Rationale:
Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function.
Objective:
The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with hypoplastic left heart syndrome.
Methods and Results:
Between January 5, 2011, and January 16, 2012, 14 patients (1.8±1.5 years) were prospectively assigned to receive intracoronary infusion of autologous CDCs 33.4±8.1 days after staged procedures (n=7), followed by 7 controls with standard palliation alone. The primary end point was to assess the safety, and the secondary end point included the preliminary efficacy to verify the right ventricular ejection fraction improvements between baseline and 3 months. Manufacturing and intracoronary delivery of CDCs were feasible, and no serious adverse events were reported within the 18-month follow-up. Patients treated with CDCs showed right ventricular ejection fraction improvement from baseline to 3-month follow-up (46.9%±4.6% to 52.1%±2.4%;
P
=0.008). Compared with controls at 18 months, cardiac MRI analysis of CDC-treated patients showed a higher right ventricular ejection fraction (31.5%±6.8% versus 40.4%±7.6%;
P
=0.049), improved somatic growth (
P
=0.0005), reduced heart failure status (
P
=0.003), and lower incidence of coil occlusion for collaterals (
P
=0.007).
Conclusions:
Intracoronary infusion of autologous CDCs seems to be feasible and safe in children with hypoplastic left heart syndrome after staged surgery. Large phase 2 trials are warranted to examine the potential effects of cardiac function improvements and the long-term benefits of clinical outcomes.
Clinical Trial Registration:
URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01273857.
Age (>or=50 years) and concurrent endocrine therapy can promote the development of radiation-induced BOOP syndrome after breast-conserving therapy. Physicians should carefully follow patients who received breast-conserving therapy, especially those who are older than 50 years and received concurrent endocrine therapy during radiotherapy.
We performed interictal FDG-PET- and MRI-based hippocampal volumetric measurements on 18 adult patients with complex partial epilepsy of temporal lobe origin in whom we had identified their ictal focus by video-telemetry EEG. Sixteen patients (89%) had regional hypometabolism, 11 (61%) had focal 1.5-tesla T2-weighted MRI (two structural abnormalities, nine hippocampal formation [HF] increased T2 signal), and nine (50%) had absolute HF atrophy ipsilateral to the temporal ictal focus. Ten (55%) had abnormal L/R HF ratios, nine ipsilateral to the EEG focus. All patients with abnormal MRI volumetric studies had focal PET abnormalities. Only seven had both abnormal HF volume ratios and T2 MRI (all increased HF T2 signal). There was a significant correlation between hippocampal volume and inferior mesial and lateral temporal lobe cerebral metabolic rate of glucose asymmetry index (p < 0.01), suggesting that hypometabolism may reflect hippocampal atrophy. PET is more sensitive than MRI volumetry in identifying the ictal focus but does not provide additional information when HF atrophy is present.
We used positron emission tomography (PET) with 18F-2-deoxyglucose (FDG) and 15O water in 20 patients with complex partial seizures to compare glucose metabolism and blood flow in temporal lobe epileptic foci identified by ictal scalp-sphenoidal video-EEG telemetry. Glucose metabolism was measured 20 minutes after blood flow without moving the patient from the scanner. We also studied 11 patients with 99mTc-HMPAO single-photon emission computed tomography (SPECT). Both local cerebral metabolic rate of glucose (LCMRGlc) and regional cerebral blood flow (rCBF) were significantly decreased in temporal cortex ipsilateral to the EEG focus. However, LCMRGlc was reduced by 11.2% in inferior lateral and 11.1% in inferior mesial temporal cortex and rCBF by only 3.2% and 6.1%. The ratio of LCMRGlc to rCBF was significantly reduced in inferior lateral temporal cortex ipsilateral to the ictal focus (p < 0.009). Moreover, using standardized criteria, blinded raters found that 16 of 20 patients had focal FDG-PET hypometabolism, all in the epileptogenic region; 10 of 20 had focal 15O water PET hypoperfusion, but it was falsely lateralized in two of these 10; and five of 11 had focal 99mTc-HMPAO SPECT hypoperfusion, but it was falsely lateralized in two of these five. Our data suggest that interictal glucose metabolism and blood flow may be uncoupled in epileptogenic cortex.
BackgroundNonalcoholic fatty liver disease is associated with a risk of coronary artery disease (e.g., diabetes mellitus, dyslipidemia, metabolic syndrome). We evaluated whether nonalcoholic hepatic steatosis is associated with high-risk plaques as assessed by multidetector computed tomography (CT).MethodsThis retrospective study involved 414 participants suspected of having coronary artery disease. Nonalcoholic hepatic steatosis was defined as a liver-to-spleen fat ratio of <1.0 and the presence and appropriate characteristics of coronary-artery plaques as assessed by coronary CT angiography. High-risk plaques were identified, as were low-density plaques, positive remodeling, and spotty calcification.ResultsCompared with patients who did not have nonalcoholic hepatic steatosis, patients with nonalcoholic hepatic steatosis had more low-density plaques (21% vs. 44%, p<0.01), positive remodeling (41% vs. 58%, p = 0.01), and spotty calcification (12% vs. 36%, p<0.01). The number of high-risk plaques in patients with nonalcoholic hepatic steatosis was greater than in those without nonalcoholic hepatic steatosis (p<0.01). Patients with nonalcoholic hepatic steatosis were more likely to have high-risk plaques than were those with only an elevated level of visceral adipose tissue (≥86 cm2; 35% vs. 16%, p<0.01). Multivariate analyses that included nonalcoholic hepatic steatosis, amount of visceral adipose tissue, and the presence/absence of traditional risk factors demonstrated that nonalcoholic hepatic steatosis was an independent predictor of high-risk plaques (odds ratio: 4.60; 95% confidence interval: 1.94–9.07, p<0.01).ConclusionsDiagnosis of nonalcoholic hepatic steatosis may be of value when assessing the risk of coronary artery disease.
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