Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes with Donor-Specific Anti-HLA Antibodies against HLA-DP.

The presence of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) against anti-HLA-A, -B, -C, and -DRB1 in HLA-mismatched hematopoietic stem cell transplantation (HSCT) is associated with graft failure. DSAs against HLA-A, -B, -C, and -DRB1 with a mean fluorescence intensity (MFI) of greater than > 1,000 was shown to increase the risk of graft failure in single-unit umbilical cord blood transplantation (UCBT). Nevertheless, the impact of DSAs against HLA-DP or -DQ on transplantation outcomes is not fully understood. In this report, we present a case of UCBT in a patient with myelodysplastic syndrome who was positive for DSAs against HLA-DP with MFI of 1,263 before UCBT but successfully achieved neutrophil engraftment. If HLA-DP or -DQ is mismatched in UCBT, evaluating DSAs against HLA-DP or -DQ is crucial to avoid graft failure. However, the criteria for DSAs against HLA-A, -B, -C, and -DRB1 may not be directly applicable to those against HLA-DP or -DQ.

Bioelectrical impedance analysis for perioperative water management in adult cardiovascular valve disease surgery.

PURPOSE: Bioelectrical impedance analysis (BIA) has been used recently to measure the body water of patients with acute heart failure. We used BIA in this study to better understand, and possibly identify a predictive marker for, perioperative water behavior in cardiac surgery patients. METHODS: We measured body water and studied its behavior in 44 patients undergoing surgery for cardiac valvular disease at our hospital. Measurements included the levels of extracellular water (ECW), intracellular water (ICW), and total body water, the edema index (EI), and the ratio of ECW to total body water. The first measured EI was defined as the "preoperative EI" and the maximum as the "peak EI". RESULTS: A negative correlation was found between the preoperative EI and the preoperative estimated glomerular filtration rate (eGFR) (R = 0.644, p < 0.001). Positive correlations were found between the peak EI and the ICU stay (R = 0.625, p < 0.001), the peak EI and the ventilation time (R = 0.366, p < 0.01), and the preoperative EI and the ICU stay (R = 0.464, p = 0.026). CONCLUSION: The EI is possibly a predictive marker for perioperative water management in cardiac surgery.

[Endoventricular Stepwise Plication for Left Ventricular Aneurysm].

A 69-year-old man was treated with oral anticoagulation for the left ventricular (LV) aneurysm. Echocardiography revealed dyskinetic apex with a mobile thrombus. The estimated LV end-diastolic and end-systolic volume index (LVEDVI, LVESVI) was 76 and 44 ml/m2, respectively. After the LV was opened at the apex parallel to the left anterior descending artery, removal of LV thrombus was performed. LV volume was 70 ml, and diameter of LV aneurysm was 3 cm. After setting a neo-apex, the boundary between the normal and aneurysmal scar tissue were doubly encircled by a pledgeted 2-0 polypropylene suture, and preserved the same diameter as the "aneurysmal neck" (3 cm) in order to secure the minimal residual LV volume. Similarly, second and third circular stitches were placed toward the neo-apex to make the ventricle into an elliptical shape. A postoperative echocardiography showed a well-reconstructed physiologic shape, LV volume( LVEDVI 62 ml/m2, LVESVI 27 ml/m2), and improved LV function.

Glycogen synthase kinase-3 inhibitors suppress the AR-V7-mediated transcription and selectively inhibit cell growth in AR-V7-positive prostate cancer cells.

