Age-matched Healthy Controls Research Articles

Cardiopulmonary fitness in children/adolescents with chronic kidney disease and the impact of exercise training: a systematic review and meta-analysis of observational study and randomized controlled trials

Background This systematic review and meta-analysis aimed to evaluate differences in cardiopulmonary fitness between healthy controls and children/adolescents with chronic kidney disease (CKD) and the effects of exercise training. Methods PubMed, Embase, Scopus and Web of Science were searched for published studies from reception to 14 June 2023, and updated search on 15 October 2023. The included observational studies reported on cardiorespiratory fitness, included maximal oxygen uptake (VO2max), peak oxygen consumption (VO2peak) and 6-minute walk distance (6MWD), in children/adolescents with CKD and age-matched healthy controls, as well as clinical intervention trials of exercise training on cardiorespiratory fitness in samples of children and/or adolescents up to 19. Results Fifteen observational studies and five clinical trials were included, respectively. The studies found that the mean cardiopulmonary fitness was 1.82 standardized mean differences (SMDs) units (95% confidence interval (95% CI) 1.43–2.20) lower in children/adolescents with CKD than in healthy controls or reference values. Except for pre-dialysis CKD patients, peritoneal dialysis, haemodialysis and kidney transplant recipients had significantly lower cardiorespiratory fitness than healthy controls. The results of a meta-analysis based on a pre-post single-arm trial showed that compared to baseline, exercise training improved the 6MWD by approximately 58.17 m (95% CI 16.27–100.06), with very low evidence. Conclusions This systematic review and meta-analysis of observational studies and clinical trials that included children/adolescents with CKD found that cardiorespiratory fitness is severely reduced in this population and that exercise training may be an effective strategy for improvement. Given the low evidence certainty, additional high-quality trials are necessary.

The characteristics of intestinal microflora in infants with rotavirus enteritis, changes in microflora before and after treatment and their clinical values

Rotavirus (RV) is a leading pathogen causing diarrhea in children. In this study, a total of 51 fecal samples from children with RV enteritis, 29 post-treatment fecal samples, and 38 fecal samples from age-matched healthy controls were collected. Microbial DNA was isolated from the samples followed by high throughput Illumina sequencing targeting 16 S rRNA gene. Compared to the healthy group, the RV-infected group exhibited reduced microbial diversity. Both groups shared Firmicutes as the dominant phylum. Additionally, the abundance of Proteobacteria increased significantly in the RV-infected group. At the genus level, among the top 50 most abundant genera, 34 showed significant differences, with these differential genera correlating with certain clinical indicators such as dehydration levels and C-reactive protein (CRP). Notably, there were no significant differences in the microbiota before and after treatment in RV-infected children. Only 8.82% (3/34) of the differential genera in the post-treatment group showed a recovery trend towards the healthy state. This study enhances the understanding of how RV infection alters the gut microbiota structure in children and provides a scientific basis for improving clinical diagnosis and treatment strategies.

Interactions between ABC gene polymorphisms and processing speed in predicting depression severity

BackgroundABC family genes encode ATP-binding cassette proteins, which are involved in the transport of various substances and are associated with major depressive disorder (MDD); however, their clinical significance in MDD remains unclear. Therefore, this study aimed to investigate whether ABC family genes are associated with cognitive function, and the combined effects of genes and cognitive function on the severity of depression.MethodLinear models or logistic regression models were used to investigate the associations of ABC family gene variants with clinical symptoms and cognitive function in 805 MDD patients (12–65 years old) and 1493 age-matched healthy controls (HCs). Seven single nucleotide polymorphisms (rs28401781, rs4148739, rs3747802, rs1109866, rs1109867, rs3731885, and rs3755047) of ABCB1 and ABCB6 were selected. The cognitive function was assessed by the Wisconsin Card Sorting Test (WCST), Tower of Hanoi Test (TOH), Trail Making Test (TMT), and Verbal Fluency Test (VF).ResultsSignificant differences in gene frequency and genotype frequency were observed at the rs1109866 (X2 = 8.22, p = 0.004; X2 = 9.82, p = 0.007) and rs1109867 (X2 = 7.35, p = 0.007; X2 = 9.15, p = 0.010) between MDD patients and HCs, even after correction. While rs28401781 (t = 2.78, p = 0.006) and rs4148739 (t = 3.08, p = 0.003) were associated with the TOH test. And both rs1109866 and rs1109867 interacted with TMT results to influence depression severity in MDD patients.ConclusionThe results suggest that ABC family genes influence the severity of depression through cognitive functioning, providing possible evidence for genetic markers in MDD patients.

Circular RNA encoded by PPARG in the peripheral blood and a lipopolysaccharide-induced cardiomyocyte inflammation model is identified as a marker of fulminant myocarditis.

