Isolated Hyperacute T-Waves in West Nile Encephalitis Indicating Atypical Variant of Stress-Induced Cardiomyopathy

Several cardiac outcomes have been reported with West Nile-encephalitis;however, the underlying pathophysiology remains complex. We present a 42-year-old female, with multiple sclerosis, whose neurological symptoms and respiratory decline were finally explained by the diagnosis of West Nile-encephalitis. During her admission, the isolated peaked T-waves indicated the underlying stress-induced cardiomyopathy. The absence of all other causes of hyperacute T-waves, their subsequent resolution with the resolution of infection and improvement in wall motion abnormalities, further supported the association. This case highlights the importance of considering hyperacute T-waves in an approach towards the diagnosis of WNV-encephalitis related atypical variant of stress-induced cardiomyopathy.

Consistency between magnetic resonance diffusion-weighted images and pathological findings in a hyperacute cerebral infarction rabbit model

BACKGROUND： Because magnetic resonance diffusion-weighted imaging is sensitive to water molecule movement, it has particular advantages for early diagnosis of cerebral infarction. However, the relationship between apparent diffusion coefficient changes with ischemia time, particularly relative apparent diffusion coefficient and tissue pathological changes remains controversial. OBJECTIVE： To explore the correlation between apparent diffusion coefficient changes and pathologic changes in hyperacute cerebral infarction. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment of neuroimaging. The study was performed at the Laboratory of Radiology Department, Longgang Central Hospital of Shenzhen from October 2007 to October 2008. MATERIALS： Magnetic resonance scanner was purchased from Philips Medical Systems, Best, the Netherlands. METHODS： A total of 42 healthy, adult, New Zealand rabbits were randomly assigned into sham-operation, ischemia 0.5-, 1-, 2-, 3-, 4-, and 6-hour groups, with six animals in each group. Local cerebral ischemia model was established by right middle cerebral artery occlusion, and cranial MRI scanning and pathologic observation were performed, respectively, at 0.5, 1,2, 3, 4, and 6 hours following ischemia. The middle cerebral artery of sham-operation group was only exposed, but not occluded. Images at the above-mentioned time points were also collected. MAIN OUTCOME MEASURES： Apparent diffusion coefficient and relative apparent diffusion coefficient values of abnormal signal on diffusion-weighted imaging were calculated and compared with pathological changes in the ischemic region. RESULTS： No abnormal diffusion-weighted imaging signals or pathological changes were observed in the sham-operation group. Abnormal signal intensity on diffusion-weighted imaging was first observed in the 0.5-hour group. Apparent diffusion coefficient and relative apparent diffusion coefficient values decreased in all middle cerebral artery occlusion rabbits and reached lowest levels at 3 hours, followed by a gradual increase. The right ischemic basal ganglia region with high signal intensity on diffusion-weighted imaging extended with increasing time of occlusion, and the pathologic outcome corresponded with MRI changes. CONCLUSION： Relative apparent diffusion coefficient values changed regularly with ischemia time and displayed good correspondence to pathological manifestations.

A PROSPECTIVE STUDY TO EVALUATE THE SAFETY AND EFFICACY USING REMOVING BLOOD STASIS HERBALS FOR PATIENTS WITH INTRACRANIAL HEMORRHAGE OF HYPERACUTE STAGE AND RELATIVE FACTORS OF HEMATOMA ENLARGEMENT(A MULTICENTER PROSPECTIVE RANDOMIZED DOUBLE-BLIND PLACEBO

The aim was to investigate whether using a removing blood stasis method in hyperacute intracranial hemorrhage stage can lead to hematoma enlargement and its clinical efficacy.A multicenter retrospective randomized double-blind placebo-controlled clinical study.We recruited patients aged 18 years or older and presenting at less than 6 h from symptom onset in 8 research centers.All the patients

Autologous peripheral blood-derived orthobiologics:Different types and their effectiveness in managing knee osteoarthritis

