Subclinical Changes Research Articles

Early expression of osteopontin glycoprotein on the ocular surface and in tear fluid contributes to ocular surface diseases in type 2 diabetic mice.

Osteopontin (OPN) is a glycosylated, secreted phosphoprotein known to be elevated in both human and mouse retinas during various stages of diabetic retinopathy. However, its specific roles in modulating ocular surface dynamics and immune responses in diabetes remain unexplored. This study aims to investigate the role of OPN in the development of ocular surface disease (OSD) in type 2 diabetic (T2D) mice. Three- to four-week-old C57BL/6 wild-type (WT) and OPN-knockout (OPN-/-) mice were fed a high-fat diet (HFD) and were rendered diabetic by streptozotocin (STZ; 40 mg/kg body weight) in citrate buffer (vehicle); non-diabetic controls were injected with vehicle alone. Diabetes was confirmed if blood glucose levels were >200 mg/dL, measured 1-2 weeks post-STZ injection. Control, age- and sex-matched db/db diabetic mice fed a standard chow diet were also included in this study. Ocular surface inflammation was assessed using ELISA to quantify inflammatory cytokine proteins and wheat germ agglutinin (WGA) staining was utilized to highlight corneal surface irregularities. Clinical signs were evaluated by corneal fluorescein staining, tear production measurements, and tear sodium (Na+) concentration assessments. These evaluations were conducted 4, 6, 8 and 16-weeks post-diabetes onset in WT and OPN-/- mice and were compared to those obtained in non-diabetic controls. Statistical analysis was performed using a two-way ANOVA, with significance set at P < 0.05. Both WT and OPN-/- mice developed T2D within 4 and 8 weeks, respectively, following HFD + STZ treatment. Corneal OPN levels in WT diabetic mice increased ~2-fold at 2 weeks and ~4-fold at 16 weeks compared to non-diabetic controls, with similar elevations observed in their tear fluid. Diabetic db/db mice also exhibited elevated OPN levels in the blood and ocular surface, which persisted as diabetes progressed. Enhanced fluorescein staining, indicating corneal irregularities, appeared in WT mice at 8 weeks and in OPN-/- mice at 10 weeks post-T2D induction. Additionally, WGA staining showed a significant reduction in fluorescence intensity in WT mice treated with HFD and STZ, confirming corneal surface irregularities that were delayed in OPN-/- mice. Elevated tear sodium concentration was observed in both WT and OPN-/- diabetic mice without affecting tear production rates. Notably, OPN levels increased early, at week 2, following HFD and STZ treatment, preceding changes in interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9). Upregulation of IL-6 became apparent at 6 weeks in WT mice and was delayed until 10 weeks in OPN-/- mice post-T2D induction. Elevated OPN levels were detected early post-T2D induction in diabetic WT and db/db mice corneas without initial subclinical changes. This early increase in OPN precedes other proinflammatory cytokines associated with eventual ocular surface inflammation as diabetes progresses. Persistence of OPN also correlated with clinical signs such as increased corneal surface irregularities and elevated tear Na+ concentration. Future research will explore OPN's role as a biomarker in ocular surface disease (OSD), including dry eye disease (DED), and investigate its impact on inflammatory processes and other mechanistic pathways in diabetic ocular complications.

Advanced quantitative magnetic resonance imaging of lower extremity muscle microtrauma after marathon: a mini review

This article reviews the existing literature and outlines recent advances in quantitative Magnetic Resonance Imaging (MRI) techniques for the assessment of lower extremity muscle microtrauma following a marathon. Single-modality quantitative MRI techniques include T2 mapping to assess the dynamics of muscle inflammatory edema and variability at the site of injury, Diffusion Tensor Imaging (DTI) to detect subclinical changes in muscle injury, Intravoxel Incoherent Motion (IVIM) imaging to provide simultaneous information on perfusion and diffusion in muscle tissue without the need for intravenous contrast, and Magnetic Resonance Spectroscopy (MRS) to noninvasively detect intramyocellular lipid (IMCL) content in muscle before and after marathon exercise to explain the use of fatty acids as an energy source in skeletal muscle during long-distance running. As well as Chemical Exchange Saturation Transfer (CEST) is particularly suitable for detecting changes in free creatine, pH values and lactate concentrations in muscles before and after exercise, providing a more detailed picture of muscle physiology and chemistry. These metabolic MRI methods enhance the understanding of biochemical alterations occurring in muscles pre- and post-exercise. Multimodal techniques combine different modalities to provide a comprehensive evaluation of muscle structural and functional changes. These advanced techniques aim to better assess microtrauma and guide clinical treatment, though further validation with larger studies is needed to establish their potential over traditional qualitative methods.

