Pattern Of Remodeling Research Articles

Patterns of left ventricular remodeling according to the type of sport in a cohort of elite athletes assessed by speckle tracking echocardiography

Abstract Background Athletic training is associated with hemodynamic demands leading to physiological cardiac changes referred to as athlete’s heart. Whilst some studies support the hypothesis with predicted eccentric left ventricular hypertrophy (LVH) from endurance training, data confirming concentric-type effects of resistance training are inconsistent. Also, whether specific geometric adaptations are associated with specific changes of LV myocardial performance is undefined. Purpose To assess patterns of LV remodeling in relation to the type of sport, using speckle tracking echocardiography (STE) in a cohort of elite athletes (EA). Methods 132 EA (23±5 years) referred for resting echocardiography during annual check-up were prospectively enrolled.They were involved in competitive sports for >10 hours/week for over 3 years and had no history of cardiac/non-cardiac disease or sudden cardiac death. A control group of 15 healthy volunteers (25±3 years), either sedentary or engaged in <6 h of non-competitive training/week, was enrolled. An echocardiogram was performed in all subjects. Global myocardial work (MW) indices - work index (GWI), constructive work (GCW), work efficiency (GWE) and wasted work (GWW)- were calculated using a software able to construct a noninvasive LV pressure-strain loop based on STE-derived global longitudinal strain (GLS) and LV pressure from systolic cuff pressure. Analysis was performed by an experienced investigator blinded to the sport history of each subject. Results Four subgroups of EA were defined according to the sports disciplines: power (n=27), endurance (n=30), mixed (n=62) and skill (n=13). Mean values of LV volumes, wall thickness and mass were significantly higher in EA compared with controls. Normal LV geometry was present in >50% of EA in each group and >70% of power and skill EA. LVH was more prevalent in endurance (23.3%) and mixed (19.4%) as compared to skill (7.7%) and power (7.4%) EA. Eccentric hypertrophy was found only in endurance and mixed EA (<15% each group). Including age, BSA, gender, sport discipline, duration and intensity of training in binary logistic regression to predict LVH, increasing age was the only significant predictor (p=0.01). Conventional and advanced parameters of LV systolic and diastolic function were within normal range in all subjects. The one-way ANOVA revealed no significant differences between groups of EA and controls regarding mean values of GLS, LV ejection fraction and MW indices. However, among EA, endurance EA exhibited the highest values of GCW(2075±228 mmHg%), GWI(1767±222 mmHg%) and GWE(95.5±1.7%) and lowest GWW(76±35 mmHg%) with statistic significance for GWW(p=0.03) and marginally for GWE(p=0.05). Conclusion In our study, the type of sport was not related to the presence of LVH. The most significant LV remodeling was observed in EA, as expected, associated with a resting myocardial work profile characterized by highest values of GWI, GCW and GWE and lowest GWW. MW parameters and the type of sport

Association between perforator stroke after middle cerebral artery elective stenting and arterial remodeling patterns: a high-resolution MRI-based retrospective cohort study.

Patterns of arterial remodeling may be associated with outcomes in patients with severe middle cerebral artery (MCA) stenosis after endovascular treatment (EVT). This study aims to investigate the potential correlation between arterial remodeling patterns in patients with severe MCA stenosis, and plaque characteristics and procedure-related perforator stroke (PS). Consecutive patients with MCA atherosclerotic disease who underwent EVT at the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2023 were retrospectively enrolled in this study. The clinical and surgical data of the patients were evaluated. Remodeling index values >1.05, 0.95-1.05, and <0.95 indicated positive remodeling (PR), intermediate remodeling (IR), and negative remodeling (NR), respectively. Based on the remodeling index values calculated by high-resolution magnetic resonance imaging (HR-MRI), the arterial remodeling patterns were classified as NR or non-NR; non-NR was defined as both PR and IR. The primary endpoint was procedure-related PS. Plaque characteristics included the plaque area, plaque burden, contrast-enhancement ratio, and plaque distribution. Plaque features and the incidence of procedure-related PS were compared between the NR and non-NR groups. Differences in the categorical variables between the patients with NR and non-NR were assessed using the Chi-square test (χ2) or Fisher's exact test. Differences in the continuous variables between the two groups were assessed using the Student t-test or Mann-Whitney U-test. A total of 65 patients (mean age: 57.6 years) were enrolled in the study. Of the patients, 45 (69.2%) showed NR and 20 (30.8%) showed non-NR. The primary endpoint of procedure-related PS occurred in 3 patients (3/65, 4.6%). On HR-MRI, the entire cohort had a mean plaque area of 10.0 mm2, a mean plaque burden of 92.0 %, and a mean enhancement ratio of 1.3. Compared to the non-NR group, the NR group had a smaller plaque area (9.2 vs. 11.6 mm2, P=0.001). The probability of the primary end point was 15.0% in the non-NR group and 0.0% in the NR group (P=0.026). PS after MCA elective stenting may be related to non-NR based on HR-MRI. Further prospective and multicenter studies need to be conducted to confirm these findings.