Fulminant myocarditis (FM), a critical cardiac disease, is characterised by atypical initial symptoms and rapid progression and tends to lead to cardiomyocyte degeneration or necrosis. Reliable biological markers for FM screening remain lacking. Circular RNAs (circRNAs) are highly stable in peripheral blood due to their special closed-loop structure, and reports have described their involvement in regulating inflammatory responses and cell injury in cardiomyocytes. This study attempted to identify the abnormal expression of circRNAs in the peripheral blood of patients with FM and to evaluate the potential diagnostic value. Peripheral blood was collected from 5 children with FM and 5 sex- and age-matched healthy controls; total RNA was extracted from each sample, and the extracted RNA from each group was pooled. After RNase R treatment, high-throughput sequencing was performed to screen for differentially expressed circRNAs in the peripheral blood of patients. Biological function classification and enrichment analysis were used to explore the main action pathways involving differentially expressed circRNAs. A lipopolysaccharide (LPS)-induced cardiomyocyte inflammation model was used to explore the effect of inflammation on the expression of these dysregulated circRNAs. Receiver operating characteristic (ROC) curves were used to evaluate the potential clinical value of FM-related circRNAs as biomarkers in a large sample of patients. CircRNA expression profiling of peripheral blood samples from patients revealed 6,435 and 3,678 circRNAs with upregulated and downregulated expression, respectively, compared with healthy controls. The expression of 1,749 circRNAs did not significantly differ between the groups. GO and KEGG analysis revealed that the genes encoding the dysregulated circRNAs were associated with various biological functions related to the risk of FM development, including infectious diseases, the immune system, and signal transduction. The high expression of hsa_circ_0064338 (circ_PPARG) was confirmed in both the myocardial cell inflammation model and peripheral blood from a large sample of FM patients. ROC curve analysis showed that the level of circ_PPARG in peripheral blood had a good ability to distinguish patients with FM from healthy controls. Large numbers of abnormally regulated circRNAs were identified in peripheral blood from patients with FM; among these, the highly expressed circ_PPARG could distinguish patients from healthy controls to a certain extent. It is expected to become a potential clinical biomarker of FM in the future.

Abnormal Brain State in Major Depressive Disorder: A Resting-State Magnetic Resonance Study.

Background: Respective changes in resting-state linear and nonlinear measures in major depressive disorder (MDD) have been reported. However, few studies have used integrated measures of linear and nonlinear brain dynamics to explore the pathological mechanisms underlying MDD. Method: Forty-two patients with MDD and 42 sex- and age-matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging to calculate multiscale entropy (MSE) and regional homogeneity (ReHo). The MSE-ReHo coupling of the whole gray matter and the MSE/ReHo ratio (the complexity of intensity homogeneity per unit time series) of each voxel were compared between the two groups. To evaluate the discriminative capacity of ratio features between patients with MDD and HC, we employed the support vector machine (SVM) learning method. Results: We observed that patients with MDD displayed increased MSE/ReHo ratio mainly in the orbitofrontal cortex, sensorimotor areas, and visual cortex. Moreover, significant correlations were observed between MSE/ReHo ratio and clinical indicators, including depression severity and cognitive function tests. The SVM model demonstrated high accuracy in differentiating patients with MDD from HC, highlighting the potential of the MSE/ReHo ratio as a diagnostic and prognostic tool. Conclusions: The aberrant MSE/ReHo ratio implicated the underlying mechanisms of depressive symptoms and cognitive impairment in patients with MDD. It may represent a critical state of the brain region, reflecting the degree of chaos and order in the brain region. Integrating linear and nonlinear combinations of brain signals holds promise for diagnosing psychiatric disorders.

ANALYSIS OF HENLE FIBER LAYER AND OUTER RETINAL LAYERS IN CONE DYSTROPHY.

To evaluate Henle fiber layer (HFL) thickness and volume parameters in patients with cone photoreceptor atrophy with directional optical coherence tomography. Macular 20°×20° standard and directional optical coherence tomography images were acquired from patients diagnosed with hereditary cone dystrophy with evident foveal ellipsoid zone defect in optical coherence tomography and age-matched healthy controls. Thickness and volume parameters of HFL, outer nuclear layer (ONL), and retinal layers between ellipsoid zone and Bruch membrane complex (EZ-BM) were calculated from manual segmentation through directional optical coherence tomography images, and comparative analysis is performed. Twelve eyes of six patients were compared with 12 eyes of six age-matched healthy controls (mean age: 29.5 ± 16.6 and 26.6 ± 3.9 years, respectively; P = 0.162). Patients had lower total HFL volume (0.45 ± 0.03 and 0.85 ± 0.15 mm 3 ; P < 0.001) and mean HFL thickness (16.1 ± 1.1 and 30.1 ± 5.3 µ m; P < 0.001) than healthy controls. Central subfield, parafoveal, and perifoveal ETDRS zone HFL parameters in patients were significantly lower than healthy controls. A centrifugal correlation was found between central outer nuclear layer and the corresponding parafoveal HFL (Spearman rho: 0.785; P < 0.001). Henle fiber layer assessment might be a useful optical coherence tomography biomarker in patients with cone photoreceptor atrophy. Henle fiber layer thinning is observed in foveal, parafoveal, and perifoveal areas of patients with cone photoreceptor atrophy, while volume reduction in outer nuclear layer and ellipsoid zone and Bruch membrane complex components were limited to central and parafoveal zones.

