Characteristics of Inoperable Patients with Severe Aortic Valve Stenosis —In the Era of Transcatheter Aortic Valve Replacement

Purpose: Transcatheter aortic valve replacement (TAVR) has emerged as a therapeutic option for severe aortic valvular stenosis (AS). To determine the indication for TAVR, it is mandatory to clarify the characteristics of the patients who were judged as inoperable for conventional aortic valve replacement (cAVR).Methods: Of 185 patients newly diagnosed as severe AS from March 2010 to April 2011, we studied the characteristics of 61 (33%) patients (mean age, 86 ± 8 years) who were judged as inoperable.Results: Younger patients (<85 years old, n = 22) had more major comorbidities and lower left ventricular ejection fraction than older patients (≥85 years old, n = 39). Mean estimated mortality for cAVR by Japan score was 7.0% ± 7.4%. Japan score did not correlate to age and was calculated relatively low in the older age group (6.2% ± 7.0%) than the younger age group (8.3% ± 8.1%).Conclusion: One thirds of severe AS patients were judged as inoperable. In advanced age patients, age itself and other factors, which are not included in the conventional scoring systems, might have contributed to the decision making not to perform cAVR by cardiologists. Further study is necessary to define risk factors except for age.     

Contrast echocardiography can save nondiagnostic exams in mechanically ventilated patients

Patients in an intensive care unit (ICU) under mechanical ventilation (MV) are very difficult to image by transthoracic echocardiography, diminishing the beneficial information that could be obtained by this noninvasive approach. The objective of this study is to assess whether the addition of a contrast agent to fundamental imaging (FI) can improve or change the initial diagnosis in cardiac postoperative patients under mechanical ventilation by enhancing endocardial border delineation and Doppler flow signal. Thirty mechanically ventilated post-cardiac surgery patients (20 men, mean age 61 +/- 13 years) were evaluated with FI before and after intravenous injection of contrast. Left ventricular endocardial border delineation score index (EBDSI), estimated left ventricular ejection fraction (LVEF), and color and spectral Doppler were analyzed. The use of contrast resulted in a significant increase in the number of well-delineated segments, with a salvage rate of 77% of nondiagnostic studies. EBDSI was 1.62 +/- 0.61, before contrast, increasing to 2.05 +/- 0.53 after it (P < 0.001). There was a change in the LVEF estimation in 5 exams, and a new wall motion abnormality was detected in other 4 exams, after the use of contrast. Moreover, a significant change was observed in the quantification of mitral regurgitation in 5 patients, in the aortic transvalvular peak gradient in 1 patient, and measurement of tricuspid regurgitation peak flow velocity in 8 patients. It is concluded that in cardiac postoperative patients under mechanical ventilation, intravenous injection of a contrast agent using FI resulted in a high salvage rate of studies and changed the initial diagnosis in a significant number of patients.     

Biliary adenofibroma with ominous features of imminent malignant changes

Biliary adenofibroma (BAF) is a rare, benign liver tumor. Herein, we report a case of BAF with histological features of imminent malignant changes. Ultrasound and CT revealed a solid 2.5-cm mass in the right liver lobe. The patient was asymptomatic and had no past medical history including liver disease. A general examination that included the abdomen and the laboratory data were normal. Because of the increase of its size, this tumor was surgically resected. Grossly, a 3.5-cm nodular mass abutted on the hepatic capsule was found, and its cut surface showed a well-circumscribed, whitish, and firm lesion that showed microcystic changes in the periphery and solid changes in the central parts. Histologically, the tumor showed a proliferation of tubulocystic structures embedded in a fibrous stroma. Microcysts were prevalent in the periphery, while tubular components with abundant fibrous stroma were in the central parts. The tubules were variably dilated and branched. This case closely resembled the previously reported cases of BAF, except that there were complicated papillary projections with fine fibrovascular cores in some of the microcysts and that the epithelial component in papillary projections showed dysplastic changes and increased cellular proliferative activities, implicating ominous features of imminent malignant changes. These dysplastic and papillary changes may be an intermediate lesion leading to malignancy, which have occasionally been reported in BAF.     

Gonadotropin-inhibitory hormone (GnIH): discovery, progress and prospect

A hypothalamic neuropeptide, gonadotropin-releasing hormone (GnRH), is the primary factor regulating gonadotropin secretion. An inhibitory hypothalamic neuropeptide for gonadotropin secretion was, until recently, unknown, although gonadal sex steroids and inhibin can modulate gonadotropin secretion. Findings from the last decade, however, indicate that GnRH is not the sole hypothalamic regulatory neuropeptide of vertebrate reproduction, with gonadotropin-inhibitory hormone (GnIH) playing a key role in the inhibition of reproduction. GnIH was originally identified in birds and subsequently in mammals and other vertebrates. GnIH acts on the pituitary and on GnRH neurons in the hypothalamus via a novel G protein-coupled receptor (GPR147). GnIH decreases gonadotropin synthesis and release, inhibiting gonadal development and maintenance. Such a down-regulation of the hypothalamo-pituitary-gonadal (HPG) axis may be conserved across vertebrates. Recent evidence further indicates that GnIH operates at the level of the gonads as an autocrine/paracrine regulator of steroidogenesis and gametogenesis. More recent evidence suggests that GnIH also acts both upstream of the GnRH system and at the level of the gonads to appropriately regulate reproductive activity across the seasons and during times of stress. The discovery of GnIH has fundamentally changed our understanding of hypothalamic control of reproduction. This review summarizes the discovery, progress and prospect of GnIH, a key regulator of vertebrate reproduction.     