Comparison of early postoperative left ventricular function with 3d ef and strain measurements according to graft selection

BackgroundGraft choices other than left anterior descending artery (LAD)–internal thoracic artery (ITA) anastomosis in coronary artery bypass grafting (CABG) surgery are still controversial. Although 2-dimensional transthoracic echocardiography (2D TTE) is still the most commonly used method, more is needed to diagnose myocardial dysfunction. Ventricular strain values obtained by speckle tracking echocardiography (STE) or tissue Doppler imaging (TDI) methods can much better detect subclinical changes. This study aims to detect early postoperative myocardial function changes compared to single ITA/Bilateral Internal Thoracic Artery (BITA) use by measuring 3-dimensional ejection fraction (3D EF) and ventricular strain values and comparing them according to graft preference.MethodsThe study included 35 isolated CABG patients. All patients underwent on-pump CABG via sternotomy. The patients were divided into two groups using single ITA and BITA. Preoperative and postoperative 1st-week 3D EF and ventricular strain values of the patients were calculated using semi-automatic software. The recorded data were compared and evaluated between the two groups.ResultsOf The 35 patients participating in the study, 74.3% (n = 26) were male, 25.7% (n = 9) were female, and their average age was 62.7 ± 7.9 years. Preoperative 3D EF values of the patients were 54.4 ± 8.3% and postoperative 49.5 ± 8.2%. The mean preoperative Apical Long Axis Longitudinal Strain (APLAX LS) was calculated as − 16.2 ± 5.0%, 4 Chambers Longitudinal Strain (4CH LS)–16.8 ± 4.6%, 2 Chambers Longitudinal Strain (2CH LS) − 17.0 ± 4.9%, and Global Longitudinal Ventricular Strain (GLVS) − 16.7 ± 4.2%. Postoperative strain values were measured as − 15.1 ± 4.8%, − 14.7 ± 4.9%, − 14.6 ± 5.6% and − 14.8 ± 4.6%, respectively. When the groups were evaluated within themselves, the mean preoperative 3D EF of the patients in the single ITA group was 52.5 ± 8.8%, while the postoperative mean was 47.7 ± 6.0%. In the BITA group, preoperative 3D EF was 56.3 ± 7.5 and postoperative 51.4 ± 9.8. A decrease in strain values was detected in all groups except APLAX planes.ConclusionsIn our study, no statistically significant difference was observed in terms of myocardial function changes according to the use of ITA/BITA. However, the decline in postoperative strain values of patients in the BITA group was more remarkable, and it was thought that this may be due to prolonged aortic cross clamp (CC) and cardiopulmonary bypass (CPB) times.

HIV is associated with subtle impairments in left ventricular function: insights from a large prospective cohort study of well-treated people with HIV

Abstract Background Human Immunodeficiency Virus (HIV) has become a treatable, chronic condition, but people with HIV still face an elevated risk of cardiovascular disease, including heart failure. Purpose To assess echocardiographic alterations in left ventricular (LV) function in a contemporary cohort of well-treated people with HIV compared to the general population. Methods We included 744 people with HIV frequency matched 1:1 on age and sex with controls from the general population. Both people with HIV and controls underwent echocardiography, physical examination, questionnaires and blood sampling according to similar study protocols. LV systolic dysfunction was defined as LV ejection fraction (LVEF) &amp;lt;50% or absolute global longitudinal strain (GLS) &amp;lt;16%. LV diastolic function was defined as abnormal if the following was true for half or more available parameters: (1) average E/e’&amp;gt;14, (2) septal e’ velocity &amp;lt; 7 cm/s or lateral e’ velocity &amp;lt;10cm/s, (3) tricuspid regurgitation velocity &amp;gt;2.8 m/s, (4) left atrial volume index &amp;gt;34ml/m2. Associations between HIV status and LV function were assessed using linear and logistic regression models adjusted for age, sex, smoking, hypertension, diabetes mellitus, total cholesterol and high-sensitivity C-reactive protein. Among people with HIV, the association between HIV-specific characteristics and LV function were assessed using logistic regression models with adjustment for the same potential confounders. Results Mean age was 53.4 years and 88% were male. For people with HIV, median time since HIV diagnosis was 18 years and 99% received antiretroviral therapy. People with HIV had lower adjusted mean absolute GLS [17.6 vs. 18.5%, p&amp;lt;0.001], E/A ratio [1.0 vs. 1.2, p&amp;lt;0.001] and average e’ [9.5 vs. 10.5 cm/s, p&amp;lt;0.001] than controls, while LVEF and E/e’ were not significantly different between people with HIV and controls (Figure 1). HIV was associated with impaired systolic function as assessed by GLS [odds ratio 1.70, 95% CI: 1.17-2.46, p=0.005], but not when assessed by LVEF [odds ratio 1.06, 95% CI: 0.78-1.45, p=0.69](Figure 2). Living with HIV was not associated with diastolic dysfunction compared to controls [odds ratio 0.97, 95% CI: 0.61-1.52, p=0.88], but longer HIV-duration was associated with higher odds of diastolic dysfunction among people with HIV (odds ratio 1.06, 95% CI: 1.02-1.10 per year, p=0.004). Current antiretroviral medication type, previous AIDS defining conditions, current CD4+ count and detectable viral load were not associated with LV dysfunction. Conclusion People with HIV show signs of early impairments in longitudinal LV systolic function compared to the general population. These subclinical changes may underlie the increased risk of heart failure observed in PWH.

