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BACKGROUND: We hypothesized that transcutaneous gas determinations of O2 and CO2 (TcPO2 and TcPCO2 ) are associated with the severity of PAH. METHODS: In this cross-sectional study, we included consecutive patients with PAH (group 1 PH; n = 34). Transcutaneous gas determinations were compared to those of age- and gender-matched healthy controls (n = 14), nongroup 1 PH (n = 19) or patients with high estimated RVSP on echocardiography but without hemodynamic evidence of PH (n = 12). RESULTS: In patients with PAH, TcPO2 , and TcPCO2 were significantly associated with PaO2 (R = 0.44, p = 0.03) and PaCO2 (R = 0.77, p < 0.001), respectively. TcPO2 /FiO2 (mean difference: -65.0 [95% CI: -121.3, -8.7]) and TcPCO2 (mean difference: -7.4 [95% CI: -11.6, -3.1]) were significantly lower in patients with PAH than healthy controls. TcPCO2 was useful in discriminating PAH patients from other individuals (AUC: 0.74 [95% CI: 0.62, 0.83]). TcPO2 /FiO2 ratio was significantly associated with mean PAP, TPG, PVR, CI, SVI, DLCO, six-minute walk distance and components of the CAMPHOR questionnaire. CONCLUSIONS: Transcutaneous pressure of CO2 was lower in patients with PAH. Transcutaneous pressure of O2 over inspired fraction of O2 ratio was inversely associated with severity of disease in patients with PAH.
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Dióxido de Carbono/sangue , Hipertensão Pulmonar/sangue , Oxigênio/sangue , Adulto , Idoso , Monitorização Transcutânea dos Gases Sanguíneos/métodos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND & AIMS: Selected-ion flow-tube mass spectrometry can precisely identify trace gases in the human breath, in the parts-per-billion range. We investigated whether concentrations of volatile compounds in breath samples correlate with the diagnosis of alcoholic hepatitis (AH) and the severity of liver disease in patients with AH. METHODS: We recruited patients with liver disease from a single tertiary care center. The study population was divided between those with AH with cirrhosis (n = 40) and those with cirrhosis with acute decompensation from etiologies other than alcohol (n = 40); individuals without liver disease served as control subjects (n = 43). We used selected-ion flow-tube mass spectrometry to identify and measure 14 volatile compounds in breath samples from fasted subjects. We used various statistical analyses to compare clinical characteristics and breath levels of compounds among groups and to test the correlation between levels of compounds and severity of liver disease. Logistic regression analysis was performed to build a predictive model for AH. RESULTS: We identified 6 compounds (2-propanol, acetaldehyde, acetone, ethanol, pentane, and trimethylamine [TMA]) whose levels were increased in patients with liver disease compared with control subjects. Mean concentrations of TMA and pentane (TAP) were particularly high in breath samples from patients with AH, compared with those with acute decompensation or control subjects (for both, P < .001). Using receiver operating characteristic curve analysis, we developed a model for the diagnosis of AH based on breath levels of TAP. TAP scores of 36 or higher identified the patients with AH (area under the receiver operating characteristic curves = 0.92) with 90% sensitivity and 80% specificity. The levels of exhaled TMA had a low level of correlation with the severity of AH based on model for end-stage liver disease score (r = 0.38; 95% confidence interval, 0.07-0.69; P = .018). CONCLUSIONS: Based on levels of volatile compounds in breath samples, we can identify patients with AH vs patients with acute decompensation or individuals without liver disease. Levels of exhaled TMA moderately correlate with the severity of AH. These findings might be used in diagnosis of AH or in determining patient prognosis.
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Biomarcadores/análise , Testes Respiratórios/métodos , Hepatite Alcoólica/diagnóstico , Compostos Orgânicos Voláteis/análise , Adulto , Idoso , Feminino , Humanos , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Centros de Atenção TerciáriaRESUMO
Our goal was to replace the previous composite graft with a bioprosthesis. The approach involved axillary artery and femoral vein cannulation and cardiopulmonary bypass with moderate hypothermia for re-entry of the chest and deep hypothermia with circulatory arrest to get control of and to clamp the aorta when entering the pseudoaneurysm. The myocardial protection strategy was general cooling and retrograde cardioplegia through direct coronary sinus cannulation and antegrade cardioplegia in the coronary ostia when possible. After the pseudoaneurysm was entered, the graft was divided in the middle, and the distal end was dissected out under circulatory arrest sufficiently to allow clamping and to resume systemic circulation. The graft was not dissected out beyond the previous anastomosis. Under another period of circulatory arrest, the distal graft was removed to the mid-arch, and a new graft was attached with a hemiarch anastomosis. Then the root was dissected out, and both coronary ostia were mobilized. The mechanical aortic valve and previous graft material were explanted. A new bioprosthetic valved conduit was used to replace the aortic root, and the coronary buttons were re-implanted directly in the new graft.
