Doing a double take: when transthoracic echocardiography fails for mitral valve annuloplasty ring endocarditis with Streptococcus pyogenes: a case report.

BACKGROUND: This case highlights several complications of a late and rare presentation of culture-negative Streptococcus pyogenes endocarditis of a previously repaired mitral valve with an annuloplasty ring including recurrent cardioembolic strokes, which was initially missed on transthoracic echocardiography. CASE PRESENTATION: A 66-year-old Caucasian female with prior mitral valve prolapse status post mitral valve annuloplasty and left atrial appendage occlusion, followed by two strokes, presented with supraventricular tachycardia that resolved spontaneously. During an inpatient admission, she developed symptoms of another stroke, and imaging studies were suggestive of recurrent cardioembolic phenomenon. Additional workup revealed two small intra-atrial masses adherent to the mitral annuloplasty ring missed on prior evaluation for recurrent stroke. She underwent surgical repair in the setting of a chronic culture-negative infectious endocarditis with Streptococcus pyogenes and recovered well with no further cardioembolic phenomenon. CONCLUSION: This case serves to highlight the importance of having a higher index of suspicion in any cardiac prosthesis patient for endocarditis when presenting with symptoms such as recurrent stroke, arrhythmias, and abnormal cardiac lab work. It also demonstrates the need for appropriate imaging with transthoracic echocardiography followed by transesophageal echocardiography and reviews surgical indications to diagnose and treat culture-negative endocarditis.

A Privacy-Preserving Framework Using Homomorphic Encryption for Smart Metering Systems.

Smart metering systems (SMSs) have been widely used by industrial users and residential customers for purposes such as real-time tracking, outage notification, quality monitoring, load forecasting, etc. However, the consumption data it generates can violate customers' privacy through absence detection or behavior recognition. Homomorphic encryption (HE) has emerged as one of the most promising methods to protect data privacy based on its security guarantees and computability over encrypted data. However, SMSs have various application scenarios in practice. Consequently, we used the concept of trust boundaries to help design HE solutions for privacy protection under these different scenarios of SMSs. This paper proposes a privacy-preserving framework as a systematic privacy protection solution for SMSs by implementing HE with trust boundaries for various SMS scenarios. To show the feasibility of the proposed HE framework, we evaluated its performance on two computation metrics, summation and variance, which are often used for billing, usage predictions, and other related tasks. The security parameter set was chosen to provide a security level of 128 bits. In terms of performance, the aforementioned metrics could be computed in 58,235 ms for summation and 127,423 ms for variance, given a sample size of 100 households. These results indicate that the proposed HE framework can protect customer privacy under varying trust boundary scenarios in SMS. The computational overhead is acceptable from a cost-benefit perspective while ensuring data privacy.

Morbidity and Mortality Associated With Blood Transfusions in Elective Adult Cardiac Surgery.

OBJECTIVES: Perioperative transfusion thresholds have garnered increasing scrutiny as restrictive strategies have been shown to be noninferior. The study authors used data from a statewide academic collaborative to test the association between transfusion and 30-day mortality. DESIGN: All adult patients undergoing coronary artery bypass grafting (CABG) and/or valve surgeries between 2013 and 2019 in the authors' Academic Cardiac Surgery Consortium were examined. The relationship between the number of overall packed red blood cell (pRBC) and coagulation product (CP) (fresh frozen plasma, cryoprecipitate, platelets) transfusions on 30-day mortality was evaluated. Multivariate regression was used to evaluate predictors of transfusion and study endpoints. Machine learning (ML) models also were developed to predict 30-day mortality and rank transfusion-related features by relative importance. SETTING: At an Academic Cardiac Surgery Consortium of 5 institutions. PARTICIPANTS: Patients ≥18 years old undergoing CABG and/or valve surgeries. MEASUREMENTS AND MAIN RESULTS: Of the 7,762 patients (median hematocrit [HCT] 39%, IQR 35%-43%) who were included in the final study cohort, >40% were transfused at least 1 unit of pRBC or CP. In adjusted analyses, higher preoperative HCT was associated with reduced odds of mortality (adjusted odds ratio [aOR] 0.95, 95% CI 0.92-0.98), renal failure (aOR 0.95, 95% CI 0.92-0.98), and prolonged mechanical ventilation (aOR 0.97, 95% CI 0.95-0.99). In contrast, perioperative transfusions were associated with increased 30-day mortality after adjustment for preoperative HCT and other baseline features. The ML models were able to predict 30-day mortality with an area under the curve of 0.814-to-0.850, with perioperative transfusions displaying the highest feature importance. CONCLUSIONS: The present analysis found increasing HCT to be associated with a lower incidence of mortality. The study authors also found a direct dose-response association between transfusions and all study endpoints examined.