A real-world data of serum neurofilament light chain in a large cohort of Egyptian multiple sclerosis patients: Hospital-based study.

Serum neurofilament light chain (sNFL) is a promising biomarker for neuroaxonal injury in multiple sclerosis (MS). Traditional clinical and radiological examinations often fail to capture the underlying neurodegeneration, particularly in the absence of clinical relapses or gadolinium-enhanced lesions. This study aims to assess sNFL levels in real-world MS patients who have no evidence of activity, to evaluate the potential of sNFL as a biomarker for smoldering-associated worsening (SAW). A cross-sectional study, involved 162 MS patients without evidence of disease activity and 40 healthy, age, sex, and education matched controls (HCs). Patients were classified according to MS subtype, DMT status, and type. sNFL levels were measured using an enzyme-linked immunosorbent assay (ELISA) and levels were compared in each group. sNFL levels were significantly higher in MS patients compared to (HCs) (p < 0.001). Median sNFL levels were lowest in the clinically isolated (CIS) group and steady increase in RRMS and reaching the highest levels in the SPMS group (p < 0.001). Despite a slight decrease in sNFL levels in patients who started DMT for a year or less than in the naïve group, sNFL levels were highest in patients who were on DMTs for longer durations (p = 0.003). EDSS score was the sole independent predictor of sNFL levels (B = 0.415, p = 0.002). A cut-off value of 23.25 pg/ml was set to distinguish cases and HCs (92 % specificity and 90 % sensitivity), and 75.48 pg/ml was set to distinguish progressive forms (70.00 % sensitivity and 78.30 % specificity). sNFL is sensitive for detecting subclinical neurodegeneration in the absence of relapse or gadolinium-enhanced lesions, supporting the utility of sNFL measurements into routine clinical practice to improve monitoring and management of MS.

Abstract 34: White Matter Alteration after Stroke Is Correlated with Neuroinflammation: A Combined Fixel-based Diffusion MRI Analysis and 18F-THK-5351 PET Study

Introduction: Neuroinflammation plays a major role in post-stroke neuronal injury. Previous studies applied 18F-THK-5351 tau PET to identify the existence of neuroinflammation after infarction. Meanwhile, post-stroke microstructural degradation of white matter (WM) fibers can be observed using fixel-based analysis (FBA) of diffusion MRI (dMRI). We integrate 18F-THK-5351 tau PET and FBA-dMRI in ischemic stroke patients to investigate the relationship between poststroke neuroinflammation process and WM fiber alterations. Methods: 33 patients with lacunar infarcts received 18F-THK-5351 PET and dMRI (Siemens Biograph mMR PET-MR 3 Tesla scanner) at 3 months poststroke. 27 age-matched healthy controls were recruited. The reference region of 18F-THK-5351 PET was set at cerebellar cortex. FBA-dMRI metrics included microstructural fiber density (FD), fiber cross-section (FC, macrostructural morphometry), and combined-FD/FC (FDC, the overall fiber bundle connectivity). Clinical severity assessments included infarction volume, NIHSS, BI, and mRS. The whole-brain fixel-wise statistical analysis used the general linear model. Correlation anlaysis was for FBA metrics and clinical severity. Non-parametric testing &gt;5000 permutations was used for multiple comparisons, p &lt;0.05 using a strong family-wise error control as statistical significance. Results: All patients had lacunar infarcts at internal capsule, including 19 left and 14 right lacunes. The mean age was 64.9±7.7 in patients v.s. 61.3±9.4 in controls ( p =0.47). FBA-dMRI showed significant reductions in FD, FC, and FDC at corticospinal tract in patients compared to the controls. Tau PET demonstrated the highest uptake of 18F-THK-5351 at ischemia core. The spatial patterns of 18F-THK-5351 retention were highly consistent with the fixel metrics reduction distributions (Figure 1). Infarct volumes and clinical severity significantly negatively correlated with the fixel measures in patients. Larger infarct volume or more severity corresponds to lower FBA value (Figure 2). Conclusions: Integrating 18F-THK-5351 PET and FBA-dMRI demonstrates fiber-specific WM reductions associated with the neuroinflammation process, showing consistent spatial patterns between neuroinflammation and WM degeneration in stroke patients. Tract-specific WM reductions correlated with infarct volume and functional outcomes 3 month poststroke. Our findings have implications for understanding the mechanisms underlying functional impairment after ischemic stroke.

Disentangling the component processes in complex planning impairments following ventromedial prefrontal lesions.

