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Abstract Ratiometric quantitation is used in mass spectrometry to account for variations in ionization efficiencies due to heterogenous sample matrixes. Isotopes are most commonly used to achieve ratiometric quantitation because of their ability to co-elute chromatographically with each other and to have similar ionization efficiencies. In the work presented here, a new non-isotopic quantitative tagging approach is presented which allows chromatographic co-elution and similar ionization efficiencies. Using two variations of maleimide tags, t -butyl and cyclohexyl maleimide, thiols are quantified with a high degree of linearity up to five-fold concentration differences. Because these two tags have similar hydrophobcities, they elute simultaneously which allows them to be used for ratiometric quantitation. Beyond the five-fold linear range, signal compression is observed. This technique was able to quantify thiol changes in both in vitro pharmacological treatments as well as in vivo diabetic tissue. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

OBJECTIVES: Right anterior minithoracotomy with central arterial cannulation is our preferred technique of minimally invasive aortic valve replacement (AVR). We compared perioperative outcomes with this technique to those via sternotomy. METHODS: Between March 1999 and December 2013, 492 patients underwent isolated AVR via either sternotomy (SAVR, n = 198) or minimally invasive right anterior thoracotomy (MIAVR, n = 294) in our institution. Univariate comparisons between groups were made to evaluate overall outcomes and adverse events. To control treatment selection bias, propensity scores were constructed from core patient characteristics. A propensity score-stratified analysis of outcome and adverse events was then performed. RESULTS: Overall mortality was 2.5 and 1.0% in the SAVR and MIAVR groups, respectively. Hospital and ICU stays were shorter, there was less intraoperative blood product usage, and fewer wound infections in the MIAVR group. There were no differences in other adverse events, including strokes. The composite end-point of alive and adverse event-free was significantly more common in the MIAVR group (83 vs 74%, P = 0.002). After adjusting for the propensity score, hospital and ICU stays remained shorter and intraoperative blood product usage remained less in the MIAVR group. There was no difference in mortality, stroke or other adverse events between groups. CONCLUSION: Minimally invasive AVR via an anterior right thoracotomy with predominately central cannulation can be performed with morbidity and mortality similar to that of a sternotomy approach. There appear to be advantages to this minimally invasive approach when compared with sternotomy in terms of less intraoperative blood product usage, lower wound infection rates and decreased hospital stays. If mortality and the occurrence of adverse events are taken together, MIAVR may be associated with better outcomes. As minimally invasive AVR becomes more common, further long-term follow-up is needed and a prospective multicentre randomized trial would be warranted. [ABSTRACT FROM AUTHOR]

Pulmonary sequestration refers to segmental lung tissue that has no connection with the bronchial tree or pulmonary arteries. In adults, the clinical sequelae are usually related to infection. Patients are typically referred for sequestrectomy even when they are asymptomatic. There are no guidelines for treating patients who have pulmonary sequestration and coexisting cardiac valvular disease, in which case the venous drainage patterns of sequestra pose the additional risks of infective endocarditis and volume overload. We present the cases of 2 adult patients--one symptomatic and one asymptomatic--who had concurrent aortic valvular disease and pulmonary sequestration, and we discuss the factors involved in our evaluation of their cardiac risk and our treatment decisions. In view of the sparse data to predict cardiac risks, we think that pulmonary sequestrectomy in adult patients with concurrent valvular conditions should be considered on a case-by-case basis. [ABSTRACT FROM AUTHOR]

The development of transcatheter aortic valve implantation (TAVI) has increased the use of balloon aortic valvuloplasty (BAV) in treating aortic stenosis. We evaluated our use of BAV in an academic tertiary referral center with a developing TAVI program. We reviewed 69 consecutive stand-alone BAV procedures that were performed in 62 patients (mean age, 77±10 yr; 62% men; baseline mean New York Heart Association functional class, 3 ± 1) from January 2009 through December 2012. Enrollment for the CoreValve® clinical trial began in January 2011. We divided the study cohort into 2 distinct periods, defined as pre-TAVI (2009-2010) and TAVI (2011-2012). We reviewed clinical, he-modynamic, and follow-up data, calculating each BAV procedure as a separate case. Stand-alone BAV use increased 145% from the pre-TAVI period to the TAVI period. The mean aortic gradient reduction was 13±10 mmHg. Patients were successfully bridged as intended to cardiac or noncardiac surgery in 100% of instances and to TAVI in 60%. Five patients stabilized with BAV subsequently underwent surgical aortic valve replacement with no operative deaths. The overall in-hospital mortality rate (17.4%) was highest in emergent patients (61%). The implementation of a TAVI program was associated with a significant change in BAV volumes and indications. Balloon aortic valvuloplasty can successfully bridge patients to surgery or TAVI, although least successfully in patients nearer death. As TAVI expands to more centers and higher-risk patient groups, BAV might become integral to collaborative treatment decisions by surgeons and interventional cardiologists. [ABSTRACT FROM AUTHOR]

