Timing of Blood Transfusions and 30-Day Patient Outcomes After Coronary Artery Bypass Graft Surgery.

OBJECTIVE: Packed red blood cell transfusion during coronary artery bypass graft surgery is known to be associated with adverse outcomes. However, the association of the timing between transfusions in relation to discharge and 30-day postoperative outcomes has not been studied. The study authors investigated the impact of transfusion timing on 30-day surgical outcomes. DESIGN: A retrospective review. SETTING: At a single tertiary-care academic hospital. PARTICIPANTS: A total of 2,481 adult patients underwent primary coronary artery bypass graft surgery between January 2014 and December 2020. MEASUREMENTS AND MAIN RESULTS: The relationship between the timing of packed red blood cell transfusion (intraoperative, postoperative, or both) and 30-day postoperative outcome variables was calculated as an odds ratio. The influence of timing of transfusion on adjusted probability of postoperative complications was plotted against the lowest intraoperative hematocrit. The median age of the population was 67 years (60.0-74.0), body mass index was 28.5 (25.6-32.3) kg/m2, and 497 (20.0%) were female. A total of 1,588 (36%) patients received packed red blood cell transfusions; 182 (7.3%) received intraoperative transfusions, 489 (19.7%) received postoperative transfusions, and 222 (9.0%) received both (intraoperative and postoperative transfusions). Postoperative transfusion was associated with significantly higher odds of readmission (1.83 [1.32-2.54], p = 0.002) and heart failure (1.64 [1.2-2.23], p = 0.008) compared to patients with no transfusions; whereas intraoperative transfusions were not. CONCLUSION: The authors' data suggested that the postoperative timing of transfusion in patients undergoing coronary artery bypass graft surgery may be associated with an increased incidence of 30-day heart failure and readmission. Prospective research is needed to conclusively confirm these findings.

Update: Gender differences in CABG outcomes-Have we bridged the gap?

BACKGROUND: Appreciation of unique presentation, patterns and underlying pathophysiology of coronary artery disease in women has driven gender based risk stratification and risk reduction efforts over the last decade. Data regarding whether these advances have resulted in unequivocal improvements in outcomes of CABG in women is conflicting. The objective of our study was to assess gender differences in post-operative outcomes following CABG. METHODS: Retrospective analyses of institutional data housed in the Society of Thoracic Surgeons (STS) database for patients undergoing CABG between 2002 and 2020 were conducted. Multivariable regression analysis was conducted to investigate gender differences in post-operative outcomes. P-values were adjusted using Bonferroni correction to reduce type-I errors. RESULTS: Our final cohort of 6,250 patients had fewer women than men (1,339 vs. 4,911). more women were diabetic (52.0% vs. 41.2%, p<0.001) and hypertensive (89.1% vs. 84.0%, p<0.001). Women had higher adjusted odds of developing ventilator dependence >48 hours (OR: 1.65 [1.21, 2.45], p = 0.002) and cardiac readmissions (OR: 1.56 [1.27, 2.30], p = 0.003). After adjustment for comorbidity burden, mortality rates in women were comparable to those of age-matched men. CONCLUSION: The findings of our study indicate that despite apparent reduction of differences in mortality, the burden of postoperative morbidity is still high among women.

Cardiopulmonary Bypass Suppresses Forkhead Box O3 and Downstream Autophagy in the Diabetic Human Heart.

BACKGROUND: Autophagy is an integral component of cellular homeostasis and metabolism. The exact mechanism of impaired autophagy in diabetes mellitus is unknown. Forkhead Box O3 (FOXO3α) is a key regulator of oxidative stress-related responses. We hypothesize FOXO3α is a direct upstream regulator of the autophagy pathway, and its upregulation is compromised in diabetic patients during stress of cardiopulmonary bypass (CPB). METHODS: The study enrolled 32 diabetic and 33 nondiabetic patients undergoing a cardiac surgical procedure on CPB. Right atrial tissue and serum samples were collected before and after CPB per protocol. A set of key components were quantitatively assessed and compared by microarray, immunoblotting, and immunohistochemistry studies. Data were analyzed using paired or unpaired student test. A P of <.05 or less was considered significant. RESULTS: Serum microarray showed FOXO3α was upregulated in the diabetic vs nondiabetic group after CPB (P = .033), autophagy-related 4B gene and Beclin 1 gene were greatly upregulated in the nondiabetic group (P = .028 and P = .002, respectively). On immunoblotting, there was upregulation of FOXO3α in the nondiabetic patients after CPB (P = .003). There were increased levels of Beclin-1, Bcl-2, and light chain 3B after CPB in the nondiabetic group only (P = .016, P = .005, P = .002, respectively). Sirtuin 1, Unc-51-like autophagy activating kinase 1 (ULK1), peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α), and mammalian target of rapamycin (mTOR) were not significantly changed in the nondiabetic group after CPB. CONCLUSIONS: Compared with nondiabetic patients, there was no significant upregulation of FOXO3α in diabetic patients, which could possibly explain the lack of upregulation of the autophagy process after CPB. FOXO3α could potentially serve as a therapeutic target to improve cellular homeostasis.

