Ron Bin Hsu

Preoperative Proteinuria Predicts Adverse Renal Outcomes after Coronary Artery Bypass Grafting

Whether preoperative proteinuria associates with adverse renal outcomes after cardiac surgery is unknown. Here, we performed a secondary analysis of a prospectively enrolled cohort of adult patients undergoing coronary artery bypass grafting (CABG) at a medical center and its two affiliate hospitals between 2003 and 2007. We excluded patients with stage 5 CKD or those who received dialysis previously. We defined proteinuria, measured with a dipstick, as mild (trace to 1+) or heavy (2+ to 4+). Among a total of 1052 patients, cardiac surgery-associated acute kidney injury (CSA-AKI) developed in 183 (17.4%) patients and required renal replacement therapy (RRT) in 50 (4.8%) patients. In a multiple logistic regression model, mild and heavy proteinuria each associated with an increased odds of CSA-AKI, independent of CKD stage and the presence of diabetes mellitus (mild: OR 1.66, 95% CI 1.09 to 2.52; heavy: OR 2.30, 95% CI 1.35 to 3.90). Heavy proteinuria also associated with increased odds of postoperative RRT (OR 7.29, 95% CI 3.00 to 17.73). In summary, these data suggest that preoperative proteinuria is a predictor of CSA-AKI among patients undergoing CABG.

Risk Factors for Primary Bacteremia and Endovascular Infection in Patients without Acquired Immunodeficiency Syndrome Who Have Nontyphoid Salmonellosis

This study sought to find the risk factors for primary bacteremia, endovascular infection, and in-hospital death for patients without acquired immunodeficiency syndrome who have nontyphoid salmonellosis. From September 1995 through September 2001, 301 patients with nontyphoid salmonellosis were admitted to our hospital; of these patients, 121 had primary bacteremia, and 28 had endovascular infection. Of the 121 patients with primary bacteremia, 64 were aged >50 years, and 26 had endovascular infection. Overall, 90 patients (29.9%) had immunodeficiency. Predictors of primary bacteremia were age; presence of systemic lupus erythematosus; group B, group C, or group D Salmonella infection; and immunodeficiency. The positive predictor of endovascular infection in adult patients with primary bacteremia was group C Salmonella infection, and negative predictors were immunodeficiency and solid-organ cancer. The overall in-hospital mortality rate was 12%; for primary bacteremia, it was 24.8%; for endovascular infection, it was 14.3%. Predictors of in-hospital death were age, extraintestinal infection, and solid-organ malignancy.

Platelets Enhance Biofilm Formation and Resistance of Endocarditis-Inducing Streptococci on the Injured Heart Valve

Infective endocarditis is a typical biofilm-associated infectious disease frequently caused by commensal streptococci, but the contribution of host factors in biofilm formation is unclear. We found that platelets are essential for in vitro biofilm formation by Streptococcus mutans or Streptococcus gordonii grown in human plasma. The biofilms were composed of bacterial floes embedded with platelet aggregates in layers, and a similar architecture was also detected in situ on the injured valves of a rat model of experimental endocarditis. Similar to planktonic cells, the streptococci in biofilms were also able to induce platelet aggregation, which facilitates multilayer biofilm formation. Entrapping of platelets directly enhances the resistance of streptococcal biofilms to clindamycin. Prophylactic antibiotics or aspirin can reduce but not prevent or abolish biofilm formation on injured heart valves. Therefore, the platelet is a host factor for commensal streptococci in the circulation to consolidate biofilm formation and protect bacteria against antibiotics.

Poststernotomy mediastinitis due to methicillin-resistant Staphylococcus aureus endemic in a hospital.

The objective of this study was to determine the incidence of and risk factors for poststernotomy mediastinitis (PSM) due to methicillin-resistant Staphylococcus aureus (MRSA) infection in a hospital in which MRSA was endemic. A retrospective case-control study of patients with PSM after cardiac surgery during January 1997 through July 2002 was conducted. The incidence of PSM was 1.01% (48 of 4746 patients), and 31 episodes (64.6%) were due to MRSA infection. We analyzed the findings for 48 case and 65 control patients. Univariate analysis revealed that the risk factors for PSM were previous hospitalization, resternotomy, chronic renal insufficiency, longer operation time, postoperative heart failure, postoperative renal failure, and reoperation for bleeding. Multivariate analysis revealed that the independent risk factors for PSM were previous hospitalization and reoperation for bleeding. Previous hospitalization was the only significant risk factor for PSM due to MRSA infection. The hospital mortality rate associated with PSM was 41.7%, and there was a higher mortality rate associated with PSM due to MRSA infection.

