Single-Nucleus RNA Sequencing Reveals Cardiac Macrophage Landscape in Hypoplastic Left Heart Syndrome

Background:Hypoplastic left heart syndrome(HLHS)is one of the most challenging congenital heart diseases in clinical treatment.In cardiac tissues,resident macrophages fulfill critical functions in maintaining a stable cardiac state and have strong regenerative capacity and organ specificity.However,the molecular mechanisms of macro-phages in HLHS remained unclear.Methods:Single-nucleus RNA sequencing(snRNA-seq)data of HLHS and healthy control(donors)samples obtained from the Gene Expression Omnibus(GEO)database were normalized and clustered using the Seurat package.The“FindMarkers”function was used to screen differentially expressed genes(DEGs)between the HLHS and donor groups and to analyze the functional enrichment of the set of genes of interest.Finally,cell-cell communication,pseudotime,and single-cell regulatory network inference and cluster-ing(SCENIC)analyses were used to study the mechanisms of macrophages in HLHS.Results:Based on the snRNA-seq data of HLHS and donors,we identified a total of 9 cell clusters,among which the proportion of macrophages was significantly less in the HLHS group than in the control group.Subdivision of macrophage subpopulations(Macrophages 1,2,and 3)showed that Macrophages 1 was mainly involved in nervous system development,angiogenesis,and apoptotic processes.In addition,analysis of communication between Macro-phages 1 and cardiomyocytes revealed that ligand-acceptor pairs such as GAS6/AXL,IL6,IGF1,THY1,and L1CAM were present only in the donor group.Finally,pesudotime and SCENIC analyses demonstrated that FOXO3 and ELF2 played a critical role for Macrophages 1 to maintain cardiac function in patients with HLHS.Conclusion:Our study improved the current understanding of the molecular mechanisms of macrophage devel-opment in HLHS,showing that manipulating the regulatory role of macrophages in the heart can be a novel treat-ment for HLHS.

The strength-dilatancy characteristics embraced in hypoplasticity

The strength-dilatancy characteristics of frictional materials embraced in the hypoplastic model proposed by Gudehus and Bauer are investigated and compared with the revised model suggested by Huang.In the latter the deviatoric stress in the model by Gudehus and Bauer is replaced by a transformed stress according to the stress transformation technique proposed by Matsuoka.The flow rule,the failure state surface equation and the strengthdilatancy relationship embraced in both models are derived analytically.The performance of the two hypoplastic models in reproducing the relationship between the peak strength and the corresponding dilation rate under triaxial compression,plane compression and plane shearing are then extensively investigated and compared with experimental results and with the predictions made by particular classical stress-dilatancy theories.Numerical investigations show that the performance in reproducing the strength-dilatancy relationship is quite satisfactory under triaxial compression stress state in both models and the predictions made by the transformed stress based model are closer to the results obtained from classical stress-dilatancy theories for plane compression and plane shearing problems.

Emergency Hybrid Correction in a Newborn with Critical Aortic Valve Stenosis with Acute Pulmonary Edema in the First Hour after Birth

Critical aortic valve stenosis in newborns is the cause of a severe clinical condition with the onset of symptoms during first hours after birth.We present a clinical case of a successful surgical correction of a critical aortic stenosis using a hybrid method applied in a newborn during the first day of life.The infant was diagnosed with a hypoplastic left heart complex with an intact atrial septum(aortic and mitral valves stenosis variant),that led to the cardiogenic shock and acute pulmonary edema.The procedure included bilateral banding of the pulmonary artery branches and atrioseptostomy with stenting of the interatrial septum.The surgery was performed through a median sternotomy.

An improved hypoplastic constitutive model of rockfill considering effect of stress path

An incrementally nonlinear hypoplastic constitutive model was introduced, which was developed without recourse to the concepts in elastoplasticity theory such as yield surface, plastic potential and the decomposition of the deformation into elastic and plastic parts. Triaxial drained tests on rockfill were conducted on a large scale triaxial apparatus under two types of stress paths, which were the stress paths of constant stress ratio and the complex stress paths with transitional features. Motivated by the effect of stress path, the Gudehus-Bauer hypoplastic model was improved by considering the parameter variations with different ratios of stress increment. Fitting parameter a presents a piecewise linear relationship with cosine of the slope angle θ determined by instantaneous stress path. The improved hypoplastic model can present peak stress increasing and volumetric strain changing from dilatancy to contractancy with the increase of transitional confining pressure σ3t and the decrease of slope angle θ of stress path. Compared with the test data, it is shown that the model is capable of fully considering the effect of stress path on rockfill.