Latent class analysis of cardiac structure and function and association with premature cardiovascular disease: The Coronary Artery Risk Development in Young Adults (CARDIA) study

ObjectiveTo generate data-driven phenogroups of cardiac structure and function based on echocardiographic measures assessed in asymptomatic middle-aged adults free of CVD, and examine associations between these newly defined phenogroups and incident premature cardiovascular disease (CVD). MethodsData were analyzed from participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study free of CVD who underwent an echocardiogram at the Year 25 (2010-2011) in-person examination. Continuous echocardiographic measures of left heart structure, left ventricular systolic function (including strain) and diastolic function, right ventricular systolic function, and hemodynamic measures were included in latent class analysis to generate novel phenogroups. Associations between data-driven phenogroups and risk of premature CVD (coronary artery disease, stroke, or heart failure) were estimated using Cox proportional hazards regression adjusted for traditional CVD risk factors. ResultsAmong 3361 participants, mean (standard deviation) age was 50.1 (3.6) years, 57% were female, and 46% were non-Hispanic Black. Three overall phenogroups were identified and labeled as: (1) optimal cardiac mechanics (36.2%); (2) suboptimal systolic function (38.2%); and (3) suboptimal diastolic function (25.6%). Over a median 8.9 years of follow-up, 121 premature CVD events occurred. Risk of CVD was higher in the suboptimal diastolic function group (unadjusted hazard ratio [HR] 4.08 [95% CI: 2.48, 6.71] and adjusted HR 1.95 [1.12, 3.40]) compared with the optimal group. The suboptimal systolic function group had a higher unadjusted risk of CVD (1.86 [1.10, 3.15]), which was attenuated after adjustment for CVD risk factors (1.36 [0.79, 2.36]). Conclusions and relevanceUnbiased, data-driven clustering of echocardiographic measures in middle-aged adults identified distinct patterns of cardiac remodeling that were associated with risk of premature CVD. Premature CVD risk was highest with the pattern of suboptimal diastolic function. This suggests potential utility of a composite echocardiography-based index for prioritizing prevention strategies earlier in the life course.

Abstract 4136136: Left Ventricular Global Longitudinal Strain: An Imaging Marker Associated with Improved Survival in Paradoxical Low-Flow, Low-Gradient Severe Aortic Stenosis

Background: The optimal clinical management and timing of intervention are less well defined in paradoxical low-flow, low-gradient severe aortic stenosis (PLFLG AS). Left ventricular global longitudinal strain (LV-GLS) has been shown to predict outcomes in high flow severe AS, but there is lack of data in patients with PLFLG AS. Given the exaggerated LV hypertrophy and remodeling pattern in PLFLG AS, LV-GLS may be a mechanistic imaging marker for worse outcomes. Hypothesis: In patients with PLFLG AS, LV-GLS is associated with adverse clinical outcomes by detecting subclinical myocardial fibrosis resulting from myocardial remodeling due to LV pressure overload. Methods: We examined patients with PLFLG AS defined as AVA &lt;1cm 2 , mean gradient &lt;40mmHg and preserved left ventricular ejection fraction (LVEF) ≥50%, with low-flow state defined as transvalvular flow rate (Q) ≤210 ml/sec. Exclusion criteria included moderate or greater mitral or aortic regurgitation and presence of atrial fibrillation at the time of echocardiogram. LV strain analysis was performed using 2D-strain imaging software (TomTec, Chicago, IL). Clinical outcome data were obtained via the electronic health record. The primary outcome was defined as all-cause mortality. Patients were stratified by LV-GLS above and below the median value. Results: A total of 198 patients were included in the analysis, with a median LV-GLS of -12.3% [IQR: (-9.8,-16.3)]. Over a median follow-up time of 1.2 years, 130 deaths (65.6%) were identified. Patients with less negative LV-GLS (n=101) had worse survival than those with more negative LV-GLS (n=97; 22 vs 38%; p=0.02) (Fig 1). After multivariable adjustment for potential confounders (stroke volume index, aortic valve mean gradient, relative wall thickness, age, sex, heart failure, hypertension, coronary artery disease, and diabetes), less negative LV-GLS was independently associated with adverse outcomes (HR 1.56; 95% CI (1.03-2.38); p=0.04). Conclusions: In patients with PLFLG AS as defined by a transvalvular flow rate (Q) ≤210 ml/sec, reduced LV-GLS is associated with increased all-cause mortality. LV-GLS may serve as an imaging marker to help guide clinical decision making in PLFLG AS.

Abstract 4144529: Cardiac Allograft Hypertrophy (CAH) at 6 Months Post Transplant Is a Prognostic Marker of Long-Term Outcomes: Are We Missing a Simple Biomarker?

