Cancer risks of anti-hyperglycemic drugs for type 2 diabetes treatment - a clinical appraisal.

Aim: A clinical appraisal of existing scientific literature sought to assess the need for long-term prospective epidemiological studies to investigate an increased cancer risk of anti-hyperglycemic medication in type 2 diabetes.

Method: A focus statement was formulated as: "With a higher risk of cancers in patients with type 2 diabetes, all anti-hyperglycemic drugs should undergo long-term, prospective epidemiological studies for cancer risks." Field surveys were sent to practicing physicians and endocrinologists to identify the currently prevalent level of acceptance of this statement.

Novel Insights into the Direct Removal of Endotoxin by Polymyxin B Hemoperfusion.

Aim: To demonstrate the capacity of polymyxin B-direct hemoperfusion (PMX-DHP) column Toraymyxin® 20R (PMX-20R) in removing endotoxin (LPS) from perfused blood, serum and plasma.

Methods: Endotoxin-spiked bovine serum was perfused in PMX-20R as per the recommended performance testing protocol. Samples were taken at various time points to assess the amount of endotoxin removed during a 4-h session.

Once weekly glucagon-like peptide-1 receptor agonist albiglutide vs. prandial insulin added to basal insulin in patients with type 2 diabetes mellitus: Results over 52 weeks.

We have previously reported that once-weekly albiglutide was noninferior to thrice-daily lispro for glycemic lowering, with decreased weight and risk of hypoglycemia, in patients inadequately controlled on basal insulin over 26 weeks. Findings after 52 weeks reveal similar responses to albiglutide as an add-on to insulin glargine.

Design and rationale of the ODYSSEY DM-DYSLIPIDEMIA trial: lipid-lowering efficacy and safety of alirocumab in individuals with type 2 diabetes and mixed dyslipidaemia at high cardiovascular risk.

Background: Type 2 diabetes mellitus (T2DM) is often associated with mixed dyslipidaemia, where non-high-density lipoprotein cholesterol (non-HDL-C) levels may more closely align with cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). We describe the design and rationale of the ODYSSEY DM-DYSLIPIDEMIA study that assesses the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk with non-HDL-C inadequately controlled despite maximally tolerated statin therapy. For the first time, atherogenic cholesterol-lowering with a PCSK9 inhibitor will be assessed with non-HDL-C as the primary endpoint with usual care as the comparator.

Perineural Dexmedetomidine Is More Effective Than Clonidine When Added to Local Anesthetic for Supraclavicular Brachial Plexus Block: A Systematic Review and Meta-analysis.

Background: Clonidine, an α-2 agonist, has long been used as a local anesthetic adjunct with proven efficacy to prolong peripheral nerve block duration. Dexmedetomidine, a newer α-2 agonist, has a more favorable pharmacodynamic and safety profile; however, data comparing its efficacy as an adjunct to that of clonidine are inconsistent. We sought to compare the clinical efficacy of these 2 α-2 agonists by examining their effects on peripheral nerve block characteristics for upper extremity surgery.

Clinical Outcomes Associated with Achromobacter Species Infection in Patients with Cystic Fibrosis.

Rationale: Achromobacter species are increasingly identified in individuals with cystic fibrosis (CF), but the clinical outcomes in these patients remain poorly understood.

Objectives: We aimed to determine the association of Achromobacter infection on clinical outcomes in pediatric and adult patients with CF.

Methods: A cohort study of pediatric and adult patients with CF was conducted from 1997 to 2014 in Toronto, Ontario, Canada.

Efficacy and safety of alirocumab in insulin-treated patients with type 1 or type 2 diabetes and high cardiovascular risk: Rationale and design of the ODYSSEY DM-INSULIN trial.

Aims: The coadministration of alirocumab, a PCSK9 inhibitor for treatment of hypercholesterolaemia, and insulin in diabetes mellitus (DM) requires further study. Described here is the rationale behind a phase-IIIb study designed to characterize the efficacy and safety of alirocumab in insulin-treated patients with type 1 (T1) or type 2 (T2) DM with hypercholesterolaemia and high cardiovascular (CV) risk.

Methods: ODYSSEY DM-INSULIN (NCT02585778) is a randomized, double-blind, placebo-controlled, multicentre study that planned to enrol around 400 T2 and up to 100 T1 insulin-treated DM patients.

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.

Diabetes for Cardiologists: Practical Issues in Diagnosis and Management.

Diabetes mellitus (DM), a chronic metabolic disease characterized by hyperglycemia, is a profound cardiovascular (CV) risk factor. It compounds the effects of all other risk factors, leads to premature micro- and macrovascular disease, facilitates development of heart failure, worsens the clinical course of all CV diseases, and shortens life expectancy. Established DM, unrecognized DM, and dysglycemia that may progress to DM are all commonly present at the time of presentation of overt CV disease.

Pectoralis and Serratus Fascial Plane Blocks Each Provide Early Analgesic Benefits Following Ambulatory Breast Cancer Surgery: A Retrospective Propensity-Matched Cohort Study.