Implantation of a Dual-chamber Pacemaker in a Patient with Dextrocardia, Situs Inversus, and Sick Sinus Syndrome.

Situs inversus with dextrocardia is a rare congenital anomaly that presents a unique challenge for the consultant electrophysiologist. Implantation of cardiac device in these patients may be challenging owing to their individual cardiac and vascular anatomy. Consequently, adverse procedural outcomes are more common in this group and an informed pre- and intraoperative approach is critical. In this article, we present the relevant patient findings and implications for the electrophysiologist, including operative approaches. We then examine them in the context of an actual case, having implanted an intracardiac permanent pacemaker with a right-sided approach via the conventional method in a patient with dextrocardia situs inversus who had undergone multiple surgeries for structural heart disease.

Genetic Disorders of the Thoracic Aorta and Indications for Surgery.

Genetic disorders of the aorta are rare but can lead to life-threatening thoracic aortic aneurysms. Although the genetic causes of many of these connective tissue diseases are well defined, others such as familial thoracic aortic aneurysm and bicuspid aortic valve aortopathy are not. The natural history of genetic thoracic aortic aneurysms is not well understood or predictable, and surgical guidelines for treatment remain imprecise. Future research should strive to provide in-depth and detailed genetic profiling to drive clinical management, including medical and surgical therapies.

Percutaneous Repair of Aortic Pseudoaneurysms: A Case Series.

BACKGROUND: Aortic pseudoaneurysms (APSAs) are an uncommon but serious complication of aortic surgery with potentially fatal complications if left untreated. Operative repair is associated with significant morbidity and mortality. Percutaneous APSA repair may reduce the risk of these complications and represents an alternative option for patients. We report our experience with percutaneous intervention for the treatment of APSAs. METHODS AND RESULTS: We retrospectively reviewed all patients at our institution who underwent percutaneous APSA repair with Amplatzer septal occluders and vascular plugs between January 2004 and September 2014. Ten patients are included in this study, representing our first cases of percutaneous APSA repair. Follow-up was performed with serial computed tomographic angiography. The primary outcome was the success rate of device deployment. Secondary outcomes included success rate of complete APSA exclusion, postprocedural symptoms, and periprocedural and postprocedural complications. Mean clinical follow-up time was 12 months (range, 5-30 months) and mean imaging follow-up time was 29 months (range, 14-52 months). Device deployment was successful in all patients, although 2 patients required reintervention due to device malposition and the discovery of additional defects on postprocedure CT angiography. There were no periprocedural or postprocedure complications. Long-term follow-up imaging was available for 7 patients and revealed complete APSA exclusion in 4 patients. One out of the remaining 3 patients ultimately required operative intervention. CONCLUSIONS: Percutaneous APSA repair can be performed safely with a good procedural success, albeit with variable long-term results. This procedure may be considered as an alternative to surgical repair in select patients.

Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND: Antithrombotic therapy in valvular disease is important to mitigate thromboembolism, but the hemorrhagic risk imposed must be considered. METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS: In rheumatic mitral disease, we recommend vitamin K antagonist (VKA) therapy when the left atrial diameter is > 55 mm (Grade 2C) or when complicated by left atrial thrombus (Grade 1A). In candidates for percutaneous mitral valvotomy with left atrial thrombus, we recommend VKA therapy until thrombus resolution, and we recommend abandoning valvotomy if the thrombus fails to resolve (Grade 1A). In patients with patent foramen ovale (PFO) and stroke or transient ischemic attack, we recommend initial aspirin therapy (Grade 1B) and suggest substitution of VKA if recurrence (Grade 2C). In patients with cryptogenic stroke and DVT and a PFO, we recommend VKA therapy for 3 months (Grade 1B) and consideration of PFO closure (Grade 2C). We recommend against the use of anticoagulant (Grade 1C) and antiplatelet therapy (Grade 1B) for native valve endocarditis. We suggest holding VKA therapy until the patient is stabilized without neurologic complications for infective endocarditis of a prosthetic valve (Grade 2C). In the first 3 months after bioprosthetic valve implantation, we recommend aspirin for aortic valves (Grade 2C), the addition of clopidogrel to aspirin if the aortic valve is transcatheter (Grade 2C), and VKA therapy with a target international normalized ratio (INR) of 2.5 for mitral valves (Grade 2C). After 3 months, we suggest aspirin therapy (Grade 2C). We recommend early bridging of mechanical valve patients to VKA therapy with unfractionated heparin (DVT dosing) or low-molecular-weight heparin (Grade 2C). We recommend long-term VKA therapy for all mechanical valves (Grade 1B): target INR 2.5 for aortic (Grade 1B) and 3.0 for mitral or double valve (Grade 2C). In patients with mechanical valves at low bleeding risk, we suggest the addition of low-dose aspirin (50-100 mg/d) (Grade 1B). In valve repair patients, we suggest aspirin therapy (Grade 2C). In patients with thrombosed prosthetic valve, we recommend fibrinolysis for right-sided valves and left-sided valves with thrombus area < 0.8 cm(2) (Grade 2C). For patients with left-sided prosthetic valve thrombosis and thrombus area ≥ 0.8 cm(2), we recommend early surgery (Grade 2C). CONCLUSIONS: These antithrombotic guidelines provide recommendations based on the optimal balance of thrombotic and hemorrhagic risk.

Randomized trial of fondaparinux versus heparin to prevent graft failure after coronary artery bypass grafting: the Fonda CABG study.

We sought to assess the feasibility of comparing the efficacy and safety of fondaparinux versus heparin for prevention of graft failure and major CV events in patients undergoing coronary artery bypass grafting (CABG). Patients undergoing CABG were randomized to receive postoperative injections of fondaparinux or heparin in-hospital. After discharge, the fondaparinux group received fondaparinux and the heparin group received placebo injections for 30 days post surgery. Efficacy outcomes were graft failure, death, MI, and stroke at 30 days. Safety outcomes were bleeding, transfusion, and reoperation. 100 patients were recruited, 99 were randomized, 49 received fondaparinux and 50 received heparin. CT angiography was performed in 97% of patients. 188 grafts in the treatment group and 189 grafts in the heparin group were imaged. A similar proportion of patients treated with fondaparinux compared with heparin had at least one occluded graft (18.8% fondaparinux vs. 14.9% heparin, P = 0.62) and a similar number of grafts were occluded in each treatment group (all grafts: 4.8% vs. 4.8%, P = 0.99; saphenous vein grafts 4.2% vs. 4.2%, P = 0.98). There was no difference between treatment groups in death, MI, stroke, bleeding events, or reoperation. One in 10 patients undergoing CABG had at least one occluded graft at 30 days and one in 20 grafts is occluded by 30 days. Fondaparinux appears to be a safe alternative to heparin after CABG and it is feasible to conduct a definitive RCT using CT angiography to evaluate the effect of fondaparinux treatment on graft patency.

Pulmonary artery catheters: evolving rates and reasons for use.

