Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor 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. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Necrotizing acute pancreatitis current status - Emerging new strategies in surgical management

Despite that pancreatic necrosis complicates only 15 % of cases of acute pancreatitis (AP), it is associated with high morbidity and considerable mortality. In an attempt to improve prognosis, many surgical strategies have been described during the last few decades. Currently, necrosectomy remains the cornerstone in the surgical treatment of infected pancreatic necrosis and in selected cases of sterile necrotizing pancreatitis. Following necrosectomy, continuous closed lavage is recommended by many authors, while closed abdominal packing /drainage and repeated planned necrosectomies- commonly using the zipper technique-are also acceptable alternative strategies. Open abdomen (laparostomy) is rarely indicated in carefully selected cases (typically in abdominal compartment syndrome associated with necrotizing AP). During the last decade, minimally invasive techniques (including percutaneous drainage, retroperitoneal endoscopic approach, transgastric endoscopic approach etc) have been extensively studied by some groups not only in the management of pancreatic abscesses and / or pseudocysts, but also as primary methods of treatment of necrotizing AP. Results have been impressive, but experience currently is limited to only a few centers around the world. © 2012 Bentham Science Publishers

The effect of exercise-induced hypoxemia on blood redox status in well-trained rowers

Exercise-induced arterial hypoxemia (EIAH), characterized by decline in arterial oxyhemoglobin saturation (SaO2), is a common phenomenon in endurance athletes. Acute intensive exercise is associated with the generation of reactive species that may result in redox status disturbances and oxidation of cell macromolecules. The purpose of the present study was to investigate whether EIAH augments oxidative stress as determined in blood plasma and erythrocytes in well-trained male rowers after a 2,000-m rowing ergometer race. Initially, athletes were assigned into either the normoxemic (n = 9, SaO 2 [92%, V O2max: 62.0 ± 1.9 ml kg-1 min-1) or hypoxemic (n = 12, SaO2\92%, V O2max: 60.5 ± 2.2 ml kg-1 min-1, mean ± SEM) group, following an incremental V O2max test on a wind resistance braked rowing ergometer. On aseparate day the rowers performed a 2,000-m all-out effort on the same rowing ergometer. Following an overnight fast, blood samples were drawn from an antecubital vein before and immediately after the termination of the 2,000-mall-out effort and analyzed for selective oxidative stress markers. In both the normoxemic (SaO2: 94.1 ± 0.9%) and hypoxemic (SaO2: 88.6 ± 2.4%) rowers similar and significant exercise increase in serum thiobarbituric acidreactive substances, protein carbonyls, catalase and total antioxidant capacity concentration were observed post-2,000 m all-out effort. Exercise significantly increased the oxidized glutathione concentration and decreased the ratio of reduced (GSH)-to-oxidized (GSSG) glutathione in the normoxemic group only, whereas the reduced form of glutathione remained unaffected in either groups. The increased oxidation of GSH to GSSG in erythrocytes of normoxemic individuals suggest that erythrocyte redox status may be affected by the oxygen saturation degree of hemoglobin. Our findings indicate that exercise-induced hypoxemia did not further affect the increased blood oxidative damage of lipids and proteins observed after a2,000-m rowing ergometer race in highly-trained male rowers. The present data do not support any potential link between exercise-induced hypoxemia, oxidative stress increase and exercise performance. © 2011 Springer-Verlag

Retained surgical sponges: What the practicing clinician should know

Retained surgical sponges (RSS) are an avoidable complication following surgical operations. RSS can elicit either an early exudative-type reaction or a late aseptic fibrous tissue reaction. They may remain asymptomatic for long time; when present, symptomatology varies substantially and includes septic complications (abscess formation, peritonitis) or fibrous reaction resulting in adhesion formation or fistulation into adjacent hollow organs or externally. Plain radiograph may be useful for the diagnosis; however, computed tomography is the method of choice to establish correct diagnosis preoperatively. Removal of RSS is always indicated to prevent further complications. This is usually accomplished by open surgery; rarely, endoscopic or laparoscopic removal may be successful. Prevention is of key importance to avoid not only morbidity and even mortality but also medicolegal consequences. Preventive measures include careful counting, use of sponges marked with a radiopaque marker, avoidance of use of small sponges during abdominal procedures, careful examination of the abdomen by the operating surgeon before closure, radiograph in the operating theater (either routinely or selectively), and recently, usage of barcode and radiofrequency identification technology. © Springer-Verlag 2010