Type 2 diabetes individuals have a shorter QRS duration, prolonged QTc interval, flatter T wave, and reduced left ventricular cycle volumes compared to matched controls in the UK Biobank

Abstract Background Type 2 diabetes is associated with an increased risk of heart failure even in the absence of overt coronary artery disease, though underlying mechanisms are unclear. ECG and cardiac magnetic resonance (CMR) imaging provide windows into subclinical changes in myocardial structure and function and could be exploited to understand this. Purpose We investigate differences in ECG and CMR biomarkers in a large cohort of participants with type 2 diabetes, compared to a matched control cohort. We hypothesise that individuals with diabetes may exhibit concurrent differences in biomarkers, reflecting underlying cardiac remodelling. Methods We carried out a pair-matched cross-sectional study to examine the association between type 2 diabetes and multi-modal cardiac biomarkers. The exposure cohort consists of 1,781 UK Biobank participants with an imaging and ECG visit, prevalent type 2 diabetes and no known cardiovascular events at the time of visit. The control cohort is matched on age, sex and body mass index (BMI), and consists of 1,781 participants without diabetes. ECG and CMR biomarkers derived from UK Biobank data were used as outcome variables. We built four multiple multivariate linear regression models, incrementally adjusted for socio-demographic, lifestyle, and clinical covariates. Results Both cohorts were mostly male (63.6%), had a median age of 67 years [IQR: 72-85] and a median BMI of 27.8 kg/m2 [24.6-31.0]. Individuals with type 2 diabetes were more likely to be non-white (7.9% vs 2.7%, p&amp;lt;0.001), current or previous smokers (43.6% vs 40.6%, p=0.04), have lower diastolic blood pressure (79 [72-85] vs 81 [74-88] mmHg, p&amp;lt;0.001), and take cholesterol medication (72.3% vs 27.2%, p&amp;lt;0.001); anti-hypertensives (56.3% vs 27.3%, p&amp;lt;0.001); insulin (13.7% vs 0.1%, p&amp;lt;0.001); and metformin (53.1% vs 0.1%, p&amp;lt;0.001). They had a higher ventricular rate, shorter QRS duration, longer QTc interval, and flatter T wave amplitude, as well as lower left ventricular end-diastolic and end-systolic volumes, among other differences (Table 1). Covariates including cholesterol medication, metformin, and HbA1c were excluded as they were strongly correlated with diabetes, age and/or sex (Pearson correlation coefficient &amp;gt;0.3 or &amp;lt;-0.3). After full adjustment, we found that the exposure variable, diabetes, had a statistically significant association with ventricular rate, QRS duration, T wave offset, T wave amplitude in lead V3, left ventricular stroke volume and global average thickness (p&amp;lt;0.05) (Table 2). Conclusion Our results reveal that individuals with type 2 diabetes exhibit a shorter QRS, longer QTc, and lower end-diastolic and end-systolic volumes, compared to matched controls. This may be indicative of subclinical cardiac abnormalities, both electrophysiological and mechanical. Our association analysis suggests that other factors correlated with diabetes may be also responsible for certain biomarker differences and their underlying causes.

The added value of advanced echocardiography in dilated cardiomyopathy: looking at the right heart

