures are challenged by heterogeneity of phenotype and pathogenic complexity. Neurofilament light chain protein has been explored as a reliable biomarker in several neurodegenerative disorders but data on multiple system atrophy have been limited. Therefore, neurofilament light chain is not yet routinely used as an outcome measure in multiple system atrophy. We aimed to comprehensively investigate the role and dynamics of neurofilament light chain in multiple system atrophy combined with cross-sectional and longitudinal clinical and imaging scales and for subject trial selection. In this cohort study, we recruited cross-sectional and longitudinal cases in a multicentre European set-up. Plasma and CSF neurofilament light chain concentrations were measured at baseline from 212 multiple system atrophy cases, annually for a mean period of 2 years in 44 multiple system atrophy patients in conjunction with clinical, neuropsychological and MRI brain assessments. Baseline neurofilament light chain characteristics were compared between groups. Cox regression was used to assess survival; receiver operating characteristic analysis to assess the ability of neurofilament light chain to distinguish between multiple system atrophy patients and healthy controls. Multivariate linear mixed-effects models were used to analyse longitudinal neurofilament light chain changes and correlated with clinical and imaging parameters. Polynomial models were used to determine the differential trajectories of neurofilament light chain in multiple system atrophy. We estimated sample sizes for trials aiming to decrease neurofilament light chain levels. We show that in multiple system atrophy, baseline plasma neurofilament light chain levels were better predictors of clinical progression, survival and degree of brain atrophy than the neurofilament light chain rate of change. Comparative analysis of multiple system atrophy progression over the course of disease, using plasma neurofilament light chain and clinical rating scales, indicated that neurofilament light chain levels rise as the motor symptoms progress, followed by deceleration in advanced stages. Sample size prediction suggested that significantly lower trial participant numbers would be needed to demonstrate treatment effects when incorporating plasma neurofilament light chain values into multiple system atrophy clinical trials in comparison to clinical measures alone. In conclusion, neurofilament light chain correlates with clinical disease severity, progression and prognosis in multiple system atrophy. Combined with clinical and imaging analysis, neurofilament light chain can inform patient stratification and serve as a reliable biomarker of treatment response in future multiple system atrophy trials of putative disease-modifying agents.

Tau as a Biomarker of Neurodegeneration.

Less than 50 years since tau was first isolated from a porcine brain, its detection in femtolitre concentrations in biological fluids is revolutionizing the diagnosis of neurodegenerative diseases. This review highlights the molecular and technological advances that have catapulted tau from obscurity to the forefront of biomarker diagnostics. Comprehensive updates are provided describing the burgeoning clinical applications of tau as a biomarker of neurodegeneration. For the clinician, tau not only enhances diagnostic accuracy, but holds promise as a predictor of clinical progression, phenotype, and response to drug therapy. For patients living with neurodegenerative disorders, characterization of tau dysregulation could provide much-needed clarity to a notoriously murky diagnostic landscape.

Predictive value of CD8+ T cell and CD4/CD8 ratio at two years of successful ART in the risk of AIDS and non-AIDS events.

SummaryBackgroundWhile increased CD8 counts and low CD4/CD8 ratio during treated HIV correlate with immunosenescence, their additional predictive values to identify individuals with HIV at higher risk of clinical events remain controversial.MethodsWe selected treatment-naive individuals initiating ART from ACTG studies 384, 388, A5095, A5142, A5202, and A5257 who had achieved viral suppression at year 2. We examined the effect of CD8+ T cell counts and CD4/CD8 at year 2 on the probability of AIDS and serious non-AIDS events in years 3−7. We used inverse probability weighting methods to address informative censoring, combined with multivariable logistic regression models.FindingsWe analyzed 5133 participants with a median age of 38 years; 959 (19%) were female, pre-ART median CD4 counts were 249 (Q1-Q3 91–372) cell/µL. Compared to participants with CD8 counts between 500/µL and 1499/µL, those with >1500/µL had a higher risk of clinical events during years 3−7 (aOR 1.75; 95%CI 1.33−2.32). CD4/CD8 ratio was not predictive of greater risk of events through year 7. Additional analyses revealed consistent CD8 count effect sizes for the risk of AIDS events and noninfectious non-AIDS events, but opposite effects for the risk of severe infections, which were more frequent among individuals with CD8 counts <500/µL (aOR 1.70; 95%CI 1.09−2.65).InterpretationThe results of this analysis with pooled data from clinical trials support the value of the CD8 count as a predictor of clinical progression. People with very high CD8 counts during suppressive ART might benefit from closer monitoring and may be a target population for novel interventions.FundingThis research was supported by NIH/NIAID awards UM1 AI068634, UM1 AI068636, and UM1 AI106701 and Carlos III Health Institute and FEDER funds (BA21/00017 and BA21/00022).

