Serum glycomic profile as a predictive biomarker of recurrence in patients with differentiated thyroid cancer.

PURPOSE: Thyroid cancer recurrence following curative thyroidectomy is associated with increased morbidity and mortality, but current surveillance strategies are inadequate for early detection. Prior studies indicate that tissue glycosylation is altered in thyroid cancer, but the utility of serum glycosylation in thyroid cancer surveillance remains unexplored. We therefore assessed the potential utility of altered serum glycomic profile as a tumor-specific target for disease surveillance in recurrent thyroid cancer. EXPERIMENTAL DESIGN: We employed banked serum samples from patients with recurrent thyroid cancer post thyroidectomy and healthy controls. N-glycans were enzymatically released from serum glycoproteins, labeled via permethylation, and analyzed by MALDI-TOF mass spectrometry. Global level and specific subtypes of glycan structures were compared between patients and controls. RESULTS: We evaluated 28 independent samples from 13 patients with cancer recurrence and 15 healthy controls. Global features of glycosylation, including N-glycan class and terminal glycan modifications were similar between groups, but three of 35 individual glycans showed significant differences. The three glycans were biosynthetically related biantennary core fucosylated N-glycans that only varied by the degree of galactosylation (G0F, G1F, and G2F; G: galactose, F: fucose). The ratio of G0F:G1F that captures reduced galactosylation was observed in patients samples but not in healthy controls (p = 0.004) and predicted thyroid cancer recurrence (AUC = 0.82, CI 95% = 0.64-0.99). CONCLUSIONS: Altered N-glycomic profile was associated with thyroid cancer recurrence. This serum-based biomarker would be useful as an effective surveillance tool to improve the care and prognosis of thyroid cancer after prospective validation.

Novel fold of rotavirus glycan-binding domain predicted by AlphaFold2 and determined by X-ray crystallography.

The VP8* domain of spike protein VP4 in group A and C rotaviruses, which cause epidemic gastroenteritis in children, exhibits a conserved galectin-like fold for recognizing glycans during cell entry. In group B rotavirus, which causes significant diarrheal outbreaks in adults, the VP8* domain (VP8*B) surprisingly lacks sequence similarity with VP8* of group A or group C rotavirus. Here, by using the recently developed AlphaFold2 for ab initio structure prediction and validating the predicted model by determining a 1.3-Å crystal structure, we show that VP8*B exhibits a novel fold distinct from the galectin fold. This fold with a ß-sheet clasping an α-helix represents a new fold for glycan recognition based on glycan array screening, which shows that VP8*B recognizes glycans containing N-acetyllactosamine moiety. Although uncommon, our study illustrates how evolution can incorporate structurally distinct folds with similar functionality in a homologous protein within the same virus genus.

Regeneration of Free Reducing Glycans from Reductive Amination-Tagged Glycans by Oxone.

Glycans are usually fluorescently tagged by reductive amination for analytic tools. However, free reducing glycan regeneration is sometimes important and necessary for further structural or functional studies. Here, we introduce a new method for efficiently removing fluorescent tags from glycoconjugates by a simple treatment with Oxone. This method is proven to be fast and general after being tested on a series of common saccharides and widely used tags. We successfully achieved N-glycopeptide synthesis by using the regenerated glycans.

SARS-CoV-2 and other coronaviruses bind to phosphorylated glycans from the human lung.

SARS-CoV, MERS-CoV, and potentially SARS-CoV-2 emerged as novel human coronaviruses following cross-species transmission from animal hosts. Although the receptor binding characteristics of human coronaviruses are well documented, the role of carbohydrate binding in addition to recognition of proteinaceous receptors has not been fully explored. Using natural glycan microarray technology, we identified N-glycans in the human lung that are recognized by various human and animal coronaviruses. All viruses tested, including SARS-CoV-2, bound strongly to a range of phosphorylated, high mannose N-glycans and to a very specific set of sialylated structures. Examination of two linked strains, human CoV OC43 and bovine CoV Mebus, reveals shared binding to the sialic acid form Neu5Gc (not found in humans), supporting the evidence for cross-species transmission of the bovine strain. Our findings, revealing robust recognition of lung glycans, suggest that these receptors could play a role in the initial stages of coronavirus attachment and entry.