Calibration and performance of two different constitutive models for rockfill materials

In this paper, two different concepts for the constitutive modeling of the mechanical behavior of creep-sensitive rockfill materials are presented. Specifically, the performance of an extended generalized plasticity model proposed by Wang is compared with a simplified version of the hypoplastic constitutive model for weathered rockfill materials proposed by Bauer. Both models can reflect the influence of the mean stress on the incremental stiffness, the peak friction angle, and the dilatancy angle. The so-called solid hardness defined for a continuum description and originally introduced by Bauer is embedded in both models. Hydrochemical, thermal, and mechanical weathering are usually caused by environmental changes and are taken into account in a phenomenological description with an irreversible and time-dependent degradation of the solid hardness. A degradation of the solid hardness is usually accompanied by creep deformation of the stressed rockfill material. It is shown that appropriate modeling of creep deformation requires at least a unified description of the interaction between the time-dependent process of degradation of the solid hardness and the stress state. In this context, the solid hardness can be understood as a key parameter for describing the evolution of the state of weathering of the rockfill material. Particular attention is also paid to the necessary procedure for determining the constitutive constants of the two different constitutive models. Finally, the performance of the two different constitutive models is demonstrated by comparing the results obtained from numerical simulations with experimental data from the creep-sensitive rockfill material.

Valvuloplasty of fetal pulmonary atresia with intact ventricular septum and hypoplastic right heart: Mid-term follow-up results

Objective:This study aimed to analyze and evaluate the results of mid-term follow-up after fetal pulmonary valvuloplasty(FPV)in fetuses with pulmonary atresia with intact ventricular septum(PA/IVS).Methods:From August 31,2018,to May 31,2019,seven fetuses with PA/IVS and hypoplastic right heart were included in this study.All underwent echocardiography by the same specialist and were operated on by the same team.Intervention and echocardiography data were collected,and changes in the associated indices noted during follow-up were analyzed.Results:All seven fetuses successfully underwent FPV.The median gestational age at FPV was 27.54 weeks.The average FPV procedural time was 6 min.Persistent bradycardia requiring treatment occurred in 4/7 procedures.Finally,five pregnancies were successfully delivered,and the other two were aborted.Compared to data before fetal cardiac interventions(FCI),tricuspid valve annulus diameter/mitral valve annulus diameter(TV/MV)and right ventricle diameter/left ventricle diameter(RV/LV)of all fetuses had progressively improved.The maximum tricuspid regurgitation velocity decreased from 4.60 m/s to 3.64 m/s.The average follow-up time was 30.40±2.05 months.During the follow-up period,the diameter of the tricuspid valve ring in five children continued to improve,and the development rate of the tricuspid valve was relatively obvious from 6 months to 1 year after birth.However,the development of the right ventricle after birth was relatively slow.It was discovered that there were individual variations in the development of the right ventricle during follow-up.Conclusion:The findings support the potential for the development of the right ventricle and tricuspid valve in fetuses with PA/IVS who underwent FCI.Development of the right ventricle and tricuspid valve does not occur synchronously during pregnancy.The right ventricle develops rapidly in utero,but the development of tricuspid valve is more apparent after birth than in utero.

Preoperative Feeding in Single Ventricle Neonates is Predictive of Shorter Time to Goal Feed