Aβ neurotoxicity depends on interactions between copper ions, prion protein, and N-methyl-D-aspartate receptors

N-methyl-d-aspartate receptors (NMDARs) mediate critical CNS functions, whereas excessive activity contributes to neuronal damage. At physiological glycine concentrations, NMDAR currents recorded from cultured rodent hippocampal neurons exhibited strong desensitization in the continued presence of NMDA, thus protecting neurons from calcium overload. Reducing copper availability by specific chelators (bathocuproine disulfonate, cuprizone) induced nondesensitizing NMDAR currents even at physiologically low glycine concentrations. This effect was mimicked by, and was not additive with, genetic ablation of cellular prion protein (PrP(C)), a key copper-binding protein in the CNS. Acute ablation of PrP(C) by enzymatically cleaving its cell-surface GPI anchor yielded similar effects. Biochemical studies and electrophysiological measurements revealed that PrP(C) interacts with the NMDAR complex in a copper-dependent manner to allosterically reduce glycine affinity for the receptor. Synthetic human Aβ(1-42) (10 nM-5 μM) produced an identical effect that could be mitigated by addition of excess copper ions or NMDAR blockers. Taken together, Aβ(1-42), copper chelators, or PrP(C) inactivation all enhance the activity of glycine at the NMDAR, giving rise to pathologically large nondesensitizing steady-state NMDAR currents and neurotoxicity. We propose a physiological role for PrP(C), one that limits excessive NMDAR activity that might otherwise promote neuronal damage. In addition, we provide a unifying molecular mechanism whereby toxic species of Aβ(1-42) might mediate neuronal and synaptic injury, at least in part, by disrupting the normal copper-mediated, PrP(C)-dependent inhibition of excessive activity of this highly calcium-permeable glutamate receptor.     

Esophageal motor dysfunction plays a key role in GERD with globus sensation - Analysis of factors promoting resistance to PPI therapy

Abstract Objective. Patients with gastroesophageal reflux disease (GERD) also have various extra-esophageal symptoms. Laryngopharyngeal reflux disease (LPRD) is a subtype of GERD associated with globus sensation, but proton pump inhibitor (PPI) therapy achieves disappointing results. This study investigated esophageal motility in GERD patients with globus sensation who were resistant to PPI therapy. Design. The subjects were 350 patients with globus sensation. All patients underwent both laryngoscopy and upper gastrointestinal endoscopy to exclude organic disease. After 4 weeks of treatment with rabeprazole sodium (20 mg daily), the patients were divided into PPI-responsive and PPI-resistant groups. Then we investigated esophageal motility in the PPI-resistant group by a multichannel intraluminal impedance and manometry study. Results. A total of 119 patients (55.6%) were resistant to PPI therapy, among whom 57 patients (47.9%) had abnormal esophageal motility. They included 36 patients (66.4%) with ineffective esophageal motility, 9 patients (14.4%) with achalasia, 6 patients (9.6%) with diffuse esophageal spasm, 5 patients (8%) with nutcracker esophagus, and 1 patient (1.6%) with hypertensive lower esophageal sphincter. There were significant differences of upper esophageal sphincter pressure and esophageal body peristalsis between the patients with PPI-resistant LPRD and healthy controls matched for age and sex. Conclusion. Among patients with PPI-resistant LPRD, 47.9% had abnormal esophageal motility.     

Enhancement of Hemocompatibility of the MERA Monopivot Centrifugal Pump: Toward Medium‐Term Use

The MERA monopivot centrifugal pump has been developed for use in open‐heart surgery, circulatory support, and bridge‐to‐decision for up to 4 weeks. The pump has a closed‐type, 50‐mm diameter impeller with four straight paths. The impeller is supported by a monopivot bearing and is driven by a radial‐flux magnet‐coupling motor. Because flow visualization experiments have clarified sufficient pivot wash and stagnation at the sharp corner of the pivot support was suggested, sharp corners were removed in the design stage. The index of hemolysis of the pump operating at more than 200 mm Hg was found to be lower than that of a commercial pump. Four‐week animal tests were then conducted two times; improvement of thrombus formation was seen in the female pivot through modification of female pivot geometry. Overall antithrombogenicity was also recorded. Finally, to assure mid‐term use, an additional 4‐week durability test revealed that the rate of the axial pivot wear was as small as 1.1 µm/day. The present in vitro and in vivo studies revealed that the MERA monopivot centrifugal pump has sufficient hemocompatibility and durability for up to 4 weeks.