Structural analysis of carbohydrate binding by the macrophage mannose receptor CD206.

The human mannose receptor expressed on macrophages and hepatic endothelial cells scavenges released lysosomal enzymes, glycopeptide fragments of collagen, and pathogenic microorganisms and thus reduces damage following tissue injury. The receptor binds mannose, fucose, or N-acetylglucosamine (GlcNAc) residues on these targets. C-type carbohydrate-recognition domain 4 (CRD4) of the receptor contains the site for Ca2+-dependent interaction with sugars. To investigate the details of CRD4 binding, glycan array screening was used to identify oligosaccharide ligands. The strongest signals were for glycans that contain either Manα1-2Man constituents or fucose in various linkages. The mechanisms of binding to monosaccharides and oligosaccharide substructures present in many of these ligands were examined in multiple crystal structures of CRD4. Binding of mannose residues to CRD4 results primarily from interaction of the equatorial 3- and 4-OH groups with a conserved principal Ca2+ common to almost all sugar-binding C-type CRDs. In the Manα1-2Man complex, supplementary interactions with the reducing mannose residue explain the enhanced affinity for this disaccharide. Bound GlcNAc also interacts with the principal Ca2+ through equatorial 3- and 4-OH groups, whereas fucose residues can bind in several orientations, through either the 2- and 3-OH groups or the 3- and 4-OH groups. Secondary contacts with additional sugars in fucose-containing oligosaccharides, such as the Lewis-a trisaccharide, provide enhanced affinity for these glycans. These results explain many of the biologically important interactions of the mannose receptor with both mammalian glycoproteins and microbes such as yeast and suggest additional classes of ligands that have not been previously identified.

Limited Neonatal Carbohydrate-Specific Antibody Repertoire Consecutive to Partial Prenatal Transfer of Maternal Antibodies.

Despite the prominence of carbohydrate-specific antibodies in human sera, data on their emergence and antigen specificities are limited. Whereas maternal IgG are transferred prenatally to the fetal circulation, IgM present in cord blood originate from fetal B lymphocytes. Considering the limited exposure of the fetus to foreign antigens, we assessed the repertoire of carbohydrate-specific antibodies in human cord blood and matched maternal blood samples using glycan arrays. Carbohydrate-specific IgM was absent in cord blood, whereas low cord blood IgG reactivity to glycans was detectable. Comparing IgG reactivities of matched pairs, we observed a general lack of correlation in the antigen specificity of IgG from cord blood and maternal blood due to a selective exclusion of most carbohydrate-specific IgG from maternofetal transfer. Given the importance of intestinal bacteria in inducing carbohydrate-specific antibodies, we analyzed global antibody specificities toward commensal bacteria. Similar IgG reactivities to specific Bacteroides species were detected in matched cord and maternal blood samples, thus pointing to an efficient maternal transfer of anti-microbial IgG. Due to the observed selectivity in maternofetal IgG transfer, the lack of fetal antibodies to carbohydrate epitopes is only partially compensated by maternal IgG, thus resulting in a weak response to carbohydrate antigens in neonates.

Timing of Recognition for Perioperative Strokes Following Cardiac Surgery.

INTRODUCTION: More than half of reported perioperative strokes following cardiac surgery are identified beyond postoperative day one. The objective of our study was to determine preoperative and intraoperative factors that are associated with stroke following cardiac surgery and to identify factors that may contribute delayed recognition of perioperative stroke. METHODS: Patients undergoing coronary artery bypass surgery or isolated valve surgery from January 2, 2015 to April 28, 2017 at an academic health system were identified from the Society of Thoracic Surgeons Registry. We determined preoperative and intraoperative factors associated with perioperative stroke. Two neurologists performed retrospective chart reviews on perioperative stroke patients to determine the last seen well time and the stroke cause. RESULTS: During the study period, 2795 patients underwent coronary artery bypass surgery or isolated valve surgery (mean age 64 ± 11 years, 71% male, 72% Caucasian, 9% history of stroke), of which 43 (1.5%) had a perioperative stroke; 31 (72%) patients had an embolic mechanism of stroke based on neuroimaging. In multivariable analysis, perioperative strokes were independently associated with increasing age (OR 1.04, 95% 1.01-1.07), history of stroke (OR 2.73, 95% CI 1.47-5.06), and history of thoracic aorta disease (OR 3.36, 95% CI 1.16-9.71). Strokes were identified after postoperative day one in 32 (74%) patients of which 26 (81%) had a preoperative last seen well time. CONCLUSION: Given the high frequency of preoperative last seen well time in perioperative stroke patients who are identified after postoperative day one, delayed stroke recognition may contribute to the bimodal distribution in timing of perioperative stroke. Frequent neurological monitoring within 24 hours after CABG or isolated valve surgery should be considered for all patients undergoing cardiac surgery, particularly elderly patients and those with a history of stroke or thoracic aorta disease, to improve early stroke recognition.

