Overexpression of VIRMA confers vulnerability to breast cancers via the m6A-dependent regulation of unfolded protein response.

Virilizer-like m6A methyltransferase-associated protein (VIRMA) maintains the stability of the m6A writer complex. Although VIRMA is critical for RNA m6A deposition, the impact of aberrant VIRMA expression in human diseases remains unclear. We show that VIRMA is amplified and overexpressed in 15-20% of breast cancers. Of the two known VIRMA isoforms, the nuclear-enriched full-length but not the cytoplasmic-localised N-terminal VIRMA promotes m6A-dependent breast tumourigenesis in vitro and in vivo. Mechanistically, we reveal that VIRMA overexpression upregulates the m6A-modified long non-coding RNA, NEAT1, which contributes to breast cancer cell growth. We also show that VIRMA overexpression enriches m6A on transcripts that regulate the unfolded protein response (UPR) pathway but does not promote their translation to activate the UPR under optimal growth conditions. Under stressful conditions that are often present in tumour microenvironments, VIRMA-overexpressing cells display enhanced UPR and increased susceptibility to death. Our study identifies oncogenic VIRMA overexpression as a vulnerability that may be exploited for cancer therapy.

Ultraprecise single-molecule localization microscopy enables in situ distance measurements in intact cells.

Single-molecule localization microscopy (SMLM) has the potential to quantify the diversity in spatial arrangements of molecules in intact cells. However, this requires that the single-molecule emitters are localized with ultrahigh precision irrespective of the sample format and the length of the data acquisition. We advance SMLM to enable direct distance measurements between molecules in intact cells on the scale between 1 and 20 nm. Our actively stabilized microscope combines three-dimensional real-time drift corrections and achieves a stabilization of <1 nm and localization precision of ~1 nm. To demonstrate the biological applicability of the new microscope, we show a 4- to 7-nm difference in spatial separations between signaling T cell receptors and phosphatases (CD45) in active and resting T cells. In summary, by overcoming the major bottlenecks in SMLM imaging, it is possible to generate molecular images with nanometer accuracy and conduct distance measurements on the biological relevant length scales.

Macrophage development and activation involve coordinated intron retention in key inflammatory regulators.

Monocytes and macrophages are essential components of the innate immune system. Herein, we report that intron retention (IR) plays an important role in the development and function of these cells. Using Illumina mRNA sequencing, Nanopore direct cDNA sequencing and proteomics analysis, we identify IR events that affect the expression of key genes/proteins involved in macrophage development and function. We demonstrate that decreased IR in nuclear-detained mRNA is coupled with increased expression of genes encoding regulators of macrophage transcription, phagocytosis and inflammatory signalling, including ID2, IRF7, ENG and LAT. We further show that this dynamic IR program persists during the polarisation of resting macrophages into activated macrophages. In the presence of proinflammatory stimuli, intron-retaining CXCL2 and NFKBIZ transcripts are rapidly spliced, enabling timely expression of these key inflammatory regulators by macrophages. Our study provides novel insights into the molecular factors controlling vital regulators of the innate immune response.

Can single molecule localization microscopy detect nanoclusters in T cells?

Nanoclusters of cell surface receptors have been detected with single molecule localization microscopy (SMLM) and are thought to mediate signal transduction. Clustering of the T cell receptor (TCR), for example, was reported to control signalling efficiency and antigen discrimination. However, the ability to detect nanoclusters with SMLM has been questioned. Here, we review the detection limits of SMLM as defined by both the physical limits and data processing, as well as evidence for nanoclusters arising from complementary techniques. We conclude with an outlook of how future data analysis can reveal the implications of molecular self-organization for signalling.

Laparoscopic repair of a migrated adjustable gastric band connecting tube with colonic erosion.

Laparoscopic adjustable gastric bands are a popular and effective surgical option to treat morbid obesity. The overall complication rate is 10-20% and the most common complication is of 'slippage'. Although other complications such as gastric band migration and erosion have been reported, the phenomenon of a migrated gastric band connecting tube eroding into the colon (after port removal) is seldom reported in the literature. In this article we describe such a case of an incidentally found colonic erosion on colonoscopy and describe the subsequent laparoscopic repair, as well as a review of the literature.

Translation. An RNA biosensor for imaging the first round of translation from single cells to living animals.