Background: Pectoralis and serratus blocks have been described recently for use in breast surgery, but evidence supporting their analgesic benefits is limited. This cohort study evaluates the benefits of adding a pectoralis or serratus block to conventional opioid-based analgesia (control) in patients who underwent ambulatory breast cancer surgery at Women's College Hospital between July 2013 and May 2015. We tested the joint hypothesis that adding a pectoralis or serratus block reduced postoperative in-hospital (predischarge) opioid consumption and nausea and vomiting (PONV).

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol.

Background: In a previous study, a single injection of inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained reductions in low-density lipoprotein (LDL) cholesterol levels over the course of 84 days in healthy volunteers.

Methods: We conducted a phase 2, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial of inclisiran administered as a subcutaneous injection in patients at high risk for cardiovascular disease who had elevated LDL cholesterol levels. Patients were randomly assigned to receive a single dose of placebo or 200, 300, or 500 mg of inclisiran or two doses (at days 1 and 90) of placebo or 100, 200, or 300 mg of inclisiran.

Pilot trial of tobramycin inhalation powder in cystic fibrosis patients with chronic Burkholderia cepacia complex infection.

There is no effective chronic suppressive therapy Burkholderia cepacia complex infection in cystic fibrosis (CF) patients. This was a pilot, open-label clinical trial of tobramycin inhalation powder (TIP) delivered via Podhaler twice daily for 28days in adults and children with CF and chronic B. cepacia complex infection in Toronto, Canada.

Oxidation and degradation of polypropylene transvaginal mesh.

Polypropylene (PP) transvaginal mesh (TVM) repair for stress urinary incontinence (SUI) has shown promising short-term objective cure rates. However, life-altering complications have been associated with the placement of PP mesh for SUI repair. PP degradation as a result of the foreign body reaction (FBR) has been proposed as a contributing factor to mesh complications.

Aldosterone Does Not Predict Cardiovascular Events Following Acute Coronary Syndrome in Patients Initially Without Heart Failure.

Background: Aldosterone may have adverse effects in the myocardium and vasculature. Treatment with an aldosterone antagonist reduces cardiovascular risk in patients with acute myocardial infarction complicated by heart failure (HF) and left ventricular systolic dysfunction. However, most patients with acute coronary syndrome do not have advanced HF.

The Search for a Peripheral Biopsy Indicator of α-Synuclein Pathology for Parkinson Disease.

The neuropathological hallmark of Parkinson disease (PD) is abnormal accumulation of α-synuclein (α-syn). Demonstrating pathological α-syn in live patients would be useful for identifying and monitoring PD patients. To date, however, imaging and biofluid approaches have not permitted premortem assessment of pathological α-syn.

Association of Fenofibrate Therapy With Long-term Cardiovascular Risk in Statin-Treated Patients With Type 2 Diabetes.

Importance: Patients with type 2 diabetes are at high risk of cardiovascular disease (CVD) in part owing to hypertriglyceridemia and low high-density lipoprotein cholesterol. It is unknown whether adding triglyceride-lowering treatment to statin reduces this risk.

Objective: To determine whether fenofibrate reduces CVD risk in statin-treated patients with type 2 diabetes.

Associations between ventilator settings during extracorporeal membrane oxygenation for refractory hypoxemia and outcome in patients with acute respiratory distress syndrome: a pooled individual patient data analysis : Mechanical ventilation during ECMO.

Purpose: Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for patients with acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate associations between ventilatory settings during ECMO for refractory hypoxemia and outcome in ARDS patients.

Methods: In this individual patient data meta-analysis of observational studies in adult ARDS patients receiving ECMO for refractory hypoxemia, a time-dependent frailty model was used to determine which ventilator settings in the first 3 days of ECMO had an independent association with in-hospital mortality.

A Multicenter Randomized Trial Assessing the Efficacy of Helium/Oxygen in Severe Exacerbations of Chronic Obstructive Pulmonary Disease.

Rationale: During noninvasive ventilation (NIV) for chronic obstructive pulmonary disease (COPD) exacerbations, helium/oxygen (heliox) reduces the work of breathing and hypercapnia more than air/O, but its impact on clinical outcomes remains unknown.

Objectives: To determine whether continuous administration of heliox for 72 hours, during and in-between NIV sessions, was superior to air/O in reducing NIV failure (25-15%) in severe hypercapnic COPD exacerbations.

Methods: This was a prospective, randomized, open-label trial in 16 intensive care units (ICUs) and 6 countries.

Hyperpolarized 13C Metabolic MRI of the Human Heart: Initial Experience.

Rationale: Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used in longitudinal studies would be useful for understanding therapeutic approaches that target metabolism.

Objective: To demonstrate the first hyperpolarized C metabolic magnetic resonance imaging of the human heart.

Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.

Background: Regulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown.

Methods: We randomly assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly semaglutide (0.

Psychological and Physiological Markers of Stress in Concussed Athletes Across Recovery Milestones.

Background: Sport-related concussions are associated with a range of physical, cognitive, and behavioral disturbances that are highly variable across individuals. Much remains unknown about the effects of sport concussion, and changes in markers of psychological and physiological stress over the recovery timeline.

Objective: To examine psychological (mood, stress, sleep quality, and symptoms) and physiological (heart rate variability and salivary cortisol) measures in concussed athletes over clinical recovery milestones.