OBJECTIVE: Randomized trials have demonstrated risks and failed to establish a clear benefit for the use of the pulmonary artery catheter. We assessed rates of pulmonary artery catheter use in multiple centers over 5 yrs, variables associated with their use, and how these variables changed over time (2002-2006). DESIGN: A multicenter longitudinal study using the Hamilton Regional Critical Care Database. A two-level multiple logistic regression analysis was used to determine significant variables associated with pulmonary artery catheter use and whether these varied over time. SETTING: Academic intensive care units in Hamilton, Canada. PATIENTS: We identified patients from five intensive care units who received a pulmonary artery catheter within the first 2 days of intensive care unit admission. INTERVENTIONS: Pulmonary artery catheter use over a 5-yr period. MEASUREMENTS AND MAIN RESULTS: Among 15,006 patients, 1,921 (12.8%) had a pulmonary artery catheter. Adjusted rates of pulmonary artery catheter use decreased from 16.4% to 6.5% over 5 yrs. Determinants of pulmonary artery catheter use included Acute Physiology and Chronic Health Evaluation II score (odds ratio [OR], 1.05; confidence interval [CI], 1.04-1.06; p < .0001), elective surgical status (OR, 2.82; CI, 2.29-3.48; p < .0001), postabdominal aortic aneurysm repair (OR, 10.91; CI, 8.24-14.45; p < .0001), cardiogenic shock (OR, 5.31; CI, 3.35-8.42; p < .0001), sepsis (OR, 2.83; CI, 1.94-4.13; p < .0001), vasoactive infusion use (OR, 4.04; CI, 3.47-4.71; p < .0001), and mechanical ventilation (OR, 2.21; CI, 1.86-2.63; p < .0001). Physician's base specialty and local intensive care unit were also associated with pulmonary artery catheter use (p < .0001). The determinants of pulmonary artery catheter use did not change over time. CONCLUSIONS: We observed a >50% reduction in the rate of pulmonary artery catheter use over 5 yrs. Patient factors predicting pulmonary artery catheter use were illness severity, specific diagnoses, and the need for advanced life support. Nonpatient factors predicting pulmonary artery catheter use were intensive care unit and the attending physician's base specialty.

Randomized trial of aspirin and clopidogrel versus aspirin alone for the prevention of coronary artery bypass graft occlusion: the Preoperative Aspirin and Postoperative Antiplatelets in Coronary Artery Bypass Grafting study.

BACKGROUND: Routine use of postoperative aspirin after coronary artery bypass grafting (CABG) reduces graft failure and cardiovascular events. The efficacy and safety of adding clopidogrel to aspirin for the prevention of graft failure and cardiovascular events after CABG are unknown. We performed a pilot study measuring safety and efficacy outcomes of aspirin and clopidogrel therapy after CABG. METHODS: We randomized 100 patients undergoing CABG to receive placebo or clopidogrel started after surgery and for 30 days. All patients received aspirin 81 mg daily. Graft patency was measured by cardiac computed tomography angiography at 30 days. RESULTS: Clinical follow-up was complete for 99 patients, and 79 (80%) underwent computed tomography angiography. The proportion of patients with ≥1 occluded graft was not significantly different between placebo and clopidogrel groups (9/39 [23.1%] vs 7/40 [17.5%], relative risk 0.95, 95% CI 0.80-1.14, P=.54). Among radial artery grafts, the placebo group had a significantly higher number of occlusions or "string signs" compared with the clopidogrel group (7/16 [43.8%] vs 2/19 [10.5%], relative risk 0.24, 95% CI 0.06-1.00, P=.05). There was no difference between placebo and clopidogrel groups in the safety outcomes of total postoperative bleeding, transfusions, bleeding events, and reexploration and in the efficacy outcomes of nonfatal myocardial infarction, stroke, and death. CONCLUSIONS: This pilot study confirms a high rate of graft occlusion after CABG surgery and suggests that the addition of clopidogrel to aspirin is feasible and safe and may be superior for prevention of graft failure in radial artery grafts.

