Network Tomography for Understanding Phenotypic Presentations in Aortic Stenosis

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.

Epidemiologic attributes of invasive non-typhoidal Salmonella infections in Michigan, 1995--2001.

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.     

Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis

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.     

A novel mechanism for regulating hepatic glycogen synthesis involving serotonin and cyclin-dependent kinase-5

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.     

Successful treatment of calcific uremic arteriolopathy with sodium thiosulfate in a renal transplant recipient

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.     

Vascular catastrophes following pancreas transplantation: an evolution in strategy at a single center

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.     

Detrusor myectomy: Long‐term functional outcomes

Objectives: Detrusor myectomy is a recognized method of bladder augmentation for treating refractory detrusor overactivity. Herein we report the long‐term outcomes of this procedure at the University Hospital of Wales in Cardiff, UK. Methods: Detrusor myectomy was carried out in 33 patients (7 males, 26 females) with urodynamically proven detrusor overactivity between 1995 and 2002. The mean patient age was 33 years (range 5–62). A total of 18 patients had idiopathic detrusor overactivity, whereas 15 had neurogenic detrusor overactivity. Results: A total of 24 patients had a detrusor myectomy alone, whereas eight patients had a detrusor myectomy with implantation of artificial urinary sphincter. One patient had detrusor myectomy with transuretero‐ureterostomy. The mean follow up was 148 months (range 108–192). A total of 10 of the 18 patients with idiopathic detrusor overactivity (55.5%) and six of the 15 patients with neurogenic detrusor overactivity (40%) showed marked improvement in symptoms. Detrusor overactivity was completely abolished in 11 patients and significantly reduced in five. Postoperatively, mean cystometric capacity improved from 290 to 458 mL, whereas mean maximum amplitude of detrusor contraction was reduced from 44 cm/H₂O to 20 cm/H₂O. An overall success rate of 48.5% (16/33 patients) was achieved. Intermittent self catheterization was needed to achieve bladder emptying in 12 of the 16 (75%) patients. Of the remaining 17 patients who did not improve, six had CLAM enterocystoplasty carried out and two await the operation. An ileal conduit diversion and suprapubic catheter insertion was carried out in one patient each, whereas seven patients declined any further intervention. Conclusions: Detrusor myectomy offers a reasonable long‐term success rate to patients undergoing surgical treatment for refractory detrusor overactivity.     

Oral bisphosphonate use in the elderly is not associated with acute kidney injury

Intravenous bisphosphonates can cause acute kidney injury; however, this risk was not found with oral bisphosphonates in randomized clinical trials with restrictive eligibility criteria. In order to provide complementary safety data, we studied the risk of acute kidney injury in a population-based cohort of 122,727 patients aged 66 years and older discharged from hospital following a new fragility fracture and no history of bisphosphonate use in the prior year. Bisphosphonate treatment was identified within 120 days after discharge and event rates were measured from 90 days of therapy initiation. The primary outcome was hospitalization with acute kidney injury with secondary outcomes of new nephrology consultation and, in a subset of patients with laboratory values, acute kidney injury was defined as an increase in serum creatinine. We identified 18,286 bisphosphonate users and 104,441 non-users with a mean age of 81 years. Of 5772 patients with laboratory values, 40% had chronic kidney disease (eGFR <60?ml/min per 1.73?m(2)). Overall, there was no statistically significant difference in the risk of acute kidney injury among bisphosphonate users compared to non-users (adjusted odds ratio 1.03), and no significant differences in other outcomes or in subgroups of patients with baseline chronic kidney disease. Thus, in this older population-based cohort, oral bisphosphonate use was not associated with acute kidney injury.