Introduction: Cardiac hypertrophy is a known adverse prognostic marker in various non-transplant pathologies. In heart transplant patients, due to many confounders, it has been controversial on the relevance and timing of cardiac hypertrophy as an adverse remodeling vs acute injury pattern in an immunologically hostile environment. Previous studies have shown prognostication of hypertrophy on echocardiogram at 1-year post-heart transplant. Research Questions: Does cardiac hypertrophy within a year after transplant have long-term prognostic implications? Methods: We collected relevant clinical variables for all heart transplants using EPIC EHR’s Clarity database. Hypertrophy was defined based on LV Mass Indexed to body surface area where LV Mass = 0.8 x (1.04 x (((LVIDD + IVSd + PWd) 3 - LVIDD 3 ))) + 0.6. Relative Wall Thickness was defined as RWT = 2 x PWd / LVIDD. We used a rule-based natural language processing program validated by correlation with manual readings by trained cardiologists (r=0.96, p=0.007) to abstract echo variables. Results: Inclusion criteria were heart transplants performed from 2015 to 2023 at our center, with an echocardiogram closest to 6 months (+/- 1 month). Ten percent (n=33) showed hypertrophy on echocardiograms at 6 months (Table 1). Of these, 20 (61%) had mild, 3 (9%) severe, and 10 (30%) moderate hypertrophy. Of 33 patients, 28 (85%) had concentric, and 5 (15%) had eccentric hypertrophy. Patients with hypertrophy at 6 months had significantly worse survival at 5 years (p=0.01) and 10 years (p=0.05) compared to patients without hypertrophy (Fig 1). Survival at 5 and 10 years was not statistically different for patients with hypertrophy at 3 months (5 yrs p=0.17, 10 yrs p=0.06), 12 months (5 yrs p=0.38, 10 yrs p=0.30), and 18 months (5 yrs p=0.15, 10 yrs p=0.08) compared to those without hypertrophy. Conclusion: Cardiac hypertrophy on echocardiogram at 6 months predicts adverse long-term survival, while other time points did not.

Acromegaly in Speckle Tracking Echocardiography-A New Cardiac Hypertrophy Phenotype? Case Report and Review.

This study aims to provide a comprehensive overview of speckle tracking echocardiography (STE) findings in patients diagnosed with acromegaly, exploring a potential application for the differential diagnosis of cardiac hypertrophy and guiding clinicians in patient management. To our knowledge, this is the first review showcasing changes in the bull's-eye pattern in myocardial function after acromegaly treatment, suggesting a possible pattern in this aetiology of left ventricular hypertrophy. A review of PubMed articles using the search term "speckle tracking echocardiography acromegaly" yielded 11 relevant papers published between 2017 and 2023. The final analysis evaluated each paper's substantial value and summarised pertinent information. A clinical case of myocardial strain changes before and after pharmacological and neurosurgical treatment is also described. The 11 analysed papers, with patient groups ranging from 19 to 50 individuals, revealed varying results in STE parameters between acromegalic and control groups. Left ventricular strain parameters were commonly assessed, showing discrepancies in different studies. Notably, the MAGYAR-Path Study emphasised left ventricular twist and radial strain abnormalities in acromegaly patients. Furthermore, the interplay between acromegaly and diabetes influenced myocardial function. Drug treatment with somatostatin receptor ligands demonstrated a favourable impact on left ventricular systolic function. The case study we describe in this manuscript showed changes in the posterior basal LV segment, which may be a specific pattern of acromegaly remodelling. Somatostatin therapy and neurosurgery led to the normalisation of global longitudinal strain (GLS) and improvement in myocardial work, as well as improved diastolic function, including enhanced left atrial strain (LAS) as well as a visible elastic recoil sign (ERS). While the available literature on STE in acromegaly is limited, our analysis suggests potential applications in differentiating hypertrophy aetiologies and monitoring cardiac function post-treatment. The results underscore the need for more interdisciplinary research to optimise patient management. The bull's-eye pattern with posterior basal segment strain impairment we describe may be used to differentiate this entity.

Rac1 inhibition regenerates wounds in mouse fetuses via altered actin dynamics

Mammalian wounds leave visible scars, and there are no methods for complete regeneration. However, mouse fetuses regenerate their skin, including epidermal and dermal structures, up to embryonic day (E)13. This regeneration pattern requires the formation of actin cables in the wound margin epithelium; however, the molecular mechanisms are not fully understood. Rac1 alters actin in cells and is involved in the formation of filopodia. We investigated whether actin remodeling and skin regeneration patterns can be reproduced through the regulation of Rac1 signaling. Rac1 expression was downregulated in E13 wounds and upregulated after E15 when scars remained. NSC23766, a Rac1-specific inhibitor, altered actin dynamics at the cell margin from filopodia formation to cable formation and inhibited the migration of mouse epidermal keratinocyte, PAM212, by Rac1 signaling suppression. NSC23766 suppressed Rac1 activity and completely regenerated the fetal mouse wounds, even at E14, by changing actin dynamics. Knocked-out Rac1 transgenic mice experienced delayed epithelialization of wounds with suppressed epidermal migration in adults; however, in fetuses, complete wound regeneration via Rac1 signal suppression was observed. Therefore, Rac1 suppression in the wound epidermis can achieve regenerative wound healing in fetuses and may be a potential candidate for healing scars.

