Impact of prior coronary artery bypass grafting and coronary lesion complexity on outcomes of transcatheter aortic valve replacement for severe aortic stenosis.

OBJECTIVE: To investigate the impact of prior coronary artery bypass grafting (CABG) and coronary lesion complexity on transcatheter aortic valve replacement (TAVR) outcomes for aortic stenosis. METHODS: Clinical outcomes of TAVR were retrospectively compared between patients with and without prior CABG, and between patients with prior CABG and without coronary artery disease (CAD). The impact of the CABG SYNTAX score was also evaluated in patients with prior CABG. RESULTS: The study included 1042 patients with a median age and follow-up of 82 years and 25 (range: 0-72) months, respectively. Of these, 175 patients had a history of CABG, while 401 were free of CAD. Patients with prior CABG were more likely to be male and had higher rates of diabetes, peripheral artery disease and atrial fibrillation compared with patients without prior CABG. After 2 : 1 propensity score matching, all-cause mortality (P = 0.17) and the composite of all-cause mortality, stroke and coronary intervention (P = 0.16) were similar between patients with (n = 166) and without (n = 304) prior CABG. A 1 : 1 propensity score-matched analysis, however, showed lower rates of all-cause mortality (P = 0.04) and the composite outcome (P = 0.04) in patients with prior CABG (n = 134) compared with patients without CAD (n = 134). The median CABG SYNTAX score was 16 (interquartile range: 9.0-23), which was not associated with better/worse clinical outcomes in patients with prior CABG. CONCLUSION: Prior CABG may positively affect mid-term TAVR outcomes for aortic stenosis compared with no CAD when adjusted for other comorbidities. The CABG SYNTAX score did not influence the prognosis after TAVR.

Impact of coronary artery disease and revascularization on outcomes of transcatheter aortic valve replacement for severe aortic stenosis.

BACKGROUND/PURPOSE: To evaluate the impact of coronary artery disease (CAD), percutaneous coronary intervention (PCI), and coronary lesion complexity on outcomes of transcatheter aortic valve replacement (TAVR) for aortic stenosis. METHODS/MATERIALS: This retrospective study included 1042 patients divided into two groups by the presence or absence of CAD (SYNTAX score 0, no history of revascularization). Propensity score matching was used to compare the two groups. The effect of PCI, SYNTAX score, and residual SYNTAX score was also analyzed. RESULTS: The median age of the cohort was 82 years, and 641 patients had CAD. After propensity score matching, 346 pairs were analyzed. During 5 years of follow-up (median: 25, range 0-72 months), the rate of coronary intervention was significantly higher in CAD patients (p = 0.018). However, all-cause mortality, composite of all-cause mortality, stroke, and coronary intervention, and overt bleeding defined by VARC-3 were comparable. After stratification, in patients with creatinine ≥1.5 mg/dl, CAD was associated with a worse composite outcome (p = 0.016). Neither PCI nor SYNTAX score was associated with all-cause mortality in CAD patients. Similarly, residual SYNTAX score showed no association with mortality in patients undergoing PCI (all p values >0.7). PCI did not reach a significant difference in overt bleeding in CAD patients (adjusted p = 0.06). CONCLUSIONS: Despite a higher incidence of coronary interventions, major clinical outcomes were similar between patients with and without CAD after TAVR. In patients with chronic kidney disease, CAD may be associated with an adverse composite outcome. Neither PCI nor SYNTAX/residual SYNTAX score influenced all-cause mortality.

Improved Hemodynamics With Self-Expanding Compared to Balloon-Expandable Transcatheter Aortic Valve Implantation in Small Annulus Patients: A Propensity-Matched Analysis.