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Falso Aneurisma , Aorta Torácica , Humanos , Aorta Torácica/cirurgia , Falso Aneurisma/etiologia , Falso Aneurisma/cirurgia , Aorta/cirurgia , Ponte Cardiopulmonar , Cateterismo , ReoperaçãoRESUMO
OBJECTIVES: We hypothesized that tissue characteristics vary significantly along zone zero, which may be reflected by regional differences in stored elastic energy. Our objectives were to (1) characterize the regional variation in stored elastic energy within tissues of the aortic zone zero and (2) identify the association between this variation and patient characteristics. METHODS: From February 2018 to January 2021, 123 aortic tissue samples were obtained from the aortic root and proximal and distal ascending aortas of 65 adults undergoing elective ascending aorta replacement. Biaxial biomechanics testing was performed to obtain tissue elastic energy at the inflection point and compared with patient demographics and preoperative computed tomography imaging. Coefficient models were fit using B-spline to interrogate the relationship among elastic energy, region, and patient characteristics. RESULTS: Mean elastic energy at inflection point was 24.3 ± 15.6 kJ/m3. Elastic energy increased significantly between the root and proximal, and root and distal ascending aorta and decreased with increasing age. Differences due to history of connective tissue disorder and bicuspid aortic valve were significant but diminished when controlled for other patient characteristics. Among covariates, age and region were found to be the most important predictors for elastic energy. CONCLUSIONS: Aortic tissue biomechanical metrics varied across regions and with patient characteristics within the aortic zone zero. Assessment of endovascular outcomes in the ascending aorta must closely consider the region of deployment and variable tissue qualities along the length of the landing zone. Regional variation in tissue characteristics should be incorporated into existing patient-specific models of aortic mechanics.
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Aorta , Doença da Válvula Aórtica Bicúspide , Adulto , Humanos , Fenômenos Biomecânicos , Aorta/diagnóstico por imagem , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgiaRESUMO
Exhaled breath volatile organic compounds (VOCs) are elevated in heart failure (HF). The ability of VOCs to predict long term cardiovascular mortality and morbidity has not been independently verified. In 55 patients admitted with acute decompensated heart failure (ADHF), we measured exhaled breath acetone and pentane levels upon admission and after 48 h of diuresis. In a separate cohort of 51 cardiac patients undergoing cardiopulmonary exercise testing (CPET), we measured exhaled breath acetone and pentane levels before and at peak exercise. In the ADHF cohort, admission acetone levels correlated with lower left ventricular ejection fraction (LVEF, r = -0.297, p = 0.035). Greater weight loss with diuretic therapy correlated with a greater reduction in both acetone levels (r = -0.398, p = 0.003) and pentane levels (r = -0.309, p = 0.021). In patients with above-median weight loss (≥4.5 kg), patients demonstrated significantly greater percentage reduction in acetone (59% reduction vs. 7% increase, p < 0.001) and pentane (23% reduction vs. 2% reduction, p = 0.008). In the CPET cohort, admission acetone and pentane levels correlated with higher VE/VCO2 (r = 0.39, p = 0.005), (r = 0.035, p = 0.014). However, there were no significant correlations between baseline or peak exercise acetone and pentane levels and peak VO2. In longitudinal follow-up with a median duration of 33 months, patients with elevated exhaled acetone and pentane levels experienced higher composite adverse events of death, ventricular assist device implantation, or orthotopic heart transplantation. In patients admitted with ADHF, higher exhaled breath acetone levels are associated with lower LVEF and poorer outcomes, and greater reductions in exhaled breath acetone and pentane tracked with greater weight loss. Exhaled acetone and pentane may be novel biomarkers in heart failure worthy of future investigation.