Abstract Introduction and aims Right ventricular (RV) dilation and dysfunction significantly impact the prognosis of dilated cardiomyopathy (DCM) patients, and early detection of subclinical changes is mandatory. Furthermore, right atrial (RA) size and function are still often neglected in DCM patients. Accordingly, our aims were to evaluate (i) right heart chambers and tricuspid annulus (TA) subclinical remodeling, and (ii) the prognostic value of RA compared to left atrial (LA) size and function in patients with DCM without clinical RV involvement, RV pressure/volume overload or sustained atrial tachyarrhythmias by advanced echocardiography techniques. Materials and methods Sixty-eight patients out of a cohort of 106 patients with DCM (mean age 60 years, 35 men) were evaluated by comprehensive transthoracic two- (2DE) and three-dimensional (3DE) and speckle-tracking (2DSTE) echocardiography, were compared to 62 age- and sex-matched healthy controls (mean age 61 years, 32 men), and were followed-up for 37 ± 16.6 months. Results DCM patients have RV and RA global longitudinal dysfunction by 2DSTE, and higher RA minimum volumes (Vmin) and TA areas despite having normal RV volumes and ejection fraction (EF) and RA maximum volumes (Vmax) by 3DE compared to controls (Table). RA and RV strain correlate with each other (r=0.360, p=0.013 for RA reservoir and r=0.347, p=0.017 for conduit strain). TA area correlates with RA contractile strain (r=-.293, p=0.046) and RV free-wall strain (r=0.373, p=0.008), RA Vmax (r=0.513, p&amp;lt;0.001), RV (r=0.404, p=0.004 for end-diastolic and r=0.444, p=0.001 for end-systolic) and left ventricular (LV) volumes (r=0.394, p=0.016) and LV EF (r=-.361, p=0.028). RA reservoir strain (AUC=0.769) has higher value for outcome prediction compared to LA strain (p=0.02 between them). Conclusion Patients with DCM have RV longitudinal dysfunction and decreased RA function, in the absence of clinical RV involvement or atrial arrhythmias, and decreased RA strain is associated with an increased risk of hospitalization and cardiac death.Comparison of right heart parametersPrognostic value of atrial function

The condition of myocardium reserves score from a cloud-based analytics platform of Holter ECG data indicates better cardiometabolic function in heart failure

Abstract Introduction Cardiometabolic dysregulation, particularly type 2 diabetes mellitus (T2DM), is associated with subtle myocardial pathologies, even in individuals without known cardiovascular disease. These subclinical changes, often undetectable by standard electrocardiogram (ECG) analytics, can offer valuable insights into the relationship between metabolic health and cardiac function. Novel ECG markers, developed through machine learning and artificial intelligence (AI), may provide the sensitivity needed to detect such changes. Aim This study aims to evaluate novel composite cardiac parameters from an analytics platform in the context of heart failure (HF), seeking to understand their relationship to cardiometabolic dysregulation. Methods Data from the MyoVasc study, a prospective cohort on HF, were analysed. Participants underwent extensive clinical phenotyping, including a Holter ECG assessment. Holter ECG data was processed based on machine learning and AI models on a cloud-based analytics platform (Cardiolyse, Helsinki, Finland), generating both traditional and proprietary ECG, and heart rate variability cardiac health markers. LASSO-penalized logistic regression adjusted for sex and age was performed to select the marker most strongly associated with T2DM. The identified marker was then evaluated in relation to cardiac function and structure as well as HF-related outcome. Results A total of 953 subjects (mean±SD age 64.6±10.5 years; 35.7% women) were included in the analyses. Symptomatic HF stage C/D was present in 54.8% (n=522) of subjects and diabetes mellitus in 22.4% (n=213). The Condition of Myocardium Reserves Score (CMRS) was the novel composite cardiac parameter selected based on its relationship with T2DM. In a Poisson regression model with robust variance adjusted for sex and age, a lower score was associated with T2DM (Prevalence ratio per SD 1.24, 95% confidence interval [1.14;1.36], P=0.0002). In multivariable linear regressions adjusted for traditional cardiovascular risk factors, comorbidities, and medication, a higher CMRS was associated with better global longitudinal strain (β per SD –0.82 [–1.11;–0.53], P&amp;lt;0.0001), diastolic function (left ventricular E/e’; β per SD –0.04 [–0.06;–0.01], P=0.0059) and systolic function (LV ejection fraction; β per SD 2.06 [1.46;2.67], P&amp;lt;0.0001). A lower CMRS independently predicted all-cause death (Hazard ratio per SD 1.25 [1.09;1.45], P=0.0020) and worsening of HF (HR per SD 1.44 [1.21;1.72], P&amp;lt;0.0001) in Cox regression analysis adjusted for the same confounders. Conclusion The Condition of Myocardium Reserves Score exhibited a strong association with cardiometabolic dysregulation. A higher CMRS indicated preserved cardiac function, while a lower score independently predicted increased risk of all-cause death and worsening HF. This novel score offers potential as a non-invasive tool for assessing cardiometabolic health and stratifying risk in patients with HF.