Analysis of single molecules in living cells has provided quantitative insights into the kinetics of fundamental biological processes; however, the dynamics of messenger RNA (mRNA) translation have yet to be addressed. We have developed a fluorescence microscopy technique that reports on the first translation events of individual mRNA molecules. This allowed us to examine the spatiotemporal regulation of translation during normal growth and stress and during Drosophila oocyte development. We have shown that mRNAs are not translated in the nucleus but translate within minutes after export, that sequestration within P-bodies regulates translation, and that oskar mRNA is not translated until it reaches the posterior pole of the oocyte. This methodology provides a framework for studying initiation of protein synthesis on single mRNAs in living cells.

Transcription mediated insulation and interference direct gene cluster expression switches.

In yeast, many tandemly arranged genes show peak expression in different phases of the metabolic cycle (YMC) or in different carbon sources, indicative of regulation by a bi-modal switch, but it is not clear how these switches are controlled. Using native elongating transcript analysis (NET-seq), we show that transcription itself is a component of bi-modal switches, facilitating reciprocal expression in gene clusters. HMS2, encoding a growth-regulated transcription factor, switches between sense- or antisense-dominant states that also coordinate up- and down-regulation of transcription at neighbouring genes. Engineering HMS2 reveals alternative mono-, di- or tri-cistronic and antisense transcription units (TUs), using different promoter and terminator combinations, that underlie state-switching. Promoters or terminators are excluded from functional TUs by read-through transcriptional interference, while antisense TUs insulate downstream genes from interference. We propose that the balance of transcriptional insulation and interference at gene clusters facilitates gene expression switches during intracellular and extracellular environmental change.

Drosophila Syncrip modulates the expression of mRNAs encoding key synaptic proteins required for morphology at the neuromuscular junction.

Localized mRNA translation is thought to play a key role in synaptic plasticity, but the identity of the transcripts and the molecular mechanism underlying their function are still poorly understood. Here, we show that Syncrip, a regulator of localized translation in the Drosophila oocyte and a component of mammalian neuronal mRNA granules, is also expressed in the Drosophila larval neuromuscular junction, where it regulates synaptic growth. We use RNA-immunoprecipitation followed by high-throughput sequencing and qRT-PCR to show that Syncrip associates with a number of mRNAs encoding proteins with key synaptic functions, including msp-300, syd-1, neurexin-1, futsch, highwire, discs large, and α-spectrin. The protein levels of MSP-300, Discs large, and a number of others are significantly affected in syncrip null mutants. Furthermore, syncrip mutants show a reduction in MSP-300 protein levels and defects in muscle nuclear distribution characteristic of msp-300 mutants. Our results highlight a number of potential new players in localized translation during synaptic plasticity in the neuromuscular junction. We propose that Syncrip acts as a modulator of synaptic plasticity by regulating the translation of these key mRNAs encoding synaptic scaffolding proteins and other important components involved in synaptic growth and function.

Syncrip/hnRNP Q influences synaptic transmission and regulates BMP signaling at the Drosophila neuromuscular synapse.

Synaptic plasticity involves the modulation of synaptic connections in response to neuronal activity via multiple pathways. One mechanism modulates synaptic transmission by retrograde signals from the post-synapse that influence the probability of vesicle release in the pre-synapse. Despite its importance, very few factors required for the expression of retrograde signals, and proper synaptic transmission, have been identified. Here, we identify the conserved RNA binding protein Syncrip as a new factor that modulates the efficiency of vesicle release from the motoneuron and is required for correct synapse structure. We show that syncrip is required genetically and its protein product is detected only in the muscle and not in the motoneuron itself. This unexpected non-autonomy is at least partly explained by the fact that Syncrip modulates retrograde BMP signals from the muscle back to the motoneuron. We show that Syncrip influences the levels of the Bone Morphogenic Protein ligand Glass Bottom Boat from the post-synapse and regulates the pre-synapse. Our results highlight the RNA-binding protein Syncrip as a novel regulator of synaptic output. Given its known role in regulating translation, we propose that Syncrip is important for maintaining a balance between the strength of presynaptic vesicle release and postsynaptic translation.

A laparoscopic transgastric approach to the treatment of sphincter of Oddi dysfunction postgastric bypass.