Increased Antibody Response to Fucosylated Oligosaccharides and Fucose-Carrying Bacteroides Species in Crohn's Disease.

Inflammatory bowel disease is associated with intestinal dysbiosis and with elevated antibody production toward microbial epitopes. The underlying processes linking the gut microbiota with inflammation are still unclear. Considering the constant induction of antibodies by gut microbial glycans, the aim of this study was to address whether the repertoire of carbohydrate-specific antibodies is altered in Crohn's disease or ulcerative colitis. IgG and IgM reactivities to oligosaccharides representative of mucosal glycans were tested in blood serum from 20 healthy control subjects, 17 ulcerative colitis patients, and 23 Crohn's disease patients using glycan arrays. An increased IgG and IgM reactivity toward fucosylated oligosaccharides was detected in Crohn's disease but not in ulcerative colitis. To address the antibody reactivity to the gut microbiota, IgG binding to members of a complex intestinal microbiota was measured and observed to be increased in sera of patients with Crohn's disease. Based on the elevated reactivity to fucosylated oligosaccharides, gut bacteria were tested for recognition by the fucose-binding Aleuria aurantia lectin. Bacteroides stercoris was detected in IgG- and lectin-positive fractions and reactivity of A. aurantia lectin was demonstrated for additional Bacteroides species. IgG reactivity to these Bacteroides species was significantly increased in inflammatory bowel disease patients, indicating that the increased reactivity to fucosylated oligosaccharides detected in Crohn's disease may be induced by fucose-carrying intestinal bacteria. Enhanced antibody response to fucosylated epitopes may have systemic effects by altering the binding of circulating antibodies to endogenous glycoproteins.

Structural Characterization of Cuta- and Tusavirus: Insight into Protoparvoviruses Capsid Morphology.

Several members of the Protoparvovirus genus, capable of infecting humans, have been recently discovered, including cutavirus (CuV) and tusavirus (TuV). To begin the characterization of these viruses, we have used cryo-electron microscopy and image reconstruction to determine their capsid structures to ~2.9 Å resolution, and glycan array and cell-based assays to identify glycans utilized for cellular entry. Structural comparisons show that the CuV and TuV capsids share common features with other parvoviruses, including an eight-stranded anti-parallel ß-barrel, depressions at the icosahedral 2-fold and surrounding the 5-fold axes, and a channel at the 5-fold axes. However, the viruses exhibit significant topological differences in their viral protein surface loops. These result in three separated 3-fold protrusions, similar to the bufaviruses also infecting humans, suggesting a host-driven structure evolution. The surface loops contain residues involved in receptor binding, cellular trafficking, and antigenic reactivity in other parvoviruses. In addition, terminal sialic acid was identified as the glycan potentially utilized by both CuV and TuV for cellular entry, with TuV showing additional recognition of poly-sialic acid and sialylated Lewis X (sLeXLeXLeX) motifs reported to be upregulated in neurotropic and cancer cells, respectively. These structures provide a platform for annotating the cellular interactions of these human pathogens.

Amplification and Preparation of Cellular O-Glycomes for Functional Glycomics.