Cardiovascular (reverse) remodelling induced by pregnancy: looking at the right side of the heart

Abstract Introduction Many studies have focused on pregnancy-induced left ventricular remodelling, overlooking the changes in right cardiac chambers. Purpose To characterize the right cardiovascular (CV) remodelling and reverse remodelling (RR) induced by pregnancy and postpartum, respectively, and the impact of CV risk (CVR) factors on these processes. Methods This prospective cohort was recruited at two tertiary centers from 2019 to 2022, including 51 healthy and 79 obese and/or hypertensive and/or with gestational diabetes and/or smoking habits pregnant women (cardiovascular risk [CVR] group). Women were evaluated by transthoracic echocardiography at the 1st trimester (1T) and 3rd trimester (3T) of pregnancy, as well as one-month (PP1), six-months (PP2), and one-year postpartum (PP3). Generalized linear mixed-effects models were used for the analysis of right CV remodelling and RR and to evaluate the impact of CVR factors on these processes. Results This study included 130 pregnant women, 60.8% primiparous, with a median age of 33 years. Despite all echocardiographic results being within the normality range, we describe the progression of right heart adaptations throughout pregnancy and postpartum (Table 1), namely: 1) Similar enlargement of the right atrium (RA) and right ventricle (RV) dimensions throughout pregnancy, recovering at PP2 except for RA in the CVR group; 2) Preserved RV systolic function throughout pregnancy in both groups, while the postpartum hemodynamic normalization triggers a reduction of (TAPSE) and tricuspid S' wave velocity; 3) Reduced RA strain in both groups during pregnancy, more evident in CVR group, which had a slower postpartum recovery; 4) Preserved RV global longitudinal strain (GLS) throughout follow-up time, being significantly reduced in 3T of CVR group and recovering at PP2; 5) Reduction of tricuspid E/A ratio from 1T to 3T in both groups with an early recovery at PP1, being these values significantly higher in the healthy group, and 6) Steady pulmonary artery systolic pressure (PASP) values throughout follow-up time, showing consistently higher values in the CVR group. Conclusion This study describes the subclinical right cardiac functional and structural changes within the physiological range, which recover 6 months after delivery. CVR factors impact the magnitude of the subclinical RV diastolic function changes, PASP and myocardial deformation (strain) without any impact on classic RV systolic function.

Improving cardiovascular risk stratification with ECG-predicted risk factors in primary prevention

Abstract Background Cardiovascular risk- and screening scores guide clinical practice. Built upon simple risk factors, they could benefit from information on actual, subclinical cardiac changes. The ECG provides proxies for various cardiac states, which can be detected using machine learning. We systematically assess the added value of ECG-based cardiovascular risk factor estimates for six outcomes in two population-based cohorts: Study of Health in Pomerania (SHIP-Start) and UK Biobank (UKB). Methods We employed convolutional neural networks to analyze ECGs from the Hamburg City Health Study (HCHS) for the assessment of multiple risk factors, including age, weight, diabetes, atrial fibrillation (AF) and heart failure. Cox models were fitted on UKB and SHIP to predict 5 and 15 year time-to-event. Endpoints were death, cardiovascular death, AF, stroke, heart failure and myocardial infarction. Covariates were sex, age, body mass index, diabetes, hypertension and smoking (Cox-RF), ECG-predicted risk factors (Cox-AI), and a combination (Cox-RF/AI). Stratified Monte Carlo cross-validation was used as validation and groups of C-indices were compared using Mann-Whitney U tests. Results The study included 9103 HCHS participants (mean age 62.0±8.4 years, 51% women), 3546 SHIP participants (age 49.7±16.4, 51% women), and 32828 UKB participants (age 64±7.6 years, 52% women). Cox-AI performed comparable or better than Cox-RF for AF (SHIP: 0.88 vs. 0.84, UKB: 0.71 vs. 0.72) and heart failure (SHIP: 0.8 vs. 0.79, UKB: 0.76 vs. 0.75), but was less strong for the other outcomes. The combination of information on cardiovascular risk factors and ECG information (Cox-RF/AI) significantly improved the predictive ability compared to risk factors alone (Cox-RF) for AF (SHIP: 0.89 vs. 0.84, UKB: 0.76 vs. 0.72), cardiovascular death (SHIP: 0.90 vs. 0.89, UKB: 0.75 vs. 0.74) and heart failure (SHIP: 0.81 vs. 0.79, UKB: 0.80 vs. 0.75). Discussion ECG-based risk factors complement risk stratification by incorporating nuanced information on cardiac function and structure, improving risk prediction and thus possibly clinical decision making and patient outcomes.