Knees are the most commonly impacted weight-bearing joints in osteoarthritis(OA),affecting millions of people worldwide.With increasing life spans and obesity rates,the incidence of knee OA will further increase,leading to a significant increase in the economic burden.Conventional treatment modalities utilized to manage knee OA have limitations.Over the last decade,the role of various autologous peripheral blood-derived orthobiologics(APBOs)for the treatment of knee OA has been extensively investigated.This editorial provided an overview and focused on defining and shedding light on the current state of evidence based on the most recent published clinical studies concerning the use of APBO for the management of knee OA.While numerous studies have demonstrated promising results for these preparations,a notable gap exists in the comparative analysis of these diverse formulations.This absence of head-to-head studies poses a considerable challenge for physicians/surgeons in determining the optimal preparation for managing knee OA and achieving sustained longterm results.Thus,more adequately powered,multicenter,prospective,doubleblind,randomized controlled trials with longer follow-ups are needed to establish the long-term efficacy and to aid physicians/surgeons in determining the optimal APBO for the management of knee OA.

EXPRESSION OF HUMAN α-GALACTOSIDASE AND α1,2-FUCOSYL-TRANSFERASE GENES MODIFIES THE CELL SURFACE GALα1,3GAL ANTIGEN AND CONFERS RESISTANCETO HUMAN SERUM-MEDIATED CYTOLYSIS

Objective To explore the strategies which reduce the amount of xenoantigen Galα1, 3 Gal. Methods Human α-galactosidase gene and α1,2-fucosyltransferase gene were transferred into cul-tured porcine vascular endothelial cells PEDSV.15 and human α-galactosidase transgenic mice were produced. The Galα1,3Gal on the cell surface and susceptibility of cells to human antibody-mediated lysis were analyzed. Results Human α-galactosidase gene alone reduced 78% of Galα1,3Gal on PEDSV.15 cell surface while human α-galactosidase combined with α1,2-fucosyltransferase genes removed Galα1,3Gal completely. Decrease of Galα1,3Gal could reduce susceptibility of cells to human antibody-mediated lysis, especially during co-expression of α-galactosidase gene and α1,2-fucosyltransferase gene. RT-PCR indicated positive human α-galactosidase gene expression in all organs of positive human α-galacto-sidase transgenic F1 mice including heart, liver, kidney, lung, and spleen, the amount of Galα1,3Gal antigens on which was reduced largely. 58% of spleen cells from F1 mice were destroyed by comp-lement-mediated lysis compared with 24% of those from normal mice. Conclusions Human α-galactosidase gene and α1,2-fucosyltransferase gene effectively reduce the expression of Galα1,3Gal antigens on endothelial cell surface and confers resistance to human serum-mediated cytolysis. The expression of human α-galactosidase in mice can also eliminate the Galα1,3Gal antigens in most tissues and decrease the susceptibility of spleen cells to human serum-mediated cytolysis.

Updates on antibody-mediated rejection in intestinal transplantation

Antibody-mediated rejection(ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation(ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibodymediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation.

The Synergistic Effect of HT and Complement Regulatory Proteins in Resisting the Immunological Rejection of Heterogenic Transplantation

Objective：To establish the polytransgenic mice expressing the human HT and complement regulatory proteins （CRPs） and discuss their ability to resist the hyperacute rejection （HAR） and delayed xenograft rejection （DXR） of heterogenic transplantation. Methods ：Transgenic mice were produced by microinjection to construct gene for human HT, delay acceleration factor （DAF） and/or CD59 into the male pronucleus of zygote. PCR and Southern blot were used to screen the positive trarisgenic mice. Flow cytometry （FCM） was used to detect the expression of HT, ct-Gal and DAF or CD59 on the PBMCs of transgenic mice. The survival time and function of the heart of transgenic mice were determined by a modified Langendorff cardiac perfusion apparatus： The change of proteinosis on IgM,IgG, C3c and C9 from different cardiac vascular iendothelial cells of transgenic mice were detected by immunohistochemistry. Results：HT, DAF or CD59 were highly expressed on the positive transgenic mice by FCM. The deposition of IgM,IgG,C3c or C9 in the cardiac vascular endothelial cells of the positive transgenic mice were de- creased. The survival time and function of the heart of the co-transgenic mice with AB serum perfusion were significantly longer and higher than that of the single HT positive transgenic mice（P 〈0.05）. Conclusion ：The mice co-expressing HT/DAF or HT/CD59 could resist the HAR,which was better than those expressing HT alone. It is feasible to use HT and CRPs co-transgenic methods to resist the HAR and DXR.