Patients with small aortic annuli (SAA) pose a challenge in patients undergoing aortic valve replacement because of the potential for prosthesis-patient mismatch (PPM). This study aimed to compare the clinical and hemodynamic outcomes of self-expandable valve (SEV) versus balloon-expandable valve (BEV) transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis and SAA. All patients who underwent TAVI for severe native aortic stenosis with a SAA between January 2018 and December 2022 were retrospectively included in the study from a single center. Propensity score matching was performed to balance the baseline characteristics. Bioprosthesis valve dysfunction was based on modified Valve Academic Research Consortium 3 criteria. A total of 1,170 TAVI procedures were performed between 2018 and 2022. After applying the exclusion criteria, 332 patients reported a SAA at computed tomography scan, and the matching created 109 balanced pairs. Echocardiographic data at discharge showed higher mean transvalvular gradients (p <0.001), higher grades of mitral regurgitation (p = 0.029), and lower ejection fraction (p <0.043) in BEVs than SEVs. At follow-up, significant differences favoring the SEV group regarding bioprosthesis valve dysfunction were observed (p = 0.002), especially in terms of severe PPM (p = 0.046) and at least moderate structural valve deterioration (p = 0.040). In conclusion, TAVI in patients with SAA using a BEV was associated with lower valve areas, higher mean pressure gradients, and PPM (including severe) than a SEV. Short- and midterm all-cause and cardiac-related mortality did not differ between the 2 groups. Future randomized studies with extended follow-ups are warranted to validate these outcomes.

Clinical utility of plasma Aß42/40 ratio by LC-MS/MS in Alzheimer's disease assessment.

Introduction: Plasma Aß42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear. Methods: Aß42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecutive clinical specimens submitted for Aß42/40 testing. Results: High diagnostic sensitivity and negative predictive value (NPV) for Aß-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aß42/40 values for individuals with positive vs. negative Aß-PET results. Assuming a moderate prevalence of Aß-PET positivity, a cutpoint was identified with 99% NPV, which could help predict that AD is likely not the cause of patients' cognitive impairment and help reduce PET evaluation by about 40%. Conclusion: High-throughput plasma Aß42/40 LC-MS/MS assays can help identify patients with low likelihood of AD pathology, which can reduce PET evaluations, allowing for cost savings.

New plasma LC-MS/MS assays for the quantitation of beta-amyloid peptides and identification of apolipoprotein E proteoforms for Alzheimer's disease risk assessment.

Early detection of Alzheimer's disease (AD) represents an unmet clinical need. Beta-amyloid (Aß) plays an important role in AD pathology, and the Aß42/40 peptide ratio is a good indicator for amyloid deposition. In addition, variants of the apolipoprotein E (APOE) gene are associated with variable AD risk. Here, we describe the development and validation of high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for plasma Aß40 and Aß42 quantitation, as well as apolipoprotein E (ApoE) proteotype determination as a surrogate for APOE genotype. Aß40 and Aß42 were simultaneously immunoprecipitated from plasma, proteolytically digested, and quantitated by LC-MS/MS. ApoE proteotype status was qualitatively assessed by targeting tryptic peptides from the ApoE2, ApoE3, and ApoE4 proteoforms. Both assays were validated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Within-run precision was 1.8%-4.2% (Aß40), 1.9%-7.2% (Aß42), and 2.6%-8.3% (Aß42/40 ratio). Between-run precision was 3.5%-5.9% (Aß40), 3.8%-8.0% (Aß42), and 3.3%-8.7% (Aß42/40 ratio). Both Aß40 and Aß42 were linear from 10 to 2500 pg/mL. Identified ApoE proteotypes had 100% concordance with APOE genotypes. We have developed a precise, accurate, and sensitive high-throughput LC-MS/MS assay for plasma Aß40, Aß42, and proteoforms of ApoE.

Direct aortic cannulation versus femoral arterial cannulation for early outcomes in acute type A aortic dissection: A study-level meta-analysis.