Baseline predictors of progression of Parkinson\u2019s disease in a sample of Egyptian patients: clinical and biochemical

BackgroundClinical progression of Parkinson’s disease (PD) is highly heterogeneous, and its predictors are generally lacking. Identifying predictors of early disease progression is important for patients’ management and follow-up. The current study aims to identify clinical, neuroimaging and biochemical baseline predictors of motor progression in patients with PD. Forty-five PD patients were assessed at baseline, 6 months and 1 year using MDS-UPDRS total and subscores, Hoehn and Yahr (H&Y), Schwab and England (S&E), International Physical Activity Questionnaire (IPAQ). Baseline New Freezing of Gait Questionnaire (NFOG-Q), Berg Balance Scale (BBS), Ten-Meter Walking Test (10-MWT), and Time Up and Go Test (TUG), Non-Motor Symptoms Scale (NMSS), Beck Depression Inventory (BDI), PD questionnaire 39 (PDQ-39), MRI brain, uric acid, lipid profile and glycated hemoglobin were performed.ResultsSignificant worsening of MDS-UPDRS total, part III scores, H&Y, S&E and IPAQ (p < 0.001) was detected. One-year progression of H&Y and S&E were significantly correlated to disease duration (p = 0.014, p = 0.025, respectively). Progression of H&Y was correlated to baseline TUG (p = 0.035). S&E progression was correlated to baseline MDS-UPDRS total score (rho = 0.478, p = 0.001) and part III (rho = 0.350, p = 0.020), H&Y (rho = 0.401, p = 0.007), PIGD (rho = 0.591, p < 0.001), NFOG-Q (rho = 0.498, p = 0.001), and TUG (rho = 0.565, p = 0.001). Using linear regression, there was no predictors of clinical progression among the used baseline variables.ConclusionDespite the significant motor and physical activity progression over 1 year that was correlated to baseline motor and gait severity, but without predictive value, further similar and longitudinal studies are warranted to detect predictors of early progression and confirm findings.

Cognitive dysfunction and mortality in multiple sclerosis: Long-term retrospective review

Background: Cognitive dysfunction as a predictor of clinical progression and mortality in multiple sclerosis (MS) is still a matter of debate. Objective: The aim of this study was to explore the long-term outcome associated with neuropsychological performance in a cohort of patients with MS. Methods: A series of 408 MS patients had previously undergone a comprehensive neuropsychological assessment and a contemporaneous neurological evaluation (T1). A retrospective review of the clinical records was conducted 102–192 months after T1. Demographic and clinical data regarding the last clinical appointment with EDSS measurement (T2) were collected and the date of the last clinical contact or death (TS) was recorded. Results: This review revealed that cognitive dysfunction (T1) was associated with higher odds of transitioning from relapsing–remitting course to a progressive disease course (adjusted odds ratio (OR) = 2.29, p = 0.043) and higher hazard of death in the total sample (adjusted hazard ratio (HR) = 3.07, p = 0.006) and the progressive disease course subgroup (adjusted HR = 3.68, p = 0.007), even when adjusting for other covariates. Discussion: The study results demonstrate that cognitive dysfunction in MS is predictive of poorer prognosis and mortality.

Associations between Brain Reserve Proxies and Clinical Progression in Alzheimer's Disease Dementia.

