Institutional Marfan syndrome surgical volume influences mitral valve surgical strategy in patients with Marfan syndrome.

BACKGROUND/AIM: The goal of this study was to evaluate trends in mitral valve (MV) operations performed on patients with Marfan syndrome (MfS) and determine the influence of an institution's MfS and MV surgical volume on MV surgical strategy in the US. METHODS: The Nationwide Inpatient Sample was queried from 1998 to 2011 and a total of 1126 patients with MfS were identified who underwent MV operations meeting our inclusion criteria. Linear regression was performed to assess trends of MV repair (MVr) rates over time. Patients were stratified into tertiles depending on the institution's annual MfS and MV surgical volumes. Multivariate analysis was used to determine the impact of institutional MV and MfS surgical volume on whether a patient received an MV replacement (MVR). RESULTS: The MVR rate was 60% for the entire cohort. There was a decreasing trend of MVR rates during the study period (82% in 1998-99 vs 49% in 2010-2011, P < .05). Multivariate analysis revealed that patients operated on at high (odds ratio [OR], 0.65; P < .05) and medium (OR, 0.66; P < .05) volume MfS centers were less likely to undergo MVR when compared to lower-volume MfS centers. In contrast, MV volume was not a significant predictor of surgical strategy in this cohort. CONCLUSION: The national MVR rate in the MfS population is higher than published reports. Data from this study suggest that MfS patients with indications for MV surgery should be referred to high-volume MfS surgical centers to have the best opportunity for MVr.

Long-term failure of Amplatzer plugs in the treatment of aortic pathology.

We present two cases of Amplatzer® device deployment that exhibited long-term failure necessitating surgical correction. The first case illustrates recanalization of a ruptured Valsalva aneurysm with worsening aortic insufficiency after percutaneous repair with the Amplatzer Vascular Plugs and Amplatzer duct occluder, while the second case illustrates recanalization after deployment of the Amplatzer septal occluder in a patient with a pseudoaneursym in a bovine aorta after type I aortic dissection repair. These two cases illustrate the potential long-term complications and limitations in durability with these devices.

Disaster Averted: Surgical Treatment of Paradoxical Embolus in Transit.

A 46-year-old woman presented with a syncopal episode and was found to have a large thrombus traversing an atrial septal defect extending across the mitral valve. She was taken to the operating room for emergent thrombectomy. We present the case, imaging, and a review of published cases. (Level of Difficulty: Beginner.).

Bumblebees exhibit the memory spacing effect.

Associative learning is key to how bees recognize and return to rewarding floral resources. It thus plays a major role in pollinator floral constancy and plant gene flow. Honeybees are the primary model for pollinator associative learning, but bumblebees play an important ecological role in a wider range of habitats, and their associative learning abilities are less well understood. We assayed learning with the proboscis extension reflex (PER), using a novel method for restraining bees (capsules) designed to improve bumblebee learning. We present the first results demonstrating that bumblebees exhibit the memory spacing effect. They improve their associative learning of odor and nectar reward by exhibiting increased memory acquisition, a component of long-term memory formation, when the time interval between rewarding trials is increased. Bombus impatiens forager memory acquisition (average discrimination index values) improved by 129% and 65% at inter-trial intervals (ITI) of 5 and 3 min, respectively, as compared to an ITI of 1 min. Memory acquisition rate also increased with increasing ITI. Encapsulation significantly increases olfactory memory acquisition. Ten times more foragers exhibited at least one PER response during training in capsules as compared to traditional PER harnesses. Thus, a novel conditioning assay, encapsulation, enabled us to improve bumblebee-learning acquisition and demonstrate that spaced learning results in better memory consolidation. Such spaced learning likely plays a role in forming long-term memories of rewarding floral resources.

Concomitant repair for mild aortic insufficiency and continuous-flow left ventricular assist devices.

OBJECTIVES: Aortic insufficiency (AI) after continuous-flow left ventricular assist device (CF-LVAD) implantation has become a highly relevant subject. However, management of pre-existing mild AI is unknown. We examined the fate of pre-existing mild AI during CF-LVAD support. METHODS: From March 2004 to October 2015, 446 consecutive patients received CF-LVAD. Of these, 56 (12.6%) patients with pre-existing mild AI were identified. Outcomes were compared between patients who underwent repair [n = 41 (73.2%); Group A] and those who did not [n = 15 (26.8%); Group B]. RESULTS: Group A patients were more likely to have destination therapy intent at device insertion than Group B. Otherwise both groups displayed similar clinical/echocardiographic findings at baseline. There was no difference with respect to the occurrence of postoperative adverse events between groups. Kaplan-Meier analyses revealed the estimated 2-year on-device survival to be 63.3 ± 10.7 and 84.0 ± 10.6% (P = 0.41) and freedom from AI ≥moderate at 2 years to be 81.8 ± 9.7 and 45.0 ± 21.1% (P = 0.031) in Groups A and B, respectively. Furthermore, 83.3% (5 of 6) of Group B patients with large (>1.94 cm/m2; 75th percentile) body surface area-indexed aortic diameter developed ≥moderate AI, while none of the Group B individuals with smaller aortic root (0 of 9) did. In contrast, Group A patients with large indexed aortic root (n = 7) have all been free of AI at 2 years. CONCLUSIONS: AI progression among CF-LVAD-supported patients with baseline mild AI is highly prevalent. Baseline aortic root diameter may help identify patients with 'borderline' AI lesion needing repair at device insertion.

Regeneration and experimental orthotopic transplantation of a bioengineered kidney.