PURPOSE: To investigate the impact of direct aortic cannulation (DAC) versus femoral arterial cannulation (FAC) on clinical outcomes of surgery for acute type A aortic dissection. METHODS: PubMed/MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials were searched until August 25, 2023, to conduct a meta-analysis. Primary endpoints of the study were operative mortality and postoperative stroke. Secondary endpoints were cardiopulmonary bypass time, myocardial ischemic time, hypothermic circulatory arrest time, temporary neurological dysfunction (TND), combined stroke and TND, re-exploration for bleeding, and need for renal replacement therapy. A random-effect model was used to estimate the pooled effect size, and a leave-one-out method was used for the primary endpoints for sensitivity analysis. RESULTS: 15 studies met our eligibility criteria, including a total of 7941 samples. Operative mortality was significantly lower in the DAC group with a pooled odds ratio (OR) of 0.72 [95% confidence interval (CI): 0.61-0.85)]. Incidence of postoperative stroke was also lower in the DAC group with a pooled OR of 0.79 (95% CI: 0.66-0.94). However, after excluding one study with the greatest weight, the difference became nonsignificant. DAC was also associated with a lower incidence of postoperative TND, and re-exploration for bleeding with a pooled OR of 0.52 (95% CI: 0.37-0.73), and 0.60 (95% CI: 0.47-0.77), respectively. CONCLUSIONS: This meta-analysis showed that patients who underwent ATAAD repair with DAC had a lower incidence of operative mortality, postoperative stroke, TND, and re-exploration for bleeding compared to those who underwent FAC.

Aortic versus axillary cannulation in acute type A aortic dissection repair: A meta-analysis.

BACKGROUND: Research comparing the effectiveness of central aortic cannulation to axillary artery cannulation in repairing acute type A aortic dissection is limited and controversial. This meta-analysis aimed to compare early outcomes of central aortic cannulation versus axillary artery cannulation for surgery for acute aortic dissection type A. METHODS: A comprehensive systematic search was conducted across PubMed/MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials up to September 1, 2023. The primary endpoints were operative mortality and incidence of postoperative stroke. Secondary endpoints encompassed cardiopulmonary bypass time, myocardial ischemic time, hypothermic circulatory arrest time, postoperative temporary neurological dysfunction, combination of stroke and temporary neurological dysfunction, as well as the need for reexploration for bleeding, renal replacement therapy, and tracheotomy. A random-effect model was utilized to calculate the pooled effect size. RESULTS: Eleven studies met our eligibility criteria, enrolling a total of 7204 patients (2760 underwent aortic cannulation and 4444 underwent axillary cannulation). The operative mortality and incidence of postoperative stroke did not show statistical differences between the two groups, with a pooled odds ratio of 1.07 (95% confidence interval: 0.73-1.55) and 1.17 (0.95-1.42), respectively. Similarly, none of the secondary endpoints exhibited significant statistical differences between the two groups. CONCLUSIONS: Aortic cannulation can be a viable alternative to axillary artery cannulation for repair of acute aortic dissection type A, as both approaches present similar early clinical outcomes.

Impact of mitral stenosis on early and late outcomes of transcatheter aortic valve replacement for aortic stenosis: a single-center analysis.

OBJECTIVES: To assess the impact of concomitant mitral stenosis (MS) on early and late outcomes of transcatheter aortic valve replacement (TAVR) for aortic stenosis. METHODS: This study involved 952 patients undergoing TAVR for severe tricuspid aortic stenosis. The patients were classified into 3 groups: without MS, with progressive MS, and severe MS (mitral valve area ≤ 1.5 cm2). Clinical outcomes between these groups were compared. RESULTS: The median age of the overall cohort was 82 years, and patients in the progressive (n = 49) and severe (n = 24) MS groups were more likely to be female than those in the no-MS group (n = 879). Periprocedural mortality rate was lowest in the no-MS group (1.8%) compared with the progressive (4.1%) and severe (4.2%) MS groups, which were not significantly different (P = .20). During 5 years of follow-up (median: 27, range: 0-72 months), there was no significant difference in all-cause mortality (log-rank P = .99), a composite of all-cause mortality or rehospitalization for heart failure (log-rank P = .84), or cardiovascular death (log-rank P = .57) between groups. Although crude analysis showed a significant difference in rehospitalization for heart failure in the severe MS group compared with the no-MS group (P = .049), the difference was not significant in the multivariate analysis (adjusted hazard ratio: 1.36 [95% CI, 0.66-2.80], P = .41). CONCLUSIONS: TAVR can be safely performed in patients with severe tricuspid aortic stenosis and concomitant MS, with early and mid-term outcomes comparable to those in patients without MS.