BACKGROUND: Recent evidence suggests that androgen receptor (AR) splice variants, including AR-V7, play a pivotal role in resistance to androgen blockade in prostate cancer treatment. The development of new therapeutic agents that can suppress the transcriptional activities of AR splice variants has been anticipated as the next generation treatment of castration-resistant prostate cancer. METHODS: High-throughput screening of AR-V7 signaling inhibitors was performed using an AR-V7 reporter system. The effects of a glycogen synthase kinase-3 (GSK3) inhibitor, LY-2090314, on endogenous AR-V7 signaling were evaluated in an AR-V7-positive cell line, JDCaP-hr, by quantitative reverse transcription polymerase chain reaction. The relationship between AR-V7 signaling and ß-catenin signaling was assessed using RNA interference. The effect of LY-2090314 on cell growth in various prostate cancer cell lines was also evaluated. RESULTS: We identified GSK3 inhibitors as transcriptional suppressors of AR-V7 using a high-throughput screen with an AR-V7 reporter system. LY-2090314 suppressed the reporter activity and endogenous AR-V7 activity in JDCaP-hr cells. Because silencing of ß-catenin partly rescued the suppression, it was evident that the suppression was mediated, at least partially, via the activation of ß-catenin signaling. AR-V7 signaling and ß-catenin signaling reciprocally regulate each other in JDCaP-hr cells, and therefore, GSK3 inhibition can repress AR-V7 transcriptional activity by accumulating intracellular ß-catenin. Notably, LY-2090314 selectively inhibited the growth of AR-V7-positive prostate cancer cells in vitro. CONCLUSIONS: Our findings demonstrate the potential of GSK3 inhibitors in treating advanced prostate cancer driven by AR splice variants. In vivo evaluation of AR splice variant-positive prostate cancer models will help illustrate the overall significance of GSK3 inhibitors in treating prostate cancer.

An administration of TAK-683 at a minimally effective dose for luteinizing hormone stimulation under the absence of the ovary induces luteinizing hormone surge in ovary-intact goats.

The present study aimed to evaluate hormonal responses and their association with the TAK-683 blood concentrations in goats administered TAK-683 at a low dose, which had been previously determined as the minimally effective dose for luteinizing hormone (LH) stimulation in ovariectomized goats. In Experiment 1, 5 µg of TAK-683 treatment had no significant stimulatory effect on LH secretion in ovariectomized Shiba goats (n = 4). In Experiment 2, cycling goats received the treatment of prostaglandin F2α and progesterone-releasing controlled internal drug releasing (CIDR) to induce the follicular phase, then they were treated with 5 µg of TAK-683 (hour 0) intravenously (n = 4, IV) or subcutaneously (n = 3, SC) or with vehicle intravenously (n = 4, control) at 12 h after CIDR removal. Blood samples were collected at 10-min (-2-6 h), 2-h (6-24 h), or 6-h (24-48 h) intervals. Ovarian ultrasonographic images were assessed daily to confirm ovulation after the treatment. A surge-like release of LH was immediately observed after injection in all animals in the IV (peak time: 4.2 ± 0.6 h, peak concentration: 73.3 ± 27.5 ng/ml) and SC (peak time: 4.6 ± 0.4 h, peak concentration: 62.6 ± 23.2 ng/ml) groups, but not in the control group. Ovulation was detected within 3 days after TAK-683 injection in all animals in the IV and SC groups, and the interval period from TAK-683 administration to ovulation in the IV group was significantly (P < 0.05) shorter than that of the control group. No significant changes were observed between the IV and SC groups in terms of luteal diameter and blood progesterone levels after ovulation. The present findings suggest that the involvement of one or more ovarian factor(s) is indispensable for a TAK-683-induced LH surge leading to ovulation in goats.

Growth Inhibition by Testosterone in an Androgen Receptor Splice Variant-Driven Prostate Cancer Model.

