Transcatheter Aortic Valve Replacement for Severe Symptomatic Aortic Stenosis Using a Repositionable Valve System : 30-Day Primary Endpoint Results From the REPRISE II Study

Background

Transcatheter aortic valve replacement provides results comparable to those of surgery in patients at high surgical risk, but complications can impact long-term outcomes. The Lotus valve, designed to improve upon earlier devices, is fully repositionable and retrievable, with a unique seal to minimize paravalvular regurgitation (PVR).

Objectives

The prospective, single-arm, multicenter REPRISE II study (REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus Valve System: Evaluation of Safety and Performance) evaluated the transcatheter valve system for treatment of severe symptomatic calcific aortic valve stenosis.

Methods

Patients (n = 120; aortic annulus 19 to 27 mm) considered by a multidisciplinary heart team to be at high surgical risk received the valve transfemorally. The primary device performance endpoint, 30-day mean pressure gradient, was assessed by an independent echocardiographic core laboratory and compared with a pre-specified performance goal. The primary safety endpoint was 30-day mortality. Secondary endpoints included safety/effectiveness metrics per Valve Academic Research Consortium criteria.

Results

Mean age was 84.4 years, 57% of the patients were female, and 76% were New York Heart Association functional class III/IV. Mean aortic valve area was 0.7 ± 0.2 cm². The valve was successfully implanted in all patients, with no cases of valve embolization, ectopic valve deployment, or additional valve implantation. All repositioning (n = 26) and retrieval (n = 6) attempts were successful; 34 patients (28.6%) received a permanent pacemaker. The primary device performance endpoint was met, because the mean gradient improved from 46.4 ± 15.0 mm Hg to 11.5 ± 5.2 mm Hg. At 30 days, the mortality rate was 4.2%, and the rate of disabling stroke was 1.7%; 1 (1.0%) patient had moderate PVR, whereas none had severe PVR.

Conclusions

REPRISE II demonstrates the safety and effectiveness of the Lotus valve in patients with severe aortic stenosis who are at high surgical risk. The valve could be positioned successfully with minimal PVR. (REPRISE II: REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve System - Evaluation of Safety and Performance; NCT01627691)     

Quantitative tissue pH measurement during cerebral ischemia using amine and amide concentration-independent detection (AACID) with MRI

Tissue pH is an indicator of altered cellular metabolism in diseases including stroke and cancer. Ischemic tissue often becomes acidic due to increased anaerobic respiration leading to irreversible cellular damage. Chemical exchange saturation transfer (CEST) effects can be used to generate pH-weighted magnetic resonance imaging (MRI) contrast, which has been used to delineate the ischemic penumbra after ischemic stroke. In the current study, a novel MRI ratiometric technique is presented to measure absolute pH using the ratio of CEST-mediated contrast from amine and amide protons: amine/amide concentration-independent detection (AACID). Effects of CEST were observed at 2.75 parts per million (p.p.m.) for amine protons and at 3.50 p.p.m. for amide protons downfield (i.e., higher frequency) from bulk water. Using numerical simulations and in vitro MRI experiments, we showed that pH measured using AACID was independent of tissue relaxation time constants, macromolecular magnetization transfer effects, protein concentration, and temperature within the physiologic range. After in vivo pH calibration using phosphorus (³¹P) magnetic resonance spectroscopy (³¹P-MRS), local acidosis is detected in mouse brain after focal permanent middle cerebral artery occlusion. In summary, our results suggest that AACID represents a noninvasive method to directly measure the spatial distribution of absolute pH in vivo using CEST MRI.     

Impact of adverse pancreatic injury at surgical procurement upon islet isolation outcome

The consequence of a pancreas injury during the procurement for islet isolation purpose is unknown. The goal of this work was to assess the injuries of the pancreata procured for islet isolation, and to determine their effect on the islet yield. Between January 2007 and October 2013, we prospectively documented every injury of the pancreata processed in our centre for islet isolation. Injuries involving the main duct were classified as major, the others as minor. Donors’ characteristics and islet yields were compared between the groups of injuries. A pancreas injury was identified in 42 of 452 pancreata received for islet isolation (9.3%). In 15 cases, the injury was major (3.3% of all pancreata). Although a minor injury did not affect the islet yield, a major injury was significantly associated with unfavourable outcomes (postpurification mean islet equivalent of 364 ± 181, 405 ± 190 and 230 ± 115 × 10³ for absence of injury, minor injury and major injury, respectively). A major injury was significantly more prevalent in lean and short donors. We recommend assessing the quality of the pancreas in the islet isolation centre before starting the isolation procedure. Each centre should determine its own policy based on its financial resources and on the wait list.     