Sex-specific Associations between Left Ventricular Remodeling at MRI and Long-term Cardiovascular Risk.

Background Left ventricular mass (LVM) is an established marker of cardiovascular risk; however, long-term follow-up studies in individuals with low to intermediate risk are lacking. Purpose To assess the sex-specific association of LVM measured with cardiac MRI with cardiovascular outcomes in those with a less than 20% 10-year risk of cardiovascular disease (CVD). Materials and Methods A total of 1528 volunteers older than 40 years of age with no history of CVD, a 10-year risk of CVD of less than 20%, and a B-type natriuretic peptide level greater than their sex-specific median underwent cardiac MRI between June 2008 and February 2013 as part of the Tayside Screening for Cardiac Events, or TASCFORCE, prospective study. LVM was indexed to body surface area, and the LVM-to-volume ratio was calculated. Follow-up for cardiovascular events was performed using national electronic health records. Cox proportional hazard models and Kaplan-Meier curves were applied to assess the impact of LVM. Results A total of 1495 participants (mean age, 54.5 years ± 8.3 [SD]; 925 female, 570 male) completed cardiac MRI, with a median follow-up of 10 years (IQR, 3 years). In female participants, LVM was associated with age, blood pressure, smoking status, and cholesterol level, while in male participants, LVM was associated with age and blood pressure. In female participants, the LVM-to-volume ratio was associated with cardiovascular events (hazard ratio [HR], 2.3 [95% CI: 1.1, 4.9] for the highest quartile vs the lowest quartile), while the LVM was not. In male participants, the LVM was associated with cardiovascular events (HR, 3.2 [95% CI: 1.5,7.0] for the highest quartile vs the lowest quartile), while the LVM-to-volume ratio was not. Conclusion In those with low to intermediate risk without established CVD, different remodeling patterns predict cardiovascular events, with increased LVM predictive in male participants, while LVM-to-volume ratio is predictive in female participants. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Garot and Duhamel in this issue.

How different types of cardiomyopathy with hypertrophic phenotype affect left atrial remodeling and function

Abstract Background Left atrial (LA) dysfunction is a common feature in hypertrophic cardiomyopathies. How the underlying etiology and pathophysiology of different cardiomyopathies affects LA remodeling and function remains unexplored. Purpose The aim of our study is to investigate the influence of various cardiomyopathies with hypertrophic phenotype on LA remodeling and function. Methods Patients with left ventricular (LV) hypertrophic phenotype who underwent cardiac magnetic resonance (CMR) were included. A group of patients with a normal CMR was included as a control group. CMR acquisitions used for clinical indication of heart failure diagnosis and etiology were retrospectively analyzed to obtain LA reservoir, conduit, and booster strain, left atrioventricular coupling index (LACI) and LA sphericity. Differences between groups were assessed. To investigate the independent clinical associates of LA reservoir, conduit and booster strain, multivariable linear regression analyses were performed. Results A total of 375 individuals were analyzed including 321 patients diagnosed with LV hypertrophy and 54 patients with a normal CMR. Of the 321 patients with LV hypertrophy, 148 were diagnosed with hypertrophic cardiomyopathy (HCM), 35 with cardiac amyloidosis (CA), 41 with hypertensive cardiomyopathy (HTN) and 97 with severe asymptomatic aortic stenosis (AS). CMR LA characteristic and strain analysis results are summarized in Figure 1. The indexed LA end-systolic volume (iLAVmax), indexed LA end-diastolic volume (iLAVmin) and LA sphericity were larger in patients with CA when compared to other groups (all p&amp;lt;0.05). CA patients displayed more left atrioventricular uncoupling (lower LACI) when compared to individuals with HCM, HTN, AS, and controls (all p&amp;lt;0.001), while no significant differences were observed across other groups. CA patients exhibited lower LA reservoir and booster strains compared to the other groups (all p&amp;lt;0.05), whereas no significant differences were observed across other hypertrophic phenotype diseases. Age, iLAVMax and LACI were independently associated with all the three LA strain components (Figure 2, all p&amp;lt;0.05). Conclusions LA remodeling and function are affected differently across the various etiologies of LV hypertrophy. CA patients exhibit more pronounced atrial involvement, whereas those with HCM, asymptomatic AS, and HTN display similar patterns of atrial dysfunction and remodeling. Additionally, CMR-derived iLAVmax and LACI are independently correlated with LA function.

