Acute kidney injury (AKI) is relatively common after cardiothoracic surgery for type A acute aortic dissection (TA-AAD) and increases mortality. We investigated the incidence and risk factors for AKI ...in patients with TA-AAD and its impact on their outcomes. The records of 375 consecutive patients who underwent surgical treatment for TA-AAD from October 2007 to March 2013 were analyzed retrospectively. We defined AKI using the Kidney Disease Improving Global Outcomes criteria, which are based on serum creatinine concentration or glomerular filtration rate. We used Kaplan-Meier methods and multivariate Cox proportional hazards regression to assess the impact of AKI on both mortality and major adverse cardiovascular and cerebrovascular events. We also examined the association between risk factors and AKI using logistic regression modeling. Postoperative AKI was observed in 165 patients (44.0%). The overall 30-day and mid- to long-term mortality was 1.6% and 8.8%, respectively. Mortality and major adverse cardiovascular and cerebrovascular events correlated significantly with the severity of AKI, and multivariate analysis showed that AKI stage 3 (the most sever stage) was an independent risk factor for mortality (hazard ratio 6.83, 95% confidence interval 2.52 to 18.52) after adjustment for important confounding factors. Extracorporeal circulation time, body mass index, perioperative peak serum C-reactive protein concentration, renal malperfusion, and perioperative sepsis were found to be risk factors for AKI. In conclusion, AKI was common in patients who underwent surgery for type A acute aortic dissection. The severity of AKI strongly influences patient outcomes, so it should be recognized promptly and treated aggressively when possible.
Background Flaky tail (ma/ma Flg ft/ft ) mice have a frameshift mutation in the filaggrin (Flg ft ) gene and are widely used as a model of human atopic dermatitis associated with FLG mutations. These ...mice possess another recessive hair mutation, matted ( ma ), and develop spontaneous dermatitis under specific pathogen-free conditions, whereas genetically engineered Flg −/− mice do not. Objective We identified and characterized the gene responsible for the matted hair and dermatitis phenotype in flaky tail mice. Methods We narrowed down the responsible region by backcrossing ma / ma mice with wild-type mice and identified the mutation using next-generation DNA sequencing. We attempted to rescue the matted phenotype by introducing the wild-type matted transgene. We characterized the responsible gene product by using whole-mount immunostaining of epidermal sheets. Results We demonstrated that ma , but not Flg ft , was responsible for the dermatitis phenotype and corresponded to a Tmem79 gene nonsense mutation (c.840C>G, p.Y280*), which encoded a 5-transmembrane protein. Exogenous Tmem79 expression rescued the matted hair and dermatitis phenotype of Tmem79 ma/ma mice. Tmem79 was mainly expressed in the trans -Golgi network in stratum granulosum cells in the epidermis in both mice and humans. The Tmem79 ma/ma mutation impaired the lamellar granule secretory system, which resulted in altered stratum corneum formation and a subsequent spontaneous dermatitis phenotype. Conclusions The Tmem79 ma/ma mutation is responsible for the spontaneous dermatitis phenotype in matted mice, probably as a result of impaired lamellar granule secretory system and altered stratum corneum barrier function.
Abstract Background Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme affected in heart/muscle-specific MnSOD-deficient mice (H/M-SOD2−/− ), which develop progressive ...congestive heart failure and exhibit pathology typical of dilated cardiomyopathy. Methods In this study we investigated the beneficial effects of epigallocatechin gallate (EGCG) on the cardiac remodeling and telomere biology in H/M-SOD2−/− mice. H/M-SOD2−/− mice were divided into three groups: those receiving normal drinking water (KO), a low dose of EGCG (L: 10 mg/L), and a high dose of EGCG (H: 100 mg/L) beginning at eight weeks of age and lasting for eight weeks. Results The mice in the KO group exhibited significantly dilated cardiac remodeling with reduced contractility, which was prevented by the administration of EGCG. Although the mortality of KO mice was about 50% at 16 weeks of age, the mice that received EGCG had a high survival rate. The cardiac dilatation with reduced cardiac contraction in KO mice was prevented by EGCG treatment. The levels of myocardial oxidative stress and free fatty acids were lower in the group treated with EGCG compared with the KO group. The increased expression of nitric oxide synthase 2, nitrotyrosine, fatty acid synthase, Toll-like receptor 4, and Sirt1 in the KO mice were prevented by EGCG treatment. The shortening of the telomere length, decreased telomerase activity in KO mice were also prevented by EGCG. Conclusions H/M-SOD2−/− mice receiving EGCG have a lower mortality rate and exhibit less inflammation and a better preserved cardiac function and telomere biology.
Abstract d -Bifunctional protein (DBP) deficiency is an autosomal recessive disorder of peroxisomal fatty acid oxidation caused by mutations in HSD17B4 . It is typically fatal by the age of two years ...with symptom onset during the neonatal period, and survival until late childhood is rare. We herein report the case of a patient with DBP deficiency surviving until adulthood, who showed severe sensorineural deafness, disturbances in language acquisition, slowly progressive cerebellar ataxia, and peripheral neuropathy. This patient, in whom findings of prior investigations were nondiagnostic, had been followed up as having an early-onset spinocerebellar degeneration of unknown etiology. Whole-exome sequencing analysis at the age of 36 showed two heterozygous variants in the gene HSD17B4 , which encodes DBP in this patient. A panel of peroxisomal investigations showed normal levels of very long chain fatty acids (VLCFAs) in plasma and elevated serum phytanic acid levels. Recently, an increasing number of patients with DBP deficiency surviving until adolescence/adulthood have been reported, in whom abnormalities in the levels of VLCFAs and other peroxisomal metabolites are marginal or nonexistent. Genetic analysis of HSD17B4 should be considered in adult patients with cerebellar ataxia, peripheral neuropathy, and pyramidal signs in addition to sensorineural auditory disturbance since childhood.