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OBJECTIVES: We evaluate the independent effects of patient and aortic tissue characteristics on biaxial physiologic mechanical metrics in aneurysmal and nonaneurysmal tissues, and uniaxial failure metrics in aneurysmal tissue, comparing longitudinal and circumferential behavior. METHODS: From February 2017 to October 2022, 382 aortic specimens were collected from 134 patients; 268 specimens underwent biaxial testing, and 114 specimens underwent uniaxial testing. Biaxial testing evaluated Green-Lagrange transition strain and low and high tangent moduli. Uniaxial testing evaluated failure stretch, Cauchy stress, and low and high tangent moduli. Longitudinal gradient boosting models were implemented to estimate mechanical metrics and covariates of importance. RESULTS: On biaxial testing, nonaneurysmal tissue was less deformable and exhibited a lower transition strain than aneurysmal tissue in the longitudinal (0.18 vs 0.30, P < .001) and circumferential (0.25 vs 0.30, P = .01) directions. Older age and increasing ascending aortic length contributed most to predicting transition strain. On uniaxial testing, longitudinal specimens failed at lower stretch (1.4 vs 1.5, P = .003) and Cauchy stress (1.0 vs 1.9 kPa, P < .001) than circumferential specimens. Failure stretch and Cauchy stress were most strongly associated with tissue orientation and decreased sharply with older age. Age, ascending aortic length, and tissue thickness were the most frequent covariates predicting mechanical metrics across 10 prediction models. CONCLUSIONS: Age was the strongest predictor of mechanical behavior. After adjusting for age, nonaneurysmal tissue was less deformable than aneurysmal tissue. Differences in longitudinal and circumferential mechanics contribute to tissue dysfunction and failure in ascending aneurysms. This highlights the need to better understand the effects of age, ascending aortic length, and thickness on clinical aortic behavior.
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Background: Published trials have shown that transcatheter aortic valve replacement (TAVR) is a safe alternative to surgical aortic valve replacement (SAVR) after prior coronary artery bypass grafting (CABG). However, differences in morbidity and discharge location between the 2 procedures are less thoroughly characterized. Methods: From January 1, 2006 to January 7, 2020, 1059 patients with severe aortic stenosis after CABG underwent either SAVR (n = 315/30%), transfemoral TAVR (TF-TAVR) (n = 575/54%), or alternative access TAVR (n = 169/16%) at a single, tertiary care, academic institution. Propensity-weighted matching was used to compare morbidity, mortality, length of postprocedure stay, and nonhome discharge between TF-TAVR (effective n = 163) and SAVR (effective n = 163) groups. Results: Among propensity-weighted groups, the TF-TAVR group experienced fewer transfusions than the SAVR group (effective n = 16 [9.5%] vs. 132 [81%]; p < 0 .0001), less new-onset atrial fibrillation (effective n = 5.1 [3.1%] vs. 43 [27%]; p = 0.009), and less prolonged mechanical ventilation >24 âhours (effective n = 0.41 [0.25%] vs. 30 [18%]; p <0.0001). Permanent pacemaker implant was 9.3% (effective n = 13) after TF-TAVR vs. 5.5% (effective n = 7.9; p = 0.2) after SAVR, stroke 0.41% (effective n = 0.67) vs. 2.1% (effective n = 3.5; p = 0.2), and operative mortality 0.5% (effective n = 0.8) vs. 1.7% (effective n = 2.8; p = 0.8). The TF-TAVR group had shorter postprocedure lengths of stay (2.0 vs. 7.6 days; p < 0.0001). Discharge home was more common after TF-TAVR than SAVR (effective n = 156 [95%] vs. 118 [73%]; p = 0.01). Conclusions: For patients developing severe aortic stenosis after CABG, TF-TAVR rather than SAVR should be strongly considered because of lower morbidity, shorter length of stay, and greater likelihood of home discharge.
