Performance of Passive Muscle Stiffness in Diagnosis and Assessment of Disease Progression in Duchenne Muscular Dystrophy.

The aim of this study was to evaluate the performance of passive muscle stiffness in diagnosing and assessing disease progression in Duchenne muscular dystrophy (DMD). Boys with DMD and age-matched controls were recruited. Shear wave elastography (SWE) videos were collected by performing dynamic stretching of the gastrocnemius medius (GM). At ankle angles from plantar flexion (PF) 30° to dorsiflexion (DF) 20°, the shear modulus of the GM was measured for each 10° of ankle movement. Shear modulus at each ankle angle was compared between the DMD and control group. Correlation between passive muscle stiffness and motor function grading was also analyzed. A total of 26 patients with DMD and 20 healthy boys were enrolled. At multiple stretch levels, passive muscle stiffness of the GM was significantly higher in patients with DMD than in those in the control group (all p values <0.05). The shear modulus of GM at an ankle angle of DF 10° had the largest area under the receiver operating characteristic curve in differentiating DMD patients from normal subjects (AUC = 0.902, 95% confidence interval: 0.814-0.990). Motor function grading was a significant determinant of passive muscle stiffness at an ankle angle of DF 10° (B = 21.409, t = 3.372, p = 0.003). Passive muscle stiffness may potentially serve as a useful non-invasive tool to monitor disease progression in DMD patients.

Measurement consistency of dynamic stretching muscle stiffness evaluated using shear wave elastography: comparison among different stretched levels and ROI sizes.

AIM: To investigate the reliability of quantitative analysis of dynamic stretching muscle stiffness using shear wave elas-tography (SWE), and to evaluate the influence of stretched levels and region of interest (ROI) sizes on the repeatability of SWE measurements. MATERIALS AND METHODS: SWE videos of the gastrocnemius medius were collected during ankle movement from plantar flexion (PF) 40° to dorsiflexion (DF) 30°. Shear wave imageswere collected of ankle angles at PF 25°, 0°, DF 15°, and DF 30°, representing the slack status, mildly stretched level, moderately stretched level, and maximal stretched level of the gastrocnemius medius, respectively. ROI circles with diameters of 2 mm, 5 mm, and 8 mm were applied to measure the shear modulus. Intra-observer, and inter-observer repeatability of the measurements were compared among different stretched levels and ROI sizes. RESULTS: Twenty-one healthy volunteers were enrolled. Muscle stiffness increased as the ankle DF increased. Intraclass correlation coefficients (ICCs) of intra-observer and inter-observer repeatability obtained for ROI sizes of 2 mm, 5 mm and 8 mm indicated good to excellent repeatability at all stretched levels. CONCLUSIONS: Shear wave elastography appeared to be a reliable tool to evaluate the dynamic stretching muscle stiffness with satisfactory repeatability at various stretched levels of gastrocnemius medius. Good to excellent repeatability was found using different ROI sizes.

Quantitative evaluation of passive muscle stiffness by shear wave elastography in healthy individuals of different ages.

OBJECTIVES: To investigate age-related changes on passive muscle stiffness in healthy individuals and measure the shear modulus in different age groups. METHODS: Shear wave elastography (SWE) movies of gastrocnemius medialis (GM) were collected during passive stretching induced by ankle rotation from plantarflexion (PF) to dorsiflexion (DF). A series of SWE images at ankle angles of PF 40°, PF 30°, PF 20°, PF 10°, 0°, DF 10°, DF 20°, and DF 30° were collected and shear moduli measured accordingly for analyses. RESULTS: Eighty-six healthy volunteers (27 children, 31 middle-aged adults, and 28 older people) were recruited. No significant difference was observed in the shear modulus between the three groups at ankle angles of PF 40°, PF 30°, PF 20°, PF 10°, and 0° (p > 0.05). The difference in the shear modulus among the three groups became significant as DF increased. At ankle angles of DF 10°, DF 20°, and DF 30°, the shear modulus was the greatest in the older group, followed by the middle-aged group and then the children group (p = 0.007, 0.000, and 0.000, respectively). CONCLUSIONS: Passive muscle stiffness increases with age, and the difference between age groups was pronounced only after reaching a certain degree of stretching. KEY POINTS: • The influence of age on passive muscle stiffness becomes pronounced only after reaching a certain degree of stretching. • Age should be considered when evaluating passive muscle stiffness in muscular disorders.

Corrigendum: Atropine Premedication Facilitates Ultrasound-Guided Reduction by Saline Enema in Children With Intussusception.