Clinical utility of plasma Aß42/40 ratio by LC-MS/MS in Alzheimer's disease assessment.

INTRODUCTION: Plasma Aß42/40 ratio can be used to help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear. METHODS: Aß42/40 ratio was measured by LC-MS/MS in 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and 6,192 consecutive clinical specimens submitted for Aß42/40 testing. RESULTS: High diagnostic sensitivity and negative predictive value (NPV) for Aß-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aß42/40 values for individuals with positive vs negative Aß-PET results. Assuming a moderate prevalence of Aß-PET positivity, a cutpoint was identified with 99% NPV, which could help predict that AD is likely not the cause of patients' cognitive impairment and help reduce PET evaluation by about 40%. DISCUSSION: Using high-throughput plasma Aß42/40 LC-MS/MS assays can help reduce PET evaluations in patients with low likelihood of AD pathology, allowing for cost savings.

Antibody-Free Quantification of Serum Chromogranin A by Targeted Mass Spectrometry.

BACKGROUND: Chromogranin A (CgA) is a 48 kDa protein that serves as a diagnostically sensitive, but nonspecific, serum biomarker for neuroendocrine tumors. Immunoassays for CgA are not standardized and have a narrow dynamic range, which requires dilution of concentrated specimens. We developed and validated an antibody-free, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method for CgA without these limitations. METHODS: CgA was extracted from serum using a mixed-mode anion exchange solid-phase extraction plate, digested with trypsin, and analyzed by LC-MS/MS using well-characterized CgA calibration standards. After validation, the mass spectrometry method was compared with the CISBIO immunoassay using 200 serum specimens previously submitted for CgA analysis. Specimens with discordant results were reanalyzed by high-resolution mass spectrometry- (HRMS) -based methods to assess the contribution of truncated and post-translationally modified forms of CgA. RESULTS: The assay had a linear range of 50 to 50 000 ng/mL, recoveries between 89% and 115%, and intra- and interassay imprecision <10%. LC-MS/MS assay results showed a Pearson's correlation of r = 0.953 with the CISBIO immunoassay, with CgA values being a mean 2- to 4-fold higher. Concordance for CgA between the 2 assays was 80.9% (95% CI 72.8%-89.2%), showing substantial agreement. Truncation and posttranslational modification, including 2 phosphorylation sites that had not been previously observed or predicted to our knowledge, did not appear to contribute directly to discordance between the 2 assays. CONCLUSION: Quantification of CgA by LC-MS/MS provides an analytically sensitive and reproducible alternative to commercially available immunoassays.

Transcatheter and ministernotomy aortic valve replacement after bioprosthetic valve failure.

BACKGROUND: Transcatheter valve-in-valve implantation (TViV) and minimally invasive reoperative aortic valve replacement (MIrAVR) have rapidly increased as alternatives to conventional reoperative surgical AVR. This study reports a single-center experience of patients undergoing TViV and MIrAVR after bioprosthetic valve failure. METHODS: In this retrospective review between March 2009 and October 2018, 68 patients without reoperative full sternotomies, concomitant procedures, active endocarditis, and prior homografts or coronary artery bypass grafting underwent isolated AVR for degenerated aortic bioprostheses. Society of Thoracic Surgeons (STS) risk scores and age are reported as median (interquartile range [IQR]) and length of stay is reported as mean (standard deviation [SD]) due to their characteristics of the distribution. RESULTS: Forty-one (60.3%) patients underwent TViV, and 27 (39.7%) patients underwent MIrAVR. Median [IQR] STS risk scores were 5.7 [4.0-7.8] and 2.0 [1.5-3.4] for TViV and MIrAVR, respectively (p ≤ .001). The median [IQR] age for TViV patients was higher (78 [71-84] vs. 66 [53-72] years, p ≤ 0.001). More permanent pacemakers were implanted (22.2% vs. 9.8%) following MIrAVR. The MIrAVR group had a higher rate of atrial fibrillation (18.5% vs. 9.8%, p = .466). Average (SD) length of stay was less in TViV (5.3 days, SD: 3.4 vs. 8.6 days, SD: 7.4, p = .001). Survival at 1 year was not significantly different for TViV and MIrAVR (94.9% [95% confidence interval [CI]: 81.0%, 98.7%] and 86.9% [95% CI: 64.0%, 95.7%], respectively [p = .969]). CONCLUSIONS: Despite being at higher-risk, patients undergoing TViV had reduced rates of permanent pacemaker implantations and atrial fibrillation, and a shorter hospital stay as compared to MIrAVR. Survival at 1-year was similar between the two groups.