Effects of moderate-intensity aerobic training on cardiac structure and function in type 2 mellitus diabetic rats: Based on echocardiography and speckle tracking

PurposeThe present study aimed to evaluate the cardiac function changes using Layer-specific Speckle-tracking echocardiography (LS-STE) induced by Moderate-intensity aerobic training (MIAT) in Type 2 diabetes mellitus (T2DM) rats. MethodsTwenty-six rats were divided into four groups: the Control group (Con), the Training control group (CT), the T2DM group (DM), and the T2DM training group (DT). The CT and DT groups underwent an 8 weeks MIAT. Cardiac structure and function were evaluated by echocardiography and LS-STE. ResultsCompared with the Con group, left atrial diameter (LAD), left ventricular end-diastolic diameter(LVEDD), relation wall thickness (RWT), and left ventricular mass (LVM) were significantly higher, and the endo-, mid-, and epi-longitudinal strain (LS), global radial strain (GRS), and endo- and mid-circumferential strain (CS) were significantly lower in DM rats (all p < 0.05). The endo-, mid-, and epi-LS, GRS, endo- and mid-CS were increased in DT rats compared with DM rats (all p < 0.05). Compared with Con rats, CT rats had a significant increase in LVEDD and LVM (all p < 0.05), meanwhile myocardial strains had no significant differences (all p > 0.05). ConclusionLS-STE was a sensitive method to assess subclinical myocardial changes in T2DM rats. MIAT had the benefit of reversing cardiac systolic subclinical dysfunction in T2DM rats.

Genetic testing in pediatric kidney transplant recipients to promote informed choice and improve individualized monitoring

BackgroundThe growing body of research on kidney disease in children has identified a broad spectrum of genetic etiologies.MethodsWe conducted a prospective study to evaluate the efficacy of an optimized genetic test and subclinical changes in a real-world context before kidney transplantation. All cases involved recipients under the age of 18 who underwent whole exome sequencing (ES) between 2013 and 2022.ResultsThe study population included 244 children, with a median age of 13.1 years at transplantation. ES provided a molecular genetic diagnosis in 114 (46.7%) probands with monogenic variants in 15 known disease-causing genes. ES confirmed the suspected clinical diagnosis in 74/244 (30.3%) cases and revised the pre-exome clinical diagnoses in 40/244 (16.4%) cases. ES also established a specific underlying cause for kidney failure for 19 patients who had previously had an unknown etiology. Genetic diagnosis influenced clinical management in 88 recipients (36.1%), facilitated genetic counseling for 18 families (7.4%), and enabled comprehensive assessment of living donor candidates in 35 cases (14.3%).ConclusionsGenetic diagnosis provides critical insights into the pathogenesis of kidney disease, optimizes clinical strategies concerning risk assessment of living donors, and enhances disease surveillance of recipients.

Electrocardiogram Features of Left Ventricular Excessive Trabeculation with Preserved Cardiac Function in Light of Cardiac Magnetic Resonance and Genetics.

Background and Objectives: Although left ventricular excessive trabeculation (LVET) can cause heart failure, arrhythmia and thromboembolism, limited literature is available on the ECG characteristics of primary LVET with preserved left ventricular function (EF). We aimed to compare the ECG characteristics and cardiac MR (CMR) parameters of LVET individuals with preserved left ventricular EF to a control (C) group, to identify sex-specific differences, and to compare the genetic subgroups of LVET with each other and with a C population. Methods: In our study, we selected 69 LVET individuals (EF > 50%) without any comorbidities and compared them to 69 sex- and age-matched control subjects (42% females in both groups, p = 1.000; mean age LVET-vs-C: 38 ± 14 vs. 38 ± 14 years p = 0.814). We analyzed the pattern and notable parameters of the 12-lead ECG recordings. We determined the volumetric and functional parameters, as well as the muscle mass values of the left and right ventricles (LV, RV) based on the CMR recordings. Based on the genotype, three subgroups were established: pathogenic, variant of uncertain significance and benign. Results: In the LVET group, we found normal but elevated volumetric and muscle mass values and a decreased LV_EF, wider QRS, prolonged QTc, higher RV Sokolow index values and lower T wave amplitude compared to the C. When comparing MR and ECG parameters between genetic subgroups, only the QTc showed a significant difference. Over one-third of the LVET population had arrhythmic episodes and a positive family history. Conclusions: The subclinical morphological and ECG changes and the clinical background of the LVET group indicate the need for follow-up of this population, even with preserved EF.

Subclinical Cardiopulmonary Changes of Heart Failure with Preserved Ejection Fraction (HFpEF) in CKD

Subclinical Cardiopulmonary Changes of Heart Failure with Preserved Ejection Fraction (HFpEF) in CKD

Corneal biomechanics in patients with allergic conjunctivitis.