Background:Patients with single ventricle anatomy are at increased risk of growth failure and malnutrition.Amongst cardiac centers,there is little standardization of feeding practices in this complex population.We hypothesized that initiation of our center’s preoperative feeding protocol would result in decreased gastrostomy tube(G-tube)use,decreased length of stay and would not result in increased Necrotizing Enterocolitis(NEC)rates.Methods:A single institution review of 52 patients who had undergone stage I single ventricle palliative repair was performed.Patient diagnoses were hypoplastic left heart syndrome(39%),atrioventricular canal(15%),and other(46%).Postoperative parameters such as time to goal feed and need for gastrostomy tube(G-tube)were compared among preoperatively fed and non-preoperatively fed groups.Time to goal feed was calculated as time from first postoperative enteral feed to goal volume of 100 mL/kg.Results:Of the 26 patients who met inclusion criteria for preoperative feeding,22 patients(85%)were fed prior to surgery.Cox proportional hazard ratio revealed that age at surgery(p=0.047)and being preoperatively fed(p=0.001)were associated with reaching goal feed sooner.Multivariable analysis revealed that being preoperatively fed made a patient twice as likely to reach goal feed sooner(p=0.047).Univariable logistic regression revealed that days on total parenteral nutrition(p=0.018),length of hospitalization(p=0.008),and time to 1st postoperative feed(p=0.020)were significantly associated with higher odds of needing a G-tube postoperatively.Multivariable logistic regression did not show any predictors of postoperative G-tube usage.However,there was a trend towards lower G-tube usage in the preoperatively fed group.Conclusions:Implementing a standardized preoperative feeding protocol in single ventricle neonates can result in significantly shorter time to goal feed in preoperatively fed patients.It is beneficial for institutions to begin implementing standard feeding protocols to improve nutrition and growth outcomes.

A 20-Year Follow-up after the Fontan Operation in a Population with Hypoplastic Left Heart Syndrome

Background:Thromboembolic events are a cause of significant morbidity and mortality in the Fontan population.We previously reported on coagulation profile changes in a cohort of patients with hypoplastic left heart syndrome(HLHS)from Stage I through Fontan completion.In this report,we examine their clinical status,anticoagulation and incidence of thromboembolic events up to 20 years post Fontan.Methods:A retrospective chart review was conducted for twenty(20)surviving patients,from 1998 through December 2020.Patients who underwent orthotopic heart transplantation(OTx)were followed until their transplant.Patients who were found in the original study to have a factor VIII activity level>160%,were examined separately.Results:Most patients had follow-up within the last two years(2018–2020).Two patients underwent OTx and two patients died.Anticoagulation strategy was variable.Most patients were on aspirin monotherapy.There was a total of twelve thrombotic events(63.2%).These included six cerebrovascular accidents(two of which were fatal).Three out of the seven patients with elevated factor VIII activity from the original study had thromboembolic events(42.9%).Fontan complications were variable.Some degree of Fontan Associated Liver Disease was universal.Conclusions:This retrospective review of a group of single-ventricle patients post Fontan,illustrates the variability in anticoagulation therapy that exists in this population.A large proportion of patients suffered a significant thromboembolic event,including the patients with elevated factor VIII.Further investigation into the patients with elevated factor VIII may help determine whether a different antithrombotic strategy post Fontan would be beneficial.

A Ring-Reinforced Right Ventricle to Pulmonary Artery Conduit Is Associated with Better Regional Mechanics after Stage I Norwood Operation

Background:The right ventricle to pulmonary artery conduit(RVPAC)may impair right ventricular(RV)function in patients with functional single right ventricles.Modification of the RVPAC using a ring-reinforced end with dunked insertion into the RV through a limited ventriculotomy may reduce the impact on RV function.We compared RV segmental strain between patients with a traditional RVPAC and ring-reinforced RVPAC using feature tracking cardiovascular magnetic resonance(CMR)imaging.Methods:Patients with CMR examinations after Stage I operation with RVPAC between 2000 and 2018 were reviewed.Ventricular mass,volumes,late gadolinium enhancement(LGE),and peak radial and circumferential strain of the 4 segments near the RVPAC insertion site were analyzed.Results:The study included 71 CMR examinations in 61 patients(30 traditional RVPAC,31 ring-reinforced RVPAC).Prior to Stage II,the ring-reinforced RVPAC group had better peak radial strain and circumferential strain in 1 of 4 segments proximal to the RVPAC insertion site compared to the traditional RVPAC group.Prior to Stage III operation,the ring-reinforced group had better peak radial and circumferential strain in 2 of 4 segments.LGE at the RVPAC insertion site was observed in 97%of patients before Stage II and 95%of patients before Stage III.RVPAC type and regional strain were not associated with transplant-free survival during a median follow-up of 6.3 years.Conclusions:Compared to a traditional RVPAC,the ring-reinforced RVPAC is associated with improved regional mechanics at the conduit insertion site.Further investigation of long-term outcomes after ring-reinforced RVPAC is warranted.