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OBJECTIVES: Bicuspid aortic valve (BAV) aortopathy is defined by 3 phenotypes-root, ascending, and diffuse-based on region of maximal aortic dilation. We sought to determine the association between aortic mechanical behavior and aortopathy phenotype versus other clinical variables. METHODS: From August 1, 2016, to March 1, 2023, 375 aortic specimens were collected from 105 patients undergoing elective ascending aortic aneurysm repair for BAV aortopathy. Planar biaxial data (191 specimens) informed constitutive descriptors of the arterial wall that were combined with in vivo geometry and hemodynamics to predict stiffness, stress, and energy density under physiologic loads. Uniaxial testing (184 specimens) evaluated failure stretch and failure Cauchy stress. Boosting regression was implemented to model the association between clinical variables and mechanical metrics. RESULTS: There were no significant differences in mechanical metrics between the root phenotype (N = 33, 31%) and ascending/diffuse phenotypes (N = 72, 69%). Biaxial testing demonstrated older age was associated with increased circumferential stiffness, decreased stress, and decreased energy density. On uniaxial testing, longitudinally versus circumferentially oriented specimens failed at significantly lower Cauchy stress (50th [15th, 85th percentiles]: 1.0 [0.7, 1.6] MPa vs 1.9 [1.3, 3.1] MPa; P < .001). Age was associated with decreased failure stretch and stress. Elongated ascending aortas were also associated with decreased failure stress. CONCLUSIONS: Aortic mechanical function under physiologic and failure conditions in BAV aortopathy is robustly associated with age and poorly associated with aortopathy phenotype. Data suggesting that the root phenotype of BAV aortopathy portends worse outcomes are unlikely to be related to aberrant, phenotype-specific tissue mechanics.
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The ascending aorta has a unique microstructure and biomechanical properties that allow it to absorb energy during systole and return energy during diastole (Windkessel effect). Derangements in aortic architecture can result in changes to biomechanics and inefficiencies in function. Ultimately biomechanical failure may occur resulting in aortic dissection or rupture. By measuring aortic biomechanics with either in vivo or ex vivo methods, one may be able to predict tissue failure in patients with aortic disease such as aneurysms. An understanding of the biomechanical changes that lead to these tissue-level failures may help guide therapy, disease surveillance, surgical intervention, and aid in the development of new treatments for this deadly condition.
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Anti-Hipertensivos , Epoprostenol/análogos & derivados , Hipertensão Pulmonar Primária Familiar/fisiopatologia , Iontoforese/métodos , Microcirculação , Microvasos/fisiopatologia , Pele/irrigação sanguínea , Estudos de Casos e Controles , Hipertensão Pulmonar Primária Familiar/diagnóstico , Feminino , Humanos , Hipertermia Induzida , Fluxometria por Laser-Doppler/métodos , Masculino , Doenças Vasculares/diagnóstico , Doenças Vasculares/fisiopatologiaRESUMO
OBJECTIVES: Loeys-Dietz syndrome (LDS) is an aggressive connective tissue disorder associated with increased risk of aortic dissection and aneurysm rupture at an early age and smaller aortic diameters. We report our experience with LDS to better understand its natural history and treatment outcomes and help establish treatment guidelines. METHODS: We retrospectively reviewed all patients with LDS who underwent medical or surgical treatment at Cleveland Clinic before April 27, 2017. Primary endpoints were postoperative in-hospital morbidity and mortality. Secondary endpoints were aorta-related reoperations and short- and long-term mortality. RESULTS: We identified 53 patients with LDS. Of these, 33 (62%) underwent aortic surgery. Mean age was 39 ± 14 years, and mean maximum aortic diameter was 4.3 cm. There were 2 (6%) deaths after urgent or emergency surgery. Twenty-two patients (67%) required no aortic reoperation; 20 of these had prophylactic surgery. Multiple aortic operations were performed on 11 (33%) patients, 9 of whom experienced aortic dissections. Six patients (18%) required total aortic replacement. Among 19 patients with modified root reimplantation, no aorta- or valve-related complications occurred. Overall, 33 patients underwent 58 aortic and 81 cardiovascular operations, with 1 late death. Kaplan-Meier survival of the aortic-surgery cohort was 89% at 10 years (median follow-up 5.2 years). There were no late deaths in the non-aortic surgery group (20/53; 38%). CONCLUSIONS: Prophylactic aortic surgical outcomes in LDS are excellent. Surgical reintervention remains high, particularly after aortic dissections. Close surveillance of medically managed and postoperative patients and early prophylactic surgery are crucial to avoid aortic catastrophe and achieve a good long-term prognosis.
