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991.
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Objectives

This study sought to build a patient?patient similarity network using multiple features of left ventricular (LV) structure and function in patients with aortic stenosis (AS). The study further validated the observations in an experimental murine model of AS.

Background

The LV response in AS is variable and results in heterogeneous phenotypic presentations.

Methods

The patient similarity network was developed using topological data analysis (TDA) from cross-sectional echocardiographic data collected from 246 patients with AS. Multivariate features of AS were represented on the map, and the network topology was compared with that of a murine AS model by imaging 155 animals at 3, 6, 9, or 12 months of age.

Results

The topological map formed a loop in which patients with mild and severe AS were aggregated on the right and left sides, respectively (p < 0.001). These 2 regions were linked through moderate AS; with upper arm of the loop showing patients with predominantly reduced ejection fractions (EFs), and the lower arm showing patients with preserved EFs (p < 0.001). The region of severe AS showed >3 times the increased risk of balloon valvuloplasty, and transcatheter or surgical aortic valve replacement (hazard ratio: 3.88; p < 0.001) compared with the remaining patients in the map. Following aortic valve replacement, patients recovered and moved toward the zone of mild and moderate AS. Topological data analysis in mice showed a similar distribution, with 1 side of the loop corresponding to higher peak aortic velocities than the opposite side (p < 0.0001). The validity of the cross-sectional data that revealed a path of AS progression was confirmed by comparing the locations occupied by 2 groups of mice that were serially imaged. LV systolic and diastolic dysfunction were frequently identified even during moderate AS in both humans and mice.

