Peripheral nerve injury is a challenging orthopedic condition that can be treated by autograft transplantation, a gold standard treatment in the current clinical setting. Nevertheless, limited ...availability of autografts and potential morbidities in donors hampers its widespread application. Bioactive scaffold‐based tissue engineering is a promising strategy to promote nerve regeneration. Additionally, magnesium (Mg) ions enhance nerve regeneration; however, an effectively controlled delivery vehicle is necessary to optimize their in vivo therapeutic effects. Herein, a bisphosphonate‐based injectable hydrogel exhibiting sustained Mg2+ delivery for peripheral nerve regeneration is developed. It is observed that Mg2+ promoted neurite outgrowth in a concentration‐dependent manner by activating the PI3K/Akt signaling pathway and Sema5b. Moreover, implantation of polycaprolactone (PCL) conduits filled with Mg2+‐releasing hydrogel in 10 mm nerve defects in rats significantly enhanced axon regeneration and remyelination at 12 weeks post‐operation compared to the controls (blank conduits or conduits filled with Mg2+‐absent hydrogel). Functional recovery analysis reveals enhanced reinnervation in the animals treated with the Mg2+‐releasing hydrogel compared to that in the control groups. In summary, the Mg2+‐releasing hydrogel combined with the 3D‐engineered PCL conduit promotes peripheral nerve regeneration and functional recovery. Thus, a new strategy to facilitate the repair of challenging peripheral nerve injuries is proposed.
Mg‐encapsulated HA‐Pam‐Mg hydrogel demonstrates substantial shear thinning and injectability. This hydrogel combined with the 3D‐engineered PCL conduit can promote peripheral nerve regeneration and functional recovery overtime via regulating PI3K/Akt and Sema5b, demonstrating the great potential of Mg‐based biomaterials for nerve repair.
Studies suggested heterogeneity of physical and psychological predictors of quality of life (QOL) among congenital heart disease patients. This cross-sectional study aimed to examine the ...interrelationships of QOL, health status, resilience, personality traits, illness perception, and clinical data of grown-up congenital heart (GUCH) patients in a tertiary center in Hong Kong.
GUCH patients (N = 208, male = 103) were invited to complete self-report questionnaires: 36-item Short Form Health Survey version 2 (SF36), Satisfaction with Life Scale (SWLS), Connor-Davidson Resilience Scale (RISC), Hospital Anxiety and Depression Scale (HADS), and NEO Five Factor Inventory (NEOFFI-3); results on these measures were compared to 104 healthy peers. GUCH patients also completed Brief Illness Perception Questionnaire (BIPQ). Disease complexity, illness severity, New York Heart Association (NYHA) class and Warnes-Somerville Ability Index (WSAI) grades of patients were obtained. The interrelationships between these patient-reported outcome (PRO) measures, clinical indices and functional status were assessed.
QOL scores and health status were lower in GUCH patients than healthy peers, and were associated with greater disease severity and worse functional class (all p-values < 0.01). SWLS and health status correlated positively with RISC, but negatively with HADS and negative illness perception (all p < 0.001). In multivariate regression, lower RISC, negative illness perception, and greater neuroticism were predictors of lower SWLS (all p < 0.05); higher WSAI grade, lower RISC and negative illness perception were predictors of lower PCS (all p < 0.05); and greater neuroticism and HADS were predictors of lower MCS (all p < 0.01).
Reduced QOL and health status among GUCH patients were associated with both clinical and psychological attributes. Resilience and illness perception might be the potential targets of intervention.
This study determined the circulating levels of TGF-β1 and its association with aortic dilation and elastic properties in congenital heart patients. Forty-six patients after tetralogy of Fallot (TOF) ...repair, 21 patients post arterial switch and 15 patients post atrial switch for transposition of the great arteries (TGA), 27 patients post Fontan procedure, and 36 controls were studied. Aortic dimensions and elastic properties and ventricular function were assessed by echocardiography. Serum TGF-β1, metalloproteinase (MMP)-2 and MMP-9 levels were quantified. Compared with controls, all groups of patients had significantly larger ascending aortic dimensions and worse elastic properties (all p < 0.05). Aortic stiffness correlated positively with sinus dimension (r = 0.48, p < 0.001) and negatively with indices of ventricular deformation (all p < 0.001). Patients with repaired TOF had significantly higher levels of TGF-β1 (p = 0.005), MMP-2 (p = 0.001) and MMP-9 (p < 0.001) than controls, while patients after atrial switch operation (p = 0.034) and Fontan procedures (p < 0.001) had higher MMP-2 levels. In patients as a group, circulating TGF-β1 levels correlated with MMP-9 (r = 0.44, p < 0.001) and aortic sinus dimension (r = 0.22, p = 0.035). In conclusion, increased circulating TGF-β1, MMP-2, and MMP-9 levels were found in patients with repaired TOF, and increased circulating MMP-2 levels were also evident in patients after atrial switch operation and Fontan procedure.