Obesity is endemic and bariatric surgery is increasing in an attempt to reduce the physiological and social cost. As the prevalence of bariatric surgery increases, in particular laparoscopic roux-en-Y gastric bypass (LRYGB), the need to investigate and treat subsequent pathology in the gastric remnant and biliary tree will accrue. We describe a novel combined surgical and endoscopic technique addressing the challenges of postoperative anatomy, allowing investigation and treatment of the gastric remnant and biliary tract. We present the case of a patient with sphincter of Oddi dysfunction post-LRYGB who underwent laparoscopic transgastric endoscopic injection of Botox into the ampulla with an excellent symptomatic relief. Subsequent laparoscopic transgastric sphincterotomy allowed definitive treatment and allowed symptom resolution at 6 months follow-up. Laparoscopic transgastric endoscopic investigation and treatment is a novel approach to circumvent the restrictions of post-LRYGB anatomy and may assume greater importance in an ageing obese population.

Drosophila patterning is established by differential association of mRNAs with P bodies.

The primary embryonic axes in flies, frogs and fish are formed through translational regulation of localized transcripts before fertilization. In Drosophila melanogaster, the axes are established through the transport and translational regulation of gurken (grk) and bicoid (bcd) messenger RNA in the oocyte and embryo. Both transcripts are translationally silent while being localized within the oocyte along microtubules by cytoplasmic dynein. Once localized, grk is translated at the dorsoanterior of the oocyte to send a TGF-α signal to the overlying somatic cells. In contrast, bcd is translationally repressed in the oocyte until its activation in early embryos when it forms an anteroposterior morphogenetic gradient. How this differential translational regulation is achieved is not fully understood. Here, we address this question using ultrastructural analysis, super-resolution microscopy and live-cell imaging. We show that grk and bcd ribonucleoprotein (RNP) complexes associate with electron-dense bodies that lack ribosomes and contain translational repressors. These properties are characteristic of processing bodies (P bodies), which are considered to be regions of cytoplasm where decisions are made on the translation and degradation of mRNA. Endogenous grk mRNA forms dynamic RNP particles that become docked and translated at the periphery of P bodies, where we show that the translational activator Oo18 RNA-binding protein (Orb, a homologue of CEPB) and the anchoring factor Squid (Sqd) are also enriched. In contrast, an excess of grk mRNA becomes localized inside the P bodies, where endogenous bcd mRNA is localized and translationally repressed. Interestingly, bcd mRNA dissociates from P bodies in embryos following egg activation, when it is known to become translationally active. We propose a general principle of translational regulation during axis specification involving remodelling of transport RNPs and dynamic partitioning of different transcripts between the translationally active edge of P bodies and their silent core.

Optimizing selective cerebral perfusion: deleterious effects of high perfusion pressures.

OBJECTIVE: Selective cerebral perfusion is a proven adjunct to hypothermia for neuroprotection in complex aortic surgery. The ideal conditions for the provision of selective cerebral perfusion, however, including optimal perfusion pressure, remain unknown. We investigated the effects of various perfusion pressures during selective cerebral perfusion on cerebral physiology and outcome in a long-term porcine model. METHODS: Thirty piglets (26.3 +/- 1.4 kg), cooled to 20 degrees C on cardiopulmonary bypass with alpha-stat pH management (mean hematocrit 23.6%), were randomly assigned to 90 minutes of selective cerebral perfusion at a pressure of 50 (group A), 70 (group B), or 90 (group C) mm Hg. With fluorescent microspheres and sagittal sinus sampling, cerebral blood flow and cerebral oxygen metabolism were assessed at baseline, after cooling, at two points during selective cerebral perfusion, and for 2 hours after cardiopulmonary bypass. Visual evoked potentials were monitored during recovery. Neurobehavioral scores were assessed blindly from standardized videotaped sessions for 7 postoperative days. RESULTS: Cerebral blood flow during selective cerebral perfusion was significantly increased by higher-pressure perfusion (P = .04), although all groups sustained similar levels of cerebral oxygen metabolism during selective cerebral perfusion (P = .88). After the end of cardiopulmonary bypass, the cerebral oxygen metabolism increased to above baseline in all groups, with the highest levels seen in group C (P = .06). Intracranial pressure was significantly higher during selective cerebral perfusion in group C (P = .0002); visual evoked potentials did not differ among groups. Neurobehavioral scores were significantly better in group A (P = .0002). CONCLUSION: Selective cerebral perfusion at 50 mm Hg provides neuroprotection superior to that at higher pressures. The increased cerebral blood flow with higher-pressure selective cerebral perfusion is associated with cerebral injury, reflected by high post-cardiopulmonary bypass cerebral oxygen metabolism and poorer neurobehavioral recovery.