Conclusions

Multifeature assessments of patient similarity by machine-learning processes may allow precise phenotypic recognition of the pattern of LV responses during the progression of AS.  相似文献   
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995.
OBJECTIVES: To determine: (1) the incidence of invasive salmonellosis, (2) the distribution of specific Salmonella serotypes associated with invasive disease, and (3) the role of demographic characteristics in invasive salmonellosis in Michigan. DESIGN: We conducted a cross-sectional study using laboratory-confirmed cases of salmonellosis reported to the Michigan Department of Community Health between 1995 and 2001. METHODS: Average annual incidences (AAIs) for invasive salmonellosis were computed, and Poisson regression analysis was used to model the association between demographic attributes and invasive salmonellosis. RESULTS: Of 6797 cases of salmonellosis, 347 (5.1%) were characterized as invasive having an AAI of 0.5/100000. A covariate-adjusted Poisson model showed children aged <1 year to be at higher risk for invasive salmonellosis compared to adults aged 40-49 years (rate ratio (RR) 8.98, 95% confidence interval (CI) 5.69-14.17). No significant differences were found between males and females (RR 1.02, 95% CI 0.83-1.26), African-Americans and Caucasians (RR 0.95, 95% CI 0.64-1.42), and urban and rural residents (RR 0.98, 95% CI 0.76-1.26). Among the most common serotypes associated with invasive salmonellosis (Heidelberg, Typhimurium, and Enteritidis), Salmonella serotype Heidelberg had the highest blood invasiveness ratio (15.79/100). CONCLUSIONS: Children aged <1 year, especially of minority groups, are at higher risk for invasive Salmonella infections. Invasive salmonellosis may be included in the differential diagnosis of acute bacterial infections in young children with positive stool cultures for Salmonella.  相似文献   
996.
OBJECTIVE: To investigate differences between HLA-B27(-) and HLA-B27(+) patients with ankylosing spondylitis (AS). METHODS: A total of 1080 patients with AS responded to a questionnaire containing 30 questions; 945 (87.5%) knew their HLA-B27 status, 10% of them being B27(-). RESULTS: The average age at disease onset was 27.7 years in B27(-) and 24.8 years in B27(+) AS (P < 0.01). The average age at diagnosis was 39.1 and 33.2 years and the average diagnosis delay 11.4 and 8.5 years, respectively. The distribution in age at disease onset was significantly wider in B27(-) (standard deviation 10.0 years) than in B27(+) AS (8.3 years). The percentages with childhood (age < 16 years) disease onset did not differ significantly (7.6% vs. 6.2%, respectively), whereas the percentage of late onset (age > 40 years) was significantly greater among B27(-) (13%) than among B27(+) (5%) patients with AS. There is a difference in average age at disease onset between male (25.7 years) and female (24.2 years) AS patients, and no difference between patients with primary AS and AS associated with psoriasis, inflammatory bowel disease, or reactive arthritis. Acute anterior uveitis was significantly less frequent in B27(-) (26%) than in B27(+) (41%) patients with AS. CONCLUSIONS. This study of a much larger number of B27(-) AS patients than have been studied previously confirms earlier reports indicating a significantly older average age at disease onset and a less frequent prevalence of acute anterior uveitis in B27(-) than in B27(+) AS. The frequency of late disease onset (after 40 years of age) is significantly higher in B27(-) AS. We provide the first report on significant differences in the distribution curves for the age at disease onset and for the age at diagnosis between B27(-)and B27(+) patients with AS. The average delay between the first spondyloarthritic symptoms and the diagnosis is significantly longer in B27(-) than in B27(+) AS. The frequency of juvenile disease onset (before age 16 years) is nearly the same, irrespective of the B27 status.  相似文献   
997.
998.
Hepatic autonomic nerves regulate postprandial hepatic glucose uptake, but the signaling pathways remain unknown. We tested the hypothesis that serotonin (5-hydroxytryptamine [5-HT]) exerts stimulatory and inhibitory effects on hepatic glucose disposal. Ligands of diverse 5-HT receptors were used to identify signaling pathway(s) regulating glucose metabolism in hepatocytes. 5-HT had stimulatory and inhibitory effects on glycogen synthesis in hepatocytes mediated by 5-HT1/2A and 5-HT2B receptors, respectively. Agonists of 5-HT1/2A receptors lowered blood glucose and increased hepatic glycogen after oral glucose loading and also stimulated glycogen synthesis in freshly isolated hepatocytes with greater efficacy than 5-HT. This effect was blocked by olanzapine, an antagonist of 5-HT1/2A receptors. It was mediated by activation of phosphorylase phosphatase, inactivation of glycogen phosphorylase, and activation of glycogen synthase. Unlike insulin action, it was not associated with stimulation of glycolysis and was counteracted by cyclin-dependent kinase (cdk) inhibitors. A role for cdk5 was supported by adaptive changes in the coactivator protein p35 and by elevated glycogen synthesis during overexpression of p35/cdk5. These results support a novel mechanism for serotonin stimulation of hepatic glycogenesis involving cdk5. The opposing effects of serotonin, mediated by distinct 5-HT receptors, could explain why drugs targeting serotonin function can cause either diabetes or hypoglycemia in humans.  相似文献   
999.
Abstract Calcific uremic arteriolopathy (CUA) is a rare but life-threatening disorder of arteriolar calcification. It frequently leads to severe ischemia, intense pain, and tissue necrosis with non-healing skin ulcerations. CUA usually occurs in patients with chronic kidney disease (CKD), especially those on dialysis, and its occurrence is rare in kidney transplant recipients. The treatment of this disorder is not clearly defined, and no randomized prospective trials are available. Treatment has focused on optimizing dialysis treatment, control of bone mineral parameters, wound care, experimental anticalcification therapies-using bisphosphonates, cinacalcet, parathyroidectomy, and hyperbaric oxygen. Such treatments are based on the pathophysiological considerations and evidences from case reports or series. Recently, several cases have reported about the emerging benefits of intravenous sodium thiosulfate (STS) in the treatment of CUA. STS has resulted in rapid pain relief, wound healing, and prevention of death. We report a case of CUA in a 63-year-old Caucasian man with a functioning renal allograft. In this patient, intravenous STS was administered for 8 months, which was the principal therapy, which resulted in complete resolution of the CUA and skin healing.  相似文献   
1000.
Fridell JA, Johnson MS, Goggins WC, Beduschi T, Mujtaba MA, Goble ML, Powelson JA. Vascular catastrophes following pancreas transplantation: an evolution in strategy at a single center.
Clin Transplant 2012: 26: 164–172.
© 2011 John Wiley & Sons A/S. Abstract: Introduction: Complications of pancreas transplantation involving the arterial anastomosis are potentially life threatening. In this report, we review our experience with such vascular catastrophes. Methods: Pancreas transplants performed between January 2003 and December 2009 were reviewed. All cases of pseudoaneurysm (PA) or arterioenteric fistula (AEF) were included. Results: Of 346 pancreas transplants, 10 vascular catastrophes in nine recipients were identified. There were five PAs, one involving the pancreas allograft, one involving the donor iliac artery Y‐graft stump following allograft pancreatectomy, two involving the kidney allograft, and one involving the bifurcation of the Y‐graft. The latter was treated with coil embolization, but subsequently developed into an AEF. There were five AEFs including the recipient mentioned above. Four had a failed allograft and three had discontinued immunosuppression. The final case had a clamp injury to the proximal common iliac artery that fistulized to the donor duodenum. The management, course and outcome of all nine recipients are described in detail. Conclusion: Vascular catastrophes such as PA and AEF are potentially life‐threatening complications of pancreas transplantation. Immediate treatment at the time of bleeding is essential and covered stenting of the involved artery may provide immediate vascular control in these situations.  相似文献   
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