Mucin-type O-glycans play key roles in many cellular processes, and they are often altered in human diseases. A major challenge in studying the role of O-glycans through functional O-glycomics is the absence of a complete repertoire of the glycans that comprise the human O-glycome. Here we describe a cellular O-glycome preparation strategy, Preparative Cellular O-Glycome Reporter/Amplification (pCORA), that introduces 4-N3-Bn-GalNAc(Ac)3 as a novel precursor in large-scale cell cultures to generate usable amounts of O-glycans as a potential O-glycome factory. Cultured human non-small cell lung cancer (NSCLC) A549 cells take up the precursor, which is extended by cellular glycosyltransferases to produce 4-N3-Bn-α-O-glycans that are secreted into the culture medium. The O-glycan derivatives can be clicked with a fluorescent bifunctional tag that allows multidimensional HPLC purification and production of a tagged glycan library, representing the O-glycome of the corresponding cells. We obtained ∼5% conversion of precursor to O-glycans and purified a tagged O-glycan library of over 100 O-glycan derivatives, many of which were present in >100 nmol amounts and were sequenced by sequential MS fragmentation (MSn). These O-glycans were successfully printed onto epoxy glass slides as an O-glycome shotgun microarray. We used this novel array to explore binding activity of serum IgM in healthy persons and NSCLC patients at different cancer stages. This novel strategy provides access to complex O-glycans in significant quantities and may offer a new route to discovery of potential diagnostic disease biomarkers.

Heparin-Induced Thrombocytopenia in Patients Undergoing Valvular and Aortic Surgery: A Modern Assessment of Risk.

OBJECTIVE: The incidence and outcomes of patients with heparin-induced thrombocytopenia (HIT) are well defined for general cardiac surgical populations. The purpose of this study was to define the outcomes of patients with HIT in a population excluding patients who underwent coronary artery bypass grafting (CABG). METHODS: The local Society of Thoracic Surgeons cardiac surgical database was queried between January 2008 and May 2017 for patients who underwent either open valvular surgery or aortic surgery. Patients who underwent either isolated or combined CABG procedures were excluded. Cohorts were formed based on the presence or absence of postoperative HIT. Logistic regression models were built to determine the association between postoperative HIT and outcomes, adjusted for both preoperative and intraoperative variables. RESULTS: Of the total cohort (8,107 patients), 176 patients (2.2%) developed HIT after surgery. HIT patients experienced an increased incidence of morbidities postoperatively, including reoperation for bleeding, reoperation for cardiac and noncardiac etiologies, postoperative stroke, perioperative myocardial infarction, postoperative sternal infection, postoperative arrhythmia, new-onset renal failure, and dialysis (all with P < 0.01). The unadjusted 30-day mortality was 14.8% in HIT patients vs 4.9% in those without HIT (P < 0.01). After risk adjustment, reoperation for noncardiac events, renal failure, new dialysis, postoperative stroke, arrhythmia, and sternal wound infection remained significantly elevated in patients who developed postoperative HIT. CONCLUSIONS: Patients who developed HIT after non-CABG cardiac surgery experienced increased postoperative rates of morbidity and mortality. Early diagnosis and treatment remained mainstays of therapy. Early identification of patients at highest risk should prompt careful risk stratification when possible.

Self-reported sleep disturbance in Crohn's disease is not confirmed by objective sleep measures.

Sleep disturbance and fatigue are commonly reported among patients with Crohn's disease (CD). In this prospective study, we aimed to define sleep quality in CD patients at various disease activity states and compare to healthy controls using objective and subjective measures. A prospective observational cohort study of CD patients seen at a tertiary academic inflammatory bowel diseases (IBD) clinic was compared to healthy volunteers. CD activity was assessed using the Harvey-Bradshaw Index (HBI). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) and objectively over 1-week using actigraphy (motion-based) and morning urinary melatonin metabolite. 121 subjects (CD patients N = 61; controls N = 60) completed the study. 34 had active CD (HBI > 4). Sleep disturbance was more frequently reported by CD subjects than controls (PSQI: 57% vs. 35%, p = 0.02) and in patients with active CD versus in remission state (PSQI 75.8% vs. 33.3%, p < 0.01; ESS: 45.5% vs. 19%, p = 0.03). Sleep parameters as measured by actigraphy and urine melatonin metabolite did not vary by group. Crohn's patients report significantly more disturbed sleep than controls. However, poor sleep was not confirmed by objective measures of sleep quality. Excessive daytime sleepiness in CD patients may be driven by factors beyond objectively measured poor sleep.

O-Benzylhydroxylamine (BHA) as a Cleavable Tag for Isolation and Purification of Reducing Glycans.