Background In nonsyndromic conotruncal cardiac defects, the use of next-generation sequencing for clinical diagnosis is increasingly adopted, but gene-disease associations in research are only ...partially translated to diagnostic panels, suggesting a need for evidence-based consensus. Methods and Results In an exome data set of 245 patients with conotruncal cardiac defects, we performed burden analysis on a high-confidence congenital heart disease gene list (n=132) with rare (<0.01%) and ultrarare (absent in the Genome Aggregation Database) protein-altering variants. Overall, we confirmed an excess of rare variants compared with ethnicity-matched controls and identified 2 known genes (
) and 4 candidate genes supported by the literature (
, and
). Ultrarare variant analysis was performed in combination with 3 other published studies (n=1451) and identified 3 genes (
) to be significant, whereas a subgroup analysis involving 391 Chinese subjects identified only
as significant. Conclusions We suggest that these significant genes in our rare and ultrarare burden analyses warrant prioritization for clinical testing implied for rare inherited and de novo variants. Additionally, associations on ClinVar for these genes were predominantly variants of uncertain significance. Therefore, a more stringent assessment of gene-disease associations in a larger and ethnically diverse cohort is required to be prudent for future curation of conotruncal cardiac defect genes.
Background
The QRS-T angle has been associated with adverse cardiovascular events and sudden cardiac deaths. We determined frontal QRS-T angle in patients with complete transposition of the great ...arteries (TGA) after atrial switch operation and repaired tetralogy of Fallot (TOF) and explored its relationships with ventricular mechanics.
Methods
Thirty TGA patients aged 32.3 ± 4.4 years after atrial switch operation and 47 repaired TOF patients aged 28.7 ± 6.0 years were studied. The frontal planar QRS-T angle and QRS duration were measured from 12-lead electrocardiograms. Right (RV) and left ventricular (LV) strain parameters were determined using speckle tracking echocardiography.
Results
Compared with TOF patients, TGA patients after atrial switch operation had significantly greater frontal QRS-T angle (136.3° ± 43.5° vs 74.5° ± 59.6°,
p
< 0.001), greater prevalence of QRS-T angle ≥ 100° (83.3% vs 29.8%,
p
< 0.001), and showed progressive increase in QRS-T angle over a duration of 3.3 ± 1.0 years (
p
= 0.035). The QRS-T angle correlated positively with QRS duration in both the TGA (
r
= 0.61,
p
< 0.001) and TOF (
r
= 0.30,
p
< 0.043) groups. Among TGA patients, QRS-T angle was found to correlate negatively with systemic RV global longitudinal strain (
r
= − 0.49,
p
= 0.007), early diastolic strain rate (
r
= − 0.41,
p
= 0.026), and fractional area change (
r
= − 0.38,
p
= 0.045), but not subpulmonary LV strain indices. By contrast, among repaired TOF patients, there were no significant correlations between QRS-T angle and systemic and subpulmonary ventricular strain indices (all
p
> 0.05).
Conclusion
Increased frontal QRS-T angle is prevalent in TGA patients after atrial switch operation and is related to worse systemic RV mechanics.
Pulp and nail atrophy and asymmetry are commonly seen in thumb duplication. In hypoplasia of both digits, conventional reconstruction or Bilhaut-Cloquet procedure and its modifications may not be ...possible or may lead to a poor cosmetic outcome. The purpose of the study was to review a reconstruction technique with a neurovascular island flap developed to improve the aesthetic and functional results of treatment.
Fourteen patients with thumb duplication aged 8 to 18 months were operated between 2002 and 2013 in our center. All patients had significant hypoplasia and asymmetry of the pulp and nail of the digit planned to be retained. A neurovascular island flap including part of the pulp tissue, nail bed, with or without the associated phalangeal bone, was raised from the planned ablated digit base on its single neurovascular bundle. The nail bed, nail fold, and pulp tissue from the 2 digits were apposed with fine sutures under magnification. All patients were followed to monitor the aesthetic, functional, and radiological outcome.