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Síndrome de Loeys-Dietz , Adulto , Aorta/cirurgia , Procedimentos Cirúrgicos Cardíacos , Procedimentos Endovasculares , Feminino , Humanos , Síndrome de Loeys-Dietz/epidemiologia , Síndrome de Loeys-Dietz/mortalidade , Síndrome de Loeys-Dietz/cirurgia , Masculino , Pessoa de Meia-Idade , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Thoracic aortic aneurysm (TAA) is usually clinically silent and progresses slowly until a tipping point is reached, after which the aortic diameter can expand more rapidly and the condition can potentially end in aortic dissection or rupture. Causes include bicuspid aortic valve and genetic syndromes (Marfan, Loeys-Dietz, and Ehlers-Danlos syndromes) and familial associations, but many cases are idiopathic. Clinicians should therefore be alert for clues on chest imaging, and consider screening in first-degree relatives of patients known to have aortic disease. Early referral to a cardiologist specializing in aortic disease is key.
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Aneurisma da Aorta Torácica/diagnóstico , Aconselhamento/métodos , Encaminhamento e Consulta , HumanosRESUMO
Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of Fbn1mgR/mgR aortas. TAAD and Fbn1mgR/mgR aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene, ADAMTS5, was seen in TAAD. Fbn1mgR/mgR mice with ascending aortic dissection and/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and/or reduced proteolytic turnover, and correlates with aortic dissection/rupture in Fbn1mgR/mgR mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair.
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Agrecanas/metabolismo , Aneurisma da Aorta Torácica/patologia , Dissecção Aórtica/patologia , Versicanas/metabolismo , Proteína ADAMTS5/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/etiologia , Dissecção Aórtica/prevenção & controle , Animais , Aorta Torácica/patologia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/etiologia , Aneurisma da Aorta Torácica/cirurgia , Biomarcadores/metabolismo , Modelos Animais de Doenças , Feminino , Fibrilina-1/genética , Perfilação da Expressão Gênica , Humanos , Masculino , Síndrome de Marfan/complicações , Síndrome de Marfan/genética , Síndrome de Marfan/patologia , Camundongos Knockout , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Medição de Risco/métodos , Túnica Média/patologiaRESUMO
BACKGROUND: Retrograde false lumen perfusion is a common mode of failure after stent grafting chronic aortic dissection. Open fenestration during the first-stage elephant trunk (ET) creates a landing zone for second-stage endovascular ET completion in patients with a false lumen aneurysm. Our objectives were to assess long-term safety and durability of this technique. METHODS: From 2007 to 2014, 56 patients with thoracoabdominal dissection and aneurysm underwent stage 1 ET and open fenestration. Fifteen (26.8%) patients had DeBakey type III dissection, and 41 (73%) had type I, 38 (68%) with previous ascending repair. Mean maximum diameter was 5.8 ± 1 cm. Imaging follow-up was complete in all survivors. RESULTS: Endovascular ET completion was performed in 49 patients (87.5%), urgently in 11 (22%). Operative mortality after the first stage was 1.8%. The ET in 8 patients was performed prophylactically. Complications after the first stage included transient ischemic attack in 1 patient (1.8%), subdural hemorrhage in 1 (1.8%), tracheostomy in 1 (1.8%), bleeding in 5 (8.9%), and paraplegia in 1 (1.8%). All 48 patients had false lumen thrombosis in the treated segment without endoleak or retrograde perfusion. The aneurysm sac shrunk in 67%, with a mean overall aortic diameter reduction of 1 ± 0.8 cm. Median follow-up was 33.8 months. Eight patients (16%) underwent 11 late reinterventions, comprising thoracic endovascular aortic repair extension in 4 patients (36%), thoracic endovascular aortic repair and false lumen embolization in 3 (27%), open thoracoabdominal aortic aneurysm completion repair in 2 (18%), and redo proximal repair for infection in 2 (18%). There were 6 late deaths. CONCLUSIONS: Open aortic fenestration to create a distal landing zone during stage 1 ET facilitates endovascular completion for chronic dissection with false lumen aneurysm. The technique is safe, effective, and durable. It promotes reverse aortic remodeling and eliminates retrograde false lumen flow.