The purpose of this study was to investigate whether brain and cognitive reserves were associated with the clinical progression of AD dementia. We included participants with AD dementia from the Alzheimer’s Disease Neuroimaging Initiative, provided they were followed up at least once, and candidate proxies for cognitive (education for early-life reserve and Adult Reading Test for late-life reserve) or brain reserve (intracranial volume [ICV] for early-life reserve and the composite value of [18F] fluorodeoxyglucose positron emission tomography regions of interest (FDG-ROIs) for late-life reserve) were available. The final analysis included 120 participants. Cox proportional hazards model revealed that FDG-ROIs were the only significant predictor of clinical progression. Subgroup analysis revealed a significant association between FDG-ROIs and clinical progression only in the larger ICV group (HR = 0.388, p = 0.028, 95% CI 0.167–0.902). Our preliminary findings suggest that relatively preserved cerebral glucose metabolism might delay further clinical progression in AD dementia, particularly in the greater ICV group. In addition to ICV, cerebral glucose metabolism could play an important role as a late-life brain reserve in the process of neurodegeneration. Distinguishing between early- and late-life reserves, and considering both proxies simultaneously, would provide a wider range of factors associated with the prognosis of AD dementia.

Global longitudinal strain predicts clinical disease progression in stable asymptomatic heart failure patients better than left ventricular ejection fraction

Abstract Background Previous studies have shown that left ventricular (LV) global longitudinal strain (GLS) is a feasible and reliable predictor for outcomes in heart failure (HF) patients with greater accuracy than LV ejection fraction (LVEF). However, these studies rarely included stable or asymptomatic patients. Purpose To assess the predictive value of GLS, as compared to LVEF, in asymptomatic stable HF patients. Methods This is a retrospective study, including patients with HF with reduced and mid-range ejection fraction (HFrEF: LVEF&amp;lt;40%; HFmrEF: LVEF 40–49%) in NYHA I with no history of decompensation within the previous 6 months. All patients underwent comprehensive baseline echocardiographic assessment. The primary endpoint was the composite of cardiovascular death, hospitalization and need for intensification of HF treatment within a 12 month follow-up period. Results Out of 837 patients with LVEF &amp;lt;50% that underwent follow-up in our HF unit between January 2016 and December 2017, 153 patients were included in the study. The mean age was 74 (±10.2) years and 82% were male. The cumulative incidence of HF progression was 17.8%, with a median time to event of 193 days. Death and hospitalization due to HF accounted for three-quarters of the events. The mean LVEF was 40.9% (± 6.96),without significant differences between patients with and without clinical progression (39.5% vs 43%, p=0.093). We did not find significant differences between the two groups, concerning LV and atrial dimensions, as well as mitral inflow, PSAP and tricuspid annular systolic plane excursion (TAPSE). LV GLS was significantly lower (i.e. less negative) in patients that presented clinical progression, that in patients without disease progression (−7.7 vs −12.2, p&amp;lt;0.001). Receiver operating characteristic curve and univariate Cox regression analysis identified GLS as the most accurate predictor for clinical progression among all continuous variables (AUC: 0.809, cut-off: −8.5%, sensitivity: 74.1%, specificity: 89%, HR: 14.78 (95% CI: 6.2–35.1), p&amp;lt;0.001). LVEF predicted HF progression less precisely (AUC: 0.654, cut-off: 42%, sensitivity: 70.4%, specificity: 54%, HR: 2.38 (95% CI: 1.1–5.2), p=0.03). Conclusion In asymptomatic stable HF patients (in NYHA I), LV GLS showed to be a more accurate predictor of clinical disease progression than LVEF. Funding Acknowledgement Type of funding sources: None. Global longitudinal strain (GLS)Receiver operating characteristic (ROC)

Hospitalization for COVID-19 is associated with significant changes in body composition

Background & aimsCOVID-19 is a severe viral infection of the respiratory tract and has become a worldwide pandemic. Months after the initial infection several people report persistent limitations in daily life. Previous studies have identified body composition as a predictor of clinical progression in cases of COVID-19. However, body impedance measurements were limited to baseline and not repeated in serial measurements. In this study we analyzed the impact of a moderate oxygen-dependent COVID-19 infection on body composition during hospitalization.MethodsWe enrolled 12 consecutive patients hospitalized due to an oxygen-dependent SARS-CoV-2 infection. Body impedance analysis was performed within 24 h of admission and repeated on day 3 ± 1 as well as on the day of discharge. Endpoints were any significant changes in body composition.ResultsMedian age of enrolled patients was 70.6 years with a BMI of 30.8 kg/m2. Patients were hospitalized for 14 days. Median oxygen demand was 3 l/min, 2 patients required mechanical ventilation. Body water and fat remained unchanged during the study period. We observed a significant decrease of phase angle (−0.6, p < 0.01) and body cell mass (−2.3%, p < 0.01) with an increase in extracellular mass on day 3. Values returned to baseline along recovery.ConclusionWe found a significant reduction in body cell mass and phase angle during the active infection with slow regression towards hospital discharge. Future studies are needed to clarify if nutrition and training programs during and after COVID-19 might limit these changes and have a positive impact on clinical course and rehabilitation.