[This corrects the article DOI: 10.3389/fphar.2019.00043.].

Pelvic Ultrasound in Diagnosing and Evaluating the Efficacy of Gonadotropin-Releasing Hormone Agonist Therapy in Girls With Idiopathic Central Precocious Puberty.

Background and Objective: Idiopathic central precocious puberty (ICPP) is characterized by early pubertal changes, the acceleration of growth velocity, and rapid bone maturation that often results in reduced adult height. Gonadotrophin-releasing hormone agonist (GnRHa) is currently considered to be an effective therapeutic agent. At present, GnRH stimulation test is adopted as a gold standard for the diagnosis of ICPP and the efficacy evaluation of GnRHa therapy. However, it is difficult to operate in practice due to the cumbersome procedures and multiple blood samples required. This study was conducted to establish the value of pelvic ultrasound in diagnosing ICPP and evaluating the efficacy of GnRHa therapy. Materials and Methods: One hundred and twenty-two girls with ICPP (ICPP group) were enrolled in the study. Pelvic ultrasound and levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were examined before and after GnRHa therapy for 3 months. Eighty normal prepubertal girls were enrolled as the control group. The difference in pelvic ultrasound parameters between the ICPP group before GnRHa therapy and the control group was compared by independent-sample t-test, while paired t-test for ICPP group before and after GnRHa therapy. Receiver operating characteristic (ROC) curve was used to explore the optimal pelvic ultrasound parameters for diagnosing ICPP. Pearson correlation analysis was performed between the pelvic ultrasound parameters and serum sexual hormone level. Results: The pelvic ultrasound parameters (length of the uterine body, anteroposterior diameter of the uterine body, transverse diameter of the uterine body, volume of the uterine body, uterine body-cervix ratio, length of the ovary, transverse diameter of the ovary, anteroposterior diameter of the ovary, volume of the ovary, number of increased follicles and maximum diameter of the follicle) in the ICPP group before GnRHa therapy were significantly larger than those of the control group (P < 0.05). All the above pelvic ultrasound parameters in the ICPP group were significantly decreased after GnRHa therapy compared with those before treatment (P < 0.05). The volume of the uterine body had the largest area under the ROC curve in differentiating between patients with ICCP and the control group. Pelvic ultrasound parameters were significantly correlated with serum sexual hormone levels (P < 0.05). Conclusion: This study indicates pelvic ultrasound is a simple and reliable tool to diagnose ICPP and evaluates the efficacy of GnRHa therapy by dynamically observing the morphology of internal genitalia. The volume of uterine body was the best ultrasound parameter to distinguish patients with ICPP from normal girls.

Atropine Premedication Facilitates Ultrasound-Guided Reduction by Saline Enema in Children With Intussusception.

Background and Objective: Intussusception is the most frequent pediatric abdominal emergency. Intestinal spasm, ischemia, necrosis and even death may occur without prompt diagnosis and treatment. The ultrasound-guided reduction by saline enema is a preferred non-surgical procedure for intussusception. Muscular relaxants can relieve the intestinal spasm and edema by relaxing the intestinal smooth muscle, which may facilitate the treatment of intussusception. However, controversy persists on whether muscular relaxants are effective in the procedure. Therefore, the purpose of our study was to assess the efficacy of atropine known as a muscular relaxant in ultrasound-guided reduction by saline enema in children with intussusception. Methods: All patients with intussusception diagnosed and treated in our department from July 2016 to February 2018 were included. Four hundred and thirty-seven children were enrolled and randomly divided into two groups: an atropine group and a control group. Intramuscular atropine at a dose of 0.02 mg per kilogram of body weight was administrated 15 min before ultrasound-guided reduction by saline enema in the atropine group. In the control group, the ultrasound-guided reduction was performed without using any muscular relaxants. The success rate, duration of the reduction, volume of saline, maximum intra-rectal pressure and complications were recorded and compared between the two groups. Results: The success rate was 95.9% (212 out of 221) and 94.9% (205 out of 216) in the atropine group and the control group, respectively. No significant difference was observed in the success rate between the two groups (P > 0.05). The duration of reduction was significantly lower in the atropine group than in the control group (P < 0.01). The volume of saline was also significantly lower in the atropine group than in the control group (P < 0.05). The maximum intra-rectal pressure showed no difference between the two groups (P > 0.05). Conclusion: Atropine premedication can facilitate ultrasound-guided reduction by saline enema in children with intussusception, by reducing the duration of reduction and the volume of saline in the procedure.