Lateral Pressure of RC Silos with Static and Dynamic Granular Materials

This paper aims at analyzing material-induced lateral pressure of RC cylinder silo in both static and dynamic condition using the finite element method( FEM). In the finite element software ABAQUS,concrete material is modeled by concrete damaged plasticity model,and stored materials in silo is modeled by the hypoplastic theory.In terms of numerical model,shell elements( S4R) and solid elements( C3D8) are applied for model silo wall and stored materials respectively. The interaction between silo wall and stored materials is simulated by Coulomb friction model and penalty contact constrain provided by ABAQUS.The numerical results are verified with the existing experimental data that are designed to ensure the validation of such numerical model using FEM and it obtains good agreements between numerical results and experimental data. Then the material parameters are analyzed in both static and dynamic condition.According to the analysis,it is clear that critical friction angle,initial void ratio and minimum void ratio have an obvious effect on static lateral pressure while all the material parameters affect dynamic lateral pressure at different levels. In addition,differences of silo wall between elastic and plastic state are analyzed in dynamic condition. The numerical results show that it contributes to increasing dynamic pressure when silo wall enters into the plastic state. Finally,this paper discusses the time-history lateral pressure at different heights along silo wall,and analytical results indicate that larger acceleration values play main roles in producing the maximum lateral pressure at higher part of the silo wall.

Left recurrent laryngeal nerve palsy following aortic arch stenting: A case report

BACKGROUND Aortic arch stenting is continuously emerging as a safe and effective option to alleviate aortic arch stenosis and arterial hypertension.CASE SUMMARY We present a 15-year-old girl with aortic arch hypoplasia who had undergone implantation of an uncovered 22 mm Cheatham-Platinum stent due to severe(native)aortic arch stenosis.On follow-up seven months later,she presented a significant re-stenosis of the aortic arch.A second stent(LD Max 26 mm)was implanted and both stents were dilated up to 16 mm.After an initially unremarkable post-interventional course,the patient presented with hoarseness five days after the intervention.MRI and CT scans ruled out an intracranial pathology,as well as thoracic hematoma,arterial dissection,and aneurysm around the intervention site.Laryngoscopy confirmed left vocal fold paresis attributable to an injury to the left recurrent laryngeal nerve(LRLN)during aortic arch stenting,as the nerve loops around the aortic arch in close proximity to the area of the implanted stents.Following a non-invasive therapeutic approach entailing regular speech therapy,the patient recovered and demonstrated no residual clinical symptoms of LRLN palsy after six months.CONCLUSION Left recurrent laryngeal nerve palsy is a rare complication of aortic arch stenting not previously reported.

Longitudinal Evaluation of Right Ventricle Function after Right Ventricle-Pulmonary Artery Shunt vs.Blalock-Taussig Shunt

Background:Still little is known about the impact on right ventricle function of the 2 main approaches to Norwood palliation in Hypoplastic left heart syndrome,the right ventricle-pulmonary artery shunt(RVPAS)and the modified Blalock-Taussig shunt(mBTS).Methods:The cohort included 27 patients with Hypoplastic left heart syndrome(10 in the mBTS group,17 in the RVPAS group).Longitudinal strain,tricuspid annulus peak systolic excursion and fractional area change were evaluated before Norwood and in four different breakpoints in the steady-state after Norwood procedure(30-days,90-days,140-days and 200-days after Norwood).Results:No significant differences were found in all standard echocardiographic functional parameters between the two groups at any times.However,when we compared right ventricle function before and after Norwood procedure,longitudinal strain significantly improved in mBTS group compared to pre-surgical assessment(after 90-days:mBTS+27,35%±43,47 vs.RVPAS-8,20%±25,25,p=0,03;after 200-days:mBTS+10.19%±36.58 vs.RVPAS-21.64%±30.43,p=0.04).Conclusion:The mBTS group,which did not receive any ventriculotomy,showed a significant increase in right ventricle longitudinal strain during convalescence.These data support the use of longitudinal strain in Hypoplastic left heart syndrome evaluation and may suggest potential value in terms of cardiac mechanics in using mBTS,preserving the right ventricle integrity.