BACKGROUND: Castration resistance creates a significant problem in the treatment of prostate cancer. Constitutively active splice variants of androgen receptor (AR) have emerged as drivers for resistance to androgen deprivation therapy, including the next-generation androgen-AR axis inhibitors abiraterone and enzalutamide. In this study, we describe the characteristics of a novel castration-resistant prostate cancer (CRPC) model, designated JDCaP-hr (hormone refractory). METHODS: JDCaP-hr was established from an androgen-dependent JDCaP xenograft model after surgical castration. The expression of AR and its splice variants in JDCaP-hr was evaluated by immunoblotting and quantitative reverse transcription-polymerase chain reaction. The effects of AR antagonists and testosterone on JDCaP-hr were evaluated in vivo and in vitro. The roles of full-length AR (AR-FL) and AR-V7 in JDCaP-hr cell growth were evaluated using RNA interference. RESULTS: JDCaP-hr acquired a C-terminally truncated AR protein during progression from the parental JDCaP. The expression of AR-FL and AR-V7 mRNA was upregulated by 10-fold in JDCaP-hr compared with that in JDCaP, indicating that the JDCaP and JDCaP-hr models simulate castration resistance with some clinical features, such as overexpression of AR and its splice variants. The AR antagonist bicalutamide did not affect JDCaP-hr xenograft growth, and importantly, testosterone induced tumor regression. In vitro analysis demonstrated that androgen-independent prostate-specific antigen secretion and cell proliferation of JDCaP-hr were predominantly mediated by AR-V7. JDCaP-hr cell growth displayed a bell-shaped dependence on testosterone, and it was suppressed by physiological concentrations of testosterone. Testosterone induced rapid downregulation of both AR-FL and AR-V7 expression at physiological concentrations and suppressed expression of the AR target gene KLK3. CONCLUSIONS: Our findings support the clinical value of testosterone therapy, including bipolar androgen therapy, in the treatment of AR-overexpressed CRPC driven by AR splice variants that are not clinically actionable at present. Prostate 76:1536-1545, 2016. © 2016 Wiley Periodicals, Inc.

Bacteremia induced by Bifidobacterium breve in a newborn with cloacal exstrophy.

Bifidobacterium breve is an effective probiotic agent used in the field of neonatology. Although B. breve has been considered safe, a case of B. breve bacteremia has been reported. The pathogenic mechanism underlying the bacteremia is unknown. Herein, we report a second case of B. breve bacteremia that developed in a neonate with multiple abdominal organ anomalies. Following surgical repair immediately after birth, B. breve treatment was started. After 1 week, the infant developed B. breve bacteremia following the onset of adhesive ileus. The bacteremia was thought to have been associated with an intestinal obstruction. A pediatric culture bottle is theoretically unsuitable for incubating B. breve because B. breve is an obligate anaerobic bacterium. It was, however, cultured from pediatric culture bottles in the present case, suggesting that pediatric culture bottles may be useful for procuring B. breve and for determining antimicrobial susceptibility for screening purposes in neonatal patients.

Surgical Ligation for Patent Ductus Arteriosus in Extremely Premature Infants: Strategy to Reduce their Risk of Neurodevelopmental Impairment.

Surgical ligation for patent ductus arteriosus (PDA) in extremely low birth weight infants (ELBWIs) has been shown a possible association with neurodevelopmental impairment (NDI) because of its invasiveness. However, we have undergone surgical ligation for ELBWIs immediately after cyclooxygenase inhibitor failed to close a hemodynamically significant PDA (hsPDA) to maintain proper systemic circulation. We aimed to determine the effect of surgical ligation for hsPDA on NDI in ELBWIs. In enrolled 71 ELBWIs, the clinical parameters, including the developmental quotient (DQ), were collected and compared among three groups that were divided by closure mode: spontaneous closure (n = 11), cyclooxygenase inhibitor therapy (n = 37) and surgical ligation (n = 23). No significant differences in DQ at the age of 36 months among the three groups were found: Median (interquartile range): 92.0 (31.0), 89.0 (22.0) and 92.0 (24.5), respectively. In a comparison between groups of DQ < 70 (n = 15) and DQ ≥ 70 (n = 56), a significant difference was found in the parameters related to prematurity (p < 0.05 for each): gestational age [23.9 (1.70) vs. 25.4 (2.50) weeks], birth weight [595 (183) vs. 714 (192) g], Apgar score < 5 (1 min) (67% vs. 36%), and laser photocoagulation for retinopathy of prematurity (73% vs. 43%), but there was no significant association with hsPDA. Therefore, we propose that surgical ligation for hsPDA in ELBWIs should be immediately carried out for preventing future neurodevelopmental deterioration if the cyclooxygenase inhibitor failed to close hsPDA.

Differential micro ribonucleic acid expression profiling in ovarian endometrioma with leuprolide acetate treatment.