Innominate Vein Injury Secondary to First-Time Sternotomy.

Innominate vein injury is a known potential complication of redo sternotomy, but transection of the innominate vein after first-time median sternotomy has not been previously described. A 71-year-old woman experienced left innominate vein transection upon division of the sternum for coronary artery bypass grafting. Subsequent massive bleeding required digital compression of the transected vessel ends, open manual cardiac massage, institution of a massive transfusion protocol, and pharmacologic support before hemodynamic control was gained by instituting cardiopulmonary bypass. Left innominate vein injury can occur with both first-time and redo sternotomy.

Prevalence and Outcomes of Isolated Tricuspid Valve Surgery Among Medicare Beneficiaries.

We sought to characterize the clinical outcomes and to identify predictors of mortality undergoing isolated tricuspid valve surgery in the United States. We identified 5,164 patients undergoing isolated tricuspid valve surgery from the Centers for Medicare and Medicaid Services Medicare Provider Analysis and Review data between January 2003 and December 2014. The primary outcome was all cause 1-year mortality. A backward elimination method was performed to identify predictors of 1-year mortality. Tricuspid valve repair was performed in 2,494 (48.3%) patients and tricuspid valve replacement was performed in 2,670 (51.7%) patients. Perioperative and 1-year mortality rates were 9.9% and 24.1%, respectively. Predictors of 1-year mortality were age (p <0.001), chronic heart failure (p = 0.001, cirrhosis (p <0.001), carcinoid syndrome (p <0.001), chronic kidney disease (p = 0.001), secondary pulmonary hypertension (p = 0.023), endocarditis (p = 0.005), decubitus ulcer (p <0.001), malnutrition (p <0.001), replacement (p = 0.013), emergency procedure (p <0.001), and preprocedural shock (p <0.001). The C-statistic for 1-year mortality was 0.70 (95% confidence interval, 0.67 to 0.73). In conclusion, isolated tricuspid valve surgery is infrequently performed in the United States, and is associated with high 1-year mortality. Patients at higher risk for mortality can be identified based on the presence of a number of comorbidities at the time of surgery.

Changes in Tricuspid Annular Geometry in Patients with Functional Tricuspid Regurgitation.

OBJECTIVE: To determine whether the indices of tricuspid annular dynamics that signify irreversible tricuspid valvular remodeling can improve surgical decision making by helping to better identify patients with functional tricuspid regurgitation who could benefit from annuloplasty. DESIGN: Retrospective analysis study. SETTING: Tertiary hospital. PARTICIPANTS: A total number of 55 patients were selected, 18 with functional tricuspid valve (TV) regurgitation and 37 normal nonregurgitant TVs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: When comparing the basal, mid, and longitudinal diameters of the right ventricle between the nonregurgitant valve (NTR) group and the functional tricuspid regurgitation (FTR) group, tricuspid annulus was more dilated (p < 0.001, p = 0.001, and p = 0.006, respectively) and less nonplanar (p < 0.001) in the FTR group. At end-systole (ES), the posterolateral-anteroseptal axis was significantly greater in the FTR group than in the NTR group (mean difference = 7.15 mm; p < 0.001). The right ventricle in the FTR group was also significantly dilated with greater leaflet restriction (p = 0.015). CONCLUSIONS: As compared to NTR TVs, FTR is associated with identifiable indices of tricuspid annular structural changes that are indicative of irreversible remodeling.

Tricuspid annulus: A spatial and temporal analysis.