Initial application of three-dimensional speckle-tracking echocardiography to detect subclinical left ventricular dysfunction and stratify cardiomyopathy associated with Duchenne muscular dystrophy in children.

Three-dimensional (3D) speckle-tracking echocardiography (STE) is a new imaging modality used for quantitative analysis of left ventricular (LV) function. The aim of this study is to assess the value of 3D STE in early detection of subclinical myocardial involvement in children with Duchenne muscular dystrophy (DMD). Fifty-six children with DMD (mean age, 8.8 ± 1.9 years) and 31 age-matched control subjects were studied. Patients were subdivided into two groups by age: ≤ 8 or > 8 years. Standard echocardiography examinations were performed to measure LV size and ejection fraction (EF). 3D STE was performed to assess LV 3D global strain and LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF. Standard and 3D echocardiography measures were compared between children with DMD and those in the control group as well as between different patient groups. The areas under the receiver-operating characteristic (ROC) curve were calculated to determine the capability of 3D global strain indices to discriminate between patients and control subjects. No significant difference was detected in either LVEF derived from M-mode or 3D echocardiography between the two groups, and they were both within the normal range. Compared with control subjects, children with DMD had significantly reduced LV 3D global longitudinal strain (GLS; - 16.6 ± 4.7 vs. - 19.5 ± 3.7, p = 0.003), global circumferential strain (GCS; - 13.7 ± 2.9 vs. - 15.8 ± 2.6, p = 0.001), global radial strain (GRS; 42.5 ± 9.7 vs. 50.3 ± 10.4, p = 0.001), and global area strain (GAS; - 25.3 ± 4.9 vs. - 30.7 ± 4.1, p = 0.000). The older DMD children (age > 8 years) had lower GLS (- 15.1 ± 4.43 vs. - 18.6 ± 4.35, p < 0.05), GCS (- 12.8 ± 3.48 vs. - 14.8 ± 2.83, p < 0.001), GAS (- 23.8 ± 4.7 vs. - 29.0 ± 5.4, p < 0.001), and GRS (40.7 ± 8.8 vs. 47.3 ± 11.5, p < 0.05) than younger patients (age ≤ 8 years). The AUC of GAS was 0.80, and the cutoff value of - 29.5 had a sensitivity of 85.7% and a specificity of 71.0% for differentiating DMD patients from control. 3D speckle-tracking echocardiography is useful for detecting subclinical myocardial dysfunction and stratifying cardiomyopathy in children with DMD.

Effect of computed tomographic venography on donor selection in submandibular gland transplantation in patients with severe dry eye.

BACKGROUND: A reliable anterior facial vein (AFV, donor vein) is cardinal for the success of submandibular gland (SMG) transplantation. This study determined the impact of computed tomographic (CT) venography in identifying AFV variations for SMG transplantation. METHODS: CT venography was performed in consecutive patients with severe dry eye prior to SMG transplantation in order to identify disadvantageous AFV variations for vascular anastomosis, namely, AFVs that did not drain the SMG and those that did not match the superficial temporal vein (STV, recipient vein; AFV:STV caliber ratio, ≥3). The CT results were compared with the intraoperative findings for the diagnostic accuracy. RESULTS: Forty-two donors were included. Compared with the intraoperative findings, the CT results accurately identified AFV-STV caliber mismatches (P = 1.00; sensitivity and specificity, 100%). In the identification of AFVs not draining the SMG, CT showed 94.7% sensitivity and 100% specificity (P = 0.25). According to the CT findings, 10 contralateral SMGs with AFVs (23.8%), instead of ipsilateral donors, were selected for transplantations (conventionally ipsilateral donor was the first choice). The surgical success rate was 95.2% (40/42). CONCLUSION: CT venography is valuable in determining disadvantageous AFV variations for anastomosis and choosing a reliable donor for SMG transplantation.

Atrial mechanics after surgical repair of tetralogy of Fallot.