AIM: Micro ribonucleic acids (miRNAs) play an important pathological role in endometriosis. Leuprolide acetate, an analog of gonadotropin-releasing hormone, is widely used to treat endometriosis; however, the molecular mechanisms involved in endometriotic tissue regression remain unclear. We performed miRNA expression profiling of clinical ovarian endometrioma to obtain insight into the effects of leuprolide acetate treatment. METHODS: We obtained clinical samples from nine normal eutopic endometrium, eight ovarian endometriotic, and 12 leuprolide acetate-treated endometriotic tissues. We compared the miRNA expression profiles of the three groups by performing TaqMan Array MicroRNA Card and bioinformatic analysis. RESULTS: Two miRNAs, miR-939 and miR-154, were upregulated in endometriotic tissue and downregulated in leuprolide acetate-treated endometriotic tissue. Five miRNAs (miR-146a, miR-142-3p, miR-136*, miR-125b-1* and miR-15b*) were unchanged in endometriotic tissue but were upregulated under leuprolide acetate treatment. Ingenuity pathway analysis using predicted target genes for the seven identified miRNAs suggested the involvement of a range of pathways, including axonal guidance, bone morphogenetic protein, phosphatase and tensin homolog and nitric oxide signaling; molecular mechanisms of cancer; and the adipogenesis and signal transducer and activator of transcription 3 (STAT3) pathways. CONCLUSIONS: To our knowledge, this is the first report profiling the miRNAs of endometrioma under leuprolide acetate treatment. The expression of seven miRNAs was modulated, concomitant with the disease state. This result gives new insight into the effects of leuprolide acetate treatment. Further investigation using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry will allow us to validate the results of this study and to explore new therapeutic targets and biomarkers of endometriosis.

Differential mRNA expression profiling in ovarian endometriotic tissue with versus without leuprolide acetate treatment.

AIM: Leuprolide acetate, an analog of gonadotropin-releasing hormone (GnRH), regresses endometriotic tissue and reduces pain, resulting in clinical improvement upon treatment. The molecular mechanisms involved in the regression of endometriotic tissue, however, remain to be elucidated. In this study, we performed genome-wide gene expression profiling of clinical specimens of ovarian endometrioma to obtain insight into the effects of leuprolide acetate treatment. METHODS: We obtained clinical samples from nine normal eutopic endometrium tissues, eight ovarian endometriotic tissues, and 12 leuprolide acetate-treated endometriotic tissues. We compared the gene expression profiles of the three groups using Affymetrix GeneChip Human genome arrays and bioinformatic analysis, including molecular concept analysis. RESULTS: Leuprolide acetate-treated endometriotic tissue showed downregulated genes associated with the biological functions of steroid hormone regulation, cell proliferation, inflammation, and intracellular signaling. These genes included PTGDS, GRP, APLP2, PLTP, and FGFRL1. In contrast, genes upregulated by leuprolide acetate treatment were associated with cell growth inhibition and apoptosis. These genes included CARD11 and USP18. CONCLUSIONS: These preliminary results based on GeneChip analysis suggest that leuprolide acetate treatment induces a modulation of gene expression that allows for cooperative alterations in disease state. This study gives new insight into the effects of leuprolide acetate treatment. Further investigations with quantitative reverse transcription-polymerase chain reaction and immunohistochemistry are needed to validate this study and to explore new therapeutic targets and biomarkers of endometriosis.

Asymmetric α-hydroxylation of a lactone with vinylogous pyridone by using a guanidine-urea bifunctional organocatalyst: catalytic enantioselective synthesis of a key intermediate for (20S)-camptothecin analogues.

We have developed a catalytic asymmetric synthesis of (S)-4-ethyl-6,6-(ethylenedioxy)-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,10(4H)dione (5 a), a synthetic intermediate for (20S)-camptothecin analogues. A key step in this synthesis is an asymmetric α-hydroxylation of a lactone with a vinylogous pyridone structure (8 a) by using a guanidine-urea bifunctional organocatalyst. The present oxidation was successfully applied to the synthesis of C20-modified derivatives of (+)-C20-desethylbenzylcamptothecin (13).

