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Quadricuspid aortic valve is a rare congenital cardiac anomaly with an incidence of 0.008% to 0.043%. Its clinical course varies depending on cusp anatomy, function, and associated cardiac malformations. It frequently progresses to aortic valve regurgitation that may require surgical valve replacement. Detection has shifted from incidental discovery during autopsies or cardiac surgeries in the early 20th century to various cardiac imaging methods in recent decades. In addition to contributing to the literature, this report supports the use of transesophageal echocardiography more liberally to detect aortic valve abnormalities. The case presents a 48-year-old female patient with an incidentally discovered quadricuspid aortic valve.

BackgroundThe number of patients living with left ventricular assist devices (LVADs) has gradually increased in the past decade. Non-cardiac surgery (NCS) in patients with LVAD poses a unique situation with its inherent challenges.AimWe conducted a comprehensive review to investigate the perioperative complications and mortality associated with emergent or elective NCS in patients with LVAD.MethodA comprehensive literature search for any papers referring to continuous LVAD patients with NCS. All publications with at least five durable LVAD patients who had NCS were eligible for inclusion.ResultTwenty articles matching our criteria were found and included in our study. This systematic review included 6,476 LVAD patients who underwent 6,824 NCS. There were 5–3,216 LVAD patients with NCS in each study. The median age was between 39 and 65 years, and most of the patients (78.8%) were male. Thirty-day postoperative mortality ranged from 0% to 60%. Eight studies reported no death within the 30 days of the operation. Common complications include gastrointestinal (GI) bleeding, intracranial bleeding, infection, acute kidney injury (AKI), urinary tract infection (UTI), stroke, sepsis, pneumonia, and VAD exchange. Emergent abdominal surgery had the highest (up to 60%) mortality rate, and vascular and neurological operations had the highest complication rates. Due to the diverse range of patients in each publication and the combination of outcomes presented in various publications, a meta-analysis was not conducted.ConclusionIn LVAD patients, noncardiac surgery may be performed effectively and safely. LVAD patients who undergo non-cardiac surgery may require more transfusions due to their complex coagulopathies. However, perioperative management of LVAD patients undergoing emergent NCS should be optimized to reduce mortality.Systematic Review Registrationhttps://osf.io/fetsb/.

Background: The utilization of extracorporeal life support (ECLS) for intraoperative support during lung transplantation has increased over the past decade. Although veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has recently emerged as the preferred modality over cardiopulmonary bypass (CPB), many centers continue to use both forms of ECLS during lung transplantation. Our novel hybrid VA-ECMO/CPB circuit allows for seamless transition from VA-ECMO to CPB at a significant cost savings compared to a standalone VA-ECMO circuit. This study describes our initial experience and outcomes in the first 100 bilateral lung transplantations using this novel hybrid VA-ECMO/CPB circuit. Methods: Medical records from September 2017 to May 2021 of the first 100 consecutive patients undergoing bilateral lung transplantation with intraoperative hybrid VA-ECMO support were examined retrospectively. We excluded patients with single lung transplants, retransplantations, preoperative ECLS bridging, and veno-venous (VV) ECMO and those supported with CPB only. Perioperative recipient, anesthetic, perfusion variables, and outcomes were assessed. Results: Of the 100 patients supported with VA-ECMO, 19 were converted intraoperatively to CPB. Right ventricular dysfunction was seen in 37% of patients, and the median mean pulmonary artery pressure was 28 mm Hg. No oxygenator clotting was observed with a median heparin dose of 13,000 units in the VA-ECMO group. Primary graft dysfunction grade 3 at 72 hours was observed in 10.1% of all patients and observed 1-year mortality was 4%. Conclusions: The use of a hybrid VA-ECMO/CPB circuit in our institution allows for rapid conversion to CPB with acceptable outcomes across a diverse recipient group at a significantly reduced cost compared to standalone VA-ECMO circuits.