Damage to ventromedial prefrontal cortex (vmPFC) in humans disrupts planning abilities in naturalistic settings. However, it is unknown which components of planning are affected in these patients, including selecting the relevant information, simulating future states, or evaluating between these states. To address this question, we leveraged computational paradigms to investigate the role of vmPFC in planning, using the board game task 'Four-in-a-Row' (18 lesion patients, 9 female; 30 healthy control participants, 16 female), and the simpler 'Two-Step' task measuring model-based reasoning (49 lesion patients, 27 female; 20 healthy control participants, 13 female). Damage to vmPFC disrupted performance in Four-in-a-Row compared to both control lesion patients and healthy age-matched controls. We leveraged a computational framework to assess different component processes of planning in Four-in-a-Row and found that impairments following vmPFC damage included shallower planning depth, and a tendency to overlook game-relevant features. In the 'Two-Step' task, which involves binary choices across a short future horizon, we found little evidence of planning in all groups, and no behavioural differences between groups. Complex yet computationally tractable tasks such as 'Four-in-a-row' offer novel opportunities for characterising neuropsychological planning impairments, which in vmPFC patients we find are associated with oversights and reduced planning depth.Significance Statement The ability to plan in real-world settings is often disrupted after damage to ventromedial prefrontal cortex (vmPFC). However, real-world planning consists of many different cognitive processes, and it is uncertain which processes are disturbed by these lesions. Here we use rich computational models of planning to characterise behaviour in two planning tasks performed by patients with vmPFC damage and controls. VmPFC damage only affected behaviour in the more complex planning task, and behavioural modelling revealed this was associated with planning less far into the future and overlooking important features. These findings shed light on the neural mechanisms supporting complex planning, demonstrating how novel computational methods can strike the balance between task complexity and interpretability.

Left Ventricular Twist and Circumferential Strain from MRI Tagging Predict Early Cardiovascular Disease in Duchenne Muscular Dystrophy

Background/Objectives: Duchenne Muscular Dystrophy (DMD) is a prevalent fatal genetic disorder, and heart failure is the leading cause of mortality. Peak left ventricular (LV) circumferential strain (Ecc), twist, and circumferential-longitudinal shear angle (θCL) are promising biomarkers for the improved and early diagnosis of incipient heart failure. Our goals were as follows: 1) to characterize a spectrum of functional and rotational LV biomarkers in boys with DMD compared with healthy age-matched controls; and 2) to identify LV biomarkers of early cardiomyopathy in the absence of abnormal LVEF or LGE. Methods: Boys with DMD (N = 43) and age-matched healthy volunteers (N = 16) were prospectively enrolled and underwent a 3T CMR exam after obtaining informed consent. Breath-held MRI tagging was used to estimate left ventricular Ecc at the mid-ventricular level as well as the twist, torsion, and θCL between basal and apical LV short-axis slices. A two-tailed t-test with unequal variance was used to test group-wise differences. Multiple comparisons were performed with Holm–Sidak post hoc correction. Multiple-regression analysis was used to test for correlations among biomarkers. A binomial logistic regression model assessed each biomarker’s ability to distinguish the following: (1) healthy volunteers vs. DMD patients, (2) healthy volunteers vs. LGE(−) DMD patients, and (3) LGE(−) DMD patients vs. LGE(+) DMD patients. Results: There was a significant impairment in the peak mid-wall Ecc [−17.0 ± 4.2% vs. −19.5 ± 1.9%, p &lt; 7.8 × 10−3], peak LV twist (10.4 ± 4.3° vs. 15.6 ± 3.1°, p &lt; 8.1 × 10−4), and peak LV torsion (2.03 ± 0.82°/mm vs. 2.8 ± 0.5°/mm, p &lt; 2.6 × 10−3) of LGE(−) DMD patients when compared to healthy volunteers. There was a further significant reduction in the Ecc, twist, torsion, and θCL for LGE(+) DMD patients when compared to LGE(−) DMD patients. In the LGE(+) DMD patients, age significantly correlated with LVEF (r2 = 0.42, p = 9 × 10−3), peak mid-wall Ecc (r2 = 0.27, p = 0.046), peak LV Twist (r2 = 0.24, p = 0.06), peak LV torsion (r2 = 0.28, p = 0.04), and peak LV θCL (r2 = 0.23, p = 0.07). In the LGE(−) DMD patients, only the peak mid-wall Ecc was significantly correlated with age (r2 = 0.25, p = 0.006). The peak LV twist outperformed the peak mid-wall LV Ecc and EF in distinguishing DMD patients from healthy volunteer groups (AUC = 0.88, 0.80, and 0.72), as well as in distinguishing LGE(−) DMD patients from healthy volunteers (AUC = 0.83, 0.74, and 0.62). The peak LV twist and peak mid-wall LV Ecc performed similarly in distinguishing the LGE(−) and LGE(+) DMD cohorts (AUC = 0.74, 0.77, and 0.79). Conclusions: The peak mid-wall LV Ecc, peak LV twist, peak LV torsion, and peak LV θCL were significantly impaired in advance of the decreased LVEF and the development of focal myocardial fibrosis in boys with DMD and therefore were apparent prior to significant irreversible injury.

Diagnostic performance of corneal epithelium- and Bowman's layer thickness mapping in patients with unilateral Keratoconus.