Background: Residents'' duty-hour limitations and the trends towards closed-staffing for surgical critical care (SCC) have reshaped educational paradigms. No study has yet addressed the impact of these changes on resident SCC training. In our study, we investigated residents'' experiences and perceptions of SCC education and practice. Methods: At the end of the academic year 2007–2008, we distributed anonymous surveys to categorical general surgery residents in a large, university-based residency. All dedicated SCC rotations are currently completed by the end of PGY3. The survey measured residents'' ratings of teaching, experiences, satisfaction, and self-assessed comfort with common SCC diseases and procedures. Results: The response rate was 78% (n = 52/67). At the time of the survey, the 52 respondents had completed 9.3 ± 4.5 wk of SCC rotations. Despite no rotations beyond PGY3, senior residents (PGYs 4/5) reported significantly greater SCC training time (13.1 versus 7.8 wk) and comfort managing SCC diseases and procedures than juniors (PGY 3). Attendings were rated the most effective didactic teachers, and senior residents the most effective procedural teachers. The mean education satisfaction score was 3.9 ± 0.9 (5 = extremely satisfied). Residents anticipated performing minimal SCC management of their own patients, but most felt that SCC-trained surgeons should manage critically ill surgery patients. Seniors reported greater SCC fellowship interest (19% versus 0%). The addition of acute care surgery increased interest in 30% of respondents. Conclusions: Senior residents reported greater comfort with SCC management despite the lack of senior SCC rotations, whilst dedicated training time for junior residents appears to be declining. Residents wish subspecialist care for their critically ill patients, but the low interest in SCC fellowships suggests future physician shortages in this subspecialty. [Copyright &y& Elsevier]

Background: Thromboembolism-in-transit straddling a patent foramen ovale (PFO) is a rare condition that requires urgent surgical intervention to prevent arterial emboli. Case Report: We present the case of a 42-year-old female who presented with a symptomatic pulmonary embolism. Echocardiography identified a PFO, with a bridging thrombus-in-transit and evidence of right ventricular strain. Urgent surgery was performed because of the risk of systemic embolism. A large thrombus was identified during biatrial exploration. Pulmonary embolectomy and primary PFO closure were performed. Conclusion: Because of the 20%-30% incidence of PFOs in the general population, we suggest that echocardiography should be considered for routine surveillance in thromboembolism because of the risk of systemic sequelae. [ABSTRACT FROM AUTHOR]

Bicuspid aortic valve (BAV) is the most common congenital heart lesion with an estimated population prevalence of 1%. We hypothesize that specific gene variants predispose to early-onset complications of BAV (EBAV). We analyzed whole-exome sequences (WESs) to identify rare coding variants that contribute to BAV disease in 215 EBAV-affected families. Predicted damaging variants in candidate genes with moderate or strong supportive evidence to cause developmental cardiac phenotypes were present in 107 EBAV-affected families (50% of total), including genes that cause BAV (9%) or heritable thoracic aortic disease (HTAD, 19%). After appropriate filtration, we also identified 129 variants in 54 candidate genes that are associated with autosomal-dominant congenital heart phenotypes, including recurrent deleterious variation of FBN2 , MYH6 , channelopathy genes, and type 1 and 5 collagen genes. These findings confirm our hypothesis that unique rare genetic variants drive early-onset presentations of BAV disease. [Display omitted] In whole-exome sequences, we identified damaging variants of cardiac developmental genes in half of families with early-onset complications of bicuspid aortic valve (BAV) disease. The discovered gene variants may accelerate the progression of BAV disease and could be used for risk stratification or personalized therapies. [ABSTRACT FROM AUTHOR]

Bicuspid aortic valve (BAV), the most common congenital heart defect, is a major cause of aortic valve disease requiring valve interventions and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications (EBAV) to sporadic late onset disease. Rare genomic copy number variants (CNVs) have previously been implicated in the development of BAV and thoracic aortic aneurysms. We determined the frequency and gene content of rare CNVs in EBAV probands (n = 272) using genome-wide SNP microarray analysis and three complementary CNV detection algorithms (cnvPartition, PennCNV, and QuantiSNP). Unselected control genotypes from the Database of Genotypes and Phenotypes were analyzed using identical methods. We filtered the data to select large genic CNVs that were detected by multiple algorithms. Findings were replicated in a BAV cohort with late onset sporadic disease (n = 5040). We identified 3 large and rare (< 1,1000 in controls) CNVs in EBAV probands. The burden of CNVs intersecting with genes known to cause BAV when mutated was increased in case-control analysis. CNVs intersecting with GATA4 and DSCAM were enriched in cases, recurrent in other datasets, and segregated with disease in families. In total, we identified potentially pathogenic CNVs in 9% of EBAV cases, implicating alterations of candidate genes at these loci in the pathogenesis of BAV. [ABSTRACT FROM AUTHOR]