Establishment of a nomogram with EMP3 for predicting clinical outcomes in patients with glioma: A bi‐center study

AimTo demonstrate the clinical value of epithelial membrane protein 3 (EMP3) with bioinformatic analysis and clinical data, and then to establish a practical nomogram predictive model with bicenter validation.MethodsThe data from CGGA and TCGA database were used to analyze the expression of EMP3 and its correlation with clinical prognosis. Then, we analyzed EMP3 expression in samples from 179 glioma patients from 2013 to 2017. Univariate and multivariate cox regression were used to predict the prognosis with multiple factors. Finally, a nomogram to predict poor outcomes was formulated. The accuracy and discrimination of nomograms were determined with ROC curve and calibration curve in training and validation cohorts.ResultsEMP3 was significantly higher in higher‐grade glioma and predicted poor prognosis. In multivariate analysis, high expression of EMP3 (HR = 2.842, 95% CI 1.984–4.071), WHO grade (HR = 1.991, 95% CI 1.235–3.212), and IDH1 mutant (HR = 0.503, 95% CI 0.344–0.737) were included. The nomogram was constructed based on the above features, which represented great predictive value in clinical outcomes.ConclusionThis study demonstrated EMP3 as a novel predictor for clinical progression and clinical outcomes in glioma. Moreover, the nomogram with EMP3 expression represented a practical approach to provide individualized risk assessment for glioma patients.

Inflammation and microbial translocation measured prior to combination antiretroviral therapy (cART) and long-term probability of clinical progression in people living with HIV

BackgroundDespite the effectiveness of cART, people living with HIV still experience an increased risk of serious non-AIDS events, as compared to the HIV negative population. Whether pre-cART microbial translocation (MT) and systemic inflammation might predict morbidity/mortality during suppressive cART, independently of other known risk factors, is still unclear. Thus, we aimed to investigate the role of pre-cART inflammation and MT as predictors of clinical progression in HIV+ patients enrolled in the Icona Foundation Study Cohort.MethodsWe included Icona patients with ≥2 vials of plasma stored within 6 months before cART initiation and at least one CD4 count after therapy available. Circulating biomarker: LPS, sCD14, EndoCab, hs-CRP. Kaplan-Meier curves and Cox regression models were used. We defined the endpoint of clinical progression as the occurrence of a new AIDS-defining condition, severe non-AIDS condition (SNAEs) or death whichever occurred first. Follow-up accrued from the data of starting cART and was censored at the time of last available clinical visit. Biomarkers were evaluated as both binary (above/below median) and continuous variables (logescale).ResultsWe studied 486 patients with 125 clinical events: 39 (31%) AIDS, 66 (53%) SNAEs and 20 (16%) deaths. Among the analyzed MT and pro-inflammatory markers, hs-CRP seemed to be the only biomarker retaining some association with the endpoint of clinical progression (i.e. AIDS/SNAEs/death) after adjustment for confounders, both when the study population was stratified according to the median of the distribution (1.51 mg/L) and when the study population was stratified according to the 33% percentiles of the distribution (low 0.0–1.1 mg/L; intermediate 1.2–5.3 mg/L; high > 5.3 mg/L). In particular, the higher the hs-CRP values, the higher the risk of clinical progression (p = 0.056 for median-based model; p = 0.002 for 33% percentile-based model).ConclusionsOur data carries evidence for an association between the risk of disease progression after cART initiation and circulating pre-cART hs-CRP levels but not with levels of MT. These results suggest that pre-therapy HIV-driven pro-inflammatory milieu might overweight MT and its downstream immune-activation.