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Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Procedimentos Endovasculares/métodos , Complicações Pós-Operatórias/epidemiologia , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/mortalidade , Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/mortalidade , Doença Crônica , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: Coexisting aortic root and mitral valve pathology is increasingly recognized among patients undergoing surgery. We characterized the pathology and surgical outcomes of patients with combined aortic root and mitral disease. METHODS: From 1987 to 2016, 118 patients (age 52.40 ± 17.71 years) underwent concomitant aortic root and mitral procedures (excluding aortic stenosis, endocarditis, and reoperations). Aortic root pathologies included degenerative aneurysm (94%) and aortic dissection (6%). The aortic valve was bicuspid in 15% of patients and had normally functioning tricuspid leaflets in 23% of patients. Marfan syndrome was present in 34 patients (29%). Degenerative mitral disease predominated (78%). Mitral procedures were repair (86%) and replacement (14%), and root procedures were valve-preserving root reimplantation (36%), Bentall procedure (47%), and homograft root replacement (17%). In the last 10 years, the combination of valve-preserving root reimplantation and mitral repair has increased to 50%. Kaplan-Meier and competing risk analyses were used to estimate survival and reoperation. RESULTS: There were 2 (1.7%) operative deaths with survival of 79% and 71% at 10 and 15 years, respectively, and reoperation rates of 4.7% and 12% after 5 and 10 years, respectively. There were no operative deaths in patients with combined valve-preserving root reimplantation and mitral repair, with survival of 89% and reoperation rate of 7.8% at 10 years. Among patients with Bentall/homograft and mitral operation, survival was 73% and reoperation was 9.8% at 10 years. CONCLUSIONS: In patients with aortic root and mitral pathology, combined surgical risk is low and valve durability is high. When possible, valve-preserving root reimplantation and mitral repair should be considered to avoid prosthesis degeneration, anticoagulation, and lifestyle limitations.
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Aneurisma Aórtico/cirurgia , Dissecção Aórtica/cirurgia , Valva Aórtica/anormalidades , Implante de Prótese Vascular , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral/cirurgia , Adulto , Idoso , Dissecção Aórtica/etiologia , Dissecção Aórtica/mortalidade , Dissecção Aórtica/fisiopatologia , Aneurisma Aórtico/etiologia , Aneurisma Aórtico/mortalidade , Aneurisma Aórtico/fisiopatologia , Valva Aórtica/fisiopatologia , Valva Aórtica/cirurgia , Doença da Válvula Aórtica Bicúspide , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Tomada de Decisão Clínica , Feminino , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/mortalidade , Doenças das Valvas Cardíacas/fisiopatologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Masculino , Síndrome de Marfan/complicações , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/mortalidade , Insuficiência da Valva Mitral/fisiopatologia , Recuperação de Função Fisiológica , Reimplante , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: The accuracy of available noninvasive biomarkers for diagnosis, stratification, and prediction of inflammatory bowel disease (IBD) courses is limited. We analyzed volatile organic compounds (VOCs) in the breath of IBD patients and controls for diagnosis and differentiation of IBD as well as their link with disease location, activity, and phenotype. METHODS: A prospective study of diagnostic testing was conducted, recruiting Crohn's disease (CD), ulcerative colitis (UC), other inflammatory gastrointestinal diseases (OGDs), and healthy controls (HCs), as well as subjects with ileal pouch anal anastomosis (IPAA). The breath VOC profile was analyzed using selective ion flow tube-mass spectrometry. RESULTS: One hundred and twenty-four subjects (n=24 CD, n=11 UC, n=6 OGD, n=53 HC, n=30 IPAA) were included. The breath metabolome was significantly different in patients with IBD, CD, or UC compared with OGD and HC (7 out of 22 VOCs), but not between CD and UC. No link between the level of VOCs with complications, disease location, and clinical or radiologic disease activity, as well as lab parameters or type of medication was found. Breath VOCs were markedly different in patients with IPAA compared with any other group (17 out of 22 VOCs) and the presence of pouch inflammation did not alter the VOC levels. CONCLUSIONS: A specific breath metabolome is associated with IBD and markedly changes in patients with IPAA. Analysis of a broader spectrum of VOCs can potentially aid in the development of breath prints to diagnose or differentiate inflammatory bowel disorders.
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Measurement of NO and/or its metabolites in the various body compartments has transformed our understanding of biology. The inability of the current NO measurement methods to account for naturally occurring and experimental NO isotopes, however, has prevented the scientific community from fully understating NO metabolism in vivo. Here we present a mid-IR Faraday rotation spectrometer (FRS) for detection of NO isotopes. The instrument utilizes a novel dual modulation/demodulation (DM) FRS method which exhibits noise performance at only 2 times the fundamental quantum shot-noise level and provides the record sensitivity in its class. This is achieved with a system that is fully autonomous, robust, transportable, and does not require cryogenic cooling. The DM-FRS enables continuous monitoring of nitric oxide isotopes with the detection limits of 3.72â ppbv/Hz(1/2) to(14)NO and 0.53â ppbv/Hz(1/2) to(15)NO using only 45â cm active optical path. This DM-FRS measurement method can be used to improve the performance of conventional FRS sensors targeting other radical species. The feasibility of the instrument to perform measurements relevant to studies of NO metabolism in humans is demonstrated.