Bicuspid aortic valve (BAV) is the most common congenital heart malformation in adults, but it can also cause childhood-onset complications. The presentation and clinical course of young adults who present due to BAV complications are relatively uncharacterized. In a multicenter study, we found that young people who experience significant complications related to BAV disease before age 30 are distinguished from the majority of BAV cases that manifest after age 50 by a relatively severe clinical course, with higher rates of surgical interventions, more frequent second interventions, and a greater burden of congenital heart malformations. These observations highlight the need for prompt recognition, regular lifelong surveillance, and targeted interventions to address the significant health burdens of patients with early-onset BAV complications. [ABSTRACT FROM AUTHOR]

Aim: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes).Methods: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate.Structure: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease. [ABSTRACT FROM AUTHOR]

Aim: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes).Methods: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. Structure: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease. [ABSTRACT FROM AUTHOR]

Many patients who are in cardiogenic shock need mechanical support for clinical stabilization after acute insults such as myocardial infarction. However, the placement of advanced devices can be hindered by anatomic constraints or the physiologic sequelae of shock, as we describe in this report. A 67-year-old woman with prior coronary artery bypass grafting and extensive chestwall scarring from previous defibrillator implantations presented with myocardial infarction and refractory cardiogenic shock. The patient's vascular anatomy and prior surgery precluded conventional percutaneous implantation of an Impella 5.0 ventricular support device. We delivered the Impella device through the patient's tortuous, vasoconstricted axillary artery with use of a vascular sheath and other percutaneous techniques. The success of this approach suggests that combining the expertise of cardiologists and cardiovascular surgeons can improve the outcomes of patients with complex anatomic issues. [ABSTRACT FROM AUTHOR]

In Bosnia and Herzegovina, cardiovascular disease accounts for nearly 50% of deaths. Cardiovascular health of resettled Bosnian-Americans has not been well-characterized. Our study aimed to quantify cardiovascular risk in Bosnian-Americans in St. Louis, the largest non-European center of resettlement. Seven community screenings focused on Bosnian-Americans were held. Cardiovascular risk was calculated to stratify individuals into low (<10%), moderate (10-20%), and high (>20%) risk. Those with self-reported coronary heart disease (CHD) or risk equivalent were considered high-risk. Two-hundred fifty Bosnian-Americans were screened; 51% (n = 128) consented to the IRB-approved study. Twenty-one percent were smokers, 33% obese, and 33% had hypertension. Excluding risk equivalent individuals, 5.7% of subjects were high-risk, increasing to 26.6% when including high-risk equivalents. Lipid abnormalities include elevated triglycerides (29.0%) and low HDL (50.0%). Compared to general American population studies, Bosnian-Americans have greater ten-year hard CHD risk. A community-based approach identified potential culturally-based lifestyle interventions including diet, exercise, and smoking. [ABSTRACT FROM AUTHOR]

Analysis of metabolites is often performed using separations coupled to mass spectrometry which is challenging due to their vast structural heterogeneity and variable charge states. Metabolites are often separated based on their class/functional group which in large part determine their acidity or basicity. This charge state dictates the ionization mode and efficiency of the molecule. To improve the sensitivity and expand the coverage of the mammalian metabolome, multifunctional derivatization with sheathless CE-ESI-MS was undertaken. In this work, amines, hydroxyls and carboxylates were labeled with tertiary amines tags. This derivatization was performed in under 100 min and resulted in high positive charge states for all analytes investigated. Amino acids and organic acids showed average limits of detection of 76 nM with good linearity of 0.96 and 10% RSD for peak area. Applying this metabolomic profiling system to bovine aortic endothelial cells showed changes in 15 metabolites after treatment with high glucose. The sample injection volume on-capillary was <300 cells for quantitative analyses. Targeted metabolites were found in human tissue, which indicates possible application of the system complex metabolome quantitation. [ABSTRACT FROM AUTHOR]

Metabolomics, the study of small molecules involved in cellular processes, offers the potential to reveal insights into the pathophysiology of disease states. Analysis of metabolites by electrospray mass spectrometry is complicated by their structural diversity. Amine, hydroxyl, and carboxylate groups all affect signal responses differently based on their polarity and proton affinity. This heterogeneity of signal response, sensitivity, and resistance to competing ionization complicates metabolite quantitation. Such limitations can be mitigated by a dual derivatization scheme. In this work, primary amine and hydroxyl groups are tagged with a linear acyl chloride head containing a tertiary amine tail, followed by carboxylate groups coupled to a linear amine tag with a tertiary amine tail. This tagging scheme increases analyte proton affinity and hydrophobicity. In the case of carboxylate groups, the inherent anionic charge is inverted to a cationic charge. This dual tagging is completed within 2.5 hours, diminishes adduct formation, and improves sensitivity by ＞75-fold. The average limit of detection for 23 metabolites was 38 nM and the R2 was 0.97. This process was used to investigate metabolite changes from human tissue. Examination of diabetic and non-diabetic human tissue showed marked changes in both energy metabolites and amino acids. Further examination of the tissue showed that HbA1C value is inversely correlated with fumarate levels. This technique potentially allows for the analysis of virtually all metabolites in a single analytical run. Thus, it may lead to a more complete picture of metabolic dysfunction in human disease. [ABSTRACT FROM AUTHOR]