Design and rationale of the atrial fibrillation occurring transiently with stress (AFOTS) incidence study.

BACKGROUND: Atrial fibrillation (AF) is often detected for the first time in patients hospitalized for medical illness or non-cardiovascular surgery. AF occurring transiently with stress (AFOTS) describes this manifestation of AF, which may either be the result of a non-cardiac stressor, or existing paroxysmal AF that was not previously detected. Current estimates of AFOTS incidence are imprecise: ranging from 1 to 44%, owing to the marked heterogeneity in patient populations, identification and methods used to detect AFOTS. METHODS: The prospective, two-centre epidemiological AFOTS Incidence study will enroll 250 consecutive participants without a history of AF but with at increased risk of AF (Age ≥ 65 or >50 with one risk factor for AF) admitted to intensive care units (ICUs) for medical illness or non-cardiac surgery. Upon admission, participants will wear an ECG patch monitor that will remain in place for 14 days, or until discharge from hospital. Patients' consent to participation is deferred for up to 72 h after admission. The primary endpoint is the incidence of AF lasting ≥30 s. The study is powered to detect an AF incidence of 17% ±â€¯5%. RESULTS: We conducted a vanguard feasibility study, and 55 participants have completed participation. The median duration of monitoring was seven days. AF was detected by the clinical team in 8 participants (14%; 95% Confidence Interval 7-26%). CONCLUSIONS: The AFOTS Incidence study will employ a systematic and highly sensitive protocol for detecting AFOTS in medical illness and non-cardiac surgery ICU patients. This study is feasible and will provide a reliable estimate of the true incidence of AFOTS in this population.

Cellular immune responses to platelet factor 4 and heparin complexes in patients with heparin-induced thrombocytopenia.

Essentials The immunogenesis of Heparin-induced thrombocytopenia (HIT) is not well understood. Immunization to platelet factor 4 (PF4)-heparin occurs early in life, before any heparin exposure. PF4 and PF4-heparin complexes induce the proliferation of CD14+ cells. Reduced levels of regulatory cytokines contribute to immune dysregulation in HIT. SUMMARY: Background Heparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin characterized by thrombocytopenia and thrombotic complications. HIT is caused by pathogenic antibodies that bind to complexes of platelet factor 4 (PF4) and heparin, leading to platelet activation and inducing a hypercoagulable state. Previous studies have shown immunity to PF4-heparin complexes occurs early in life, even before heparin exposure; however, the immunogenesis of HIT is not well characterized. Objectives To investigate cellular proliferation in response to PF4-heparin complexes in patients with HIT. Patients/Methods Peripheral blood mononuclear cells (PBMCs) from healthy controls (n = 30), postoperative cardiac surgery patients who had undergone cardiopulmonary bypass (CPB) (n = 17) and patients with confirmed HIT (n = 41) were cultured with PF4 and PF4-heparin complexes. Cellular proliferation was assessed by [3 H]thymidine uptake and 5-ethynyl-2'-deoxyuridine detection. Results and Conclusions PBMCs proliferated in the presence of PF4, and this was enhanced by the addition of heparin in all study groups. CPB and HIT patients showed significantly greater proliferative responses than healthy controls. PBMC proliferation was antigen-specific, depended on the presence of platelets, and only CD14+ cells were identified as proliferating cells. Culture supernatants were tested for the levels of regulatory cytokines, and both CPB and HIT patients produced significantly lower levels of interleukin-10 and transforming growth factor-ß1 than healthy controls. These findings further demonstrate cellular immune sensitization to PF4-heparin complexes occurs before heparin exposure, and suggests immune dysregulation can contribute to HIT.

Steroids in cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction that may contribute to postoperative complications. Preventing this reaction with steroids may improve outcomes. We performed a systematic review to evaluate the impact of prophylactic steroids on clinical outcomes in patients undergoing on-pump cardiac surgery. METHODS: We searched MEDLINE, EMBASE, and Cochrane CENTRAL for randomised controlled trials (RCTs) comparing perioperative corticosteroid administration with a control group in adults undergoing CPB. Outcomes of interest included mortality, myocardial infarction, and new onset atrial fibrillation. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Fifty-six RCTs published between 1977 and 2015 were included in this meta-analysis. Mortality was not significantly different between groups [3.0% (215/7258 patients) in the steroid group and 3.5% (252/7202 patients) in the placebo group; relative risk (RR), 0.85; 95% confidence interval (CI), 0.71-1.01; P=0.07; I2 = 0%]. Myocardial injury was more frequent in the steroid group [8.0% (560/6989 patients), compared with 6.9% (476/6929 patients); RR, 1.17, 95% CI, 1.04-1.31; P=0.008; I2=0%]. New onset atrial fibrillation was lower in the steroid group [25.7% (1792/6984 patients) compared with 28.3% (1969/6964 patients), RR, 0.91, 95% CI, 0.86-0.96, P=0.0005, I2=43%]; this beneficial effect was limited to small trials (P for interaction <0.00001). CONCLUSIONS: After randomising 16 013 patients, steroid administration at the time of cardiac surgery had an unclear impact on mortality, increased the risk of myocardial injury, and the impact on atrial fibrillation should be viewed with caution given that large trials showed no effect.

