A mutation update on the LDS‐associated genes TGFB2/3 and SMAD2/3

The Loeys–Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism, and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor‐β (TGF‐β) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF‐β signaling. More recently, TGF‐β ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF‐β pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF‐β signaling in LDS pathogenesis. Since most literature so far has focused on TGFBR1/2, we provide a comprehensive review on the known and some novel TGFB2/3 and SMAD2/3 mutations. For TGFB2 and SMAD3, the clinical manifestations, both of the patients previously described in the literature and our newly reported patients, are summarized in detail. This clearly indicates that LDS concerns a disorder with a broad phenotypical spectrum that is still emerging as more patients will be identified. All mutations described here are present in the corresponding Leiden Open Variant Database.     

Establishment of Fascioloides magna in a new region of Hungary: case report

Parasitology Research - During the monitoring of red deer (N = 124) and fallow deer (N = 13) populations in four neighbouring areas, the presence of Fascioloides magna...     

Utility of the INTERMACS profile at the time of assessment for heart transplant

The Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS) profiles are associated with mortality in heart failure patients undergoing ventricular assist device (VAD) implantation and heart transplantation (HTx). We assessed the prognostic value of the INTERMACS profile at the time of assessment for HTx or durable VAD implantation as bridge to candidacy (BTC). A total of 503 consecutive patients considered for HTx or VAD between 2006 and 2016 were included. The associations between INTERMACS profile and (a) waitlist mortality or delisting, (b) probability of HTx, and (c) overall mortality or delisting were evaluated using multivariable analysis. Median follow-up time was 2.9 years (IQR: 0.9-5.5) during which 184 received VAD, 347 received HTx, and 73 died (27 waitlist, 46 post-transplant). INTERMACS I-II profile was associated with higher waitlist mortality or delisting (HR: 3.83, 95% CI: 1.22-12.03), and this risk was reversed by VAD implantation (HR: 0.12, 95% CI: 0.03-0.50). INTERMACS III-IV profile was associated with a higher probability of HTx (HR: 1.82, 95% CI: 1.37-2.40). INTERMACS profile was not associated with the composite outcome of overall mortality or delisting. These results emphasize the prognostic utility of INTERMACS at time of decision for advanced therapies and its potential value in selecting patients for different interventions.     

Robot-assisted laparoscopic Y-V plasty in 12 patients with refractory bladder neck contracture

We present preliminary results of a case series on refractory bladder neck contracture (BNC) treated with robot-assisted laparoscopic Y-V plasty (RAYV). Between 01/2013 and 02/2016, 12 consecutive adult male patients underwent RAYV in our hospital. BNC developed after transurethral procedures (n = 9), simple prostatectomy (n = 2) and HIFU therapy of the prostate (n = 1). Each patient had had multiple unsuccessful previous endoscopic treatments. All RAYV procedures were performed using a transperitoneal six-port approach (four-arm robotic setting). There were no intraoperative or major postoperative complications. During a median follow-up of 23.2 months two cases of refractory BNC were observed. In both cases a postoperative International Prostate Symptom Score (IPSS) of 20 and 25 was reported, respectively. In contrast, amongst the patients without evidence of refractory BNC the median IPSS was 6.5 reflecting an only mildly impaired voiding function in most cases, thus, suggesting a treatment success in 83.3% of patients. To the best of our knowledge, this is the first report on RAYV for refractory BNC. In our series RAYV was feasible in all patients, and only two cases of refractory BNC were reported during a median follow-up of almost 2 years. At the same time, no intraoperative or major postoperative complications were observed. More clinical data with a longer follow-up are needed in this promising field to reveal the actual efficacy and relevance of RAYV.     

Cerebral energetics and spiking frequency: the neurophysiological basis of fMRI

Functional MRI (fMRI) is widely assumed to measure neuronal activity, but no satisfactory mechanism for this linkage has been identified. Here we derived the changes in the energetic component from the blood oxygenation level-dependent (BOLD) fMRI signal and related it to changes in the neuronal spiking frequency in the activated voxels. Extracellular recordings were used to measure changes in cerebral spiking frequency (Deltanu/nu) of a neuronal ensemble during forepaw stimulation in the alpha-chloralose anesthetized rat. Under the same conditions localized changes in brain energy metabolism (DeltaCMR(O2)/CMR(O2)) were obtained from BOLD fMRI data in conjunction with measured changes in cerebral blood flow (DeltaCBF/CBF), cerebral blood volume (DeltaCBV/CBV), and transverse relaxation rates of tissue water (T(2)(*) and T(2)) by MRI methods at 7T. On stimulation from two different depths of anesthesia DeltaCMR(O2)/CMR(O2) approximately Deltanu/nu. Previous (13)C magnetic resonance spectroscopy studies, under similar conditions, had shown that DeltaCMR(O2)/CMR(O2) was proportional to changes in glutamatergic neurotransmitter flux (DeltaV(cyc)/V(cyc)). These combined results show that DeltaCMR(O2)/CMR(O2) approximately DeltaV(cyc)/V(cyc) approximately Deltanu/nu, thereby relating the energetic basis of brain activity to neuronal spiking frequency and neurotransmitter flux. Because DeltaCMR(O2)/CMR(O2) had the same high spatial and temporal resolutions of the fMRI signal, these results show how BOLD imaging, when converted to DeltaCMR(O2)/CMR(O2), responds to localized changes in neuronal spike frequency.     