BACKGROUND: Traditional two-dimensional (2D) echocardiographic evaluation of tricuspid annulus (TA) dilation is based on single-frame measurements of the septolateral (S-L) dimension. This may not represent either the axis or the extent of dynamism through the entire cardiac cycle. In this study, we used real-time 3D transesophageal echocardiography (TEE) to analyze geometric changes in multiple axes of the TA throughout the cardiac cycle in patients without right ventricular abnormalities. MATERIALS AND METHODS: R-wave-gated 3D TEE images of the TA were acquired in 39 patients undergoing cardiovascular surgery. The patients with abnormal right ventricular/tricuspid structure or function were excluded from the study. For each patient, eight points along the TA were traced in the 3D dataset and used to reconstruct the TA at four stages of the cardiac cycle (end- and mid-systole, end- and mid-diastole). Statistical analyses were applied to determine whether TA area, perimeter, axes, and planarity changed significantly over each stage of the cardiac cycle. RESULTS: TA area (P = 0.012) and perimeter (P = 0.024) both changed significantly over the cardiac cycle. Of all the axes, only the posterolateral-anteroseptal demonstrated significant dynamism (P < 0.001). There was also a significant displacement in the vertical axis between the points and the regression plane in end-systole (P < 0.001), mid-diastole (P = 0.014), and mid-systole (P < 0.001). CONCLUSIONS: The TA demonstrates selective dynamism over the cardiac cycle, and its axis of maximal dynamism is different from the axis (S-L) that is routinely measured with 2D TEE.

Prosthetic Aortic Valve Fixation Study: 48 Replacement Valves Analyzed Using Digital Pressure Mapping.

OBJECTIVE: Prostheses attachment is critical in aortic valve replacement surgery, yet reliable prosthetic security remains a challenge. Accurate techniques to analyze prosthetic fixation pressures may enable the use of fewer sutures while reducing the risk of paravalvular leaks (PVL). METHODS: Customized digital thin film pressure transducers were sutured between aortic annulus models and 21-mm bioprosthetic valves with 15 × 4-mm, 12 × 4-mm, or 9 × 6-mm-wide pledgeted mattress sutures. Simulating open and minimally invasive access, 4 surgeons, blinded to data acquisition, each secured 12 valves using manual knot-tying (hand-tied [HT] or knot-pusher [KP]) or automated titanium fasteners (TFs). Real-time pressure measurements and times were recorded. Two-dimensional (2D) and 3D pressure maps were generated for all valves. Pressures less than 80 mm Hg were considered at risk for PVL. RESULTS: Pressures under each knot (intrasuture) fell less than 80 mm Hg for 12 of 144 manual knots (5/144 HT, 7/144 KP) versus 0 of 288 TF (P < 0.001). Pressures outside adjacent sutures (extrasuture) were less than 80 mm Hg in 10 of 60 HT, zero of 60 KP, and zero of 120 TF sites for 15 × 4-mm valves; 17 of 48 HT, 25 of 48 KP, and 12 of 96 TF for 12 × 4-mm valves; and 15 of 36 HT, 17 of 36 KP, and 9 and 72 TF for 9 × 6-mm valves; P < 0.001 all manual versus TF. Annular areas with pressures less than 80 mm Hg ranged from 0% of the sewing-ring area (all open TF) to 31% (12 × 4 mm, KP). The average time per manual knot, 46 seconds (HT, 31 seconds; KP, 61 seconds), was greater than TF, 14 seconds (P < 0.005). CONCLUSIONS: Reduced operative times and PVL risk would fortify the advantages of surgical aortic valve replacement. This research encourages continued exploration of technical factors in optimizing prosthetic valve security.

Effect of flexing and massage on in vivo human skin penetration and toxicity of zinc oxide nanoparticles.

AIM: We assessed the effects of flexing and massage on human skin penetration and toxicity of topically applied coated and uncoated zinc oxide nanoparticles (˜75 nm) in vivo. MATERIALS & METHODS: Noninvasive multiphoton tomography with fluorescence lifetime imaging was used to evaluate the penetration of nanoparticles through the skin barrier and cellular apoptosis in the viable epidermis. RESULTS: All nanoparticles applied to skin with flexing and massage were retained in the stratum corneum or skin furrows. No significant penetration into the viable epidermis was seen and no cellular toxicity was detected. CONCLUSION: Exposure of normal in vivo human skin to these nanoparticles under common in-use conditions of flexing or massage is not associated with significant adverse events.

Enhanced delivery of nano- and submicron particles using elongated microparticles.

Nanodermatology is a rapidly emerging field of study receiving significant interest because of its potential application in the prevention and treatment of skin diseases. However, nanoparticulate penetration into and through the skin is not feasible through topical application alone. Many physical and chemical approaches have been developed to enhance particulate penetration into skin. The most successful have been physical penetration enhancers. We have found that elongated microparticles can significantly improve topical nano- and microsphere delivery in an in vivo porcine model. The delivery efficiency was inversely related to the diameter of the payload. These data support a role for elongated microparticle enhanced delivery of nano- and submicron particulate cosmeceutical or therapeutic applications.