To investigate the role of corneal epithelium- and Bowman's layer-thickness (ET and BLT) changes as possible early biomarkers of keratoconus (KC) development. In this cross-sectional study patients with unilateral KC (UKC) and a group of healthy controls underwent polarization sensitive optical coherence tomography (PS-OCT) for the evaluation of corneal ET and BLT. These values were compared among three subgroups of eyes, i.e., eyes with KC, topographically and tomographically normal fellow eyes (FE) of patients with UKC, and healthy eyes (HE). Twelve patients with UKC (12 eyes with KC and 12 FE) and 21 healthy age-matched controls (HE) were included. While KC eyes showed the typical epithelial "doughnut pattern" on epithelial maps, there were no differences in ET between FE and HE. BLT was significantly higher in FE compared to HE (average BLT p = 0.049, minimum BLT p = 0.02, nasal-inferior quadrant p = 0.04) as weIl as KC eyes (average BLT p = 0.048, minBLT p = 0.04, nasal-inferior quadrant p = 0.03). Increase in BLT seems to occur before epithelial thinning in FE of patients with UKC. Since many of KC patients develop the disease bilaterally, Bowman's layer thickening might represent an early biomarker of KC-development.

Cognitive Impairment in Primary Open Angle Glaucoma: A Case Control Study.

Cognitive impairment in multiple domains was observed in primary open angle glaucoma patients as compared to age and gender matched healthy controls. Evaluation of cognitive impairment in individuals with Primary Open Angle Glaucoma (POAG). In this case-control study, individuals with POAG (cases, n=70) were compared with age- and sex-matched healthy individuals (controls, n=70) using detailed ophthalmological evaluation, cognitive assessment and serum cortisol level. A multitude of tests were employed to comprehensively assess various domains of cognitive function: Addenbrooke Cognitive Examination (ACE-III; attention/orientation, memory, language, verbal fluency, and visuospatial skills), Post Graduate Institute Memory Scale (PGIMS; verbal and non verbal memory), Wisconsin Card Sorting Test (WCST; nonverbal executive functions), Go No-Go task (GNG; inhibitory control), and Trail Making Test (TMT; attention and working memory). Intraocular pressure and cup disc ratio were significantly higher (P <0.001) while retinal nerve fibre layer (RNFL) thickness and mean deviation were significantly lower in cases as compared to controls. Cases had significantly lower scores on ACE-III and PGIMS (P<0.001) and longer test completion time in TMT-A (P=0.001). The performance of cases was also significantly worse on most parameters of the WCST and GNG tasks. Serum cortisol level was significantly higher in cases (11.75±7.41mcg/dl) compared to controls (7.93±2.39 mcg/dl; P=0.02). A significant correlation was observed between serum cortisol level and WCST correct response (P=0.04), WCST error response (P=0.002) and total time taken in TMT-A (P=0.03).Visual field mean deviation also exhibited a significant correlation with serum cortisol level (P<0.001) and total time taken on WCST (P=0.03) and TMT-A (P=0.03). Individuals with POAG exhibited higher cognitive impairment and raised serum cortisol levels than age-matched healthy controls. Early recognition and management of cognitive impairment are pivotal for enhancing the quality of life and implementing comprehensive glaucoma care.

Myocardial work and aortic strain in hypertensive patients: a speckle tracking echocardiographic study

Abstract Purpose The aim of the present study was to investigate whether systemic arterial hypertension is associated with abnormal left ventricular (LV) function assessed by myocardial work determined by speckle tracking echocardiography and how such changes are related to left ventricular hypertrophy (LVH) and aortic strain. Methods We examined 102 hypertensive (mean age, 65±16 years, 53% male) and 102 sex- and age-matched healthy controls (mean age, 66±14 years, 52% male). The following three-dimensional echocardiographic parameters were evaluated: LV end-diastolic volume, LV end-systolic volume, LV stroke volume, LV ejection fraction (LVEF), LV end-diastolic mass, and LV end-diastolic mass index (LVMI). Hypertensive patients were divided into two groups: patients without LVH (group-A) and patients with LVH (group-B, LVMI&amp;gt;115g/m2 men, LVMI&amp;gt;95g/m2 women). All of them had preserved LV ejection fraction. Global LV longitudinal strain (GLS) was calculated by two-dimensional speckle tracking echocardiography. The following indices of MW were assessed: global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Corrected circumferential ascending aorta strain (AAo-S) was calculated by two-dimensional speckle tracking echocardiography as global aortic strain /pulse pressure. Data analysis was performed offline (GE EchoPAC v.R6). Results In group-A GWI and GCW were increased compared to controls (p=0.04). In group-B GWI and GCW were decreased compared to controls (p=0.01). GWW was increased in group-A(p=0.01) and group-B(p&amp;lt;0.001). GWE was decreased in group-A(p=0.004) and group-B(p&amp;lt;0.001). There was a positive correlation between GWE and AAo-S(r=0.53,p=0.02). GWE was independently associated with GLS(β=0.28,p=0.012), LV mass(β=0.33,p=0.01) and AAo-S(β=0.36,p=&amp;lt;0.01) in the whole hypertensive population. At ROC (receiver operating characteristic) analysis, optimal cutoff values of GWI, GLS, AAo-S, GWE and combination of GWE and AAo-S discriminating LV hypertrophy were 0.7413, 0.7685, 0.8167, 0.8538 and 0.9016, respectively. Conclusions In systemic hypertension, aortic strain assessment improved the ability of myocardial work variables to differentiate patients with LVH, patients without LVH, and control subjects. The decrease in GWE and AAo-S occurred even in the absence of LV hypertrophy.