High-Throughput Mass Spectrometry Assay for Quantifying ß-Amyloid 40 and 42 in Cerebrospinal Fluid.

BACKGROUND: The ratio of ß-amyloid 1-42 (Aß42) to Aß40 in cerebrospinal fluid (CSF) may be useful for evaluating Alzheimer disease (AD), but quantification is limited by factors including preanalytical analyte loss. We developed an LC-MS/MS assay that limits analyte loss. Here we describe the analytical characteristics of the assay and its performance in differentiating patients with AD from non-AD dementia and healthy controls. METHODS: To measure Aß42/Aß40, we used unique proteolytically derived C-terminal peptides as surrogate markers of Aß40 and Aß42, which were analyzed and quantified by LC-MS/MS. The assay was analytically validated and applied to specimens from individuals with clinically diagnosed AD (n = 102), mild cognitive impairment (n = 37), and non-AD dementias (n = 22), as well as from healthy controls (n = 130). Aß42/Aß40 values were compared with APOE genotype inferred from phenotype, also measured by LC-MS/MS. RESULTS: The assay had a reportable range of 100 to 25000 pg/mL, a limit of quantification of 100 pg/mL, recoveries between 93% and 111%, and intraassay and interassay CV <15% for both peptides. An Aß42/Aß40 ratio cutoff of <0.16 had a clinical sensitivity of 78% for distinguishing patients with AD from non-AD dementia (clinical specificity, 91%) and from healthy controls (clinical specificity, 81%). The Aß42/Aß40 ratio decreased significantly (P < 0.001) with increasing dose of APOE4 alleles. CONCLUSIONS: This assay can be used to determine Aß42/Aß40 ratios, which correlate with the presence of AD.

Incidence, Natural History, and Factors Associated With Paravalvular Leak Following Surgical Aortic Valve Replacement.

Objective: Our study investigates the incidence, cumulative incidence, natural history, and factors associated with intraoperative paravalvular leak (PVL) and the development of a postoperative PVL in a contemporary consecutive cohort of patients following surgical aortic valve replacement. Methods: A total of 636 patients underwent surgical aortic valve replacement from 2006 to 2016; 410 (64.5%) underwent minimally invasive aortic valve replacement and 226 (35.5%) underwent conventional aortic valve replacement. Primary outcomes were the incidence of intraoperative PVL and cumulative incidence of postoperative PVL. Secondary outcomes were the incidence of in-hospital and long-term death and need for reoperation. Results: The overall incidence of intraoperative PVL was 1.4% (95% confidence interval [CI]: 1% to 3%). All intraoperative PVLs developed in the hand-tied group. The overall incidence of postoperative PVL was 5.3% (95% CI: 4% to 7%). In the univariable and multivariable analyses, postoperative renal failure was the only factor significantly associated with the development of a postoperative PVL. Conclusions: The incidence of intraoperative PVL is low. Cumulative incidence of postoperative PVL was 3.1% (95% CI: 1.0% to 13.6%), 4.3% (95% CI: 1.3% to 16.5%), and 5.0% (95% CI: 1.4% to 17.9%) at 1, 3, and 5 years, respectively. All intraoperative PVLs occurred with hand-tied knots. A larger cohort may identify additional risk factors.

Ministernotomy aortic valve surgery in patients with prior patent mammary artery grafts after coronary artery bypass grafting.