Glycoscience has been recognized as an important area in biomedical research. Currently, a major obstacle for glycoscience study is the lack of diverse, biomedically relevant, and complex glycans in quantities sufficient for exploring their structural and functional aspects. Complementary to chemoenzymatic synthesis, natural glycans could serve as a great source of biomedically relevant glycans if they are available in sufficient quantities. We have recently developed oxidative release of natural glycans (ORNG) for large-scale release of N-glycans as free reducing glycans. While free reducing glycans can be readily derivatized with ultraviolet or fluorescent tags for high-performance liquid chromatography (HPLC) and mass spectrometry (MS) analysis, it is difficult to remove tags for the regeneration of free reducing glycans without affecting the structural integrity of glycans. To address this inconvenience, we explored the use of a cleavable tag, O-benzylhydroxylamine (BHA). Free reducing glycans are easily and efficiently labeled with BHA under mild conditions, enabling UV detection during HPLC purification. Individual glycan-BHA conjugates can then be separated using multidimensional HPLC and characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and MS/MS. The BHA tag can then be easily removed by palladium-on-carbon (Pd/C)-catalyzed hydrogenation to efficiently regenerate free reducing glycans with little effect on glycan structures. This procedure provides a simple and straightforward way to tag free reducing glycans for purification at a preparative scale using multidimensional HPLC and subsequently recover purified free reducing glycans.

CD23 is a glycan-binding receptor in some mammalian species.

CD23, the low-affinity IgE receptor found on B lymphocytes and other cells, contains a C-terminal lectin-like domain that resembles C-type carbohydrate-recognition domains (CRDs) found in many glycan-binding receptors. In most mammalian species, the CD23 residues required to form a sugar-binding site are present, although binding of CD23 to IgE does not involve sugars. Solid-phase binding competition assays, glycoprotein blotting experiments, and glycan array analysis employing the lectin-like domains of cow and mouse CD23 demonstrate that they bind to mannose, GlcNAc, glucose, and fucose and to glycoproteins that bear these sugars in nonreducing terminal positions. Crystal structures of the cow CRD in the presence of α-methyl mannoside and GlcNAcß1-2Man reveal that a range of oligosaccharide ligands can be accommodated in an open binding site in which most interactions are with a single terminal sugar residue. Although mouse CD23 shows a pattern of monosaccharide and glycoprotein binding similar to cow CD23, the binding is weaker. In contrast, no sugar binding was observed in similar experiments with human CD23. The absence of sugar-binding activity correlates with accumulation of mutations in the gene for CD23 in the primate lineage leading to humans, resulting in loss of key sugar-binding residues. These results are consistent with a role for CD23 in many species as a receptor for potentially pathogenic microorganisms as well as IgE. However, the ability of CD23 to bind several different ligands varies between species, suggesting that it has distinct functions in different organisms.

Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota.

The gut microbiota and its short chain fatty acid (SCFA) metabolites have been established to play an important protective role against neurodegenerative diseases. Our previous study demonstrated that cerebral ischemic stroke triggers dysfunctional gut microbiota and increased intestinal permeability. In this study, we aimed to clarify the mechanism by which gut microbiota and SCFAs can treat cerebral ischemic stroke in rat middle cerebral artery occlusion models and use the information to develop new therapies. Our results show that oral administration of non-absorbable antibiotics reduced neurological impairment and the cerebral infarct volume, relieved cerebral edemas, and decreased blood lipid levels by altering the gut microbiota. We also found that ischemic stroke decreased intestinal levels of SCFAs. And that transplanting fecal microbiota rich in these metabolites was an effective means of treating the condition. Compared with other SCFAs, butyric acid showed the highest negative correlation with ischemic stroke. Supplementation with butyric acid treated models of ischemic stroke effectively by remodeling the gut microbiota, enriching the beneficial Lactobacillus, and repairing the leaky gut. In conclusion, interfering with the gut microbiota by transplanting fecal bacteria rich in SCFAs and supplementing with butyric acid were found to be effective treatments for cerebral ischemic stroke.

Next-Generation Glycan Microarray Enabled by DNA-Coded Glycan Library and Next-Generation Sequencing Technology.

