Subsyndromal delirium after cardiac surgery.

OBJECTIVES: To evaluate the incidence of subsyndromal delirium (SSD) after cardiac surgery and its impact on clinical outcome. DESIGN: In this prospective study, 506 patients were screened for SSD and clinical delirium (CD) using the Intensive Care Delirium Screening Checklist. RESULTS: 150 (34%) patients were classified as having SSD and 54 (12%) patients as having CD. 2% of SSD patients developed CD. Patients' age, EuroSCORE, postoperative the Acute Physiology and Chronic Health Evaluation II, the incidences of emergency operations, and the number of aortic surgery increased from non-delirious (ND) to SSD. Intensive care unit (ICU) and hospital stays were longer in CD compared with SSD patients. ND patients did not differ from SSD patients regarding duration of ventilation, ICU stay, or hospital stay. The rate of home discharge decreased from ND over SSD to CD patients. Mortality in SSD patients did not differ from ND or CD patients. CONCLUSION: SSD showed a prevalence of 34% in patients after cardiac surgery. SSD occurred independent of CD for the majority of patients. Except for a lower rate of home discharge, the clinical outcome did not differ from that of ND patients. According to our data, SSD does not represent a preliminary or resolving stage of delirium.

CD73-dependent generation of adenosine and endothelial Adora2b signaling attenuate diabetic nephropathy.

Nucleotide phosphohydrolysis by the ecto-5'-nucleotidase (CD73) is the main source for extracellular generation of adenosine. Extracellular adenosine subsequently signals through four distinct adenosine A receptors (Adora1, Adora2a, Adora2b, or Adora3). Here, we hypothesized a functional role for CD73-dependent generation and concomitant signaling of extracellular adenosine during diabetic nephropathy. CD73 transcript and protein levels were elevated in the kidneys of diabetic mice. Genetic deletion of CD73 was associated with more severe diabetic nephropathy, whereas treatment with soluble nucleotidase was therapeutic. Transcript levels of renal adenosine receptors showed a selective induction of Adora2b during diabetic nephropathy. In a transgenic reporter mouse, Adora2b expression localized to the vasculature and increased after treatment with streptozotocin. Adora2b(-/-) mice experienced more severe diabetic nephropathy, and studies in mice with tissue-specific deletion of Adora2b in tubular epithelia or vascular endothelia implicated endothelial Adora2b signaling in protection from diabetic nephropathy. Finally, treatment with a selective Adora2b agonist (BAY 60-6583) conveyed potent protection from diabetes-associated kidney disease. Taken together, these findings implicate CD73-dependent production of extracellular adenosine and endothelial Adora2b signaling in kidney protection during diabetic nephropathy.

Histological analysis after peripheral nerve puncture with pencil-point or Tuohy needletip.

BACKGROUND: Continuous peripheral nerve blocks typically are performed with a "through-the-needle technique" and require needles with an inner diameter allowing catheter placement. In case of direct needle-nerve contact, the pencil-point needletip is currently considered less traumatic than are other needle configurations. In this study we determined whether nerve puncture with pencil-point needles is associated with fewer nerve injuries in comparison with Tuohy needles. METHODS: In 6 anesthetized pigs the brachial plexus were exposed bilaterally. Up to 8 nerves underwent nerve puncture with a pencil-point or a Tuohy needle. After 48 hours, the nerves were resected during anesthesia. The specimens were processed for visual examination and the detection of inflammatory cells, myelin damage, and intraneural hematoma. The grade of nerve injury was assessed using an objective score ranging from 0 (no injury) to 4 (severe injury). RESULTS: Fifty-eight nerves, including controls, were examined. According to the applied injury score, there was no significant difference between the pencil-point needle group [median (interquartile range) 3 (3-4)] and the Tuohy needle group [3 (3-4) P = 0.97]. The occurrence of posttraumatic regional inflammation, myelin damage, and intraneural hematoma was similarly high in both groups. CONCLUSIONS: Regardless of the needletip configuration applied for nerve puncture, pencil-point and Tuohy needletips may both lead to comparable magnitude of posttraumatic inflammation and considerable structural changes within the nerve. No significant differences were found comparing pencil-point with Tuohy tip-configured needles.

Perineural hematoma may result in nerve inflammation and myelin damage.

BACKGROUND AND OBJECTIVES: Perineural hematoma may occur during performance of peripheral nerve blocks. The aim of this study was to test the hypothesis that an iatrogenic hematoma in the immediate vicinity of a peripheral nerve may cause histologic evidence of nerve injury. METHODS: Fifty milliliters of autologous blood was injected adjacent to the right sciatic nerve in 20 anesthetized female pigs. In order to discern between blood-related volume and immune effects, 50 mL of albumin was injected at the same location in an additional 22 pigs. Either blood or albumin was injected in random order. The left sciatic nerve served as a negative control in all animals, that is, either no needle placement or needle placement without injection. After 48 hours, the nerves were resected. The grade of nerve injury was scored from 0 (no injury) to 3 (severe injury) by histologic analysis of myelin tissue and inflammatory cells. RESULTS: Eighty-two nerve specimens were examined. Injury scores were significantly (P < 0.01) higher in the blood injection (n = 20; median [interquartile range] 2 [2-2]) and albumin injection (n = 22, 1 [1-2]) conditions compared with the no needle placement (n = 22, 0 [0-1]) and "dry needle placement" (n = 20, 1 [0-1]) conditions. Widespread inflammatory changes were seen in the blood injection group, in which 15% of nerve specimens showed damage to myelin. CONCLUSIONS: Our data suggest that hematoma adjacent to nerve tissue may result in structural nerve injury and inflammatory changes.

Protective role for netrin-1 during diabetic nephropathy.

Recent studies implicate neuronal guidance molecules in the orchestration of inflammatory events. For example, previous studies demonstrate a functional role for netrin-1 in attenuating acute kidney injury. Here, we hypothesized a kidney-protective role for netrin-1 during chronic kidney disease, such as occurs during diabetic nephropathy. To study the role of netrin-1 during diabetic nephropathy, we induced diabetes in mice at the age of 8 weeks by streptocotozin (STZ) treatment. Sixteen weeks after STZ treatment, we examined the kidneys. Initial studies in wild-type mice demonstrated robust induction of renal, urinary, and plasma netrin-1 protein levels during diabetic nephropathy. Subsequent genetic studies in mice with partial netrin-1 deficiency (Ntrn1(+/-) mice) revealed a more severe degree of diabetic nephropathy, including more severe loss of kidney function (albuminuria, glomerular filtration rate, histology). We subsequently performed pharmacologic studies with recombinant netrin-1 treatment given continuously via osmotic pump. Indeed, netrin-1 treatment was associated with attenuated albuminuria and improved histologic scores for diabetic nephropathy compared to controls. Consistent with previous studies implicating purinergic signaling in netrin-1-elicited tissue protection, mice deficient in the Adora2b adenosine receptor were not protected. Taken together, these studies demonstrate a functional role for endogenous netrin-1 in attenuating diabetic kidney disease.