BACKGROUND: Ventricular diastolic dysfunction in patients with repaired tetralogy of Fallot (TOF) may affect atrial mechanics. This study aimed to explore right atrial (RA) and left atrial (LA) mechanics in repaired TOF patients and their relationship with ventricular diastolic function. METHODS: Fifty-four patients (36 males), aged 17.8 ± 8.3 years, who had undergone TOF repair at 3.9 ± 3.3 years and 40 healthy subjects aged 16.9 ± 6.3 years (P = 0.57) were studied. Right and LA peak positive, peak negative, and total strain, strain rate at ventricular systole (SRs ), early diastole (SRed ), and atrial contraction (SRac ), and electromechanical delay were determined using speckle tracking echocardiography (STE). Ventricular diastolic function was assessed by tissue Doppler imaging and STE. Ventricular volumes and pulmonary regurgitant volume were derived from 3D echocardiography. RESULTS: Compared with controls, patients had significantly lower RA and LA peak positive and total strain, SRs , SRed , and SRac (all P < 0.001). The timing of RA (178 ± 33 msec vs. 152 ± 17 msec, P < 0.001) and LA (170 ± 32 msec vs. 152 ± 24 msec, P = 0.006) electromechanical coupling (EMC) was significantly longer in patients than in controls. The RA total strain, SRs , SRed , SRac , and EMC correlated positively with corresponding LA parameters (all P < 0.001). The RA and LA total strain and SRed were associated positively with diastolic annular velocities and strain rates of respective ventricles (all P < 0.05). The LA SRed correlated negatively with pulmonary regurgitant volume (r = -0.33, P = 0.016) and RV end-diastolic volume (r = -0.33, P = 0.015). CONCLUSION: Mechanics of both atria are impaired in patients after repair of TOF and are associated with diastolic performance of the respective ventricles.

Right and left ventricular mechanics and interaction late after balloon valvoplasty for pulmonary stenosis.

AIMS: This study sought to explore right (RV) and left ventricular (LV) mechanics and ventricular-ventricular interaction in adolescents and young adults late after percutaneous balloon pulmonary valvoplasty (PBPV) for valvar pulmonary stenosis (PS). METHODS AND RESULTS: Potential late effects of PS despite PBPV on cardiac mechanics have not been well defined. Thirty-one patients aged 20.2 ± 7.6 years were studied at 18 ± 6 years after PBPV. Ventricular myocardial deformation was determined using speckle tracking echocardiography, while RV and LV volumes and ejection fraction as well as LV systolic dyssynchrony index were assessed by three-dimensional echocardiography. The results were compared with those of 30 controls. Pulmonary regurgitation, mostly trivial to mild, was present in 90% (28/31) of patients. Compared with controls, patients had significantly greater RV end-diastolic (P < 0.001), RV end-systolic (P < 0.001), and LV end-systolic (P = 0.04) volumes as well as lower LV ejection fraction (P < 0.001). For deformation, patients had significantly reduced RV longitudinal systolic strain (P = 0.004), decreased LV circumferential systolic strain (P < 0.001), and strain rate (P = 0.001) as well as greater LV mechanical dyssynchrony (P < 0.001). In patients, RV end-diastolic and end-systolic volumes correlated with LV circumferential strain (r = -0.47, P = 0.008 and r = -0.36, P = 0.049, respectively) and dyssynchrony (r = 0.53, P = 0.002 and r = 0.49, P = 0.005, respectively). Patients who had PBPV at age ≤1 year had ventricular deformation indices similar to those who had interventions beyond 1 year. CONCLUSION: Impaired RV and LV mechanics and adverse ventricular-ventricular interaction occur in adolescents and young adults late after balloon valvoplasty for isolated valvar PS.

Right ventricular mechanics in adults after surgical repair of tetralogy of fallot: insights from three-dimensional speckle-tracking echocardiography.

BACKGROUND: The clinical relevance of evaluating right ventricular (RV) myocardial deformation in congenital heart disease is increasingly recognized. The aim of this study was to explore, using three-dimensional (3D) speckle-tracking echocardiography, RV mechanics in terms of 3D global area strain and mechanical dyssynchrony in adults with repaired tetralogy of Fallot. METHODS: Twenty patients (12 men) aged 24.7 ± 8.6 years and 22 age-matched controls (11 men) were studied. Global RV peak area strain and area strain-derived systolic dyssynchrony index (SDI) were determined using 3D speckle-tracking echocardiography. RV end-diastolic volume and end-systolic volume, ejection fraction (EF), and pulmonary regurgitation fraction were measured in patients using cardiac magnetic resonance. RESULTS: Coefficients of variation for intraobserver and interobserver measurements of RV global area strain were 6.1% and 7.9%, respectively, and those for SDI were 7.6% and 10.1%, respectively. Compared with controls, patients had significantly lower global area strain (P = .005) and greater SDI (P = .008). The prevalence of RV mechanical dyssynchrony (SDI > control mean + 2 SDs) in patients was 30%. In patients, global area strain correlated inversely with SDI (r = -0.42, P = .04), RV end-diastolic volume (r = -0.48, P = .032), and RV end-systolic volume (r = -0.48, P = .031) and positively with EF (r = -0.51, P = .02), while RV SDI correlated positively with RV end-systolic volume (r = 0.55, P = .012), pulmonary regurgitation fraction (r = 0.54, P = .031), and QRS duration (r = 0.51, P = .022) and negatively with RV EF (r = -0.62, P = .004). Multivariate analysis showed that RV EF (ß = 0.22, P = .048) was a significant correlate of global area strain in patients. CONCLUSIONS: In adults after tetralogy of Fallot repair, 3D RV deformation is impaired in association with RV dyssynchrony, volume overloading, and reduced EF.