Left ventricular dilatation in patients with significant aortic regurgitation: association with mortality

Abstract Background In aortic regurgitation (AR), left ventricular (LV) dilatation occurs as a response to volume and pressure overload. Current guidelines recommend the use of LV end-systolic diameter index (LVESDi) to give indication for intervention, but recent studies suggested that volumetric measures may be more accurate in identifying LV remodeling in AR as compared to linear dimensions. Purpose To characterize LV dilatation in patients with significant AR (≥moderate), based on linear and volumetric dimensions, and to determine their prognostic value. Methods A total of 1070 patients (56 ± 18 years,65% male) were included. Cut-off values of 20 mm/m2 for LVESDi and 45 ml/m2 for end-systolic volume index (LVESVi) were used to identify the following LV remodeling patterns: No-significant LV dilatation (N=485), when both LVESDi and LVESVi were below the cut-off values; Discordant LV dilatation (N=279) if only one positive criterion was present; and Concordant LV dilatation (N=306) when both LVESDi and LVESVi were enlarged (Figure 1). The primary endpoint was all-cause mortality. Results Baseline characteristics differed across the 3 LV dilatation groups. Compared to patients with no-significant or discordant LV dilatation, those with concordant LV dilatation were more likely to be men, had a lower prevalence of systemic arterial hypertension and were more symptomatic. Concerning the echocardiographic characteristics, patients with concordant LV dilatation showed more severe AR, worse LV systolic function and larger left atrial volumes compared to the other two LV dilatation groups. During a median follow-up of 89 (IQR,54-132) months, 168 (16%) patients died and 484 (45%) underwent aortic valve surgery (AVS). Patients with concordant LV dilatation had worse 10-year survival (72%) compared to the groups (Figure 2), but benefited more from AVS based on a landmark analysis (p=0.001). In multivariable analysis, a significant association with the risk of all-cause mortality was observed for the presence of discordant (HR 1.645, 95%CI 1.077-2.513;p=0.021) or concordant LV dilatation (HR 2.695, 95% CI 1.710 to 4.249;p&amp;lt;0.001) after adjusting for the variables significant in the univariate analysis such as, age, male gender, NYHA class III-IV, AVS as a time-dependent covariate and LV ejection fraction (LVEF) ≤55%. Moreover, the addition of LV dilatation groups to a basal model including the above mentioned clinical and echocardiographic variables led to a significant increase in the predictivity of the model (Chi-square difference=21.1,p&amp;lt;0.001). Conclusion In patients with significant AR, LV dilatation detected by linear and/or volumetric measures was independently associated with increased mortality. Combining both methods for assessment of LV remodeling may improve risk stratification of these patients.

Exploring the Membrane-Active Interactions of Antimicrobial Long-Chain Fatty Acids Using a Supported Lipid Bilayer Model for Gram-Positive Bacterial Membranes.

The dynamic nature of bacterial lipid membranes significantly impacts the efficacy of antimicrobial therapies. However, traditional assay methods often fall short in replicating the complexity of these membranes, necessitating innovative approaches. Herein, we successfully fabricated model bacterially supported lipid bilayers (SLBs) that closely mimic the characteristics of Gram-positive bacteria using the solvent-assisted lipid bilayer (SALB) technique. By employing a quartz crystal microbalance with dissipation and fluorescence microscopy, we investigated the interactions between these bacterial mimetic membranes and long-chain unsaturated fatty acids. Specifically, linolenic acid (LNA) and linoleic acid (LLA) demonstrated interaction behaviors correlated with the critical micelle concentration (CMC) on Gram-positive membranes, resulting in membrane remodeling and removal at concentrations above their respective CMC values. In contrast, oleic acid (OA), while showing similar membrane remodeling patterns to LNA and LLA, exhibited membrane insertion and CMC-independent activity on the Gram-positive membranes. Particularly, LNA and LLA demonstrated bactericidal effects and promoted membrane permeability and ATP leakage in the bacterial membranes. OA, characterized by a CMC-independent activity profile, exhibited potent bactericidal effects due to its robust penetration into the SLBs, also enhancing membrane permeability and ATP leakage. These findings shed light on the intricate molecular mechanisms governing the interactions between long-chain unsaturated fatty acids and bacterial membranes. Importantly, this study underscores the potential of using biologically relevant model bacterial membrane systems to develop innovative strategies for combating bacterial infections and designing effective therapeutic agents.