Allergic conjunctivitis (AC) comprises a group of conditions triggered by environmental allergens, substantially diminishing the quality of life, particularly among children and adolescents. The mechanical impact of eye rubbing in patients with AC is known to induce biomechanical alterations in the cornea. Modern instruments enable the detection and quantification of these corneal biomechanical changes. The ocular response analyzer and CorVis ST have become standard tools for assessing corneal biomechanical properties. We conducted a review of studies that have investigated corneal biomechanics in patients with AC using both devices to elucidate the association between corneal biomechanical changes and early ectasia development. Our analysis highlights significant findings regarding the tomographic biomechanical index parameter in corneal biomechanics among patients with AC. These findings underscore the importance of ocular screening for all patients to promptly detect subclinical keratoconus changes, thereby improving disease management and outcomes.

Clinical Versus Ultrasound Assessment of Joint Activity in Patients with Asymptomatic Hyperuricemia

Background: In this study, we aimed to investigate subclinical ultrasonographic change suggestive of gouty arthritis in the hyaline cartilage, joints and tendons from asymptomatic hyperuricemia (AH) individuals with hyperuricemia. Methods: We conducted a cross-sectional, observational study including US examinations of the knees and first MTPJs as well as of the tendons and enthesis. The normal distribution of different parameters was tested by the Shapiro–Wilk normality test. Quantitative data were expressed in mean ± standard deviation and the difference between means of two groups was tested by Student’s t-test while qualitative data were expressed in frequency and the difference between proportions was tested by the chi-square test or Fisher exact test. Results: Fifty-nine AH individuals and 52 normouricemic subjects were included. A total of 118 knees, ankles and first MTPJs in patients with AH and 104 in the normouricemic subjects were studied. The most common abnormality found on USG was power Doppler signal in 1st MTPJ (37% vs. 0%; P &lt; .001) followed by joint cavity widening (31% vs. 0%; P &lt; .001). Double contour sign was found in 11% of the first MTPJs from AH individuals versus none in the control group ( P &lt; .001). Posterior tibialis tenosynovitis (6% vs. 0%; P &lt; .01) and Achilles tendon enthesopathy (8% vs. 0%; P &lt; .001). Conclusions: These data demonstrate that subclinical changes detected in the US suggestive of gouty arthritis induced by chronic hyperuricemia frequently occur in both intra- and extra-articular structures of clinically AH individuals.

Longitudinal Assessment of Selective Motor Dysfunction in Service Members With Combat-Related Mild TBI.

Evaluations of clinical outcomes in service members with mild traumatic brain injury (TBI) sustained in combat have largely focused on neurobehavioral and somatic symptoms, neurocognitive functioning, and psychological/psychiatric health. Questions remain regarding other domains, such as gross or fine motor abilities, that could be impacted and are mission-critical to functional warfighters. The objective of the current study was to evaluate longitudinal motor function in U.S. Military personnel with and without mild TBI sustained in combat to assess the possible long-term impact. Data from the EValuation Of Longitudinal outcomes in mild TBI active duty military and VEterans (EVOLVE) study were leveraged for analysis. The EVOLVE study has evaluated and followed service members from combat and following medical evacuation with and without blast-related mild TBI, as well as blunt impact mild TBI, and noninjured combat-deployed service members, tracking 1-, 5-, and 10-year outcomes. Longitudinal demographic, neuropsychological, and motor data were leveraged. Cross-sectional differences in outcomes at each year among the 4 injury groups were assessed using rank regression, adjusting for age, education, sex, branch of service (Army vs. other), subsequent head injury exposure, and separation from service. To understand the possible performance impact of time on all the measures, mixed-effects rank regression was employed, assessing time with adjustments for group, age, education, subsequent head injury exposure, and service separation status, followed by Benjamini-Hochberg correction for multiple comparisons. Evaluation for cognitive performance across 19 primary measures of interest at 1, 5, and 10 years did not identify any significant differences; however, gross motor function was found to be significantly different across groups at all time points (adjusted P < .001 at 1 year, P = .004 at 5 years, and P < .001 at 10 years) with both TBI groups consistently performing slower on the 25-Foot Walk and Grooved Pegboard than the nonblast control groups. While there were no cross-sectional differences across groups, many cognitive and motor measures were found to have significant changes over time, though not always in the direction of worse performance. Selective motor impairment in both TBI groups was identified compared to nonblast controls, but all groups were also found to exhibit a level of motor slowing when comparing performance at 1- to 10-year follow-ups. Assessment of gross motor function reflected a consistent pattern of significantly slower performances for blast and nonblast TBI groups compared to controls, over all follow-up intervals. Fine motor function performance reflected a similar significant difference pattern at 1- and 5-year follow-up intervals, with a reduced difference from control groups at the 10-year follow-up. Maintenance of high-level motor functions, including overall motor speed, coordination, and reaction time, is a primary component for active warfighters, and any motor-related deficits could create an increased risk for the service member or unit. While the service members in this longitudinal study did not meet criteria for any specific clinical motor-related diagnoses or movement disorders, the finding of motor slowing may reflect a subclinical but significant change that could be a focus for intervention to return to preinjury levels.

