Coagulation, Fibrinolysis, and Platelet Activation Following Open Surgical or Percutaneous Angioplasty Revascularization for Symptomatic Lower Limb Chronic Ischemia.

INTRODUCTION: Critical limb ischemia (CLI) is associated with a prothrombotic diathesis that involves a complex balance between the coagulation and fibrinolytic systems. Knowledge of this is essential when considering revascularization procedures but is often overlooked. The aim of this review is to summarize the available literature and provide an overview of the effects of lower limb angioplasty and open surgical revascularization on coagulation, fibrinolysis, and platelet activation. METHODS: A MEDLINE and EMBASE search was conducted between 1973 and 2014 for articles relating to the effects of revascularization for patients with CLI on the fibrinolytic and coagulation pathways. Studies with a small cohort of patients (<5) were rejected. RESULTS: Many of the studies included in this analysis had small cohorts. Multiple markers were assessed across the published literature including von Willebrand factor, tissue factor, prothrombin fragments 1 and 2, platelets, soluble platelet selectin, plasminogen activator inhibitor 1, tissue plasminogen activator, and thrombin-antithrombin complex. Percutaneous intervention causes an exaggerated prothrombotic and a disturbed fibrinolytic effect. Surgery seems to cause a similar prothrombotic derangement with reduced fibrinolysis and platelet hyperactivity, but this appears to be maintained for a considerable amount of time postoperatively. CONCLUSION: There is a sparse amount published on the effects of the coagulation and fibrinolytic systems in patients undergoing intervention for CLI. Much of these studies are small, historical, and completely heterogeneous, making it difficult to draw meaningful conclusions. The literature does identify a prothrombotic state in patients with CLI, which appears to be exacerbated by any form of intervention and prolonged in those having surgery. Understanding this may allow us to tailor the intervention offered to patients and prevent limb loss.

Empagliflozin as add-on to metformin in people with Type 2 diabetes.

AIMS: To investigate the long-term efficacy and safety of empagliflozin as add-on to metformin in people with Type 2 diabetes. METHODS: Of 637 participants treated with empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily for 24 weeks, 463 (72.7%) were treated in a double-blind extension trial for ≥ 52 weeks. Prespecified exploratory endpoints included changes from baseline in HbA1c , weight and blood pressure at week 76. RESULTS: Compared with placebo, adjusted mean changes from baseline in HbA1c (overall baseline mean ± sd 63 ± 9 mmol/mol [7.9 ± 0.9%]) were -7 mmol/mol [(-0.6%) 95% CI -8, -5 mmol/mol (-0.8, -0.5%); P < 0.001] and -8 mmol/mol [(-0.7%) 95% CI -10, -6 mmol/mol (-0.9, -0.6%); P < 0.001], for empagliflozin 10 mg and 25 mg, respectively. Compared with placebo, adjusted mean changes from baseline in weight were -1.9 kg (95% CI -2.5, -1.3; P < 0.001) and -2.2 kg (95% CI -2.8, -1.6; P < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Empagliflozin led to sustained reductions in systolic blood pressure vs. placebo. Adverse events were reported in 77.7, 80.2 and 72.0% of participants on placebo, empagliflozin 10 mg and empagliflozin 25 mg, respectively. Confirmed hypoglycaemic adverse events (glucose ≤ 3.9 mmol/l and/or event requiring assistance) were reported in 3.4, 4.1 and 4.2% of participants in these groups, respectively. CONCLUSIONS: In people with Type 2 diabetes, empagliflozin 10 mg and 25 mg given as add-on to metformin for 76 weeks were well tolerated and led to sustained reductions in HbA1c , weight and systolic blood pressure.

Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal-bolus treatment with mealtime insulin aspart in Type 1 diabetes (BEGIN(®) Basal-Bolus Type 1): 2-year results of a randomized clinical trial.