Architecture-driven quantitative nanoscopy maps cytoskeleton remodeling

Cytoskeleton remodeling which generates force and orchestrates signaling and trafficking to govern cell migration remains poorly understood, partly due to a lack of an investigation tool with high system flexibility, spatiotemporal resolution, and computational sensitivity. Herein, we developed a multimodal superresolution imaging system-based architecture-driven quantitative (ADQ) framework in spatiotemporal-angular hyperspace to enable both identification of the optimal imaging mode with well-balanced fidelity and phototoxicity and accurate postcharacterization of microtubule remodeling. In the ADQ framework, a pixel/voxel-wise metric reflecting heterogeneous intertubule alignment was proposed with improved sensitivity over previous efforts and further incorporated with temporal features to map dynamic microtubule rearrangements. The ADQ framework was verified by assessing microtubule remodeling in drug-induced (de)polymerization, lysosome transport, and migration. Different remodeling patterns from two migration modes were successfully revealed by the ADQ framework, with a front-rear polarization for individual directed migration and a contact site-centered polarization for cell-cell interaction-induced migration in an immune response model. Meanwhile, these migration modes were found to have consistent orientation changes, which exhibited the potential of predicting migration trajectory.

Evaluation of Bi-layer Silk Fibroin Grafts for Inlay Vaginoplasty in a Rat Model.

Autologous tissues derived from bowel, buccal mucosa and skin are primarily used to repair or replace diseased vaginal segments as well as create neovaginas for male-to-female transgenders. These grafts are often limited by scarce tissue supply, donor site morbidity and post-operative complications. Bi-layer silk fibroin (BLSF) biomaterials represent potential alternatives for vaginoplasty given their structural strength and elasticity, low immunogenicity, and processing flexibility. The goals of the current study were to assess the potential of acellular BLSF scaffolds for vaginal tissue regeneration in respect to conventional small intestinal submucosal (SIS) matrices in a rat model of vaginoplasty. Inlay vaginoplasty was performed with BLSF and SIS scaffolds (N = 21 per graft) in adult female rats for up to 2months of implantation. Nonsurgical controls (N = 4) were investigated in parallel. Outcome analyses included histologic, immunohistochemical and histomorphometric evaluations of wound healing patterns; µ-computed tomography (CT) of vaginal continuity; and breeding assessments. Animals in both scaffold cohorts exhibited 100% survival rates with no severe post-operative complications. At 2months post-op, µ-CT analysis revealed normal vaginal anatomy and continuity in both graft groups similar to controls. In parallel, BLSF and SIS grafts also induced comparable constructive remodeling patterns and were histologically equivalent in their ability to support formation of vascularized vaginal neotissues with native tissue architecture, however with significantly less smooth muscle content. Vaginal tissues reconstructed with both implants were capable of supporting copulation, pregnancy and similar amounts of live births. BLSF biomaterials represent potential "off-the-shelf" candidates for vaginoplasty.

Corneal Epithelial Remodeling Following Cylinder Correction With SMILE or FS-LASIK: A Contralateral Comparative Study.

To compare the corneal epithelial remodeling in eyes with high astigmatism that had small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). Seventy-four patients with myopic astigmatism of greater than -2.00 diopters (D) and little binocular difference in spherical equivalent were included in this contralateral comparative study. All patients received SMILE in one eye and FS-LASIK in the other eye randomly. The corneal epithelial remodeling pattern was mapped using the latest RTVue spectral-domain optical coherence tomographer (Optovue) by region. Satisfactory refractive correction was achieved in all enrolled eyes with either SMILE or FS-LASIK. The corneal epithelium gradually thickened following surgical cylinder correction, distributing mainly along the flat medium. The corneal epithelium proliferation is milder centrally but more pronounced in the mid-peripheral area after SMILE, compared with FS-LASIK. The flat-steep difference in corneal epithelial thickness (CET) is evident in the mid-peripheral and peripheral areas, which is more obvious in SMILE. Residual cylinder was positively correlated with CET in eyes that had FS-LASIK, but not SMILE. More importantly, these epithelial changes were positively correlated with the ablation depth and higher order aberrations following surgical refractive correction. The postoperative CET map varied between SMILE and FS-LASIK. In eyes with high astigmatism, SMILE surgery is followed by milder and more stable corneal epithelial thickening. Moreover, the corneal epithelium is sensitive to stromal ablation and corneal remodeling is crucial to the postoperative visual quality. This study rigorously distinguished the CET difference between SMILE and FS-LASIK in astigmatic eyes and shed light on subsequent research. [J Refract Surg. 2024;40(10);e728-e741.].

A comparative study of interhemispheric functional connectivity in patients with basal ganglia ischemic stroke.