Approximately 100,000 individuals in the United States currently await kidney transplantation, and 400,000 individuals live with end-stage kidney disease requiring hemodialysis. The creation of a transplantable graft to permanently replace kidney function would address donor organ shortage and the morbidity associated with immunosuppression. Such a bioengineered graft must have the kidney's architecture and function and permit perfusion, filtration, secretion, absorption and drainage of urine. We decellularized rat, porcine and human kidneys by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, a collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells and perfused these cell-seeded constructs in a whole-organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused through their intrinsic vascular bed. When transplanted in an orthotopic position in rat, the grafts were perfused by the recipient's circulation and produced urine through the ureteral conduit in vivo.

Coronary artery calcification and coronary atherosclerotic disease.

The presence of coronary artery calcium is closely associated with the presence of atherosclerotic lesions in the coronary vasculature. Detection of coronary calcium by imaging techniques has evolved over the last few decades and has become especially more sophisticated with advanced imaging technology. Whereas the status of coronary artery calcium as a marker of increased cardiovascular risk is well established, the indication for testing continues to be a topic of debate.

Organ engineering based on decellularized matrix scaffolds.

End-organ failure is one of the major healthcare challenges in the Western world. Yet, donor organ shortage and the need for immunosuppression limit the impact of transplantation. The regeneration of whole organs could theoretically overcome these hurdles. Early milestones have been met by combining stem and progenitor cells with increasingly complex scaffold materials and culture conditions. Because the native extracellular matrix (ECM) guides organ development, repair and physiologic regeneration, it provides a promising alternative to synthetic scaffolds and a foundation for regenerative efforts. Perfusion decellularization is a novel technology that generates native ECM scaffolds with intact 3D anatomical architecture and vasculature. This review summarizes achievements to date and discusses the role of native ECM scaffolds in organ regeneration.

Single incision laparoscopic surgery ovarian cystectomy in large benign ovarian cysts using conventional instruments.

We describe a technique for the management of large benign ovarian cysts by single incision laparoscopic surgery (SILS) through the umbilicus. The paucity of intra-abdominal working space in large ovarian cysts poses a technical challenge. Moreover, difficult convergence of operating instruments and competition for operating space outside the abdomen during the SILS makes the procedure quite demanding, especially with the conventional instruments. The concept of providing traction by taking sutures from the abdominal wall, as done in SILS laparoscopic cholecystectomy, was applied for SILS cystectomy in large ovarian cysts. Two sutures taken through the abdominal wall and then through the cyst wall provide excellent traction and "hang" the cyst from the abdominal wall, making it convenient to dissect and operate. This technique demonstrates that SILS ovarian cystectomy is feasible, safe and technically unchallenging even in large benign ovarian cysts.

Enhanced in vivo function of bioartificial lungs in rats.

BACKGROUND: More than 11 million Americans live with chronic lung disease; in search for an alternative to donor organs, we attempted to regenerate lungs based on perfusion decellularized lung scaffolds that can be transplanted similar to a donor organ. METHODS: Cadaveric rat lungs were decellularized by detergent perfusion. Resulting scaffolds were mounted in bioreactors and seeded with endothelial and fetal lung cells. Biomimetic organ culture was maintained for 7 days. Resulting bioartificial left lungs were transplanted in orthotopic position after left pneumonectomy in rats. Cadaveric left lung transplants and pneumonectomies served as controls. Blood gas analyses, compliance testing, and fluoroscopies were performed on postoperative days 1, 7, and 14. Lungs were removed for final analysis on day 14. RESULTS: Perfusion decellularization of cadaveric lungs yielded acellular scaffolds with intact architecture and matrix composition. Alveolar volumes, number, and size were comparable in bioartificial and native lungs, as were gas exchange, vital capacity and compliance in vitro. After using improved graft preservation and postoperative weaning protocols, animals could be fully recovered, and bioartificial lung constructs provided oxygenation as long as 7 days at levels comparable to cadaveric lung transplants. Compliance, gas exchange, and radiographic appearance gradually declined over the subsequent 7 days owing to progressive graft consolidation and inflammation. CONCLUSIONS: Perfusion decellularization of cadaveric lungs yields intact scaffolds that can be seeded with cells to generate bioartificial lung grafts. After orthotopic transplantation, grafts are perfused by the recipient's circulation, ventilated through the recipient's airway and provide gas exchange in vivo for 7 days.

Ser18 and Ser23 phosphorylation plays synergistic roles in activating p53-dependent neuronal apoptosis.

Tumor suppressor p53 is required for the neuronal apoptosis in response to DNA double-stranded break (DSB) damage. Posttranslational modifications such as phosphorylation play important roles in activating p53-dependent apoptosis after DNA damage. In support of this notion, our recent studies indicate that Ser18 and Ser23 phosphorylation together plays critical roles in activating p53 apoptotic activities in vivo. Thymocytes derived from p53(S18/23A) mice are essentially resistant to p53-dependent apoptosis after DNA DSB damage. In addition, identical to p53-deficiency, p53(S18/23A) knock-in mutation completely rescues the embryonic lethality of XRCC4(-/-) mice, which die of the massive p53-dependent apoptosis of embryonic neurons likely as a result of accumulated endogenous DNA damage. To dissect the contribution of Ser18 and Ser23 phosphorylation to p53-dependent neuronal apoptosis, we report here that neither p53(S18A) nor p53(S23A) mutation alone can rescue the embryonic lethality of XRCC4(-/-) mice. Therefore, Ser18 and Ser23 phosphorylation plays synergistic and critical roles in activating p53-dependent neuronal apoptosis.