Autoimmune thyroid disease is associated with a diagnosis of secondary Sjögren's syndrome in familial systemic lupus

BACKGROUND: Autoimmune thyroid disease is common in systemic lupus erythematosus (SLE). About 20% of patients with SLE have secondary Sj?gren's syndrome. METHODS: Families with more than one patient with SLE were identified. All patients met the revised classification criteria, although SLE-unaffected relatives were confirmed not to satisfy these criteria. Diagnosis of autoimmune thyroid disease and Sj?gren's syndrome was made on the basis of a review of medical records, interview and questionnaire administered to patients with SLE, and by a questionnaire administered to SLE-unaffected subjects. RESULTS: Of a total of 1138 patients with SLE, 169 had a diagnosis of Sj?gren's syndrome. Of these 50 (29.6%) patients also had autoimmune thyroid disease. Of the 939 patients with SLE with no diagnosis of Sj?gren's syndrome, 119 (12.7%) had autoimmune thyroid disease (chi2 = 20.1, p = 0.000009). There was no association of a diagnosis of hypertension with secondary Sj?gren's syndrome (42% vss 47%). Among 2291 SLE-unaffected relatives, 44 had diagnosed primary Sj?gren's syndrome and 16 (36.3%) of these also had autoimmune thyroid disease. 265 of 2247 (11.8%) subjects had autoimmune thyroid disease but no Sj?gren's syndrome (chi2 = 24.2, p<0.001). CONCLUSIONS: Autoimmune thyroid disease is found in excess among patients with SLE with a diagnosis of secondary Sj?gren's syndrome, as well as among their SLE-unaffected relatives with a diagnosis of primary Sj?gren's syndrome.     

Multisite reliability of cognitive BOLD data

Investigators perform multi-site functional magnetic resonance imaging studies to increase statistical power, to enhance generalizability, and to improve the likelihood of sampling relevant subgroups. Yet undesired site variation in imaging methods could off-set these potential advantages. We used variance components analysis to investigate sources of variation in the blood oxygen level-dependent (BOLD) signal across four 3-T magnets in voxelwise and region-of-interest (ROI) analyses. Eighteen participants traveled to four magnet sites to complete eight runs of a working memory task involving emotional or neutral distraction. Person variance was more than 10 times larger than site variance for five of six ROIs studied. Person-by-site interactions, however, contributed sizable unwanted variance to the total. Averaging over runs increased between-site reliability, with many voxels showing good to excellent between-site reliability when eight runs were averaged and regions of interest showing fair to good reliability. Between-site reliability depended on the specific functional contrast analyzed in addition to the number of runs averaged. Although median effect size was correlated with between-site reliability, dissociations were observed for many voxels. Brain regions where the pooled effect size was large but between-site reliability was poor were associated with reduced individual differences. Brain regions where the pooled effect size was small but between-site reliability was excellent were associated with a balance of participants who displayed consistently positive or consistently negative BOLD responses. Although between-site reliability of BOLD data can be good to excellent, acquiring highly reliable data requires robust activation paradigms, ongoing quality assurance, and careful experimental control.     

Development and evaluation of TWIST Dixon for dynamic contrast-enhanced (DCE) MRI with improved acquisition efficiency and fat suppression

Purpose:

To develop a new pulse sequence called time‐resolved angiography with stochastic trajectories (TWIST) Dixon for dynamic contrast enhanced magnetic resonance imaging (DCE‐MRI).

Materials and Methods:

The method combines dual‐echo Dixon to generate separated water and fat images with a k‐space view‐sharing scheme developed for 3D TWIST. The performance of TWIST Dixon was compared with a volume interpolated breathhold examination (VIBE) sequence paired with spectrally selective adiabatic inversion Recovery (SPAIR) and quick fat‐sat (QFS) fat‐suppression techniques at 3.0T using quantitative measurements of fat‐suppression accuracy and signal‐to‐noise ratio (SNR) efficiency, as well as qualitative breast image evaluations.

Results:

The water fraction of a uniform phantom was calculated from the following images: 0.66 ± 0.03 for TWIST Dixon; 0.56 ± 0.23 for VIBE‐SPAIR, and 0.53 ± 0.14 for VIBE‐QFS, while the reference value is 0.70 measured by spectroscopy. For phantoms with contrast (Gd‐BOPTA) concentration ranging from 0–6 mM, TWIST Dixon also provides consistently higher SNR efficiency (3.2–18.9) compared with VIBE‐SPAIR (2.8–16.8) and VIBE‐QFS (2.4–12.5). Breast images acquired with TWIST Dixon at 3.0T show more robust and uniform fat suppression and superior overall image quality compared with VIBE‐SPAIR.

Conclusion:

The results from phantom and volunteer evaluation suggest that TWIST Dixon outperforms conventional methods in almost every aspect and it is a promising method for DCE‐MRI and contrast‐enhanced perfusion MRI, especially at higher field strength where fat suppression is challenging. J. Magn. Reson. Imaging 2012;36:483–491. © 2012 Wiley Periodicals, Inc.