Voxel-mirrored homotopic connectivity (VMHC) is utilized to assess the functional connectivity of neural networks by quantifying the similarity between corresponding regions in the bilateral hemispheres of the brain. The exploration of VMHC abnormalities in basal ganglia ischemic stroke (BGIS) patients across different cerebral hemispheres has been limited. This study seeks to establish a foundation for understanding the functional connectivity status of both brain hemispheres in BGIS patients through the utilization of VMHC analysis utilizing resting-state functional magnetic resonance imaging (rs-fMRI). This study examined a total of 38 patients with left basal ganglia ischemic stroke (LBGIS), 44 patients with right basal ganglia ischemic stroke (RBGIS), and 41 individuals in a healthy control (HC) group. Rs-fMRI studies were performed on these patients, and the pre-processed rs-fMRI data were analyzed using VMHC method. Subsequently, the VMHC values were compared between three groups using a one-way ANOVA and post hoc analysis. Correlation analysis with clinical scales was also conducted. The results indicated that compared to the HC group, significant differences were detected in postcentral gyrus, extending to precentral gyrus in both BGIS groups. Post hoc analysis showed that in the pairwise ROI-based comparison, individuals with LBGIS and RBGIS exhibited reduced VMHC values compared to HC groups. There was no significant difference between the LBGIS and RBGIS groups. In the LBGIS group, the VMHC value showed a negative correlation with NIHSS and a positive correlation with BI. The analysis of VMHC in rs-fMRI revealed a pattern of brain functional remodeling in patients with unilateral BGIS, marked by reduced synchronization and coordination between hemispheres. This may contribute to the understanding of the neurological mechanisms underlying motor dysfunction in these patients.

Vascular Remodeling in Coronary Microvascular Dysfunction

BackgroundApproximately one-half of the patients with angina and nonobstructive coronary artery disease (ANOCA) have evidence of coronary microvascular dysfunction (CMD). ObjectivesThis study aims to characterize patients with ANOCA by measuring their minimal microvascular resistance and to examine the pattern of vascular remodeling associated with these measurements. MethodsThe authors prospectively included patients with ANOCA undergoing continuous thermodilution assessment. Lumen volume and vessel-specific myocardial mass were quantified using coronary computed tomography angiography (CTA). CMD was defined as coronary flow reserve <2.5 and high minimal microvascular resistance as >470 WU. ResultsA total of 153 patients were evaluated; 68 had CMD, and 22 of them showed high microvascular resistance. In patients with CMD, coronary flow reserve was 1.9 ± 0.38 vs 3.2 ± 0.81 in controls (P < 0.001). Lumen volume was significantly correlated with minimal microvascular resistance (r = −0.59 [95% CI: −0.45 to −0.71]; P < 0.001). In patients with CMD and high microvascular resistance, lumen volume was 40% smaller than in controls (512.8 ± 130.3 mm3 vs 853.2 ± 341.2 mm3; P < 0.001). Epicardial lumen volume assessed by coronary CTA was independently associated with minimal microvascular resistance (P < 0.001). The predictive capacity of lumen volume from coronary CTA for detecting high microvascular resistance showed an area under the curve of 0.79 (95% CI: 0.69-0.88). ConclusionsPatients with CMD and high minimal microvascular resistance have smaller epicardial vessels than those without CMD. Coronary CTA detected high minimal microvascular resistance with very good diagnostic capacity. Coronary CTA could potentially aid in the diagnostic pathway for patients with ANOCA.

Distinct Immune Homeostasis Remodeling Patterns after HLA-Matched and Haploidentical Transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a widely used treatment for a variety of hematopoietic disorders, and also provides a valuable platform for investigating the development of donor-derived immune cells in recipients post-HSCT. The immune system remodels from the donor to the recipient during allo-HSCT. However, little is known about the cell profile alterations as donor homeostasis rebalances to recipient homeostasis following HSCT. Here, multi-omics technology is applied at both the singlecell and bulk sample levels, as well as spectrum flow cytometry and fluorescent transgenic mouse models, to dissect the dynamics of the rebalanced homeostatic immune system in recipients after allo-HSCT. The data reveal that all immune subpopulations observed in donors are successfully restored in recipients, though with varying levels of abundance. The remodeling of immune homeostasis exhibits different patterns in HLA-matched and haploidentical HSCT, highlighting distinct biases in T cell reconstitution from the central and peripheral pathways. Furthermore, ZNF683 is critical for maintaining the persistence and quiescence of CD8 T-cell in haploidentical HSCT. The research can serve as a foundation for developing novel strategies to induce immune tolerance.

Mid-term Outcomes of Thoracic Endovascular Aortic Repair (TEVAR) in Acute Complicated Type B Aortic Dissection: A Comprehensive Analysis of Aortic Remodeling Patterns.