Tracking Macular Sensitivity and Inner Retinal Thickness in Long-Term Type 1 Diabetes: A Five-Year Prospective Examination in Patients without Diabetic Retinopathy.

The aim of the study is to compare macular sensitivity and retinal thickness in patients with long-term type 1 diabetes mellitus (DM1) without diabetic retinopathy (DR) after 5 years of follow-up. Thirty-two eyes from 32 long-term DM1 patients without DR were included. All participants underwent a complete ophthalmological examination, including microperimetry and spectral domain optical coherence tomography (SD-OCT). The data were compared with results from 5 years prior. The mean age of the DM1 patients was 43.19 ± 10.17 years, with a mean disease duration of 29.84 ± 8.98 years and good glycemic control. In 2023, patients exhibited a significantly worse best corrected visual acuity (BCVA) compared to 2018 (p < 0.001). DM1 patients did not show statistically significant changes in macular sensitivity over the 5-year follow-up period. Macular integrity showed significant differences between the two time points (p = 0.045). Retinal thickness showed significant differences, particularly in inner retinal layers (IRL) across most of the ETDRS areas. Long-term DM1 patients without DR lesions showed worsened macular integrity and a lower BCVA in 2023. Additionally, they displayed significant alterations in retinal thicknesses, especially in the IRL, between 2018 and 2023. These findings suggest that even in the absence of visible DR, long-term DM1 patients may experience subclinical retinal changes and functional deterioration over time, highlighting the importance of regular monitoring for the early detection and management of potential complications.

Speech Biomarkers in Huntington's Disease: A Longitudinal Follow-Up Study in Premanifest Mutation Carriers.

Speech alterations have been reported in manifest Huntington's disease (HD) and premanifest mutation carriers (preHD). The aim of our study was to explore these alterations in preHD and whether they can be used as biomarkers. 13 preHD mutation carriers performed reading task, sustained phonation task and syllable repetition tasks at baseline and after 21 months, as well as clinical examination and MRI. Syllable repetition capacity and self-chosen velocity of single syllable repetition differed significantly between time points. There were no changes in clinical ratings or MRI volumetry. Measurements of speech might be sensitive tools for monitoring subclinical changes in preHD.

Assessment of left ventricular myocardial systolic dysfunction in premature ovarian insufficiency patients using echocardiographic layer-specific myocardial strain imaging

BackgroundDue to the lack of oestrogen, premature ovarian insufficiency (POI) is an independent risk factor for ischaemic heart disease and overall cardiovascular disease. This study aimed to apply layer-specific myocardial strain for early quantitative evaluation of subclinical left ventricular myocardial systolic function changes in patients with POI.MethodsForty-eight newly diagnosed, untreated patients with POI (POI group) and fifty healthy female subjects matched for age, height and weight (control group) were enrolled. Standard transthoracic echocardiography was used to measure conventional parameters and layer-specific strain parameters.The layer-specific strain parameters included subendomyocardial global longitudinal strain (GLSendo), mid-layer myocardial global longitudinal strain (GLSmid), subepimyocardial global longitudinal strain (GLSepi), subendomyocardial global circumferential strain (GCSendo), mid-layer myocardial global circumferential strain (GCSmid), and subepimyocardial global circumferential strain (GCSepi). ResultsThere were no significant differences in age, body mass index (BMI), blood pressure, or left ventricular ejection fraction (LVEF) between the two groups. The end-diastolic interventricular septal thickness (IVST) was greater in the POI group (8.29 ± 1.32 vs. 7.66 ± 0.82, P = 0.008), and the POI group had lower E, E/A, and lateral e′ (all P < 0.05). As for systolic functions,the POI group had lower GLSendo, GLSmid, GLSepi, GCSendo, GCSmid, and GCSepi (all P < 0.05).The intraobserver and interobserver coefficients of GLSendo, GLSmid, GLSepi, GCSendo, GCSmid, and GCSepi were greater than 0.900. ConclusionsPOI patients with normal LVEF may suffer from subclinical left ventricular myocardial systolic dysfunction. Echocardiography of layer-specific myocardial strain could more sensitively detect subclinical impairment of left ventricular systolic function in POI patients.Graphical abstract

410.1: The effect of steroid pulse therapy for the reduction of acute rejection episode in subclinical borderline changes: An open-label, randomized clinical trial.

410.1: The effect of steroid pulse therapy for the reduction of acute rejection episode in subclinical borderline changes: An open-label, randomized clinical trial.