Arch Reconstruction in Hypoplastic Left Heart Syndrome: Handling the Diminutive Aorta

The diminutive aorta presents technical challenges in the palliation of hypoplastic left heart syndrome. Furthermore, aortic arch caliber changes and variable great vessel relationships can add complexity to an already difficult arch repair. We describe a technical approach that simplifies the aortic reconstruction and makes the procedure more generalizable and reproducible.

Hemodynamic Changes and Clinical Outcomes after the Intra/Extracardiac Fenestrated Fontan Procedure

Background: The primary concern of the Fontan procedure has been atrial arrhythmias, but little attention has been given to hemodynamic changes. This study’s purpose was to examine the hemodynamics and arrhythmias of the Intra/extracardiac fenestrated Fontan, and determine any advantages/disadvantages of this newer Fontan procedure. Methods: Patients undergoing the intra/ extracardiac fenestrated Fontan procedure at this institute between December 2009 and June 2017 were included in this retrospective evaluation of preoperative and postoperative hemodynamics during cardiac catheterization. End Diastolic Pressure (EDP), Pulmonary Artery Pressure (PAP), Left Atrial Pressure (LAP), and Transpulmonary Gradient (TPG) were the hemodynamic markers of interest. Occurrence of arrhythmias was also examined preoperatively, less than 2 weeks postoperatively, and greater than 2 weeks postoperatively. Morbidities and mortalities were also evaluated. Results: Fourteen patients underwent the procedure between December 2009 and June 2017. Preoperative data was available in all of these patients. Postoperative data was partially incomplete for atrial arrhythmias and hemodynamic data. EDP rose from 9.29 ± 3.50 mmHg to 10.33 ± 3.12 mmHg. PAP rose from 12.57 ± 2.50 mmHg to 14.27 mmHg. TPG dropped from 5.00 ± 2.29 mmHg to 3.25 ± 1.67 mmHg. LAP rose from 7.57 ± 2.87 mmHg to 10.30 ± 1.95 mmHg. Atrioventricular valve (AVV) regurgitation remained the same pre and postoperatively. 8 of 13 patients developed arrhythmias at less than 2 weeks postoperatively, and 5 of 12 patients developed arrhythmias at greater than 2 weeks postoperatively. There were no morbidities or mortalities. Conclusions: We found a statistically significant change in EDP, PAP, LAP, and TPG levels. It is unclear whether this is an advantage or disadvantage. The significance of these changes is unclear in this small population of patients. Further evaluation of hemodynamics, arrhythmias, morbidities and mortalities associated with the intra/extracardiac Fontan procedure is needed.

Creation of high position fetal balloon atrial septoplasty for hypoplastic left heart syndrome and highly restrictive atrial septum: A case report and literature review

Background:Fetal balloon atrial septoplasty(BAS)is performed through the restrictive foramen ovale in fetal cases with established hypoplastic left heart syndrome(HLHS)and an intact or highly restrictive atrial septum(RAS).Methods:In the current report,we present a case of high position BAS in a fetus with HLHS/RAS.Results:Echocardiography confirmed an adequate atrial opening above the foramen ovale and fetal pleural effusion resolved spontaneously 1 day after the procedure.Conclusion:To the best of our knowledge,the creation of a high position hole in the thinner part of the atrial septum,instead of the restrictive tiny hole,has not been reported in fetal cases with HLHS/RAS.

Unilateral hypoplastic kidney in adults:An experience of a tertiarylevel urology center

BACKGROUND Unilateral small-sized kidney is a radiological term referring to both the congenital and acquired causes of reduced kidney volume.However,the hypoplastic kidney may have peculiar clinical and radiological characterizations.AIM To evaluate the clinical presentations,complications,and management approaches of the radiologically diagnosed unilateral hypoplastic kidney.METHODS A retrospective review of the records of patients with a radiological diagnosis of unilateral hypoplastic kidney between July 2015 and June 2020 was done at Assiut Urology and Nephrology Hospital,Assiut University,Egypt.RESULTS A total of 33 cases were diagnosed to have unilateral hypoplastic kidney with a mean(range)age of 39.5±11.2(19-73)years.The main clinical presentation was loin pain(51.5%),stone passer(9.1%),anuria(12.1%),accidental discovery(15.2%),or manifestations of urinary tract infections(12.1%).Computed tomography was the most useful tool for radiological diagnosis.However,radioisotope scanning could be requested for verification of surgical interventions and nephrectomy decisions.Urolithiasis occurred in 23(69.7%)cases and pyuria was detected in 22(66.7%)cases where the infection was documented by culture and sensitivity test in 19 cases.While the non-complicated cases were managed by assurance only(12.1%),nephrectomy(15.2%)was performed for persistent complications.However,symptomatic(27.3%)and endoscopic(45.6%)approaches were used for the management of correctable complications.CONCLUSION Unilateral hypoplastic kidney in adults has various complications that range from urinary tract infections to death from septicemia.Diagnosis is mainly radiological and management is usually conservative or minimally invasive.