OBJECTIVES: Patients with patent internal thoracic artery (ITA) grafts after prior coronary artery bypass grafting surgery who require aortic valve replacement (AVR) pose unique technical challenges for safe and optimal myocardial protection. The purpose of this study is to review our short- and long-term outcomes with redo minimally invasive AVR in patients with patent in situ ITA grafts. METHODS: From 2008 to 2016, 48 patients with at least 1 patent in situ mammary artery graft underwent minimally invasive AVR. Preoperative computed tomography was performed in all patients to evaluate the relationship of patent grafts to the sternum. Retrograde coronary sinus and pulmonary vent catheters were placed via the right internal jugular vein. The in situ ITA grafts were not clamped during AVR. Transverse aortotomy, taking care to avoid the grafts arising from the aorta, was performed to expose the aortic valve. RESULTS: The median age of the patients was 78 years [Quartile 1 (Q1)-Quartile 3 (Q3): 71-81]. Thirty-nine (81%) patients were men, and 46 (96%) patients had aortic stenosis. The median cardiopulmonary bypass and cross-clamp times were 124 (Q1-Q3: 108-164) and 92 (Q1-Q3: 83-116) min, respectively. Moderate hypothermia at 28-30°C was used in all patients. Most patients received cold blood cardioplegia with antegrade induction and continuous retrograde delivery. Four patients received only retrograde delivery due to some degree of aortic insufficiency. Thirty-day mortality was 4% (2 of 48 patients). There was no conversion to full sternotomy, and no reoperations were performed for postoperative bleeding or sternal wound infection. Excluding the 2 patients who died in the hospital, the median postoperative length of stay was 7 days (Q1-Q3: 5-8). Overall survival at 1, 5 and 10 years was 94%, 87% and 44%, respectively. CONCLUSIONS: Percutaneous retrograde cardioplegia combined with antegrade cardioplegia and moderate hypothermia, without interruption of ITA flow, is a safe and reliable strategy in patients with patent ITA grafts undergoing aortic valve replacement. This strategy combined with a minimally invasive approach may reduce surgical trauma, and is a safe and effective technique in these challenging patients.

Decellularized extracellular matrix microparticles seeded with bone marrow mesenchymal stromal cells for the treatment of full-thickness cutaneous wounds.

Extracellular matrix materials mechanically dissociated into submillimeter particles have a larger surface area than sheet materials and enhanced cellular attachment. Decellularized porcine mesothelial extracellular matrix microparticles were seeded with bone marrow-derived mesenchymal stromal cells and cultured in a rotating bioreactor. The mesenchymal stromal cells attached and grew to confluency on the microparticles. The cell-seeded microparticles were then encapsulated in varying concentrations of fibrin glue, and the cells migrated rapidly off the microparticles. The combination of microparticles and mesenchymal stromal cells was then applied to a splinted full-thickness cutaneous in vivo wound model. There was evidence of increased cell infiltration and collagen deposition in mesenchymal stromal cells-treated wounds. Cell-seeded microparticles have potential as a cell delivery and paracrine therapy in impaired healing environments.

Measurement of Cortisol and Testosterone in Athletes: Accuracy of Liquid Chromatography-Tandem Mass Spectrometry Assays for Cortisol and Testosterone Measurement in Whole-Blood Microspecimens.