This study provides a comprehensive analysis of the clinical outcomes associated with endovascular treatment for acute complicated type B aortic dissection, with a focus on the complex process of aortic remodeling. We conducted a retrospective investigation using data extracted from the Songklanagarind Hospital database between January 2010 and January 2022. Electronic medical records of patients who underwent thoracic endovascular aortic repair (TEVAR) for acute complicated type B aortic dissections were reviewed. The analysis focused on in-hospital outcomes, overall survival, aorta-related survival, reintervention-free survival, and changes in aortic lumen diameter to assess aortic remodeling. Over the study period, 32 patients with acute complicated type B aortic dissections underwent TEVAR. The in-hospital mortality rate was 9.4%, with complications occurring in 21.9% of patients. Temporary acute kidney injury was observed in 9.4% of the cases, wound bleeding in 6.3%, pneumonia in 6.3%, and permanent spinal cord ischemia in 3.1%. Re-intervention was necessary in 6.3% of cases. The overall survival rates at 6 months, 1 year, 3 years, and 6 years were 78%, 75%, 65%, and 44%, respectively. Aorta-related survival rates were 87%, 87%, 83%, and 75% at the corresponding time intervals. The reintervention-free survival rates were 96%, 96%, 71%, and 71%, respectively. Survival analysis revealed that patients with ideal aortic remodeling experienced the most favorable outcomes, whereas those with undesirable aortic remodeling exhibited the least favorable survival. Notably, undesirable pattern of aortic remodeling emerged as a singular factor with a statistically significant influence on predicting survival (hazard ratio 4.37, P-value=0.021). TEVAR resulted in favorable aorta-related survival outcomes. Notably, the identification of changes in aortic lumen diameter alongside false lumen thrombosis, encapsulated within the framework of aortic remodeling patterns, has emerged as a robust predictor of post-TEVAR survival outcomes.

Computational investigation of the role of ventricular remodelling in HFpEF: The key to phenotype dissection

Recent clinical studies have reported that heart failure with preserved ejection fraction (HFpEF) can be divided into two phenotypes based on the range of ejection fraction (EF), namely HFpEF with higher EF and HFpEF with lower EF. These phenotypes exhibit distinct left ventricle (LV) remodelling patterns and dynamics. However, the influence of LV remodelling on various LV functional indices and the underlying mechanics for these two phenotypes are not well understood. To address these issues, this study employs a coupled finite element analysis (FEA) framework to analyse the impact of various ventricular remodelling patterns, specifically concentric remodelling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH), with and without LV wall thickening on LV functional indices. Further, the geometries with a moderate level of remodelling from each pattern are subjected to fibre stiffening and contractile impairment to examine their effect in replicating the different features of HFpEF. The results show that with severe CR, LV could exhibit the characteristics of HFpEF with higher EF, as observed in recent clinical studies. Controlled fibre stiffening can simultaneously increase the end-diastolic pressure (EDP) and reduce the peak longitudinal strain (ell) without significant reduction in EF, facilitating the moderate CR geometries to fit into this phenotype. Similarly, fibre stiffening can assist the CH and ‘EH with wall thickening’ cases to replicate HFpEF with lower EF. These findings suggest that potential treatment for these two phenotypes should target the bio-origins of their distinct ventricular remodelling patterns and the extent of myocardial stiffening.

3D osteocyte lacunar morphometry of human bone biopsies with high resolution microCT: From monoclonal gammopathy to newly diagnosed multiple myeloma

Osteocytes are mechanosensitive, bone-embedded cells which are connected via dendrites in a lacuno-canalicular network and regulate bone resorption and formation balance. Alterations in osteocyte lacunar volume, shape and density have been identified in conditions of aging, osteoporosis and osteolytic bone metastasis, indicating patterns of impaired bone remodeling, osteolysis and disease progression. Osteolytic bone disease is a hallmark of the hematologic malignancy multiple myeloma (MM), in which monoclonal plasma cells in the bone marrow disrupt the bone homeostasis and induce excessive resorption at local and distant sites. Qualitative and quantitative changes in the 3D osteocyte lacunar morphometry have not yet been evaluated in MM, nor in the precursor conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). In this study, we characterized the osteocyte lacunar morphology in trabecular bone of the iliac crest at the ultrastructural level using high resolution microCT in human bone biopsy samples of three MGUS, two SMM and six newly diagnosed MM. In MGUS, SMM and MM we found a trend for lower lacunar density and a shift towards larger lacunae with disease progression (higher 50 % cutoff of the lacunar volume cumulative distribution) in the small osteocyte lacunae 20–900 μm3 range compared to control samples. In the larger lacunae 900–3000 μm3 range, we detected significantly higher lacunar density and microporosity in the MM group compared to the MGUS/SMM group. Regarding the shape distribution, the MGUS/SMM group showed a trend for flatter, more elongated and anisotropic osteocyte lacunae compared to the control group. Altogether, our findings suggest that osteocytes in human MM bone disease undergo changes in their lacunae density, volume and shape, which could be an indicator for osteolysis and disease progression. Future studies are needed to understand whether alterations of the lacunae architecture affect the mechanoresponsiveness of osteocytes, and ultimately bone adaptation and fracture resistance in MM and its precursors conditions.