Dynamism of the mitral annulus: a spatial and temporal analysis.

OBJECTIVE: In this study, the authors sought to investigate the extent and timing of changes in mitral annular area during the cardiac cycle. Particularly, the authors assessed whether these changes were limited to the posterior part of the annulus or were more global in nature. DESIGN: Prospective, observational study SETTING: Tertiary care university hospital PARTICIPANTS: Twenty three patients undergoing non-valvular cardiac surgery and 3 patients undergoing vascular procedures. INTERVENTIONS: Intraoperative 3-dimensional transesophageal echocardiographic data obtained from patients with normal mitral valves undergoing non-valvular cardiac surgery were analyzed geometrically. Annular areas and diameters were measured during various stages of the cardiac cycle. Intertrigonal distance also was measured using 3D data. MEASUREMENTS AND MAIN RESULTS: Both anterior and posterior portions of the mitral annulus demonstrated dynamism throughout the cardiac cycle. The expansion phase ranged from mid-systole to early-diastole, whereas mid-diastole to early-systole was characterized by an annular contraction phase. Area changes were contributed equally by anterior and posterior parts of the annulus. Annular dimensions increased in accordance with mitral annular area (p<0.05). Echocardiographically-identified intertrigonal distance showed the least delta change. CONCLUSIONS: Both the anterior and posterior parts of the annulus contribute to changes in mitral annular area, which undergoes discrete expansion and contraction phases that extend into both systole and diastole. Compared to other annular dimensions, the echocardiographically-identified intertrigonal distance does not change significantly during the cardiac cycle.

The effect of formulation on the penetration of coated and uncoated zinc oxide nanoparticles into the viable epidermis of human skin in vivo.

The use of nanoparticulate zinc oxide (ZnO-NP) in sunscreens and other cosmetic products has raised public health concerns. The two key issues are the extent of exposure to ZnO-NP and the likely hazard after the application of ZnO-NP in sunscreen and cosmetic products to humans in vivo. Our aims were to assess exposure by the extent of ZnO-NP penetration into the viable epidermis and hazard by changes in the viable epidermal redox state for a number of topical products. Of particular interest is the role of the particle coating, formulation used, and the presence of any enhancers. Multiphoton tomography with fluorescence lifetime imaging microscopy (MPT-FLIM) was used to simultaneously observe ZnO-NP penetration and potential metabolic changes within the viable epidermis of human volunteers after topical application of various ZnO-NP products. Coated and uncoated ZnO-NP remained in the superficial layers of the SC and in the skin furrows. We observed limited penetration of coated ZnO-NP dispersed in a water-in-oil emulsion formulation, which was predominantly localized adjacent to the skin furrow. However, the presence of ZnO-NP in the viable epidermis did not alter the metabolic state or morphology of the cells. In summary, our data suggest that some limited penetration of coated and uncoated ZnO-NP may occur into viable stratum granulosum epidermis adjacent to furrows, but that the extent is not sufficient to affect the redox state of those viable cells.

Gold nanoparticle penetration and reduced metabolism in human skin by toluene.

PURPOSE: To measure penetration and metabolic effects of ion-stabilized, polar, 15 nm gold nanoparticles in aqueous solution (AuNP-Aq) and sterically stabilized, non-polar, 6 nm gold nanoparticles in toluene (AuNP-TOL) on excised human skin. METHODS: Gold nanoparticles were characterized with dynamic light scattering and transmission electron microscopy (TEM). Skin penetration studies were done on frozen or fresh excised skin using static Franz diffusion cells. Viable treated skin was assessed by dermoscopy, reflectance confocal microscopy (RCM), multiphoton tomography (MPT) with fluorescence lifetime imaging microscopy (FLIM), and TEM. RESULTS: Dermoscopy and RCM showed large aggregates in the furrows of AuNP-Aq-treated skin. Treatment of thawed and viable skin only showed enhanced permeability to nanoparticles in the AuNP-TOL group with MPT and FLIM imaging to stratum spinosum of epidermis. TEM analysis revealed gold nanoparticles within AuNP-treated stratum corneum. FLIM analysis of NAD(P)H showed a significant decrease in total NAD(P)H in all toluene-treated groups. CONCLUSIONS: Gold nanoparticles, 15 nm, in aqueous solution aggregated on the skin surface. Toluene treatment eliminated skin metabolism; skin treated with toluene/gold nanoparticles (6 nm) for 24 h, but not at 4 h, showed increased nanoparticle permeability. These results are of value to nanotoxicology.