AIMS: The goal of this study was to compare the long-term safety and efficacy of the basal insulin analogue, insulin degludec with insulin glargine (both with insulin aspart) in Type 1 diabetes, over a 2-year time period. METHODS: This open-label trial comprised a 1-year main trial and a 1-year extension. Patients were randomized to once-daily insulin degludec or insulin glargine and titrated to pre-breakfast plasma glucose values of 3.9-4.9 mmol/l. RESULTS: The rate of nocturnal confirmed hypoglycaemia was 25% lower with insulin degludec than with insulin glargine (P = 0.02). Rates of confirmed hypoglycaemia, severe hypoglycaemia and adverse events, and reductions in glycated haemoglobin and fasting plasma glucose were similar between groups. Despite achieving similar glycaemic control, insulin degludec-treated patients used 12% less basal and 9% less total daily insulin than did insulin glargine-treated patients (P < 0.01). CONCLUSIONS: Long-term basal therapy using insulin degludec in Type 1 diabetes required lower doses and was associated with a 25% lower risk for nocturnal hypoglycaemia than insulin glargine.

Management of proximal deep vein thrombosis.

Iliofemoral DVT constitutes approximately 20-25% of lower limb DVT and represents a specific subgroup of patients at highest risk for post-thrombotic syndrome (PTS). Anticoagulation alone has no significant thrombolytic activity and has not impact on PTS prevention. Early thrombus removal has reduced PTS in uncontrolled reports and reviews but major trials are awaited. The optimal timing for treatment appear to be thrombus <2 weeks old and, methods for thrombus removal include direct open or suction thrombectomy, catheter directed thrombolysis (CDT), with or without percutaneous mechanical thrombectomy (PMT) devices. Three principle types of PMT device are in use (rotational, rheolytic and ultrasound enhanced devices) and are combined with CDT in pharmocomechanical thrombolysis (PhMT) to enhance early thrombus removal. These devices have individual device specific attributes and side effects that are additional to the bleeding complications of thrombolysis. A number of additional interventions may be utilised to the improve results of CDT and PhMT. IVC filter deployment to reduce periprocedural PE, is supported by little evidence unless an indication for its use already exists. However, balloon venoplasty and vein stents undoubtedly vein patency after treatment. Early thrombus removal comes with additional upfront costs derived from devices, imaging and critical care bed usage. However, significant potential savings from reduction in PTS and rethrombosis rates may reduce overall societal costs. This review focuses on iliofemoral thrombosis, however, the less commonly encountered but clinically important subclavian vein thrombosis is also discussed.

Impact of antenatal corticosteroid therapy in very low birth weight infants on chronic lung disease and other morbidities of prematurity.

OBJECTIVE: To assess the effect of antenatal corticosteroids on very low birth weight (VLBW) infants through 36 weeks' postconceptional age. STUDY DESIGN: Data were collected prospectively on all VLBW (< or = 1500 gm) infants (n = 670) admitted to a single newborn intensive care unit from 1991 to 1996. Mortality rate and the frequency of medical morbidities attributable to prematurity were compared between VLBW infants who received antenatal corticosteroid therapy and those who did not. RESULTS: Antenatal steroid therapy was associated with a significantly lower rate of mortality (p = 0.02) and of mortality due to respiratory causes (p = 0.01). Although the frequency of chronic lung disease (oxygen requirement at 36 weeks' postconceptional age) was not significantly different between the groups (p = 0.48), the frequency of infants surviving without chronic lung disease was significantly greater in the steroid-exposed group (p = 0.02). There were no significant differences between the groups in the frequency of sepsis, necrotizing enterocolitis, length of hospital stay, or retinopathy of prematurity requiring surgery. CONCLUSION: In our study, antenatal corticosteroid therapy was associated with a beneficial effect on mortality and respiratory morbidity for VLBW infants and was not associated with any known increased risks.

Positive relationship of cortisol concentrations and oral nutrition to epidermal growth factor concentrations in preterm infants.

We have suggested from previous studies that increases in early neonatal epidermal growth factor (EGF) concentrations were dependent on adequate glucocorticoid hormone concentrations. In order to examine this relationship, matched values for cortisol and EGF in 193 preterm infants on days 2 and 6 were compared. Gestational age had a significant positive effect on EGF concentrations for those infants receiving oral nutrition and there was also a positive relationship between nutrition and cortisol concentration. Cortisol was then used as an independent factor and was significantly (p = 0. 01) related to EGF values such that as cortisol concentrations increased, EGF values also increased. In summary, we suggest that these results are consistent with a role for cortisol in the control of the EGF pattern in the newborn period.