Transgenic mice designed to express human α-1,2-fucosyltransferase in combination of human DAF and CD59 to avoid xenograft rejection

The expression of human α-1,2-fucosyltransferase (HT) or complement regulatory proteins has been proved as an strategy to overcome hypercute rejection in discordant xenogeneic organ transplantation. In this study, we examined whether peripheral blood mononuclear cells (PBMCs) from polytransgenic mice expressing the human HT, and complement regulatory proteins (DAF and CD59), can provide more effective protection against xenograft rejection. Transgenic mice were produced by co-injection of gene constructs for human HT, DAF and/or CD59. Flow Cytometry (FCM) was used to screen the positive transgenic mice. PBMCs from transgenic mice were incubated with 15% human serum to evaluate natural antibody binding, complement activation and expression of adhesion molecules. Three transgenes were strongly expressed in PBMCs of transgenic mice, and HT expression signifi- cantly reduced expression of the major xenoepitope galactose-α-1,3-galactose (α-Gal). Functional studies with PBMCs showed that co-expression of HT and DAF or CD59 markedly increased their re- sistance to human serum-mediated cytolysis when compared with single transgenic PBMCs. Moreover, the combined expression of triple transgenes in PBMCs led to the greatest protection against human serum-mediated cytolysis, avoided hyperacute rejection and reduced expression of adhesion mole- cules. Strong co-expression of triple transgenes was completely protected from xenograft hyperacute rejection and partially inhibited acute vascular rejection. The studies suggest that engineering mice to express triple molecules represents an critical step toward prolonging xenograft survival and might be more suitable for xenotransplantation.

Effect on surgery outcomes owing to the interval between onset of symptoms and surgery of patients with acute type A aortic dissection

Background:This study aimed to identify whether the interval from onset of symptoms to surgery affects the outcomes of surgery in patients with acute type A aortic dissection(AAAD).Methods:This study retrospectively examined 249 patients with AAAD who underwent Sun’s procedure.All patients were divided into 2 groups,hyperacute and acute,according to the interval from onset of symptoms to surgery.The primary endpoint was all-cause early mortality,and the secondary endpoint was early reoperation.Results:The surgery time,cardiopulmonary bypass time,clamp time,and selective cerebral perfusion time were not significantly different between the 2 groups.The intensive care unit length of stay and duration of mechanical ventilation of the 2 groups were 185.50hours versus 185.00hours(P=0.970)and 41.50hours versus 44.00hours(P=0.678),respectively.There were 52 early deaths:29 in the hyperacute group and 23 in the acute group(21.6%vs.20.0%,P=0.751).The incidence of reoperation was 0.7% and 0.9%(P>0.999),respectively.The incidence rates of postoperative acute heart failure(AHF),acute respiratory failure(ARF),nervous dysfunction,and acutekidney injury were37.3% versus 25.2%(P=0.041),51.5%versus51.3%(P=0.976),13.4% versus 7.0%(P=0.096),and 37.3% versus 37.4%(P=0.990),respectively.Multivariable analysis indicated that surgery in the hyperacute phase might be an independent risk factor for AHF(OR:1.765;95%CI:1.021–3.052;P=0.042).Conclusion:Surgery in the hyperacute phase of AAAD was associated with postoperative AHF.Therefore,early medical management or interventional therapy for complications before surgery performed by experienced surgeons is recommended,especially in the hyperacute phase.