Growth inhibition and cell cycle arrest in the G0/G1 by schizandrin, a dibenzocyclooctadiene lignan isolated from Schisandra chinensis, on T47D human breast cancer cells.

Schizandrin is one of the main dibenzocyclooctadiene lignans present in the fruit of Schisandra chinensis (Schisandraceae). Biological activities including hepatoprotective, antiviral and neuroprotective effects of schizandrin and other dibenzocyclooctadiene lignans have been reported previously. However, the antiproliferative effect of schizandrin against human cancer cells has been poorly determined to date. This study examined the antiproliferative effect of schizandrin in human breast cancer cells. Schizandrin exhibited growth inhibitory activities in cultured human breast cancer cells, and the effect was the more profound in estrogen receptor (ER)-positive T47D cells than in ER-negative MDA-MB-231 cells. When treated with the compound in T47D cells, schizandrin induced the accumulation of a cell population in the G0/G1 phase, which was further demonstrated by the induction of CDK inhibitors p21 and p27 and the inhibition of the expression of cell cycle checkpoint proteins including cyclin D1, cyclin A, CDK2 and CDK4. These results suggest that schizandrin inhibits cell proliferation through the induction of cell cycle arrest with modulating cell cycle-related proteins in human breast cancer cells.

Antithrombotic management of patients with prosthetic heart valves: current evidence and future trends.

Over 4 million people worldwide have received a prosthetic heart valve, and an estimated 300,000 valves are being implanted every year. Prosthetic heart valves improve quality of life and survival of patients with severe valvular heart disease, but the need for antithrombotic therapy to prevent thrombotic complications in valve recipients poses challenges for clinicians and patients. Here, we review antithrombotic therapies for patients with prosthetic heart valves and management of thromboembolic complications. Advances in antithrombotic therapy and valve technologies are likely to improve the management of patients with prosthetic heart valves in developed countries, but the most important unmet need and potential for benefit from these new therapies is in developing countries where a massive and rapidly increasing burden of valvular heart disease exists.

Para-aortic arch abscess secondary to Staphylococcus aureus pneumonia.

Staphylococcus aureus is a relatively common pathogen causing pneumonia in the community, hospital ward and intensive care unit. Although pneumonia is responsible for significant morbidity and mortality, especially in elderly and immunocompromised patients, it is usually uncomplicated and resolves without complications. The case of a woman who developed a para-aortic abscess after a community-acquired S aureus pneumonia infection is presented. A number of diagnostic imaging modalities were used to reach the diagnosis. This complication has not been reported previously and it is likely secondary to suppurative lymphadenitis of a station 5 or 6 node. The patient was successfully managed nonsurgically with computed tomography-guided drainage and intravenous antibiotics.

Clinical benefit of steroid use in patients undergoing cardiopulmonary bypass: a meta-analysis of randomized trials.

We sought to establish the efficacy and safety of prophylactic steroids in adult patients undergoing cardiopulmonary bypass (CPB). We performed a meta-analysis of randomized trials reporting the effects of prophylactic steroids on clinical outcomes after CPB. Outcomes examined were mortality, myocardial infarction, neurological events, new onset atrial fibrillation, transfusion requirements, postoperative bleeding, duration of ventilation, intensive care unit (ICU) stay, hospital stay, wound complications, gastrointestinal complications, and infectious complications. We included 44 trials randomizing 3205 patients. Steroids reduced new onset atrial fibrillation [relative risk (RR) 0.71, 95% confidence interval (CI) 0.59 to 0.87], postoperative bleeding [weighted mean difference (WMD) -99.6 mL, 95% CI -149.8 to -49.3], and duration of ICU stay (WMD -0.23 days, 95% CI -0.40 to -0.07). Length of hospital stay was also reduced (WMD -0.59 days, 95% CI -1.17 to -0.02), but this result was less robust. A trend towards reduction in mortality was observed (RR 0.73, 95% CI 0.45 to 1.18). Randomized trials suggest that perioperative steroids have significant clinical benefit in CPB patients by decreasing the risk of new onset atrial fibrillation, while results are encouraging for reducing bleeding, length of stay, and mortality. These data do not raise major safety concerns, however, a sufficiently powered trial is warranted to confirm or refute these findings.