Aortoplasty with pulmonary autograft patch for coarctation of the aorta combined with hypoplastic aortic arch in infant

Objective To discuss the operative techniques and results of coarctation resection plus aortoplasty with pulmonary autograft patch for coarctation of the aorta combined with hypoplastic aortic arch in infant. Methods Between May 2007 and Dec 2009,14 cases including 9 males and 5 females with coarctation of the aorta and hypoplastic aortic arch underwent coarctation resection plus aortoplasty with pulmonary autograft patch in

Hypoplastic constitutive modelling of the wetting induced creep of rockfill materials

Discrete element simulations of one-dimensional compression of breakable granular assemblies were performed to investigate the capability of the exponential compression equation suggested by Bauer.The relationship between the so-called solid hardness and the particle strength was studied so as to provide a physical background for the introduction of a time-dependent solid hardness.A hyperbolic flow rule,describing the relationship between the inclination of the strain path and the stress ratio during wetting,was proposed based on typical triaxial wetting experiments on two different rockfill materials.The flow rule was then extended and incorporated into the transformed stress based hypoplastic model to capture the direction of creep strains.Meanwhile,a new density factor was introduced to the extended model to take into account the dependence of the magnitude of creep strains on the packing density.The stiffness tensor given by the extended model was discussed and the flowchart for the integration of the constitutive equation was designed.The extended model was then embedded into a finite element program and used to simulate the triaxial compression and wetting experiments performed on the aforementioned rockfill materials.Good agreement between the model predictions and the measured results lends sufficient credibility to the extended model in reproducing the stress-stain behaviour under loading and the creep behaviour during wetting.The extended model and the finite element program were also used to investigate the deformation behaviour of an earth-rock dam at the end of construction and during first impounding.The familiar phenomena such as the wetting induced settlement of the upstream shell and the movement of the dam crest towards the upstream were successfully captured by the numerical model,which confirms the feasibility of applying the extended model to dam engineering in the future.

Hypoplastic constitutive modeling of wetting deformation of weathered rockfill materials

The wetting deformation of weathered rockfill materials has been attracting growing attention from both engineers and scientists.The importance of realistic predictions of wetting deformations for high earth and rockfill dams is a strong motivation to establish a suitable constitutive model.Recently,the hypoplastic constitutive model by Gudehus and Bauer was extended by introducing solid hardness depending on the state of weathering.The extended model takes into account the influence of the current density,the effective stress state,the rate of deformation,and the time dependent process of degradation of the solid hardness.In the present paper,the performance of this model is evaluated by comparing numerical simulations with experiments obtained from a water sensitive rockfill material.In particular,triaxial compression paths and creep deformation under deviatoric stress states are considered.Finally,the constitutive model proposed is used to study the influence of a degradation of the solid hardness on the long term behavior of a hypothetical fill dam.

Influence of pressure and density on the rheological properties of rockfills

Long-term deformations of rockfill dams can be related to the type of dam,the pre-compaction achieved during the construction of the dam,the history of loading events,the rheological properties of the rockfill material used,the seepage behavior caused by defects of the sealing,the interactions of the dam building with the foundation,and the hydrothermal phenomena of the stressed rockfill material.The present paper investigates the theological propcrtics of coarse grained rockfill materials using a hypoplastic constitutive model.Particular attention is paid to wetting deformation under different deviatoric loading states and pre-compactions.To quantify the state of weathering a so-called“solid hardness”is used in the sense of a continuum description.It is shown that an appropriate modeling of wetting deformations requires a unified description of the interaction at least between the state of weathering,the stress state,the density and the rate of deformation.The results obtained from the numerical simulations are compared with available experimental data for a rockfill material used in Xiaolangdi earth dam.