Once versus twice daily aspirin after coronary bypass surgery: a randomized trial.

Essentials Coronary artery bypass graft (CABG) failure is associated with myocardial infarction and death. We tested whether more frequent dosing improves aspirin (ASA) response following CABG surgery. Twice-daily compared with once-daily dosing reduces ASA hyporesponsiveness after CABG surgery. The efficacy of twice-daily ASA needs to be tested in a trial powered for clinical outcomes. SUMMARY: Background Acetyl-salicylic acid (ASA) hyporesponsiveness occurs transiently after coronary artery bypass graft (CABG) surgery and may compromise the effectiveness of ASA in reducing thrombotic graft failure. A reduced response to ASA 81 mg once-daily after CABG surgery is overcome by four times daily ASA dosing. Objectives To determine whether ASA 325 mg once-daily or 162 mg twice-daily overcomes a reduced response to ASA 81 mg once-daily after CABG surgery. Methods Adults undergoing CABG surgery were randomized to ASA 81 mg once-daily, 325 mg once-daily or 162 mg twice-daily. The primary outcome was median serum thromboxane B2 (TXB2 ) level on postoperative day 4. We pooled the results with those of our earlier study to obtain better estimates of the effect of ASA 325 mg once-daily or in divided doses over 24 h. Results We randomized 68 patients undergoing CABG surgery. On postoperative day 4, patients randomized to receive ASA 81 mg once-daily had a median day 4 TXB2 level of 4.2 ng mL-1 (Q1, Q3: 1.5, 7.5 ng mL-1 ), which was higher than in those randomized to ASA 162 mg twice-daily (1.1 ng mL-1 ; Q1, Q3: 0.7, 2.7 ng mL-1 ) and similar to those randomized to ASA 325 mg once-daily (1.9 ng mL-1 ; Q1, Q3: 0.9, 4.7 ng mL-1 ). Pooled data showed that the median TXB2 level on day 4 in groups receiving ASA 162 mg twice-daily or 81 mg four times daily was 1.1 ng mL-1 compared with 2.2 ng mL-1 in those receiving ASA 325 mg once-daily. Conclusions Multiple daily dosing of ASA is more effective than ASA 81 mg once-daily or 325 mg once-daily at suppressing serum TXB2 formation after CABG surgery. A twice-daily treatment regimen needs to be tested in a clinical outcome study.

Multiple daily doses of acetyl-salicylic acid (ASA) overcome reduced platelet response to once-daily ASA after coronary artery bypass graft surgery: a pilot randomized controlled trial.

BACKGROUND: The efficacy of ASA for prevention of graft failure following CABG surgery may be limited by incomplete platelet inhibition due to increased post-operative platelet turnover. OBJECTIVES: To determine whether acetyl-salicylic acid (ASA) 325 mg once-daily or 81 mg four-times daily overcomes the impaired response to ASA 81 mg once-daily in post-operative coronary artery bypass graft (CABG) patients. METHODS: We randomized 110 patients undergoing CABG surgery to either ASA 81 mg once-daily, 81 mg four times daily or 325 mg once-daily and compared their effects on serum thromboxane B2 (TXB2 ) suppression and arachidonate-induced platelet aggregation. RESULTS: One hundred patients were included in the final analysis. Platelet counts fell after surgery, reached a nadir on day 2, and then gradually increased. Although there was near complete suppression of TXB2 on the second or third post-operative day, TXB2 levels increased in parallel with the rise in platelet count on subsequent days. This increase was most marked in patients receiving ASA 81 mg once-daily and less evident in those receiving ASA four times daily. On post-operative day 4, (i) median TXB2 levels were lower with four times daily ASA than with either ASA 81 mg once-daily (1.1 ng/mL; Quartile(Q) Q1,Q3: 0.5, 2.4 and 13.3 ng/mL; Q1,Q3: 7.8, 30.8 ng/mL, respectively; P < 0.0001) or ASA 325 mg once-daily (3.4 ng/mL; Q1,Q3: 2.0, 8.2 ng/mL; P = 0.002), and (ii) ASA given four times daily was more effective than ASA 81 mg once-daily and 325 mg once-daily at suppressing platelet aggregation. CONCLUSIONS: Four times daily ASA is more effective than ASA 81 and 325 mg once-daily at suppressing serum TXB2 formation and platelet aggregation immediately following CABG surgery.