Abstract Aims We sought to investigate the outcomes of heart transplant patients supported with Impella 5.5 temporary mechanical circulatory support. Methods and results Patient demographics, perioperative data, hospital timeline, and haemodynamic parameters were followed during initial admission, Impella support, and post‐transplant period. Vasoactive‐inotropic score, primary graft failure, and complications were recorded. Between March 2020 and March 2021, 16 advanced heart failure patients underwent Impella 5.5 temporary left ventricular assist device support through axillary approach. Subsequently, all these patients had heart transplantation. All patients were either ambulatory or chair bound during their temporary mechanical circulatory support until heart transplantation. Patients were kept on Impella support median of 19 days (3–31) with the median lactate dehydrogenase level of 220 (149–430). All Impella devices were removed during heart transplantation. During Impella support, patients had improved renal function with median creatinine serum level of 1.55 mg/dL decreased to 1.25 (P = 0.007), pulmonary artery pulsatility index scores increased from 2.56 (0.86–10) to 4.2 (1.3–10) (P = 0.048), and right ventricular function improved (P = 0.003). Patients maintained improved renal function and favourable haemodynamics after their heart transplantation as well. All patients survived without any significant morbidity after their heart transplantation. Conclusions Impella 5.5 temporary left ventricular assist device optimizes care of heart transplant recipients providing superior haemodynamic support, mobility, improved renal function, pulmonary haemodynamics, and right ventricular function. Utilizing Impella 5.5 as a direct bridging strategy to heart transplantation resulted in excellent outcomes.

Coronavirus disease 2019 (COVID-19) pandemic has led to considerable morbidity and mortality across the world. Lung transplant is a viable option for a few with COVID-19–related lung disease. Whom and when to transplant has been the major question impacting the transplant community given the novelty of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe a pitfall of presumed prolonged shedding of SARS-CoV-2 in a patient with COVID-19 associated acute respiratory distress syndrome leading to COVID-19 pneumonia after lung transplant. This raises concerns that replication-competent SARS-CoV-2 virus can persist for months post-infection and can lead to re-infection of grafts in the future.

Coronavirus disease 2019 (COVID-19), a novel etiology of end-stage lung disease, has resulted in major disruptions to the process of health care delivery worldwide. These disruptions have led to team-based innovations globally, resulting in a broad range of new processes in cardiopulmonary perioperative management. A key intersection of multidisciplinary teamwork and COVID-19 is found in lung transplantation, in which diverse teams collaborate throughout the perioperative period to achieve optimal outcomes. In this article, we describe the multidisciplinary approach taken by Mayo clinic in Florida to manage patients with COVID-19 presenting for lung transplantation.

Meng Si,1,* Yanni Xia,1,* Menglin Cong,1,* Dandan Wang,2 Yong Hou,1 Hecheng Ma1 1Department of Orthopedic Surgery, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 2Jinan Center hospital affiliated to Shandong University, Shandong University, Jinan, 250012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hecheng Ma, Department of Orthopedic Surgery, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China, Tel +86-531-82166551, Email yopo2007@qq.comPurpose: Osteosarcoma is considered as the most common primary malignant bone tumor in children and adolescents, and the treatments including chemotherapy and surgery were far from satisfactory. Localized tumor treatments by hydrogels incorporating combined chemotherapeutic drugs have recently emerged as superior approaches for enhanced anti-tumor effects and reduced systemic toxicity.Methods: A novel injectable thermosensitive poly (lactide-co- glycolide)-poly (ethylene glycol)-poly(lactide-co-glycolide) triblock copolymer hydrogel containing doxorubicin and cisplatin for the localized chemotherapy of osteosarcoma were synthesized and characterized. The in vitro drug release properties of the drugs-loaded hydrogels were investigated. To study the anti-tumor efficacy of hydrogels depots in vitro, the cytotoxicity and apoptosis rate against Saos-2 and MG-63 cells were evaluated by MTT, Annexin V and PCR methods. The in vivo synergistic anti-tumor efficacy of the multi-drugs co-loaded hydrogels was investigated by human osteosarcoma xenografts. Additionally, the systemic toxic side effects were evaluated by ex vivo histological analysis of the major organs of the mice.Results: The PLGA-PEG-PLGA copolymer solution underwent a sol-gel transition at appropriate temperature and degraded in the PBS, presenting a friendly biocompatibility in vitro. The in vitro cell viability tests demonstrated that DOX and CDDP co-loaded hydrogels exhibited synergistic anti-proliferation effect, due to the sustained release of drugs from the drugs-loaded hydrogel. The treatment with DOX and CDDP co-loaded hydrogel led to the highest efficiency in inhibiting the tumor growth, enhanced tumor necrosis rate and increased regulation of the apoptosis-related gene expressions, indicating a synergistic anti-tumor efficacy in vivo. Additionally, ex vivo histological analysis of the nude mice exhibited low systemic toxicity.Conclusion: The combination treatment of osteosarcoma by localized, sustained co-delivery of DOX and CDDP by PLGA-PEG-PLGA hydrogel may serve as a promising strategy for efficient clinical treatment of osteosarcoma.Keywords: hydrogels, localized delivery, synergistic therapy, combination therapy, osteosarcoma