New three-dimensional speckle-tracking echocardiography identifies global impairment of left ventricular mechanics with a high sensitivity in childhood cancer survivors.

BACKGROUND: The aim of this case-control study was to assess the usefulness of three-dimensional (3D) speckle-tracking echocardiography in the evaluation of global left ventricular (LV) myocardial performance in adolescent and adult survivors of childhood cancers. METHODS: Fifty-three anthracycline-treated survivors of childhood cancers (mean age, 18.6 ± 5.1 years) and 38 controls were studied. Three-dimensional speckle-tracking echocardiography was performed to assess LV 3D global and segmental strain, time to peak segmental 3D strain, LV torsion, and ejection fraction. LV systolic dyssynchrony index (SDI) was calculated as the percentage of the standard deviation of times to peak strain of the 16 segments divided by the RR interval. A global performance index (GPI) was calculated as (global 3D strain × torsion)/SDI. The area under the receiver operating characteristic curve was calculated to determine the capability of various echocardiographic indices to discriminate between patients and controls. RESULTS: Compared with controls, patients had significantly reduced LV global 3D strain (P < .001), torsion (P < .001), and GPI (P < .001) and greater SDI (P < .001). All except the basal anteroseptal segment in patients had reduced regional 3D strain compared with controls (P < .05 for all). Global 3D strain (P = .018), SDI (P = .003), and GPI (P = .02) were correlated with cumulative anthracycline dose. The areas under the curves for GPI, global 3D strain, 1/SDI, torsion, and ejection fraction were 0.92, 0.79, 0.79, 0.79, and 0.78, respectively. A GPI cutoff of 10.6°/cm had sensitivity of 84.9% and specificity of 81.6% of differentiating patients from controls. CONCLUSIONS: Three-dimensional speckle-tracking echocardiography enables the derivation of an index of LV global performance that incorporates LV 3D strain, dyssynchrony, and torsion for the sensitive detection of altered LV mechanics in childhood cancer survivors.

Adiponectin increases secretion of rat submandibular gland via adiponectin receptors-mediated AMPK signaling.

Adiponectin and adiponectin receptors (AdipoR1/2) are expressed in various tissues and are involved in the regulation of multiple functions such as energy metabolism and inflammatory responses. However, the effect of adiponectin and AdipoRs in submandibular glands has not been fully evaluated. In the present study, we found that mRNA and protein of both adiponectin and AdipoR1/2 were expressed in rat submandibular glands and in the SMG-C6 cell line, as evidenced by RT-PCR and Western blot analysis. Immunofluorescence staining showed that adiponectin was diffused in the cytoplasm, while AdipoR1/2 was concentrated in the membrane of acinar cells. Saliva flow was significantly increased by full length adiponectin (fAd) or globular adiponectin (gAd) perfusion in isolated rat submandibular glands. 5-Aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR), an adenosine monophosphate activated protein kinase (AMPK) activator, also increased saliva secretion. fAd, gAd, and AICAR all increased the average width of apical tight junctions in perfused submandibular glands, and decreased transepithelial electrical resistance (TER) in SMG-C6 cells, suggesting that adiponectin promoted secretion by modulating paracellular permeability. fAd and gAd increased p-AMPK levels, while AraA, an AMPK antagonist, abolished fAd- and gAd-induced changes in secretion, tight junction ultrastructure, and TER. Moreover, both AdipoR1 and AdipoR2 were required for fAd- or gAd-induced p-AMPK and TER responses, suggesting from their inhibition following AdipoR1 or AdipoR2 knockdown, and co-knockdown of AdipoRs by RNA interference. Our results suggest that adiponectin functions as a promoter of salivary secretion in rat submandibular glands via activation of AdipoRs, AMPK, and paracellular permeability.