Salivary steroids in acute central serous chorioretinopathy.

To analyze levels of salivary steroids, including 17-OH-progesterone (17-OHP), androstenedione, dehydroepiandrosterone, cortisol, cortisone, progesterone, testosterone, and estradiol, in patients with acute central serous chorioretinopathy (CSCR) patients. Acute CSCR patients and healthy individuals were included in this observational case-control study. Levels of salivary steroids were determined by high-performance liquid chromatography with tandem mass spectrometry detection. Clinical characteristics of CSCR patients were assessed based on multimodal imaging. Seventeen CSCR patients (40.1 ± 4.6years) and fourteen age-matched healthy controls (40.6 ± 3.8years) were included. Mean central retinal thickness and subfoveal choroidal thickness in affected eye of CSCR patients were 436.2 ± 131.1µm and 464.6 ± 132.6µm, respectively. Mean best-corrected visual acuity was 0.09 ± 0.11 LogMAR. Mean symptoms duration before saliva collection was 0.9 ± 0.6months. 17-OHP was decreased compared to the normal limits established in healthy controls in 10 out of 17 patients (59%), androstenedione in 15 out of 17 patients(88%), dehydroepiandrosterone in 10 out of 17 patients (59%), cortisol in 6 out of 17 patients(35%), cortisone in 12 out of 17 patients (83%), progesterone in 9 out of 17 patients(53%), testosterone in 10 out of 17 patients (59%), and estradiol in 5 out of 17 patients(29%). In total, among CSCR patients lower level in saliva was found for all studied hormones (p < 0.05), except progesterone and estradiol. Salivary steroids are decreased in acute CSCR male patients compared with age-matched controls. This may indicate inhibition of steroidogenesis caused by chronic stress and personal reactivity preceding manifestation of CSCR.

Decreased T helper 1cell function underlies recurrent sinopulmonary infections in the 17q12 deletion syndrome.

The 17q12 deletion syndrome (17q12DS) is a heterozygous deletion of a 1.4 megabase‒spanning DNA sequence on chromosome 17. The clinical characteristics of 17q12DS include neurodevelopmental disorders, kidney and urinary tract abnormalities. In our cohort of 37 subjects with 17q12DS, we observed increased atopic disorders and recurrent sinopulmonary infections, raising the possibility of immune dysregulation in 17q12DS, a feature that has not been previously reported. We tested the hypothesis that individuals with 17q12DS have altered T-cell function, contributing to recurrent infections and atopy. Alteration of CD4+ T-cell functions was assessed on FACS sorted CD4+ T-cells using RNA-seq analysis, and flow cytometry and multiplex assays. We found that individuals with 17q12DS had a substantially decreased frequency of CD4+ T-cells producing the T helper (Th) 1 cytokine IFN-γ but not Th2 and Th17 cytokines when compared to age-matched healthy controls (HCs). RNA-seq analysis of CD4+ T-cells from subjects with 17q12DS, when compared to HCs, revealed decreased levels of TBX21 encoding the Th1 transcription factor T-bet, IFNG, and other Th1 chemokine genes. These findings were validated using flow cytometry and multiplex assay. Our study is the first to demonstrate immune alterations in 17q12DS characterized by decreased T-bet and its downstream effector cytokines such as IFN-γ. These findings warrant further investigation into underlying mechanisms, which would inform precision therapy for individuals with 17q12DS. National Institutes of HealthKL2 TR001862 to JJS, T35DK104689 to AG, 5T32AR007107 to JPY and LO, 1R01AG056728 to IK, and 1R21AI161838 to IK and JJS.