Summary: Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12–71·55], 49·11 [41·26–58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2–152·3], 80·0 [50·8–125.9] and 95·1 [63·1–143·6], compared to 55·1 [33·4-91·0] of the convalescent group. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.

Background and Objectives: Digital signal processors are widely used in energy constrained applications in which battery lifetime is a critical concern. Accordingly, designing ultra-low-energy processors is a major concern. In this work and in the first step, we propose a sub-threshold DSP processor.Methods: As our baseline architecture, we use a modified version of an existing ultra-low-power general purpose processor. Afterwards, we make some modifications to add new instructions to the processor instruction set for better adapting to signal processing applications. In the second step, employing sub-threshold cores in many-core architectures, we use the proposed processor as simple basic cores in a many-core architecture.Results: In comparison with the baseline architecture, these modifications reduce the program memory size about 42% in average. In addition, data memory accesses are reduced about 60% in average, and more than 90% speed-up is achieved. According to the improvements in total execution time (93%) and power consumption (27%), the total consumed energy is reduced about 95% in average with at most 2.6% area overhead and without increasing the process variation effects on processor specifications.Conclusion: The results show that for parallel applications, such as FFT in LTE standard, exploiting sub-threshold processors in a many-core architecture not only can satisfy the required performance, but also reduce the power consumption about 50% or even more.

Wenjun Yu,1,* Mengya Si,2,* Li Li,3,* Ping He,4 Zhiqiang Fan,4 Qiaoxin Zhang,2 Xiaoyang Jiao4 1Department of Hematology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, People’s Republic of China; 2Clinical Laboratory, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, People’s Republic of China; 3Obstetrics Department, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, People’s Republic of China; 4Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyang JiaoDepartment of Cell Biology and Genetics, Shantou University Medical College, 22 Xinling Road, Guangdong 515041, People’s Republic of ChinaEmail xyjiao@stu.edu.cnObjective: We aimed to identify the biomarkers in cerebrospinal fluid (CSF) that facilitate the diagnosis of lymphomas with central nervous system (CNS) involvement.Methods: Four cases of non-Hodgkin’s lymphoma (NHL) patients with/without CNS involvement were enrolled respectively, and non-CNS tumor patients (n=3) were selected to be the controls. Lab biomarkers, cytokines, and tight junction proteins (TJs) in CSF and serum were measured.Results: When comparing the CNS to non-CNS group, cytokine including MMP-9 (15.24 vs 0.36 ng/mL), CCL-2 (1922.04 vs 490.68 pg/mL), and sVCAM-1 (61.36 vs 9.00 pg/mL), TJs including OCLN (6.68 vs 2.59 pg/mL), and ZO-1 (710.04 vs 182.98 pg/mL) in CSF were significantly higher in lymphomas patients with CNS involvement than those without CNS involvement. However, serum biomarkers were not significantly elevated. Contrary to the major findings, all conventional biomarkers and MRI results showed no significant change.Conclusion: CSF biomarkers affecting BBB disruption are valuable in mirroring the risk of lymphoma CNS metastasis. Further study with a larger sample size is needed to verify these biomarkers in predicting lymphoma CNS involvement.Keywords: lymphoma, CNS metastasis, cytokines, tight junction protein