Interactions of glycans with proteins, cells, and microorganisms play important roles in cell-cell adhesion and host-pathogen interaction. Glycan microarray technology, in which multiple glycan structures are immobilized on a single glass slide and interrogated with glycan-binding proteins (GBPs), has become an indispensable tool in the study of protein-glycan interactions. Despite its great success, the current format of the glycan microarray requires expensive, specialized instrumentation and labor-intensive assay and image processing procedures, which limit automation and possibilities for high-throughput analyses. Furthermore, the current microarray is not suitable for assaying interaction with intact cells due to their large size compared to the two-dimensional microarray surface. To address these limitations, we developed the next-generation glycan microarray (NGGM) based on artificial DNA coding of glycan structures. In this novel approach, a glycan library is presented as a mixture of glycans and glycoconjugates, each of which is coded with a unique oligonucleotide sequence (code). The glycan mixture is interrogated by GBPs followed by the separation of unbound coded glycans. The DNA sequences that identify individual bound glycans are quantitatively sequenced (decoded) by powerful next-generation sequencing (NGS) technology, and copied numbers of the DNA codes represent relative binding specificities of corresponding glycan structures to GBPs. We demonstrate that NGGM generates glycan-GBP binding data that are consistent with that generated in a slide-based glycan microarray. More importantly, the solution phase binding assay is directly applicable to identifying glycan binding to intact cells, which is often challenging using glass slide-based glycan microarrays.

Puerariae Lobatae Radix with chuanxiong Rhizoma for treatment of cerebral ischemic stroke by remodeling gut microbiota to regulate the brain-gut barriers.

The combination of Puerariae Lobatae Radix (PLR) and Chuanxiong Rhizoma (CXR) is commonly used to treat cerebrovascular diseases. This work aimed to clarify the mechanisms of their action in treating cerebral ischemic stroke from the perspective of gut microecology. The PLR and CXR combination effectively improved the neurological function, reduced the cerebral infarction and relieved the complications of cerebral ischemic stroke, including dyslipidemia, increased blood viscosity and thrombotic risk. Cerebral ischemic stroke triggered gut microbial disturbances by enriching pathogens and opportunistic microorganisms, including Bacteroides, Escherichia_Shigella, Haemophilus, Eubacterium_nodatum_group, Collinsella, Enterococcus, Proteus, Alistipes, Klebsiella, Shuttleworthia and Faecalibacterium. Cerebral ischemic stroke also increased the intestinal permeability, disrupted the gut barrier and caused intestinal microbial translocation. Occludin, claudin-5 and ZO-1 levels in the brain-gut barriers showed a high positive correlation. However, the combination remodeled the gut microecology by modulating endogenous bacteria whose effects may mitigate cerebral damage, such as Alloprevotella, Ruminococcaceae, Oscillospira, Lachnospiraceae_NK4B4_group, Akkermansia and Megasphaera, protected the brain-gut barriers by increasing claudin-5 and ZO-1 levels; and weakened the gut microbiota translocation by decreasing diamine oxidase, lipopolysaccharide and d-lactate. Although nimodipine effectively reduced the cerebral infarction, it did not relieve the gut microbiota dysbiosis and instead aggravated the gut barrier disruption and microbiota translocation. In conclusion, cerebral ischemic stroke caused gut microbiota dysbiosis, increased intestinal permeability, disrupted the gut barrier and triggered gut microbiota translocation. The PLR and CXR combination was an effective treatment for cerebral ischemic stroke that relieved the gut microbiota dysbiosis and brain-gut barriers disruption.

Durability and safety of David V valve-sparing root replacement in acute type A aortic dissection.

BACKGROUND: Valve-sparing root replacement (VSRR) is an attractive option in type A aortic dissection (TAAD) repair for a young patient with normal cusp anatomy, but conventional root replacement using a composite valved-conduit (ROOT) remains the gold standard in this emergent clinical setting. We examine the long-term safety and durability of the David V VSRR compared with ROOT in TAAD repair. METHODS: From March 2004 to April 2017, 136 patients underwent repair of acute TAAD using either ROOT (n = 77; 56.6%) or VSRR (n = 59; 43.4%). Annual echocardiograms were performed for follow-up in VSRR patients. Univariable regression, Kaplan-Meier, and competing risk analyses were performed. RESULTS: Preoperative characteristics were similar between groups, except that VSRR patients were younger (mean age 43.5 ± 11.4 years VSRR vs 50.4 ± 3.0 years ROOT; P = .001). Both groups had similar rates of preoperative malperfusion or shock (29.3% VSRR vs 37.0% ROOT; P = .35) and ≥3+ aortic insufficiency (63% VSRR vs 76.8% ROOT). Thirty-day mortality in the VSRR group was 2/59 (3.4%) and 11/77 in the ROOT group (14.3%; P < .001). All-cause survival at 9 years was 92% (VSRR) and 59% (ROOT; P = .002). The incidence of aortic reintervention was similar between groups (20%-23% at 5 years; P = .81). At 9 years of follow-up, 5/52 (9.6%) VSRR patients had ≥2+ aortic insufficiency, and 1 patient required valve reintervention. CONCLUSIONS: In highly-selected patients, the David V VSRR provides a safe repair of acute TAAD with concomitant root pathology and valve insufficiency. In our center, the incidence of valve-related reintervention at long-term follow-up is low after emergent repair.