Cerebral ischemia or intrauterine inflammation promotes differentiation of oligodendroglial precursors in preterm ovine fetuses: possible cellular basis for white matter injury.

White matter injury in premature infants is known to be major cause of long-term neurocognitive disability, but the pathogenic mechanism remains unclear, hampering our ability to develop preventions. Periventricular leukomalacia is a severe form of white matter injury. In the present study, we explored the effects of cerebral ischemia and/or intrauterine inflammation on the development of oligodendroglia in the cerebral white matter using chronically instrumented fetal sheep. Each fetus received one of three insults: hemorrhage, inflammation and their combination. In the hemorrhage group, 40% of the fetoplacental blood volume was acutely withdrawn, and 24 hours after removal, the blood was returned to the fetus. The inflammation group received intravenous granulocyte-colony stimulating factor and intra-amniotic endotoxin and thus suffered from necrotizing funisitis and chorioamnionitis. The inflammatory hemorrhage group underwent acute hemorrhage under the inflammatory state. The sham group received no insults. Importantly, periventricular leukomalacia was not detected in the sham and the inflammation groups. Differentiating oligodendroglia at various developmental stages were identified by immunohistochemical analysis with specific antibodies. No difference in the density of oligodendroglial progenitors was detected among the four groups, whereas oligodendroglial precursors were significantly reduced in the three insult groups, compared to sham control. Moreover, the density of immature oligodendroglia was higher in the inflammation group and the inflammatory hemorrhage group, while the density of mature oligodendroglia was highest in the hemorrhage group. We propose that cerebral ischemia or intrauterine inflammation induces the differentiation of oligodendroglial precursors in preterm fetuses, eventually resulting in their exhaustion.

Robotic Beating-Heart Totally Endoscopic Coronary Artery Bypass: Impact of Chest Wall Dimensions in Single and Multivessel Bypass.

OBJECTIVE: There can be anatomical constraints on patient selection for minimally invasive surgery. For example, robot-assisted coronary artery bypass was reported to be more challenging when patients had a cardiothoracic ratio >50% and a sternum-vertebra anteroposterior and transverse diameter ratio <0.45. We sought to examine the impact of chest wall anatomic parameters on surgical outcomes in our totally endoscopic coronary artery bypass (TECAB) procedures. METHODS: We retrospectively reviewed patients who underwent robotic TECAB, all of whom had a preoperative chest radiograph at our institution from July 2017 to October 2021. The cohort was divided into 2 groups, which were patients undergoing single-vessel grafting using the left internal thoracic artery (ITA; group 1) and patients undergoing multivessel grafting with bilateral ITA grafts (group 2). We measured several anatomical parameters from the preoperative chest radiograph. RESULTS: A total of 352 patients undergoing TECAB were retrospectively analyzed. After exclusions, 193 were included in this study. In group 1 (n = 91), no parameters correlated with operative time. In group 2 (n = 102), a significant negative correlation was observed between operative time and the sternum-vertebrae anteroposterior diameter (rs = -0.228, P = 0.022) and lung anteroposterior diameter (rs = -0.246, P = 0.013). To confirm these results in group 2, a propensity-matched analysis was performed and showed a statistically significant difference in surgical time based on chest anteroposterior diameters. CONCLUSIONS: In single-vessel robotic TECAB, chest wall anatomic dimensions measured on chest radiograph did not affect operative time. In multivessel cases with bilateral ITA grafts, larger anteroposterior diameter correlated with shorter operative times.

In Situ Myocardial Regeneration With Tissue Engineered Cardiac Patch Using Spheroid-Based 3-Dimensional Tissue.