Fragala, MS, Goldman, SM, Goldman, MM, Bi, C, Colletti, JD, Arent, SM, Walker, AJ, and Clarke, NJ. Measurement of cortisol and testosterone in athletes: Accuracy of LC-MS/MS assays for cortisol and testosterone measurement in whole-blood microspecimens. J Strength Cond Res 32(9): 2425-2434, 2018-Biomarker monitoring provides insight into athletes' training tolerance but is limited by the need for office-based specimen collection. To facilitate self-collection during training, we developed liquid chromatography-tandem mass spectrometry-based tests that measure circulating total cortisol and testosterone using a finger stick volumetric absorptive microsampler. Here, we describe the analytical validation of these tests. Forty-six Division I athletes (18-22 years, 30 women, 16 men) provided a 20-µL finger stick microspecimen and a 5-ml venous blood specimen from the forearm; the venous blood sample was analyzed using both normal volume serum analysis and analysis of dried whole blood (from the microsampler). Liquid chromatography-tandem mass spectrometry on standard serum specimens obtained by venipuncture yielded total cortisol levels of 26.2 ± 11.6 µg·dl (women and men), and total testosterone levels of 37 ± 17 ng·dl in women and 564 ± 171 ng·dl in men. Analytical measurement ranges of the microspecimen assay were 0.3-440 µg·dl (CV <9%) for cortisol and 15 to 20,000 ng·dl (CV <9%) for testosterone. Deming regression and Pearson correlation indicated good test accuracy for the microspecimen tests compared with venipuncture tests for cortisol (y = 0.98x + 1.34, 95% CI of slope = 0.83-1.14; r = 0.92, p < 0.0001) and testosterone (y = 1.06x - 0.01, 95% CI of slope = 0.99-1.14; r = 0.99, p < 0.0001). Similarly, high agreement was observed between finger stick and venous microspecimens for cortisol (y = 1.00x + 0.65, 95% CI of slope = 0.9-1.11; r = 0.96, p < 0.001) and testosterone (y = 0.97x + 2.75, 95% CI of slope = 0.9-1.03; r = 0.99, p < 0.001). These findings suggest the viability of finger stick collection whole-blood microspecimens for assessment of total cortisol and testosterone in athletes.

In vivo response to decellularized mesothelium scaffolds.

Biological surgical scaffolds are used in plastic and reconstructive surgery to support structural reinforcement and regeneration of soft tissue defects. Macrophage and fibroblast cell populations heavily regulate scaffold integration into host tissue following implantation. In the present study, the biological host response to a commercially available surgical scaffold (Meso BioMatrix Surgical Mesh (MBM)) was investigated for up to 9 weeks after subcutaneous implantation; this scaffold promoted superior cell migration and infiltration previously in in vitro studies relative to other commercially available scaffolds. Infiltrating macrophages and fibroblasts phenotypes were assessed for evidence of inflammation and remodeling. At week 1, macrophages were the dominant cell population, but fibroblasts were most abundant at subsequent time points. At week 4, the scaffold supported inflammation modulation as indicated by M1 to M2 macrophage polarization; the foreign body giant cell response resolved by week 9. Unexpectedly, a fibroblast subpopulation expressed macrophage phenotypic markers, following a similar trend in transitioning from a proinflammatory to anti-inflammatory phenotype. Also, α-smooth muscle actin-expressing myofibroblasts were abundant at weeks 4 and 9, mirroring collagen expression and remodeling activity. MBM supported physiologic responses observed during normal wound healing, including cellular infiltration, host tissue ingrowth, remodeling of matrix proteins, and immune modulation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 716-725, 2018.

In vitro evaluation of decellularized ECM-derived surgical scaffold biomaterials.

Decellularized extracellular matrix (ECM) biomaterials are increasingly used in regenerative medicine for abdominal tissue repair. Emerging ECM biomaterials with greater compliance target surgical procedures like breast and craniofacial reconstruction to enhance aesthetic outcome. Clinical studies report improved outcomes with newly designed ECM scaffolds, but their comparative biological characteristics have received less attention. In this study, we investigated scaffolds derived from dermis (AlloDerm Regenerative Tissue Matrix), small intestinal submucosa (Surgisis 4-layer Tissue Graft and OASIS Wound Matrix), and mesothelium (Meso BioMatrix Surgical Mesh and Veritas Collagen Matrix) and evaluated biological properties that modulate cellular responses and recruitment. An assay panel was utilized to assess the ECM scaffold effects upon cells. Results of the material-conditioned media study demonstrated Meso BioMatrix and OASIS best supported cell proliferation. Meso BioMatrix promoted the greatest migration and chemotaxis signaling, followed by Veritas and OASIS; OASIS had superior suppression of cell apoptosis. The direct adhesion assay indicated that AlloDerm, Meso BioMatrix, Surgisis, and Veritas had sidedness that affected cell-material interactions. In the chick chorioallantoic membrane assay, Meso BioMatrix and OASIS best supported cell infiltration. Among tested materials, Meso BioMatrix and OASIS demonstrated characteristics that facilitate scaffold incorporation, making them promising choices for many clinical applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 585-593, 2017.