Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

Protected samples of lower respiratory tract secretions processed by quantitative culture techniques are recommended to diagnose nosocomial bacterial pneumonia in intubated, mechanically ventilated patients. To evaluate the accuracy of a simple and inexpensive sampling device in this setting, we compared quantitative cultures of paired single-sheathed plugged telescoping catheter (PTC) and protected specimen brush (PSB) samples in 55 patients during 78 suspected episodes of nosocomial pneumonia. PTC and PSB samples were taken in randomized order, and patients were also randomized to have PTC samples taken "blindly" or via a fiberoptic bronchoscope. Fifteen PSB and 27 PTC samples were culture positive (greater than or equal to 10(3) cfu/ml). The two sampling procedures gave similar results in 58 (74%) episodes. A major discrepancy occurred in 20 episodes, including six false negatives of PSB in episodes of proved pneumonia, four possible false positives of PSB, and 10 possible false positives of PTC (three of which rapidly evolved towards overt pneumonia). The sensitivity and specificity of PTC were 100 and 82.2%, and those of PSB were 64.7 and 93.5%, respectively. Blinded or directed PTC samples had similar concordance with PSB samples taken via bronchoscopy. We conclude that PTC is at least as accurate as PSB in the bacteriologic diagnosis of nosocomial pneumonia in intubated patients, and that its use can result in substantial cost savings, especially when fiberoptic bronchoscopy is not otherwise indicated.

Fat embolism of necrotic bone marrow could be a frequent cause of acute chest syndrome (ACS) in sickle cell syndromes (SC), as suggested by postmortem findings. To check this hypothesis in living patients, we evaluated the presence of fatty macrophages recovered by bronchoalveolar lavage (BAL) in ACS. We investigated 20 consecutive cases of ACS by BAL, and identification of alveolar cells containing fat droplets was performed using oil red O (ORO), a specific neutral fat stain. The specificity of the method was determined on control groups, including eight SC patients without acute chest syndrome and 15 non-SC patients. A cut-off of > 5% of alveolar macrophages containing fat droplets was determined from the control groups to assess the diagnosis of fat embolism. In 12 ACS episodes, BAL exhibited > 5% of fatty macrophages, ranging from 10% to 100% (median value 46.5%). In 11 cases, fat embolism was associated with proven (n = 8) or probable (n = 3) bone marrow infraction, which mostly predated ACS. Eight ACS episodes were associated with a low percentage (< or = 5%) of fatty alveolar macrophages and could be related to a cause other than fat embolism in six episodes, such as sepsis, in-situ thrombosis, or rib infarcts generating hypoventilation. This study supports the diagnostic yield of BAL for fat embolism, which can be incriminated in 60% of cases of ACS in this adult population.

B Br ro on nc ch ho oa al lv ve eo ol la ar r l la av va ag ge e d du ur ri in ng g n ne eu ut tr ro op pe en ni ic c e ep pi is so od de es s: : d di ia ag gn no os st ti ic c y yi ie el ld d a an nd d c ce el ll lu ul la ar r p pa at tt te er rn n We therefore, retrospectively, reviewed the results of 118 investigations for pneumonia in patients with malignant haematological diseases. All had bronchoalveolar lavage (BAL), and some had additional studies with protected bacteriological samples. Each BAL specimen was studied after cytocentrifugation by cytological examination for opportunistic infections, haemorrhage, virus, legionellae, and bacteriological cultures.The diagnostic yield of all endoscopic procedures (BAL, telescoping plugged catheter and protected specimen brush) was 53% in neutropenic (Group 1) and 61% in nonneutropenic (Group 2) patients. The aetiological pattern of pneumonia was nearly the same in the two groups, except for more alveolar proteinosis in Group 1 and more cytomegalovirus (CMV) in Group 2. The absolute number of alveolar cells recovered through BAL (total number, macrophages, lymphocytes and PMNs) was significantly lower in neutropenic patients.We conclude that: 1) neutropenic patients with pneumonia require the same investigative approach as non-neutropenic patients; 2) profound neutropenia may be concomitant with a decreased cellularity of alveoli, which may reflect the consequences of marrow aplasia on the pulmonary cell population and/or direct effect of chemotherapy on the lung.

Although respiratory changes induced by tobacco smoke have been extensively described, no study has focused on ciliary abnormalities associated with chronic smoking. Ciliary ultrastructure was studied in 37 adults with chronic sputum production (CSP) consisting of 13 current smokers (Group 1), 5 ex-smokers (Group 2), and 19 nonsmokers (Group 3). Five healthy nonsmokers constituted the control group (Group 4). Clinical and radiologic data and respiratory function tests were recorded. Acute respiratory infection was diagnosed by culture of tracheobronchial secretions obtained during bronchoscopy. Bronchial ciliated cells were obtained and processed for transmission electron microscopy. Within each group, the percentages of abnormal cilia were similar in patients with either chronic bronchitis or bronchiectasis and in patients with or without acute infection. The percentage of axonemal ultrastructural abnormalities (AUA) was higher in smokers (16.5% +/- 2.7%) and ex-smokers (17.5% +/- 7%) than in nonsmokers (5.2% +/- 1%) or control subjects (0.7% +/- 0.2%) (p < 0.0002). The AUA were polymorphic, characteristic of acquired ultrastructural changes. These results suggest that chronic smoking may induce an increased number of abnormal cilia which could participate in impairment of tracheobronchial clearance and which appears to be independent of the etiology of CSP.