BACKGROUND: We have developed a tissue engineered cardiac patch derived from a 3-dimensional (3D) myocardial tissue reinforced with extracellular matrix in an effort to enhance in situ myocardial regeneration. The feasibility of the patch was evaluated in a porcine model by various modalities to assess both the constructive and functional aspects of regeneration. METHODS: A spheroid-based 3D multicellular tissue was created using a 3D net mold system that incorporated cardiomyocytes and embryonic fibroblast cells. The 3D multicellular tissue was incorporated with extracellular matrix sheets and surgically implanted into the right ventricle of a healthy porcine model (n = 4). After 60 days, the implanted patches were evaluated by cardiac magnetic resonance imaging and electroanatomic mapping studies as well as by post-euthanasia analyses, including measurements of mechanical viscoelasticity. RESULTS: Cardiac magnetic resonance imaging revealed improved regional tissue perfusion in the patch area. Electroanatomic mapping exhibited regenerated electrical conductivity in the patch, as evidenced by relatively preserved voltage regions (1.11 ± 0.8 mV) in comparison to the normal right ventricle (4.7 ± 2.8 mV). Histologic and tissue analyses confirmed repopulation of site-specific host cells, including premature cardiomyocytes and active vasculogenesis. These findings were supported by quantitative reverse transcription-polymerase chain reaction. CONCLUSIONS: The tissue engineered cardiac patch effectively facilitated in situ constructive and functional myocardial regeneration, characterized by increased regional tissue perfusion and positive electrical activity in the porcine model.

Development of deep-learning models for real-time anaerobic threshold and peak VO2 prediction during cardiopulmonary exercise testing.

AIMS: Exercise intolerance is a clinical feature of patients with heart failure (HF). Cardiopulmonary exercise testing (CPET) is the first-line examination for assessing exercise capacity in patients with HF. However, the need for extensive experience in assessing anaerobic threshold (AT) and the potential risk associated with the excessive exercise load when measuring peak oxygen uptake (peak VO2) limit the utility of CPET. This study aimed to use deep-learning approaches to identify AT in real time during testing (defined as real-time AT) and to predict peak VO2 at real-time AT. METHODS AND RESULTS: This study included the time-series data of CPET recorded at the Department of Cardiovascular Medicine, Kyushu University Hospital. Two deep neural network models were developed to: (i) estimate the AT probability using breath-by-breath data and (ii) predict peak VO2 using the data at the real-time AT. The eligible CPET contained 1472 records of 1053 participants aged 18-90 years and 20% were used for model evaluation. The developed model identified real-time AT with 0.82 for correlation coefficient (Corr) and 1.20 mL/kg/min for mean absolute error (MAE), and the corresponding AT time with 0.86 for Corr and 0.66 min for MAE. The peak VO2 prediction model achieved 0.87 for Corr and 2.25 mL/kg/min for MAE. CONCLUSION: Deep-learning models for real-time CPET analysis can accurately identify AT and predict peak VO2. The developed models can be a competent assistant system to assess a patient's condition in real time, expanding CPET utility.

Cardiopulmonary exercise testing can be used to evaluate the condition of patients with heart failure during exercise. Developed deep-learning models can accurately predict a patient's anaerobic threshold in real time and peak oxygen uptake. The models can be used by clinicians for more objective and accurate assessments in real time, expanding the utility of cardiopulmonary exercise testing.

Quantifying Inferior Vena Cava Compliance and Distensibility in an In Vivo Ovine Model Using 3D Angiography.

Synthetic vascular grafts overcome some challenges of allografts, autografts, and xenografts but are often more rigid and less compliant than the native vessel into which they are implanted. Compliance matching with the native vessel is emerging as a key property for graft success. The current gold standard for assessing vessel compliance involves the vessel's excision and ex vivo biaxial mechanical testing. We developed an in vivo method to assess venous compliance and distensibility that better reflects natural physiology and takes into consideration the impact of a pressure change caused by flowing blood and by any morphologic changes present. This method is designed as a survival procedure, facilitating longitudinal studies while potentially reducing the need for animal use. Our method involves injecting a 20 mL/kg saline bolus into the venous vasculature, followed by the acquisition of pre and post bolus 3D angiograms to observe alterations induced by the bolus, concurrently with intravascular pressure measurements in target regions. We are then able to measure the circumference and the cross-sectional area of the vessel pre and post bolus. With these data and the intravascular pressure, we are able to calculate the compliance and distensibility with specific equations. This method was used to compare the inferior vena cava's compliance and distensibility in native unoperated sheep to the conduit of sheep implanted with a long-term expanded polytetrafluorethylene (PTFE) graft. The native vessel was found to be more compliant and distensible than the PTFE graft at all measured locations. We conclude that this method safely provides in vivo measurements of vein compliance and distensibility.