Perfusing the cold brain: optimal neuroprotection for aortic surgery.

BACKGROUND: Selective cerebral perfusion (SCP) may enhance the neuroprotective benefits of hypothermia during aortic surgery. However, despite its widespread adoption, there is no consensus regarding optimal implementation of SCP. We used a survival porcine model to explore the physiologic characteristics and behavioral benefits of various protocols involving hypothermic circulatory arrest (HCA) and SCP. METHODS: Thirty pigs (26.3 +/- 1.4 kg), cooled to 15 degrees C on cardiopulmonary bypass, using alpha-stat pH management (mean hematocrit 30%), were randomly allocated to differing brain protection strategies: 90 minutes of HCA (group A); 30 minutes of HCA, then 60 minutes of SCP (group B); or 90 minutes of SCP (group C). Using fluorescent microspheres and sagittal sinus sampling, cerebral blood flow (CBF [mL x 100g(-1) x min(-1)]) and cerebral metabolic rate for oxygen (CMRO2 [mL x 100g(-1) x min(-1)]) were assessed at baseline, after cooling, during SCP (where applicable), and for 2 hours after cardiopulmonary bypass. Neurobehavioral scores were assessed blindly from standardized videotaped sessions for 7 days postoperatively. RESULTS: Cerebral blood flow was significantly higher (p = 0.0001) during SCP (60 and 90 minutes) if preceded by HCA. The CMRO2 was also significantly higher in group B versus group C (p = 0.016) at 60 minutes. The CMRO2 in all three groups rebounded promptly toward baseline after weaning from cardiopulmonary bypass. Postoperative neurobehavioral scores were significantly worse in group A. CONCLUSIONS: Continuous SCP provides the best brain protection overall. However, an initial period of HCA does not seem to impair late outcome; perhaps the elevated CBF and CMRO2 observed reflect a beneficial cerebral response to a recoverable insult. Clearly, 90 minutes of HCA induces permanent brain injury, even in this carefully controlled setting.

Preservation of spinal cord function after extensive segmental artery sacrifice: regional variations in perfusion.

BACKGROUND: Sacrifice of intercostal and lumbar arteries simplifies thoracoabdominal aneurysm surgery and enables endovascular stenting. Little is known about alterations in cord perfusion after extensive segmental artery sacrifice. We explored this question using hypothermia to reduce metabolism. METHODS: Twelve juvenile Yorkshire pigs (mean weight, 22.3 kg) were randomized to segmental artery sacrifice at 32 degrees C or 37 degrees C. Cord integrity was assessed with myogenic-evoked potential (MEP) monitoring. Stepwise craniocaudal sacrifice of segmental arteries was continued until MEP diminution occurred; the last segmental artery was then reopened. Fluorescent microspheres were used to measure spinal cord blood flow (SCBF) at baseline, 5 minutes, 1 hour, and 3 hours after segmental artery sacrifice. Hind limb function was monitored for 5 days. RESULTS: All animals recovered normal hind limb function. At 32 degrees C, more segmental arteries, 16.5 versus 15 (p = 0.03), could be sacrificed without MEP loss. Baseline SCBF at 32 degrees C was 50% that at 37 degrees C (p = 0.003) and remained fairly stable throughout. At 37 degrees C, SCBF to the craniocaudal extremes of the cord (C1 to T3 and L2 to L6) increased markedly (p = 0.01) at 1 hour and returned toward normal at 3 hours. Concomitantly, SCBF fell in the middle portion of the cord (T9 to T13) at 1 hour before returning to normal at 3 hours. CONCLUSIONS: Almost all segmental arteries can be sacrificed with preservation of spinal cord function. No major change occurs in the central cord in normothermic animals, but there is significant transient hyperemia in segments adjacent to extrasegmental vessels. Hypothermia reduces SCBF and abolishes this possible steal phenomenon. Metabolic and hemodynamic manipulation should enable routine sacrifice of all segmental arteries without spinal cord injury.

Avoidance of hemodilution during selective cerebral perfusion enhances neurobehavioral outcome in a survival porcine model.