Assessing left ventricular hemodynamic forces in systemic sclerosis patients: pilot study

Abstract Background Systemic sclerosis (SSc) is a connective tissue disease characterized by sustained inflammation, microvascular pathology changes and fibrosis. Cardiac comorbidities, particularly pulmonary arterial hypertension (PAH), are the leading cause of mortality among SSc patients. Early PAH diagnosis remains difficult. Cardiovascular magnetic resonance imaging (CMR) has emerged as a great noninvasive tool to assess cardiological impact in SSc. Hemodynamic forces (HDF) are a measurement of the global force exchanged between blood volume and myocardium assessed using CMR, based on the Navier-Stokes equation measuring the relationship between pressure gradient and velocity field. Purpose To assess diagnostic value of HDF measurement in SSc compared to healthy controls, as a potential early indicator of subclinical cardiac dysfunction. Methods In a single-center study, all patients with SSc who met the American college of rheumatology, and the European League against Rheumatism classification criteria were included and a CMR exam a 1.5T was performed. HDF were obtained using a post-processing software (Medis Suites, Netherlands). Patients with atrial fibrillation were excluded. To assess HDF, movements from deformation imaging of long axis cine were used for longitudinal (Figure 1) and transversal left ventricle (LV) HDF calculation after initial feature-tracking and measurements of mitral and aortic valve width. To compare different LV sizes, HDF are normalized to LV volume and blood specific weight, thus reported as percentage of gravity acceleration. Then, we performed age matching from an external cohort of healthy controls (1). Results Of the 11 SSc patients (age 46.27±15.2 years, 19% male) recruited, 5 (46%) patients had a diffuse form and 5 (46%) patients had PAH. Two (18%) patients exhibited LV systolic dysfunction with a mean LV ejection fraction (LVEF) of 59%. Regarding the right ventricle (RV), 5 (46%) patients had RV systolic dysfunction (mean RVEF of 50%). Biventricular volumes were normal (mean LV end-diastolic volume [EDV] of 80 ml/m2, respectively mean RV EDV of 77 ml/m2). To assess the diagnostic performance of HDF values we compared HDF in 11 SSc patients and in 11 age-matched healthy controls from an external cohort. SSc patients showed larger LV longitudinal HDF in systole (both RMS and peak, p=0.029, respectively p=0.047) (Figure 2), changes which could be explained by anatomical deformation caused by increased pressure in the RV. During diastole, only one parameter was significantly lower (diastolic deceleration, p=0.040), a finding that might indicate reduced LV compliance in the context of elevated LV filling pressures. Conclusion This pilot study is the first to describe the interest of HDF in SSc patients. HDF analysis has the potential to be a more sensitive marker of cardiac deterioration than traditional volumetric and functional parameters, as patients had higher systolic HDF despite having similar LVEF to controls.

Effect of antiretroviral treatment in myocardial function of treatment naive patients with HIV

Abstract Background/Aim HIV infection is related with cardiovascular adverse events. We investigated the effects of antiretroviral treatment in myocardial and vascular function of newly diagnosed patients with HIV. Patients and methods: A total of 70 newly diagnosed HIV patients were enrolled. Patients were randomized to 4 different treatments which were descovy plus resolsta (emtricitabine/ tenofovir alafenamide), tivicay plus descovy (tenofovir alafenamide/ emtricitabine), genvoya (elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide) and descovy plus isentress (raltegravir). We measured at baseline and 12 months posttreatment: (a) Left Ventricular (LV) Global Longitudinal Strain (GLS), (b) LV Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW), Global Work Efficiency (GWE). At baseline, we compared the HIV patients with 35 healthy matched controls. Results At baseline patients with HIV had devastated myocardial function, endothelial function and endothelial glycocalyx compared with healthy controls. Twelve months after intervention HIV patients improved myocardial function, as assessed by GLS, GWI and GCW as well as endothelial function as evaluated by decrease of PBR5-25. Nevertheless, in HIV patients 12 months post treatment myocardial and endothelial function and endothelial glycocaylyx was impaired in comparison with healthy controls. Conclusions Treatment with antiretroviral therapy partially improves myocardial and arterial function 12 months post treatment.

Longitudinal Changes in Patient- and Clinical-Reported Outcomes in Early Spinocerebellar Ataxia Types 1, 2, 3, and 6 from the IDEA Study.

Clinical outcomes assessments (COAs) in spinocerebellar ataxia (SCA) need to be standardized, ataxia-specific, sensitive to change, clinically relevant, and meaningful to patients. To evaluate the longitudinal 1- and 2-year performances of different patient reported outcomes, including the Patient Reported Outcome Measure of Ataxia (PROM-Ataxia), and clinician reported outcomes, including FARS and SARA, in those with early manifest symptoms of SCA 1, 2, 3, and 6. We studied 53 patients with early stage SCA1-3 and SCA6 from The Instrumented Data Exchange for Ataxia Study and 24 age-matched healthy controls. Participants were seen every 6 months for 2 years. Mixed models were used to estimate change over 12- and 24-months of follow-up. Changes on the FARS-FS and PGI-C were used as anchors to estimate meaningful changes. Among persons with SCA, mean age was 48.7 years and mean SARA score was 9.3. Few measures showed statistically significant changes at 12 months. At 24-months, the FARS-ADL, PROM-Ataxia total, PROM-Ataxia physical, and PROM-Ataxia ADL scores showed the strongest associations of change. Patient reported or derived outcome measures, such as FARS-ADL and ADL sub domain of the PROM-Ataxia, can capture longitudinal change in patients' symptom experience over a 2-year period and its impact on daily activities, even in those with early disease. More work is needed to identify outcomes that reliably capture change earlier.