Manfei Si,1 Junji Zhang,1 Jianzhong Cao,2 Zhibo Xie,3 Shan Shu,1 Yapei Zhu,1 Jinghe Lang1 1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Vascular Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Jinghe LangDepartment of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel +86 10 6915 6204Email langjh@hotmail.comPurpose: Ovarian cancer is the leading cause of gynecologic cancer-related death worldwide. Early diagnosis of ovarian cancer can significantly improve patient prognosis. Hence, there is an urgent need to identify key diagnostic and prognostic biomarkers specific for ovarian cancer. Because high-grade serous ovarian cancer (HGSOC) is the most common type of ovarian cancer and accounts for the majority of deaths, we identified potential biomarkers for the early diagnosis and prognosis of HGSOC.Methods: Six datasets (GSE14001, GSE18520, GSE26712, GSE27651, GSE40595, and GSE54388) were downloaded from the Gene Expression Omnibus database for analysis. Differentially expressed genes (DEGs) between HGSOC and normal ovarian surface epithelium samples were screened via integrated analysis. Hub genes were identified by analyzing protein–protein interaction (PPI) network data. The online Kaplan-Meier plotter was utilized to evaluate the prognostic roles of these hub genes. The expression of these hub genes was confirmed with Oncomine datasets and validated by quantitative real-time PCR and Western blotting.Results: A total of 103 DEGs in patients with HGSOC—28 upregulated genes and 75 downregulated genes—were successfully screened. Enrichment analyses revealed that the upregulated genes were enriched in cell division and cell proliferation and that the downregulated genes mainly participated in the Wnt signaling pathway and various metabolic processes. Ten hub genes were associated with HGSOC pathogenesis. Seven overexpressed hub genes were partitioned into module 1 of the PPI network, which was enriched in the cell cycle and DNA replication pathways. Survival analysis revealed that MELK, CEP55 and KDR expression levels were significantly correlated with the overall survival of HGSOC patients (P < 0.05). The RNA and protein expression levels of these hub genes were validated experimentally.Conclusion: Based on an integrated analysis, we propose the further investigation of MELK, CEP55 and KDR as promising diagnostic and prognostic biomarkers of HGSOC.Keywords: high-grade serous ovarian cancer, integrated analysis, bioinformatic analysis, differentially expressed genes, survival, biomarker

Axillary Impella devices are increasingly employed for long-term support of patients with systolic heart failure and shock. Axillary access allows for awake support and ambulation, which carries an inherent risk of disconnection or malposition. We report a series of two cases where device replacement due to dysfunction and malposition can be completed safely through the original axillary graft using axillary graft thrombectomy, given that the clot burden could be a major source of morbidity to the patient.

Heart transplant remains the criterion standard treatment for patients in end-stage heart failure. Improvement in the post-heart transplant outcomes in the last decade has contributed to increased demand for organs. Worldwide each year, more than 5000 heart transplants are performed and 50,000 people become candidates for heart transplant. In the last 50 years, there have been several attempts to expand donor criteria to increase the donor pool. Despite making hepatitis C virus, opioid overdose death, old age allowable and changing the allocation system, the gap between supply and demand is widening and unfortunately, thousands die every year waiting due to the critical shortage of organs. New technologies for heart donation after circulatory death have emerged, particularly normothermic regional organ perfusion and ex-vivo heart perfusion using organ care systems. However, these technologies still do not fill the gap. Continuous advancements in areas such as regenerative medicine and xenotransplantation, among others, are needed to overcome the shortage of heart donors for heart transplantation.