INTRODUCTION: The ideal hematocrit (HCT) level during hypothermic selective cerebral perfusion (SCP)--to ensure adequate oxygen delivery without excessive perfusion--has not yet been determined. METHODS: Twenty pigs (26.0+/-2.6 kg) were randomized to low or high HCT management. The cardiopulmonary bypass (CPB) circuit was primed with crystalloid in the low HCT group (21+/-1%), and with donor blood in the high HCT group (30+/-1%). Pigs were cooled to 20 degrees C and SCP was carried out for 90 min. During rewarming, whole blood was added in the low HCT group and crystalloid in the high HCT group to produce equivalent HCT levels by the end of the procedure. Using fluorescent microspheres and sagittal sinus sampling, cerebral blood flow (CBF) and oxygen metabolism (CMRO2) were assessed at baseline, after cooling, at two points during SCP (30 and 90 min), and at 15 min and 2 h post-CPB. In addition, a range of physiological and metabolic parameters, including intracranial pressure (ICP), were recorded throughout the procedure. The animals' behavior was videotaped and assessed blindly for 7 days postoperatively (maximum score=5). RESULTS: HCT levels were equivalent at baseline, 2 h post-CPB, and at sacrifice, but significantly different (p<0.0001) during cooling and SCP. Mean arterial pressure, pH and pCO2, and CMRO2 were equivalent between groups throughout. ICP was similar in the two groups throughout cooling, SCP, and rewarming, but was significantly higher in the low HCT animals after the termination of CPB. CBF was similar at baseline, but thereafter markedly higher in the low HCT group. Neurobehavioral performance was significantly better in the high HCT animals (median score 3.5 vs 4.5 on day 3, and 4.5 vs 4.75 on day 7, p=0.003). CONCLUSIONS: Higher HCT levels for SCP produced a significantly superior functional outcome, suggesting that the higher CBF with a lower HCT may be injurious, possibly because of an increased embolic load.

Early clinical and hemodynamic outcomes after stented and stentless aortic valve replacement: results from a randomized controlled trial.

BACKGROUND: Stentless aortic bioprostheses were shown to be hemodynamically superior to earlier generations of stented bioprostheses. Modern stented valve designs have improved hemodynamics. A prospective randomized controlled trial was undertaken to compare stentless versus modern stented valves. Our aim was to determine any differences in early postoperative clinical and hemodynamic outcomes. METHODS: Patients with severe aortic valve stenosis (n = 161) undergoing aortic valve replacement were randomized intraoperatively to receive either the C-E Perimount (Edwards Lifesciences, Irvine, CA) pericardial stented bioprosthesis (n = 81) or the Prima Plus (Edwards Lifesciences) (porcine stentless bioprosthesis (n = 80). Transthoracic echocardiograms were performed at one week and eight weeks postoperatively to assess left ventricular mass (LVM) and transvalvular gradients (TVG). RESULTS: There were no differences between the two groups in baseline characteristics. Cardiopulmonary bypass and ischemic times were longer in the stentless group. Despite similar native aortic annular diameters, the mean size of the prosthesis used in the stentless group was 2.1 mm (SD = 2.8) larger (p < 0.001). Early (30-day) mortality (stentless 3.7% vs stented 2.5%; p = 0.68) and morbidity was similar between groups. Eight weeks postoperatively, LVM (stentless 199 +/- 70 vs stented 204 +/- 66 grams; p = 0.32) and TVG decreased in both groups (mean systolic gradient; stentless 10 +/- 3 vs stented 10 +/- 4 mm Hg; p = 0.54) but there was no significant difference between groups. CONCLUSIONS: Despite longer ischemic times in the stentless group, early postoperative outcomes were similar. Both stented and stentless aortic valve replacement offers excellent hemodynamics and can be achieved with low perioperative mortality.

The fate of the distal aorta after repair of acute type A aortic dissection.