A 24-year-old woman with chronic active Epstein-Barr virus (CAEBV) infection successfully underwent coronary artery bypass grafting for triple coronary arteries with chronic total occlusion and ...aneurysms. This case underscores the importance of accurate assessment and treatment of coronary artery lesions in patients with CAEBV infection.
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Abstract Background Rapid plaque progression and positive remodeling are recognized as vulnerable coronary plaque characteristics. This study examined whether serial carotid ultrasonography might be ...of value for assessment of coronary plaque progression and positive remodeling, measured by serial intravascular ultrasound (IVUS), in survivors of acute myocardial infarction (AMI). Methods Thirty-nine patients with AMI had repeated examinations by IVUS of culprit coronary arteries and echolucency of the coronary artery on admission (1st test) and 6 months later (2nd test). Plaque volume and external elastic membrane area of the native segment (15 ± 9 mm in length) beginning 5 mm proximal to the stent edge in the culprit coronary artery were measured using volumetric IVUS. Echolucency of the carotid artery was assessed by integrated backscatter (IBS) analysis. Lower IBS reflects an echolucent and lipid-rich plaque. Results Increase in coronary plaque volume and positive remodeling over 6 months occurred in 17 and 12 patients, respectively. The % change in carotid IBS value over 6 months was correlated with the % change in the coronary plaque volume ( r = −0.69, p < 0.001). The aggravated change in the carotid IBS was significantly associated with increase in the coronary plaque volume and positive remodeling over 6 months (OR 0.94 and 0.95, respectively, 95% CI 0.90–0.99, both p < 0.05). Conclusions Serial measurements of echolucency of the carotid artery may be of value for assessment of short-term progression and positive remodeling of coronary plaques in AMI survivors.
Abstract Background We recently showed that stromal cell-derived factor (SDF)-1α, a pro-inflammatory mediator, is produced in infarcted myocardium and is associated with left ventricular (LV) adverse ...remodeling and progressive dysfunction following acute myocardial infarction (AMI). The current study examined whether SDF-1α levels in the peripheral vein can provide prognostic information of outcomes in stable patients with a history of MI. Methods Plasma levels of SDF-1α in the peripheral vein were measured by enzyme-linked immunosorbent assay in 192 stable patients with a history of MI. All patients were followed prospectively for a period of 90 months or until occurrence of one of the following cardiac events: cardiac death, non-fatal myocardial infarction, unstable angina requiring unplanned coronary revascularization, or worsening heart failure requiring hospital admission. Results During the follow-up period (77 ± 26 months), 30 patients had cardiac events. Multivariate Cox analysis revealed that high levels of SDF-1α (≥2162 pg/mL; a cut-off value determined by receiver-operating characteristic analysis) were a significant predictor of cardiac events, independent of traditional risk factors (HR: 1.98; 95% CI: 1.38–2.85; p < 0.001). The addition of high levels of SDF-1α to conventional risk factors including brain natriuretic peptide improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.90, p < 0.0001; and IDI 0.05, p = 0.002). Conclusions High levels of SDF-1α predicted secondary cardiac events in stable patients with a history of MI. SDF-1α levels may be a useful risk assessment tool in patients with a history of MI.
Background Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that has been implicated in the ...pathogenesis of AD. Recently, we developed a novel DNA vaccine that generates neutralizing endogenous anti-MIF antibodies. Objective This study explores the preventive and therapeutic effects of this MIF-DNA vaccine in mouse models of AD. Methods Two different AD model mice (DS-Nh and NC/Nga) received MIF-DNA vaccination to analyze preventive and therapeutic effects, as assessed by clinical skin scores, histologic findings, and serum IgE levels. Results In murine models of AD, MIF-DNA vaccination prevented the occurrence of the AD skin phenotype. Furthermore, administration of MIF-DNA vaccine to mice that had already developed AD produced a rapid improvement in AD skin manifestation. There were reduced histologic signs of inflammation and lower serum IgE levels in treated mice compared with those seen in control animals. Finally, passive transfer of IgG from MIF-DNA vaccinated mice to AD mice also produced a significant therapeutic effect. These results demonstrate that MIF-DNA vaccination not only prevents the development of AD but also improves the symptoms of pre-existing AD. Conclusion Taken together, the induction of an anti-MIF autoantibody response using MIF-DNA vaccination appears to be a useful approach in the treatment of AD.
We describe the use of the Starfish 2 heart positioning device as an aid to pericardium reconstruction after en bloc resection of mediastinal tumors of the left pericardium by use of median ...sternotomy with anterolateral thoracotomy. The Starfish device, which is a tool for off-pump coronary artery procedures, allows excellent cardiac positioning and hemodynamic stability during pericardium reconstruction through a median sternotomy with anterolateral thoracotomy.
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