Valve Sparing Root Replacement Provides Similar Midterm Outcomes in Bicuspid and Trileaflet Valves.

BACKGROUND: Valve-sparing aortic root replacement (VSRR) is an established treatment for aortic root pathology for trileaflet valves. The safety and durability of VSRR in bicuspid aortopathy is unclear. In this study, outcomes of performing VSRR in the setting of bicuspid and trileaflet valves were compared. METHODS: An institutional database identified 294 patients who underwent VSRR from 2005 to 2017. Of these, 225 had trileaflet valves and 69 had bicuspid valves. Patients were followed prospectively and had annual postoperative echocardiograms. Propensity-matched comparisons were made between trileaflet and bicuspid valve patients. RESULTS: The average patient age for trileaflet valves was 46.0 ± 13.5 versus 42.7 ± 12.2 years for bicuspid patients (p = 0.07). There was a higher presence of preoperative >2+ aortic insufficiency (AI) present in bicuspid patients (63.8%) compared with trileaflet patients (31.1%) (p < 0.01). Mean follow-up was 39 months and was 98% complete. At 5 years, the cumulative incidence of >2+ AI and aortic valve replacement (AVR) was 2.0% and 4.3% in trileaflet patients and 7.7% (p = 0.75) and 7.7% (p = 0.81) in bicuspid patients. Preoperative >2+ AI was not predictive of >2+ postoperative AI (p = 0.62) nor AVR (p = 0.49). Five-year survival was no different between groups (trileaflet: 98%, bicuspid: 84%, p = 0.24). CONCLUSIONS: VSRR can be safely and effectively performed in patients with trileaflet and bicuspid valves. Operative outcomes and valve function were equivalent in bicuspid and trileaflet patients in midterm follow-up. Performance of VSRR is a viable term option in the setting bicuspid aortic valve aortopathy.

Valve-Sparing Root Replacement Provides Excellent Midterm Outcomes for Bicuspid Valve Aortopathy.

BACKGROUND: Standard therapy for aortic root dilation in the setting of bicuspid aortic valves remains use of a composite valve conduit. The long-term durability of valve-sparing root replacement (VSRR) in bicuspid aortopathy is presently unclear. In this study, the midterm results of performing VSRR in the setting of a bicuspid valve was analyzed. METHODS: A single institutional database identified 280 patients who underwent VSRR from 2005 to 2016. Outcomes were analyzed in 60 consecutive patients undergoing a VSRR in the setting of a bicuspid aortic valve with aortic insufficiency (AI). Patients were followed prospectively and had annual echocardiograms. RESULTS: The average age in this series was 42 ± 11 years. Eighty percent were men and 33% had New York Heart Association class III to IV symptoms. More than 2+ AI was present in 42% of patients preoperatively. The incidence of operative death, stroke, and renal failure was 0%. Mean follow-up was 39 ± 30 months. At latest follow-up, 62% of patients had zero AI and 87% of patients had <1+ AI. At 5 years, freedom from >2+ AI was 97% and freedom from AVR was 96%. Preoperative AI was not found to be a significant risk factor for postoperative >2+ AI (p = 0.61) or AVR (p = 0.61). CONCLUSIONS: VSRR can be safely and effectively performed in young patients with bicuspid valve anatomy regardless of degree of preoperative AI. Valve function is durable and the incidence of valve-related complications is low. VSRR is an attractive and potentially superior option to conventional root replacement in appropriately selected patients with bicuspid aortopathy.