OBJECTIVES: The residual aorta's behavior after repair of acute type A dissection is incompletely understood. We analyzed segmental growth rates, distal reoperation, and factors influencing long-term survival. METHODS: One hundred seventy-nine consecutive patients (70% male; mean age, 60 years) with acute type A dissection underwent aggressive resection of the intimal tear and open distal anastomosis (1986-2003). Hospital mortality was 13.4%. Survivors had serial computed tomographic scans: digitization yielded distal segmental dimensions. Segment-specific average rates of enlargement and factors influencing faster growth were analyzed. Distal reoperations and patient survival were examined. RESULTS: Eighty-nine (57%) patients had imaging data sufficient for growth rate calculations. The median diameters after repair were as follows: aortic arch, 3.6 cm; descending aorta, 3.7 cm; and abdominal aorta, 3.2 cm. Subsequent growth rates were 0.8, 1.0, and 0.8 mm/y, respectively. Initial size of greater than 4 cm (P = .005) and initial diameter of less than 4 cm with a patent false lumen (P = .004) predicted greater growth in the descending aorta, and male sex (P = .05) significantly affected growth in the abdominal aorta. No significant factors were found for the aortic arch. There were 25 distal aortic reoperations (16 patients), and risk of reoperation was 16% at 10 years. Risk factors reducing long-term survival after repair of acute type A dissection included age (P < .0001), new neurological deficit at presentation (P = .04), absence of preoperative thrombus in the false lumen of the ascending aorta (P = .03), and a patent distal false lumen postoperatively (P = .06) but not distal reoperation. CONCLUSIONS: Growth of the distal aorta after repair of acute type A dissection is typically slow and linear. Distal reoperation is uncommon, and late risk of death is approximately twice that of a healthy population.

Thoracic and thoracoabdominal aneurysm repair: is reimplantation of spinal cord arteries a waste of time?

BACKGROUND: The impact of different strategies for management of intercostal and lumbar arteries during repair of thoracic and thoracoabdominal aortic aneurysms (TAA/A) on the prevention of paraplegia remains poorly understood. METHODS: One hundred consecutive patients with intraoperative monitoring of motor evoked potentials (MEP) and somatosensory evoked potentials (SSEP) during TAA/A repair involving serial segmental artery sacrifice (October 2002 to December 2004) were reviewed. RESULTS: Operative mortality was 6%. The median intensive care unit stay was 2.5 days (IQ range: 1-4 days), and the median hospital stay 10.0 days (IQ range: 8-17 days). Potentials remained unchanged during the course of serial segmental artery sacrifice, or could be returned to baseline levels by anesthetic and blood pressure manipulation, in 99 of 100 cases. An average of 8.0 +/- 2.6 segmental artery pairs were sacrificed overall, with an average of 4.5 +/- 2.1 segmental pairs sacrificed between T7 and L1, where the artery of Adamkiewicz is presumed to arise. Postoperative paraplegia occurred in 2 patients. In 1, immediate paraplegia was precipitated by an intraoperative dissection, resulting in 6 hours of lower body ischemia. A second ambulatory patient had severe paraparesis albeit normal cerebral function after resuscitation from a respiratory arrest. CONCLUSIONS: With monitoring of MEP and SSEP, sacrifice--without reimplantation--of as many as 15 intercostal and lumbar arteries during TAA/A repair is safe, resulting in acceptably low rates of immediate and delayed paraplegia. This experience suggests that routine surgical implantation of segmental vessels is not indicated, and that, with evolving understanding of spinal cord perfusion, endovascular repair of the entire thoracic aorta should ultimately be possible without spinal cord injury.

Are stentless valves superior to modern stented valves? A prospective randomized trial.

BACKGROUND: It is presumed that stentless aortic bioprostheses are hemodynamically superior to stented bioprostheses. A prospective randomized controlled trial was undertaken to compare stentless versus modern stented valves. METHODS AND RESULTS: Patients with severe aortic valve stenosis (n=161) undergoing aortic valve replacement (AVR) were randomized intraoperatively to receive either the C-E Perimount stented bioprosthesis (n=81) or the Prima Plus stentless bioprosthesis (n =80). We assessed left ventricular mass (LVM) regression with transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI). Transvalvular gradients were measured postoperatively by Doppler echocardiography to compare hemodynamic performance. There was no difference between groups with regard to age, symptom status, need for concomitant coronary artery bypass surgery, or baseline LVM. LVM regressed in both groups but with no significant difference between groups at 1 year. In a subset of 50 patients, MRI was also used to assess LVM regression, and again there was no significant difference between groups at 1 year. Hemodynamic performance of the 2 valves was similar with no difference in mean and peak systolic transvalvular gradients 1 year after surgery. In patients with reduced ventricular function (left ventricular ejection fraction [LVEF] <60%), there was a significantly greater improvement in LVEF from baseline to 1 year in stentless valve recipients. CONCLUSIONS: Both stented and stentless bioprostheses are associated with excellent clinical and hemodynamic outcomes 1 year after AVR. Comparable hemodynamics and LVM regression can be achieved using a second-generation stented pericardial bioprosthesis. In patients with ventricular impairment, stentless bioprostheses may allow for greater improvement in left ventricular function postoperatively.