A 53-year-old male patient was presented to our institution with the clinical picture of biventricular failure. The echocardiogram revealed congenitally corrected transposition of the great arteries, dextrocardia with situs solitus, atrioventricular discordance and ventriculoatrial discordance, severe systemic and mitral valves regurgitation, and severe pulmonary hypertension (mean pulmonary artery pressure: 51 mm Hg). He underwent heart–lung transplant. He was discharged on postoperative day 25 with left ventricular ejection fraction of 60%–65%, and with oxygen independency.

Mengya Si,1 Xiaoyang Jiao,2 Yazhen Li,2 Huanzhu Chen,2 Ping He,2 Fang Jiang1 1The First Affiliated Hospital of Shantou University Medical College, 2Cell Biology and Genetics Department, Shantou University Medical College, Shantou, People’s Republic of China Aim: Central nervous system (CNS) metastasis is a major obstacle in the treatment of leukemia, and the underlying mechanisms of leukemia CNS metastasis are not fully understood. The present study is an investigation of the role of the CNS microenvironment in leukemia CNS metastasis.Methods: Analog blood–brain barrier (BBB) was set by coculturing human brain microvascular endothelial cells (HBMVECs) and leukemia cells (U937 and IL-60), as well as HBMVECs and sera from leukemia patients, in vitro. The permeability of the HBMVEC monolayer and the levels of tight junction proteins, cytokines and chemokines (C&Ckines) were measured.Results: The permeability of HBMVECs increased when cocultured with leukemia sera. The expression of C&Ckines was significantly upregulated in HBMVECs cocultured with leukemia sera or leukemia cells, compared to the normal sera (P

Di Wu, Mengjie Si, Hui-Yi Xue, Ho-Lun Wong Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: Breast cancer is the most common malignant disease in women worldwide, but the current drug therapy is far from optimal as indicated by the high death rate of breast cancer patients. Nanomedicine is a promising alternative for breast cancer treatment. Nanomedicine products such as Doxil® and Abraxane® have already been extensively used for breast cancer adjuvant therapy with favorable clinical outcomes. However, these products were originally designed for generic anticancer purpose and not specifically for breast cancer treatment. With better understanding of the molecular biology of breast cancer, a number of novel promising nanotherapeutic strategies and devices have been developed in recent years. In this review, we will first give an overview of the current breast cancer treatment and the updated status of nanomedicine use in clinical setting, then discuss the latest important trends in designing breast cancer nanomedicine, including passive and active cancer cell targeting, breast cancer stem cell targeting, tumor microenvironment-based nanotherapy and combination nanotherapy of drug-resistant breast cancer. Researchers may get insight from these strategies to design and develop nanomedicine that is more tailored for breast cancer to achieve further improvements in cancer specificity, antitumorigenic effect, antimetastasis effect and drug resistance reversal effect. Keywords: nanomedicine, breast cancer, targeted delivery, drug therapy, drug resistance, tumor microenvironment

Abstract Therapeutic plasma exchange (TPE) is a potentially life-saving procedure which effectively removes donor-specific human leukocyte antigen (HLA) antibodies from the bloodstream, allowing critically ill heart transplant recipients to receive a donor organ with less wait time, and reducing the risk of acute organ rejection. The bulk of coagulation factors is initially removed from the blood during TPE using albumin and is later replaced with allogeneic plasma. Coagulopathy may develop during TPE and then can persist due to intraoperative blood loss and hemodilution during surgery and cardiopulmonary bypass. We hereby describe the utility of rotational thromboelastometry to assess rapid coagulation changes during TPE and subsequent heart transplant (HT) surgery.

A 60-year-old male patient presented to an outside hospital with severe cardiogenic shock. A triple bridge of mechanical circulatory support was utilized to transition him to heart transplantation listing. Initially, coronary artery disease was percutaneously treated and Impella 2.5 was used as mechanical circulatory support for 5 days followed by the second Impella 2.5 for 4 days. Veno-arterial extracorporeal membrane oxygenation support was deployed for 16 days. This was exchanged for HeartWare ventricular assist device support as the third stage of mechanical circulatory support to heart transplantation listing. The patient experienced acute renal failure which was managed by continuous renal replacement therapy then intermittent hemodialysis with eventual complete recovery of the renal function. He was discharged home 56 days after HeartWare ventricular assist device implantation with stable hemodynamic, intact neurologic status and fully recovered renal function. Currently, the patient is listed for heart transplantation.