Cytotoxicity,Phytochemical Analysis and Antioxidant Activity of Crude Extracts from Rhizomes of Elephantorrhiza Elephantina and Pentanisia Prunelloides

Background

Elephantorrhiza elephantina (Ee) and Pentanisia prunelloides (Pp) are two medicinal plants which are widely used to remedy various ailments including diarrhoea, dysentery, inflammation, fever, rheumatism, heartburn, tuberculosis, haemorrhoids, skin diseases, perforated peptic ulcers and sore joints in southern Africa (South Africa, Swaziland, Botswana and Zimbabwe). The following study was conducted to explore the in vitro cytotoxicity, antioxidant properties and phytochemical profile of the two medicinal plants.

Materials and Methods

The cytotoxicity of the aqueous and methanol extracts and fractions of both species was studied using the brine shrimp lethality tests (BST) for the first time.

Results

The results demonstrated that the lethality (LC₅₀) for crude extracts for both plants ranged between 1.8 and 5.8 ppm and was relatively greater than that for the methanol, ethyl acetate and chloroform fractions of the extracts which ranged between 2.1 ppm and 27 ppm. This suggested that crude extracts were more potent than their respective fractions, further explaining that the different fractions of phytochemicals in these plant species work jointly (in synergy) to exert their therapeutic efficacy. Both aqueous and methanol extracts of the two medicinal plants demonstrated a high degree of antioxidant capacity against the DPPH radical with the Duh and Yen inhibition percentage ranging between 4.5% and 72%. Phytochemical studies of the rhizome extracts showed that the major compounds present include flavonoids, tannins, anthocyanidins, anthraquinones, triterpenoids (oleanolic acid), the steroidal saponin Diosgenin, the sugars, rhamnose, glucuronic acid, Arabinose and hexoses.

Conclusion

This is the first report of the detection and isolation of diosgenin and oleanolic acid from the rhizome extracts of Ee and Pp. All structures were determined using spectroscopic/spectrometric techniques (1H NMR and 13C and LC-ESI-MS) and by comparison with literature data.     

Prevalence of Candida spp., xerostomia,and hyposalivation in oral lichen planus – A controlled study

Objective

To determine the frequency of Candida spp., xerostomia, and salivary flow rate (SFR) in three different groups: patients with OLP (OLP group), patients with oral mucosal lesions other than OLP (non‐OLP group), and subjects without oral mucosal lesions (control group).

Material and methods

Xerostomia as well as SFR was investigated in the three groups. Samples for isolation of Candida spp. were collected from OLP lesions (38 patients), non‐OLP lesions (28 patients), and healthy subjects (32 subjects).

Results

There was no statistically significant difference regarding the frequency of xerostomia and hyposalivation among the three groups (P > 0.05). A higher prevalence for colonization by Candida spp. was found in the healthy subject as compared to that of patients with OLP (P = 0.03) and non‐OLP (P = 0.02) groups. Low SFR was not a factor for colonization by Candida spp.

Conclusions

Xerostomia and hyposalivation occur with similar frequency in subjects with and without oral lesions; also, the presence of oral lesions does not increase the susceptibility to colonization by Candida spp. It seems that any study implicating Candida spp. in the malignant transformation of oral lesions should be carried out mostly on a biochemical basis, that is, by testing the capability of Candida spp. to produce carcinogenic enzyme.     

应用序列特异引物PCR法对广西壮族HLA－DQA_1进行基因分型

应用序列特异引物多聚酶链反应（ＰＣＲ）方法对８２名无血缘关系的广西壮族健康人的ＨＬＡ－ＤＱＡ＿１进行基因分型。共检出７种ＤＱＡ＿１等位基因，以ＤＱＡ＿１＊０３０１的频率最高，达３１％，其次为ＤＱＡ＿１＊０１０４，０１０２和０５０１，检出率分别为２４．３％，１６．９％和１１．７％。未检出的等位基因有ＤＱＡ＿１＊０２０１，０３０２和０６０１。结果表明，壮族的ＨＬＡ－ＤＱＡ＿１等位基因频率分布除与中国南方人相似外，尚有其特点。序列特异引物ＰＣＲ方法不需要放射性同位素，简便快速、准确可靠的ＨＬＡ－ＤＱＡ＿１基因分型新方法。