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Expiração , Isótopos , Óxido Nítrico/metabolismo , Análise Espectral/métodos , Humanos , Óxido Nítrico/sangue , Óxido Nítrico/urina , Análise Espectral/instrumentaçãoRESUMO
Breath testing is increasingly being used as a non-invasive diagnostic tool for disease states across medicine. The purpose of this study was to compare the levels of volatile organic compounds (VOCs) as measured by mass spectrometry in healthy children and children with chronic liver disease (CLD). Patients between the ages of 6 and 21 were recruited for the study. Control subjects were recruited from a general pediatric population during well-child visits, while patients with CLD were recruited from pediatric gastroenterology clinic visits. The diagnosis of CLD was confirmed by clinical, laboratory, and/or histologic data. A single exhaled breath was collected and analyzed by means of selected-ion flow-tube mass spectrometry per protocol. A total of 104 patients were included in the study (49 with CLD and 55 healthy controls). Of the patients with CLD, 20 had advanced liver fibrosis (F3-F4). In the CLD cohort, levels of exhaled 1-decene, 1-heptene, 1-octene and 3 methylhexane were found to be significantly higher when compared to the control population (p < 0.001, p = 0.035, p < 0.001 and p = 0.004, respectively). Exhaled 1-nonene, (E)-2-nonene, and dimethyl sulfide levels were found to be significantly lower in patients with CLD patients when compared to controls (p < 0.001, p < 0.001 and p = 0.007, respectively). By utilizing a combination of five of the VOCs, the accuracy for predicting the presence of CLD was excellent (AUROC = 0.97). Our study demonstrates that children with CLD have a unique pattern of exhaled VOCs. Utilization of a combination of these VOCs represents a promising non-invasive diagnostic tool and may provide further insight into the pathophysiologic processes and pathways leading to pediatric liver disease. Further analysis of these compounds in external cohorts are needed to validate our findings.
Assuntos
Cirrose Hepática/metabolismo , Compostos Orgânicos Voláteis/metabolismo , Adolescente , Alcenos/análise , Alcenos/metabolismo , Área Sob a Curva , Testes Respiratórios/métodos , Estudos de Casos e Controles , Criança , Doença Crônica , Feminino , Humanos , Cirrose Hepática/diagnóstico , Hepatopatias/diagnóstico , Hepatopatias/metabolismo , Masculino , Espectrometria de Massas/métodos , Curva ROC , Sensibilidade e Especificidade , Compostos Orgânicos Voláteis/análise , Adulto JovemRESUMO
RATIONALE: Pulmonary arterial hypertension (PAH) is a pulmonary vasculopathy that leads to failure of the right ventricle and premature death. OBJECTIVES: To determine whether the sublingual microcirculation is affected in patients with PAH compared with healthy age- and sex-matched control subjects. METHODS: Using the CapiScope Handheld Video Capillaroscope we measured the sublingual microvasculature density, flow index, tortuosity, and curvature. Videos were acquired immediately after right heart catheterization, and determinations were made off-line by investigators blinded to the group assignment or hemodynamics. MEASUREMENTS AND MAIN RESULTS: In this cross-sectional pilot study, we included 26 patients with PAH (age, mean ± SD, 56.7 ± 10 yr; 77% women) and 14 healthy control subjects (age, 53.1 ± 12 yr; 71% women). Sublingual microvasculature flow index was lower (2 ± 0.66 vs. 2.7 ± 0.37, P < 0.001) with higher heterogeneity index (0.63 ± 0.63 vs. 0.25 ± 0.25, P = 0.04) in patients with PAH than control subjects. Microvasculature density was similar between the groups, but tortuosity was more pronounced in patients than control subjects (tort 0: 45 ± 19 vs. 23.6 ± 12, P = 0.001 and tort 1: 0.2 ± 0.16 vs. 0.06 ± 0.04, P < 0.001). CONCLUSIONS: Patients with PAH showed lower sublingual microvasculature flow index and higher tortuosity compared with healthy age- and sex-matched control subjects. Further investigations are needed to assess whether this methodology can provide information on disease prognosis and/or response to therapy in this condition.