Background: Cardiac transplantation can be complicated by refractory hemorrhage particularly in cases where explantation of a ventricular assist device is necessary. Recombinant activated factor VII (rFVIIa) has been used to treat refractory bleeding in cardiac surgery patients, but little information is available on its efficacy or cost in heart transplant patients. Methods: Patients who had orthotopic heart transplantation between January 2009 and December 2014 at a single center were reviewed. Postoperative bleeding and the total costs of hemostatic therapies were compared between patients who received rFVIIa and those who did not. Propensity scores were created and used to control for the likelihood of receiving rFVIIa in order to reduce bias in our risk estimates. Results: Seventy-six patients underwent heart transplantation during the study period. Twenty-one patients (27.6%) received rFVIIa for refractory intraoperative bleeding. There was no difference in postoperative red blood cell transfusion, chest tube output, or surgical re-exploration between patients who received rFVIIa and those who did not, even after adjusting with the propensity score (P = 0.94, P = 0.60, and P = 0.10, respectively). The total cost for hemostatic therapies was significantly higher in the rFVIIa group (median $10,819 vs. $1,985; P < 0.0001). Subgroup analysis of patients who underwent redo-sternotomy with left ventricular assist device explantation did not show any benefit for rFVIIa either. Conclusions: In this relatively small cohort, rFVIIa use was not associated with decreased postoperative bleeding in patients undergoing heart transplantation; however, it led to significantly higher cost.

In this review, we identify important challenges facing physicians responsible for renal and cardiac transplantation in children based on a review of the contemporary medical literature. Regarding pediatric renal transplantation, we discuss the challenge of antibody-mediated rejection, focusing on both acute and chronic antibody-mediated rejection. We review new diagnostic approaches to antibody-mediated rejection, such as panel-reactive antibodies, donor-specific cross-matching, antibody assays, risk assessment and diagnosis of antibody-mediated rejection, the pathology of antibody-mediated rejection, the issue of ABO incompatibility in renal transplantation, new therapies for antibody-mediated rejection, inhibiting of residual antibodies, the suppression or depletion of B-cells, genetic approaches to treating acute antibody-mediated rejection, and identifying future translational research directions in kidney transplantation in children. Regarding pediatric cardiac transplantation, we discuss the mechanisms of cardiac transplant rejection, including the role of endomyocardial biopsy in detecting graft rejection and the role of biomarkers in detecting cardiac graft rejection, including biomarkers of inflammation, cardiomyocyte injury, or stress. We review cardiac allograft vasculopathy. We also address the role of genetic analyses, including genome-wide association studies, gene expression profiling using entities such as AlloMap®, and adenosine triphosphate release as a measure of immune function using the Cylex® ImmuKnow™ cell function assay. Finally, we identify future translational research directions in heart transplantation in children.

The resort worldwide to edible medicinal plants for medical care has increased significantly during the last few years. Currently, there is a renewed interest in the search for new phytochemicals that could be developed as useful anti-inflammatory and anti-allergic agents to reduce the risk of many diseases. The activation of nuclear transcription factor-kappa B (NF-κB) has now been linked to a variety of inflammatory diseases, while data from numerous studies underline the importance of phytochemicals in inhibiting the pathway that activates this transcription factor. Moreover, the incidence of type I allergic disorders has been increasing worldwide, particularly, the hypersensitivity to food. Thus, a good number of plant products with anti-inflammatory and anti-allergic activity have been documented, but very few of these compounds have reached clinical use and there is scant scientific evidence that could explain their mode of action. Therefore, this paper intends to review the most salient recent reports on the anti-inflammatory and anti-allergic properties of phytochemicals and the molecular mechanisms underlying these properties.