The effect of pre-operative aspirin on bleeding, transfusion, myocardial infarction, and mortality in coronary artery bypass surgery: a systematic review of randomized and observational studies.

AIMS: To obtain estimates of the efficacy and safety of pre-operative aspirin in patients undergoing coronary artery bypass grafting (CABG). METHODS AND RESULTS: Eligible studies included randomized controlled trials (RCTs) and observational studies of patients undergoing CABG, comparing pre-operative aspirin with no aspirin/placebo, and reporting at least one of our primary outcomes. In eight RCTs (n = 805), pre-operative aspirin increased post-operative bleeding [Mean difference (MD), 104.9 mL; 95% confidence interval (CI), 19.2-190.6; P = 0.016] and reoperation [odds ratio (OR), 2.52; 95% CI, 1.18-5.38; P = 0.017), but not transfusion requirements (MD, 0.62 units; 95% CI, -0.06-1.30; P = 0.072). Subgroup analysis suggested that bleeding was increased with aspirin doses > or =325 mg/day, but not with lower doses. In 14 observational studies (n = 4485), pre-operative aspirin increased post-operative bleeding (MD, 113.6 mL; 95% CI, 45.2-182.0; P = 0.001) and transfusion requirements (MD, 0.34; 95% CI, 0.12-0.56 units; P = 0.002), but not reoperation (OR, 1.12; 95% CI, 0.69-1.83; P = 0.647). Neither analysis detected a significant effect on myocardial infarction or death. CONCLUSION: Pre-operative aspirin increases post-operative bleeding, but this may be avoided by the use of aspirin doses <325 mg/day. Most of the RCTs are old and the meta-analysis was underpowered for efficacy outcomes. A large randomized trial is necessary to determine the safety and efficacy of pre-operative aspirin in the setting of contemporary cardiac surgical practice.

Inhibition of cell proliferation through cell cycle arrest and apoptosis by thio-Cl-IB-MECA, a novel A3 adenosine receptor agonist, in human lung cancer cells.

Human A3 adenosine receptor (A3AR) agonists showed the anti-tumor activity in various in vitro and in vivo studies. The present study investigates the anti-proliferative effect of a novel adenosine analog 2-chloro-N6-(3-iodobenzyl)-4'-thioadenosine-5'-N-methyluronamide (thio-Cl-IB-MECA) in A549 human lung cancer cells. Thio-Cl-IB-MECA induced arrest of cell cycle progression in G0/G1 phase at lower concentrations (up to 20 microM) and apoptotic cell death at a higher concentration (80 microM), which were manifested by down-regulation of cyclin D1, c-myc, and CDK4, activation of caspase-3 and -9, and cleavage of poly(ADP-ribose) polymerase (PARP). The activation of Akt-mediated signaling was also inhibited by treatment with thio-Cl-IB-MECA. These data might suggest the potential therapeutic value of an adenosine analog in the treatment of human lung cancer.

Antiproliferative effects of dibenzocyclooctadiene lignans isolated from Schisandra chinensis in human cancer cells.

Dibenzocyclooctadiene lignans isolated from Schisandra chinensis showed antiproliferative effects in various human cancer cells. The methoxy groups at C-3, C-4, C-3', and C-4', the hydroxyl group at C-8', and the stereo-configuration of the biphenyl ring and the angeloyl group might have influence on these activities. Additional studies indicate that one of mechanism of action of an active compound schizantherin C in A549 human lung cancer cells was related to the inhibition of cell cycle progression in G0/G1 phase.