Autologous mesenchymal stem cells prevent transplant arteriosclerosis by enhancing local expression of interleukin-10, interferon-γ, and indoleamine 2,3-dioxygenase.

Transplant arteriosclerosis (TA) remains the major limitation of long-term graft survival in heart transplantation despite the advances in immunosuppressants. Mesenchymal stem cells (MSCs) have been demonstrated to suppress allogeneic immune responses by numerous in vitro studies. However, the immunomodulatory effects of MSCs in vivo are controversial and the underlying molecular mechanisms are not conclusive. In this study, we investigated the therapeutic potential of autologous bone marrow-derived MSCs on TA in a porcine model of femoral artery transplantation. MSCs or saline were injected into the soft tissue surrounding the arterial grafts immediately postanastomosis. Four weeks after transplantation, neointimal formation increased significantly in untreated allografts compared with the MSC-treated grafts as assessed by intravascular ultrasound (maximum luminal area stenosis: 40 ± 12% vs. 18 ± 6%, p < 0.001). Grafts harvested at 4 weeks showed dense perivascular lymphocyte infiltration accompanied by significant intimal hyperplasia in the untreated but not in the MSC-treated allografts. Serial angiographic examination showed that all of the untreated allografts became occluded at the 8th week whereas the majority of the MSC-treated grafts remained patent at the 12th week posttransplantation (n = 12 each group, p < 0.001). Quantitative PCR analysis revealed that Foxp3 expression was comparable between the untreated and the MSC-treated groups. However, expression of interleukin-10 (IL-10), interferon-γ (IFN-γ), and indoleamine 2,3-dioxygenase (IDO) was increased significantly in the MSC-treated allografts compared with that in the allograft controls (p = 0.021 for IL-10, p = 0.003 for IFN-γ, and p = 0.008 for IDO). In conclusion, local delivery of autologous MSCs alleviates TA by inducing allograft tolerance via enhanced expression of IL-10, IFN-γ, and IDO but not Foxp3-positive cells in the vessel wall. These results suggest that MSCs induce immune tolerance by activating the type 1 regulatory T-like cells.

Endocarditis Pathogen Promotes Vegetation Formation by Inducing Intravascular Neutrophil Extracellular Traps Through Activated Platelets

Background— Endocarditis-inducing streptococci form multilayered biofilms in complex with aggregated platelets on injured heart valves, but the host factors that interconnect and entrap these bacteria-platelet aggregates to promote vegetation formation were unclear. Methods and Results— In a Streptococcus mutans endocarditis rat model, we identified layers of neutrophil extracellular traps interconnecting and entrapping bacteria-platelet aggregates inside vegetation that could be reduced significantly in size along with diminished colonizing bacteria by prophylaxis with intravascular DNase I alone. The combination of activated platelets and specific immunoglobulin G–adsorbed bacteria are required to induce the formation of neutrophil extracellular traps through multiple activation pathways. Bacteria play key roles in coordinating the signaling through spleen tyrosine kinase, Src family kinases, phosphatidylinositol-3-kinase, and p38 mitogen-activated protein kinase pathways to upregulate the expression of P-selectin in platelets, while inducing reactive oxygen species–dependent citrullination in the arm of neutrophils. Neutrophil extracellular traps in turn serve as the scaffold to further enhance and entrap bacteria-platelet aggregate formation and expansion. Conclusions— Neutrophil extracellular traps promote and expand vegetation formation through enhancing and entrapping bacteria-platelet aggregates on the injured heart valves. (Circulation. 2015;131:571–581. DOI: 10.1161/CIRCULATIONAHA.114.011432.)