The effect of exercise-induced hypoxemia on blood redox status in well-trained rowers

Exercise-induced arterial hypoxemia (EIAH), characterized by decline in arterial oxyhemoglobin saturation (SaO(2)), is a common phenomenon in endurance athletes. Acute intensive exercise is associated with the generation of reactive species that may result in redox status disturbances and oxidation of cell macromolecules. The purpose of the present study was to investigate whether EIAH augments oxidative stress as determined in blood plasma and erythrocytes in well-trained male rowers after a 2,000-m rowing ergometer race. Initially, athletes were assigned into either the normoxemic ( = 9, SaO(2) > 92%, : 62.0 +/- A 1.9 ml kg(-1) min(-1)) or hypoxemic ( = 12, SaO(2) < 92%, : 60.5 +/- A 2.2 ml kg(-1) min(-1), mean +/- A SEM) group, following an incremental test on a wind resistance braked rowing ergometer. On a separate day the rowers performed a 2,000-m all-out effort on the same rowing ergometer. Following an overnight fast, blood samples were drawn from an antecubital vein before and immediately after the termination of the 2,000-m all-out effort and analyzed for selective oxidative stress markers. In both the normoxemic (SaO(2): 94.1 +/- A 0.9%) and hypoxemic (SaO(2): 88.6 +/- A 2.4%) rowers similar and significant exercise increase in serum thiobarbituric acid-reactive substances, protein carbonyls, catalase and total antioxidant capacity concentration were observed post-2,000 m all-out effort. Exercise significantly increased the oxidized glutathione concentration and decreased the ratio of reduced (GSH)-to-oxidized (GSSG) glutathione in the normoxemic group only, whereas the reduced form of glutathione remained unaffected in either groups. The increased oxidation of GSH to GSSG in erythrocytes of normoxemic individuals suggest that erythrocyte redox status may be affected by the oxygen saturation degree of hemoglobin. Our findings indicate that exercise-induced hypoxemia did not further affect the increased blood oxidative damage of lipids and proteins observed after a 2,000-m rowing ergometer race in highly-trained male rowers. The present data do not support any potential link between exercise-induced hypoxemia, oxidative stress increase and exercise performance

The Real-Life Effectiveness and Care Patterns of Type 2 Diabetes Management in Greece

Aim To investigate the prevalence of hypoglycaemia during sulfonylurea (SU) treatment of type 2 diabetes mellitus (T2DM) in Greece and its influence on glycaemic control, treatment adherence and quality of life (QoL). Patients and methods This was a retrospective cross-sectional study. We included 383 T2DM patients ≥30 years old on treatment with SU in monotherapy or in combination with metformin for at least 6 months. Patients were requested to fill in retrospective questionnaires on hypoglycaemia experience, adherence, weight gain and lifestyle/behavioural factors along with QoL (EQ-5D-3L), treatment satisfaction (TSQM), and fear of hypoglycaemia (HFS-II Worry scale). Results HbA 1c &amp;lt;7% was found in 161 (42.0%) patients. In total, 165 (43.1%) patients reported hypoglycaemic symptoms during the previous 6 months: 41.6% (67/161) of those with HbA 1c &amp;lt;7% and 44.1% (98/222) of those with HbA 1c ≥7%. Glycaemic control was achieved by 43.1% (94/218) of patients without hypoglycaemia and 50.0% (41/82), 36.8% (25/68) and 6.7% (1/15) of patients with mild, moderate or severe hypoglycaemia, respectively (p=0.013). In multivariate analysis, both occurrence (none vs. mild/moderate/severe) and severity (none vs. mild vs. moderate vs. severe) of hypoglycaemia were significantly associated with impaired global treatment satisfaction (p=0.002 and p&amp;lt;0.0001 respectively) and HFS-II Worry scale scores (both p&amp;lt;0.0001), while lower QoL (EQ-5D (UK) Index) was related to hypoglycaemia severity (p=0.024) only. Finally, treatment adherence was associated with increased (none/mild vs. moderate/severe) hypoglycaemia severity in univariate analysis (p=0.019). Conclusion A high prevalence of patient treated with SU reported hypoglycaemia in Greek healthcare settings with negative effects on treatment satisfaction, patient worry and adherence. Severity of hypoglycaemic symptoms was associated with reduced glycaemic control