Citations

Background Adenosine‐assisted transthoracic Doppler‐derived coronary flow reserve ( TDE ‐ CFR ) reflects coronary vascular function. The prognostic and incremental value of left anterior descending coronary artery TDE ‐ CFR above myocardial perfusion scintigraphy in patients with suspected myocardial ischemia has not yet been studied. Methods and Results Three hundred seventy‐one patients (mean age, 62.3±8.7 years; 46.8% males) referred to myocardial perfusion scintigraphy attributed to suspected myocardial ischemia were included in the study. The TDE ‐ CFR result was blinded to the referring physician. Patients were followed up regarding major cardiovascular events, defined as cardiovascular death, myocardial infarction, or acute revascularization during a median follow‐up time of 4.5 years. A TDE ‐ CFR value of ≤2.0 was considered reduced. Major cardiovascular events occurred during follow‐up in 60 patients (16.2%). A reduced TDE ‐ CFR was detected in 76 patients (20.5%). Patients with reduced TDE ‐ CFR had an event rate of 36.8% compared to 10.8% in patients with normal TDE ‐ CFR (unadjusted hazard ratio, 4.63; 95% CI, 2.78–7.69; P <0.001). In a multivariate model, TDE ‐ CFR remained a significant independent predictor of major cardiovascular events. The major cardiovascular events rate was 7.5% in patients without myocardial perfusion scintigraphy‐detected myocardial ischemia and normal TDE ‐ CFR (n=200), 24.2% in patients without ischemia but with reduced TDE ‐ CFR (n=33), and 46.5% in patients with both myocardial perfusion scintigraphy–detected myocardial ischemia and a reduced TDE ‐ CFR (n=43; P <0.001). Conclusions Coronary microvascular dysfunction, as determined by TDE ‐ CFR, is a strong independent predictor of cardiovascular events and adds incremental prognostic value compared with myocardial perfusion scintigraphy. The current study supports routine assessment of CFR in patients with suspected ischemic heart disease.

Summary There are few data regarding postoperative hyperglycaemia in non‐diabetic compared with diabetic patients following postoperative nausea and vomiting prophylaxis with dexamethasone. Eighty‐five non‐diabetic patients and patients with type‐2 diabetes were randomly allocated to receive intravenous dexamethasone (8 mg) or ondansetron (4 mg). Blood glucose levels were measured at baseline and then 2, 4 and 24 h following induction of anaesthesia. In non‐diabetic patients, the mean ( SD ) maximum blood glucose was higher in those who received dexamethasone compared with ondansetron (9.1 (2.2) mmol.l −1 vs. 7.8 (1.4) mmol.l −1 , p = 0.04). In diabetic patients, the mean ( SD ) maximum blood glucose was also higher in those who received dexamethasone compared with ondansetron (14.0 (2.5) mmol.l −1 vs. 10.7 (2.4) mmol.l −1 , p < 0.01). Multivariate analysis demonstrated that dexamethasone administration was a significant predictor of maximum postoperative blood glucose increase (p < 0.01) after adjusting for potential confounders. There was no interaction between baseline blood glucose level, or presence or absence of diabetes, and dexamethasone administration. We conclude that dexamethasone increases postoperative blood glucose levels in both non‐diabetics and diabetics.

A cancer-promoting histone protein Mutations in the chromatin protein histone H3 are found in a number of pediatric cancers. The lysine-36–to–methionine (K36M) “oncohistone” mutation is seen in almost all chondroblastomas. Fang et al. show that the K36M mutant histones inhibit the normal methylation of this same residue in wild-type H3 histones. They do so by interfering with the enzymes that normally methylate this residue. The altered chromatin methylation patterns alter the expression of known cancer-related genes and impart cancer-related characteristics to the chondrocyte cells. Science , this issue p. 1344

Background Probe‐based confocal laser endomicroscopy (pCLE) provides microscopic imaging during an endoscopic procedure. Its introduction as a standard modality in gastroenterology has brought significant progress in management strategies, affecting many aspects of clinical care and requiring standardisation of practice and training. Objective This study aimed to provide guidance on the standardisation of its practice and training in Barrett's oesophagus, biliary strictures, colorectal lesions and inflammatory bowel diseases. Methods Initial statements were developed by five group leaders, based on the available clinical evidence. These statements were then voted and edited by the 26 participants, using a modified Delphi approach. After two rounds of votes, statements were validated if the threshold of agreement was higher than 75%. Results Twenty‐six experts participated and, among a total of 77 statements, 61 were adopted (79%) and 16 were rejected (21%). The adoption of each statement was justified by the grade of evidence. Conclusion pCLE should be used to enhance the diagnostic arsenal in the evaluation of these indications, by providing microscopic information which improves the diagnostic performance of the physician. In order actually to implement this technology in the clinical routine, and to ensure good practice, standardised initial and continuing institutional training programmes should be established.