Patient-specific tissue engineered vascular graft for aortic arch reconstruction.

Objectives: The complexity of aortic arch reconstruction due to diverse 3-dimensional geometrical abnormalities is a major challenge. This study introduces 3-dimensional printed tissue-engineered vascular grafts, which can fit patient-specific dimensions, optimize hemodynamics, exhibit antithrombotic and anti-infective properties, and accommodate growth. Methods: We procured cardiac magnetic resonance imaging with 4-dimensional flow for native porcine anatomy (n = 10), from which we designed tissue-engineered vascular grafts for the distal aortic arch, 4 weeks before surgery. An optimal shape of the curved vascular graft was designed using computer-aided design informed by computational fluid dynamics analysis. Grafts were manufactured and implanted into the distal aortic arch of porcine models, and postoperative cardiac magnetic resonance imaging data were collected. Pre- and postimplant hemodynamic data and histology were analyzed. Results: Postoperative magnetic resonance imaging of all pigs with 1:1 ratio of polycaprolactone and poly-L-lactide-co-ε-caprolactone demonstrated no specific dilatation or stenosis of the graft, revealing a positive growth trend in the graft area from the day after surgery to 3 months later, with maintaining a similar shape. The peak wall shear stress of the polycaprolactone/poly-L-lactide-co-ε-caprolactone graft portion did not change significantly between the day after surgery and 3 months later. Immunohistochemistry showed endothelization and smooth muscle layer formation without calcification of the polycaprolactone/poly-L-lactide-co-ε-caprolactone graft. Conclusions: Our patient-specific polycaprolactone/poly-L-lactide-co-ε-caprolactone tissue-engineered vascular grafts demonstrated optimal anatomical fit maintaining ideal hemodynamics and neotissue formation in a porcine model. This study provides a proof of concept of patient-specific tissue-engineered vascular grafts for aortic arch reconstruction.

Tissue engineered vascular grafts are resistant to the formation of dystrophic calcification.

Advancements in congenital heart surgery have heightened the importance of durable biomaterials for adult survivors. Dystrophic calcification poses a significant risk to the long-term viability of prosthetic biomaterials in these procedures. Herein, we describe the natural history of calcification in the most frequently used vascular conduits, expanded polytetrafluoroethylene grafts. Through a retrospective clinical study and an ovine model, we compare the degree of calcification between tissue-engineered vascular grafts and polytetrafluoroethylene grafts. Results indicate superior durability in tissue-engineered vascular grafts, displaying reduced late-term calcification in both clinical studies (p < 0.001) and animal models (p < 0.0001). Further assessments of graft compliance reveal that tissue-engineered vascular grafts maintain greater compliance (p < 0.0001) and distensibility (p < 0.001) than polytetrafluoroethylene grafts. These properties improve graft hemodynamic performance, as validated through computational fluid dynamics simulations. We demonstrate the promise of tissue engineered vascular grafts, remaining compliant and distensible while resisting long-term calcification, to enhance the long-term success of congenital heart surgeries.

Asymmetric α-hydroxylation of tetralone-derived ß-ketoesters by using a guanidine-urea bifunctional organocatalyst in the presence of cumene hydroperoxide.

Highly enantioselective catalytic oxidation of 1-tetralone-derived ß-keto esters was achieved by using a guanidine-urea bifunctional organocatalyst in the presence of cumene hydroperoxide (CHP), a safe, commercially available oxidant. The α-hydroxylation products were obtained in 99% yield with up to 95% enantiomeric excess (ee). The present oxidation was successfully applied to synthesize a key intermediate of the anti-cancer agent daunorubicin (2).