Predictors of progression through the cascade of care to a cure for hepatitis C patients using decision trees and random forests

BackgroundThis study uses machine learning techniques to identify sociodemographic and clinical predictors of progression through the hepatitis C (HCV) cascade of care for patients in the 1945–1965 birth cohort in the Southern United States. MethodsWe compared sociodemographic and clinical variables between groups of patients for three care outcomes: linkage to care, initiation of antiviral treatment, and virologic cure. A decision tree model and random forest model were built for each outcome. ResultsPatients were primarily male, African American/Black or Caucasian/White, non-Hispanic or Latino, and insured. The average age at first HCV screening was 60 years old, and common medical diagnoses included chronic kidney disease, fibrosis and/or cirrhosis, transplanted liver, diabetes mellitus, and liver cell carcinoma. Variables used in predicting linkage to care included age at first HCV screening, insurance at first HCV screening, race, fibrosis and/or cirrhosis, other liver disease, ascites, and transplanted liver. Variables used in predicting initiation of antiviral treatment included insurance at first HCV screening, gender, other liver cancer, steatosis, and liver cell carcinoma. Variables used in predicting virologic cure included insurance at first HCV screening, transplanted liver, and ethnicity. ConclusionThese patients have a high hepatic health burden, likely reflecting complications of untreated HCV and highlighting the urgency to cure HCV in this birth cohort. We found differences in HCV care outcomes based on sociodemographic and clinical variables. More work is needed to understand the mechanisms of these differences in care outcomes and to improve HCV care.

Functional Connectomics and Disease Progression in Drug-Naïve Parkinson's Disease Patients.

Functional brain connectivity alterations may be detectable even before the occurrence of brain atrophy, indicating their potential as early markers of pathological processes. We aimed to determine the whole-brain network topologic organization of the functional connectome in a large cohort of drug-naïve Parkinson's disease (PD) patients using resting-state functional magnetic resonance imaging and to explore whether baseline connectivity changes may predict clinical progression. One hundred and forty-seven drug-naïve, cognitively unimpaired PD patients were enrolled in the study at baseline and compared to 38 age- and gender-matched controls. Non-hierarchical cluster analysis using motor and non-motor data was applied to stratify PD patients into two subtypes: 77 early/mild and 70 early/severe. Graph theory analysis and connectomics were used to assess global and local topological network properties and regional functional connectivity at baseline. Stepwise multivariate regression analysis investigated whether baseline functional imaging data were predictors of clinical progression over 2 years. At baseline, widespread functional connectivity abnormalities were detected in the basal ganglia, sensorimotor, frontal, and occipital networks in PD patients compared to controls. Decreased regional functional connectivity involving mostly striato-frontal, temporal, occipital, and limbic connections differentiated early/mild from early/severe PD patients. Connectivity changes were found to be independent predictors of cognitive progression at 2-year follow-up. Our findings revealed that functional reorganization of the brain connectome occurs early in PD and underlies crucial involvement of striatal projections. Connectomic measures may be helpful to identify a specific PD patient subtype, characterized by severe motor and non-motor clinical burden as well as widespread functional connectivity abnormalities. © 2021 International Parkinson and Movement Disorder Society.

Spatial navigation ability predicts progression of dementia symptomatology.

Spatial navigation deficits are observed in Alzheimer's disease cross-sectionally, but prediction of longitudinal clinical decline has been less examined. Cognitive mapping (CM) was assessed in 95 participants and route learning (RL) was assessed in 65 participants at baseline. Clinical progression over an average of 4 to 5 years was assessed using the clinical dementia rating (CDR) scale. Relative predictive ability was compared to episodic memory, hippocampus, and cerebrospinal fluid biomarkers (phosphorylated tau/amyloid β 42 (ptau181 /Aβ42 ) ratio). CM and RL were predictors of clinical progression (P's<0.032). All measures, except RL-Learning remained predictors with episodic memory in models (P's<0.048). Only RL-Retrieval remained a predictor when ptau181 /Aβ42 was included (P<0.001). CM interacted with hippocampus and ptau181 /Aβ42 in prediction (P's<0.013). CM, RL, and episodic memory evidenced strong diagnostic accuracy (area under the curve (AUC)=0.894, 0.794, and 0.735, respectively); CM tended to perform better than episodic memory (P=0.056). Baseline spatial navigation performance may be appropriate for assessing risk of clinical progression.