The mean follow-up period was 7 years, 11 months. Thirteen patients underwent the flap procedure and all flaps survived. In 1 patient, the flap procedure was aborted because the vascular pedicle was not well formed. The nail width and pulp circumference were restored to a similar size as the contralateral thumb.
In selected cases of thumb duplication with significant pulp hypoplasia and nail asymmetry, the neurovascular island flap is a safe and effective means to restore size and symmetry.
Therapeutic IV
We determined the occurrence of aortic regurgitation (AR), AR progression and risk factors in patients followed up for up to three decades after closure of subarterial VSD. We reviewed the outcomes ...of 86 patients categorized into three groups: group I comprised 37 patients without AR and had VSD closure alone, group II comprised 40 patients with AR and had VSD closure without aortic valvoplasty, and group III comprised 9 patients with AR and required both VSD closure and aortic valvoplasty. Patients were followed up for 18.9 ± 7.3 years (median 19.5 years, range 3.5–36.6). At latest follow up, 54.7% (47/86) of patients had AR. The prevalence of progression of AR from any one grade to the next one higher was 37.2% (32/86). Freedom from AR progression was 75.6%, 52.1%, and 22.2% at 20 years of follow-up for groups I, II and III, respectively (
p
< 0.05). On the other hand, progression to moderate to severe AR occurred only in 4.7% (4/86). Group I and II patients were free from progression to significant AR, while only 33.3% of group III patients were free from progression on follow-up (
p
< 0.001). Multivariate Cox regression analysis showed that severity of preoperative AR was the significant risk factor for persistence and progression of postoperative AR after VSD closure. In conclusion, aortic regurgitation is common and may progress even after surgical repair of subarterial VSD. Severity of preoperative AR is the most significant predictor of persistence and progression of AR after surgical closure of subarterial VSD.
Idiopathic systemic capillary leak syndrome (ISCLS) is rare, and there has been about 32 cases reported in children worldwide since this disorder was first described in 1960. Clinical guidelines on ...the management approach stemming from robust scientific evidence are lacking. This case report presents the first reported paediatric case of severe ISCLS with significant myocardial oedema and emphasizes this disease's impact on a child's cardiac function.
A Chinese boy had his first attack of severe hypovolaemic shock that responded to fluid resuscitation when he was 6 years of age. His second attack developed at 8 years of age. He was then transferred to our cardiac unit for refractory hypotensive shock. The patient's echocardiogram revealed ventricular wall thickening with significant cardiac dysfunction requiring extracorporeal membrane oxygenation support. Subsequently, he made a full recovery, including his myocardial wall thickness and function. The echocardiographic findings suggested myocardial oedema that was transient in nature. Clinical and laboratory investigation from both episodes were compatible with ISCLS.
ISCLS is rare, and therefore there is only a limited understanding on the pathophysiology of this disorder. The current treatment approach is based on a few case reports and series. During the acute phase, optimal supportive management is paramount. Our case highlights the importance of early recognition and consideration for extracorporeal membrane oxygenation support in patients with a life-threatening presentation, as it was lifesaving for this child who suffered myocardial oedema and ventricular dysfunction.
Background
Emerging data suggest that heart‐related microRNAs (miRs) may serve as circulating biomarkers of myocardial injury. We aimed to determine the circulating profile of miRs in patients with ...volume‐overloaded right ventricles after repair of tetralogy (TOF).
Materials and methods
A total of 104 TOF patients and 70 controls were recruited. The study was conducted in two phases: (1) determination of circulating heart‐related miRs described in left heart diseases (miR‐1, miR‐133a, miR‐208a, miR‐208b and miR423‐5p) by quantitative real‐time PCR in 49 patients and 30 controls and followed by validation in an independent cohort of 55 patients and 40 controls; (2) expression profiling of serum samples from eight patients and eight controls, followed by validation. Alteration in circulating miRNA expression was related to cardiac functional indices as assessed by 2D speckle tracking and 3D echocardiography.
Results
No significant differences in serum levels of left heart‐associated miRNAs were found between patients and controls. Of the candidate 19 miRNAs identified by profiling, upregulation of miR‐99b and down‐regulation of miR‐766 were validated. However, no correlations were found between miRs levels and echo indices.
Conclusion
In young adults with repaired TOF and volume‐overloaded right ventricles, circulating levels of miR‐99b and miR‐766, but not left heart‐associated miRNAs, were significantly altered.
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