Soluble PD-L1 and Serum Vascular Endothelial Growth Factor-B May Independently Predict Prognosis in Patients with Advanced Non-Small Cell Lung Cancer Treated with Pembrolizumab

Background: Previous preclinical data have shown that the dynamic cross-talk between abnormal tumor vasculature and immune cell factors in the tumor microenvironment may exert a critical role in the progression and treatment resistance of non-small cell lung cancer (NSCLC). In the clinical setting, a variety of blood-based angiogenesis- and immune-related factors are being increasingly investigated as potential biomarkers of prognosis or treatment response in immunotherapy-treated NSCLC. We herein aimed to evaluate the clinical relevance of the peripheral blood levels of vascular endothelial growth factor-A and -B (VEGF-A and VEGF-B, respectively), soluble programmed cell death-1 (sPD-1), and programmed cell death-ligand 1 (sPD-L1) in patients with advanced NSCLC treated with immune checkpoint inhibitors (ICIs). Methods: Consecutive patients with advanced-stage, non-oncogene-addicted NSCLC, eligible to receive ICIs at the Oncology Unit of Sotiria Athens General Hospital, were prospectively recruited. A group of sex- and age-matched healthy controls was also enrolled for the evaluation of the potential diagnostic significance of the examined biomarkers. Serum levels of all biomarkers were measured using ELISA, both before and after treatment, and were correlated with standard clinicopathological features of patients, treatment response, progression-free survival (PFS), and overall survival (OS). Results: A total of 55 patients and 16 healthy controls were included in the final analysis. The mean age of patients and controls was 66.5 years (SD = 8.0 years) and 65.4 years (SD = 9.1 years), respectively. The majority of patients (65.5%) received pembrolizumab in combination with chemotherapy, while the remaining patients received pembrolizumab monotherapy. ROC curve analysis showed that VEGFB and sPD-1 were the only markers with a significant diagnostic value. Higher pre-treatment values of sPD-L1 (HR = 1.68; p = 0.040) and sPD-1 (HR = 10.96; p = 0.037) as well as higher post-treatment values of VEGF-B (HR = 2.99; p = 0.049) were all significantly associated with a reduced OS in univariate Cox regression analysis. The adverse prognostic significance of higher pre-treatment values of sPD-L1 (HR = 2.10; p = 0.014) and higher post-treatment values of VEGFB (HR = 3.37; p = 0.032) was further confirmed in multivariate analysis. Conclusions: Our study results suggest that serum levels of sPD-L1 and VEGF-B may independently predict prognosis in ICI-treated advanced-stage NSCLC.

Cortical involvement of lateral trunk flexion and verticality misperception in Parkinson's disease

Abstract Lateral trunk flexion is a common form of postural abnormality in Parkinson's disease and could be associated with verticality misperception. However, the mechanisms underlying lateral trunk flexion and verticality misperception in Parkinson's disease remain unclear. In the current study, we examined whether lateral trunk flexion is associated with verticality misperception in patients with Parkinson's disease. We also identified the brain regions involved in lateral trunk flexion and altered verticality perception. In this cross-sectional study, we evaluated the verticality perception using the subjective visual vertical test in 81 patients with Parkinson's disease and 14 age-matched healthy controls. According to the 97.5th percentile upper reference limit of the body tilt angle in the healthy controls, patients with Parkinson's disease were grouped into 37 patients with lateral trunk flexion and 44 patients without lateral trunk flexion. The mean of absolute subjective visual vertical angles was compared between Parkinson's disease patients with lateral trunk flexion, those without lateral trunk flexion, and the healthy controls, and the impact of verticality misperception on lateral trunk flexion was evaluated using multivariate logistic regression models. We further performed a voxel-wise comparison of regional cerebral blood flow using N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography (height threshold of P &amp;lt; 0.001, uncorrected for multiple comparisons, extent threshold of 100 voxels) to identify the brain regions associated with lateral trunk flexion, and to investigate the relationship between verticality misperception and regional hypoperfusion. The mean of absolute subjective visual vertical angles was larger in Parkinson's disease patients with and without lateral trunk flexion than in healthy controls (P &amp;lt; 0.001 and P &amp;lt; 0.001). Additionally, the subjective visual vertical angle was associated with the presence of lateral trunk flexion (odds ratio 2.25, 95% confidence interval 1.51–3.36, P &amp;lt; 0.001). The regional cerebral blood flow in Parkinson's disease patients with lateral trunk flexion was decreased in the right inferior parietal lobule, right superior parietal lobule, right superior temporal gyrus, and right dorsal posterior cingulate cortex compared with those without lateral trunk flexion. The subjective visual vertical angle was inversely correlated with regional cerebral blood flow in these regions, except for the dorsal posterior cingulate cortex. Our study reveals that hypofunction in the right temporoparietal association cortices is involved in verticality misperception and the development of lateral trunk flexion in patients with Parkinson's disease. These results provide insights into potential therapeutic targets for addressing lateral trunk flexion.