The use of transcutaneous oximetry to predict healing complications of lower limb amputations: a systematic review and meta-analysis.

OBJECTIVE: To determine the validity of transcutaneous oximetry (TcPO(2)) as a predictor of lower limb amputation healing complications. DESIGN: A systematic review and meta-analysis. METHODS: We searched five major medical databases, relevant review articles and reference lists and included all studies that evaluated TcPO(2) for its ability to predict lower limb amputation healing failure. We selected eligible articles and conducted data abstraction independently and in duplicate. RESULTS: Thirty-one studies, enrolling 1824 patients with 1960 amputations, met our inclusion criteria. Only one study reported undertaking a multivariable analysis, which demonstrated that a TcPO(2) level below 20 mmHg was an independent predictor of re-amputation occurrence (adjusted odds ratio (OR) 3.08, 95% confidence interval (CI) 1.19-7.98). Fourteen prospective cohort studies reported data that allowed for the calculation of an unadjusted relative risk of lower limb amputation healing complications leading to amputation revision associated with a TcPO(2) level below cut-offs of 10 mmHg (1.80; 95% CI 1.19-2.72), 20 mmHg (1.75; 95% CI 1.27-2.40) 30 mmHg (1.41; 95% CI 1.22-1.62) and 40 mmHg (1.24; 95% CI 1.13-1.39). CONCLUSIONS: This review suggests that TcPO(2) predicts healing complications of lower limb amputations. A value of less than 40 mmHg results in a 24% increased risk of healing complication compared to over 40 mmHg and the risk further increases as the TcPO(2) decreases. There is, however, insufficient evidence to judge whether this tool adds important information beyond clinical data or to suggest an optimal threshold value. There is a need for a large, sufficiently powered study that adjusts for appropriate clinical variables.

Pulse low dose steroids attenuate post-cardiopulmonary bypass SIRS; SIRS I.

BACKGROUND: Cardiopulmonary bypass (CPB) initiates inflammation that contributes to multiorgan dysfunction (SIRS). Steroids have been demonstrated to attenuate this response; however, resistance to use steroids remains because of potential adverse effects of the high doses used. This study examines a lower dose steroid protocol for safety and attenuation of SIRS. METHODS: Sixty patients undergoing CPB were randomized to pulse low doses of methylprednisolone (250 mg given twice IV) or placebo in this RCT. Outcomes pertaining to hemodynamics, ventilator requirement, arrhythmia, and metabolic derangements were recorded. Post-operative glucose control and gastrointestinal prohylaxis was instituted in all patients. RESULTS: IL-6 concentrations were lower in the steroid group at 4 and 8 h post-operatively (P < 0.0001). The steroid group demonstrated more normothermia (37.2 degrees C versus 37.6 degrees C, P = 0.002), better hemodynamic stability with less requirement for inotropes or vasopressors (0% versus 27.6%, P = 0.005), higher SVRIs (1840 versus 1340 DSm2/cm5, P = 0.002), and higher mean arterial pressures (79 versus 74 mmHg, P = 0.03). The steroid group had a shorter duration of intubation (7.7 versus 10.7 h, P = 0.02), a shorter length of ICU stay (1.0 versus 2.0 days, P = 0.03), and less blood loss (505 versus 690 ml, P = 0.04) with no difference in post-operative blood glucose levels or complications. CONCLUSIONS: Patients undergoing cardiopulmonary bypass receiving low pulse dose steroids had better hemodynamics, shorter mechanical ventilation times, less blood loss, and required less time in the ICU compared to those receiving placebo. Therefore, this study demonstrates that prophylactic low dose steroids attenuate the SIRS response to CPB without resulting in any untoward side-effects.

A technique for characterizing casting behavior of dental alloys.

A technique for characterizing casting behavior of dental alloys has been developed and tested. The method employs easily reproducible specimen patterns and uses equipment and procedures generally available in dental prosthetic laboratories. A castability value is arrived at by counting complete segments of a cast alloy grid. Test results indicate that the castability evaluation procedure described can be a valuable aid in the laboratory for both selecting and using dental materials for producing cast restorations. The test method would also appear useful for the evaluation of products and techniques during research and development. An absolute minimum for the castability value determined relative to clinical and laboratory efficacy has yet to be established.