Cardiac surgery in patients with liver cirrhosis: Risk factors for predicting mortality

AIM To evaluate the results of cardiac surgery in cirrhotic patients and to find the predictors of early and late mortality. METHODS We included 55 consecutive cirrhotic patients undergoing cardiac surgery between 1993 and 2012. Child-Turcotte-Pugh (Child) classification and Model for End-Stage Liver Disease (MELD) score were used to assess the severity of liver cirrhosis. The online EuroSCORE II calculator was used to calculate the logistic EuroSCORE in each patient. Stepwise logistic regression analysis was used to identify the risk factors for mortality at different times after surgery. Multivariate Cox proportional hazard models were applied to estimate the hazard ratios (HR) of predictors for mortality. The Kaplan-Meier method was used to generate survival curves, and the survival rates between groups were compared using the log-rank test. RESULTS There were 30 patients in Child class A, 20 in Child B, and five in Child C. The hospital mortality rate was 16.4%. The actuarial survival rates were 70%, 64%, 56%, and 44% at 1, 2, 3, and 5 years after surgery, respectively. There were no significant differences in major postoperative complications, and early and late mortality between patients with mild and advanced cirrhosis. Multivariate logistic regression showed preoperative serum bilirubin, the EuroSCORE and coronary artery bypass grafting (CABG) were associated with early and late mortality; however, Child class and MELD score were not. Cox regression analysis identified male gender (HR = 0.319; P = 0.009), preoperative serum bilirubin (HR = 1.244; P = 0.044), the EuroSCORE (HR = 1.415; P = 0.001), and CABG (HR = 3.344; P = 0.01) as independent risk factors for overall mortality. CONCLUSION Advanced liver cirrhosis should not preclude patients from cardiac surgery. Preoperative serum bilirubin, the EuroSCORE, and CABG are major predictors of early and late mortality.

Non-transplant cardiac surgery for end-stage dilated cardiomyopathy in small children

Between October 1997 and December 2000, a total of 7 pediatric patients with end-stage dilated cardiomyopathy (DCM) were referred to our service for heart transplantation; non-transplant cardiac surgery was offered as a biologic bridge. Two patients died before surgery and the in-hospital surgical mortality rate was 50%: 75% in 4 patients who received emergency surgery and 0% in 2 patients who received urgent surgery. Non-transplant cardiac surgery improved clinical outcome and acted as a biologic bridge, instead of a mechanical bridge, to heart transplantation in small children with DCM and severe heart failure.

Care bundle to prevent methicillin-resistant Staphylococcus aureus sternal wound infection after off-pump coronary artery bypass

Methicillin-resistant Staphylococcus aureus (MRSA) sternal wound infection (SWI) after cardiac surgery is endemic in our hospital. An infection control care bundle with preoperative chlorhexidine showering and povidone iodine paint before bathing was introduced in 2006. From 2001 to 2012, 23 (2.3%) of 1,010 patients undergoing off-pump coronary artery bypass had SWIs. SWI significantly decreased after 2006 (1.4% vs 3.4%, respectively; P = .03). Care bundle was more protective against MRSA infection (2.3% vs 0.5%, respectively; P = .021). SWI remained a common complication after off-pump coronary artery bypass. MRSA infection was most common, and the mortality was high. Care bundle can effectively decrease the incidence of SWI, especially infection caused by MRSA.

Surgical proficiency and quality indicators in off-pump coronary artery bypass

BACKGROUND Off-pump coronary artery bypass (OPCAB) was developed to decrease postoperative mortality and morbidity. Surgeon experience influences outcome. The required levels of surgical proficiency and maturation of technical skills are uncertain. We sought to assess the surgical proficiency in OPCAB and to identify the required levels of technical maturation. METHODS We included 1,055 consecutive patients undergoing OPCAB. Patients were divided by 100s into 11 groups by timing of operation. Surgical proficiency was evaluated by 2 quality indicators: revascularization index and conversion rate in nonemergency cases. RESULTS Mode of intervention was elective in 768 patients, urgent in 185 patients, and emergent in 102 patients (9.7%). The in-hospital mortality rate was 5.1% and ranged from 3% (group 3) to 9% (group 11). The percentage of triple-vessel disease and the mean number of diseased vessels increased over time. The mean number of distal anastomoses increased over time, from 2.64 ± 0.82 in group 1 to 4.13 ± 0.98 in group 11. It reached a plateau of 4.0 at group 7 (cases 600-700). The revascularization index also increased over time, from 1.01 ± 0.20 in group 1 to 1.41 ± 0.28 in group 11. It reached a plateau of 1.4 at group 7 (cases 600-700). The conversion rate in nonemergent cases decreased rapidly as the volume of OPCAB increased, and it reached a baseline of 5% at group 3 (cases 200-300). CONCLUSIONS Surgical proficiency at performing OPCAB could be evaluated with 2 quality indicators: revascularization index of 1.4 or more and conversion rate in nonemergent cases of 5% or less. The required case number for technical maturation was 200 to 300 for conversion and 600 to 700 for complete revascularization.