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Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are severe age-related disorders with complex and multifactorial causes. Recent research suggests a critical link between neurodegeneration and the gut microbiome, via the gut-brain communication pathway. This review examines the role of trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, in the development of AD and PD, and investigates its interaction with microRNAs (miRNAs) along this bidirectional pathway. TMAO, which is produced from dietary metabolites like choline and carnitine, has been linked to increased neuroinflammation, protein misfolding, and cognitive decline. In AD, elevated TMAO levels are associated with amyloid-beta and tau pathologies, blood-brain barrier disruption, and neuronal death. TMAO can cross the blood-brain barrier and promote the aggregation of amyloid and tau proteins. Similarly, TMAO affects alpha-synuclein conformation and aggregation, a hallmark of PD. TMAO also activates pro-inflammatory pathways such as NF-kB signaling, exacerbating neuroinflammation further. Moreover, TMAO modulates the expression of various miRNAs that are involved in neurodegenerative processes. Thus, the gut microbiome-miRNA-brain axis represents a newly discovered mechanistic link between gut dysbiosis and neurodegeneration. MiRNAs regulate the key pathways involved in neuroinflammation, oxidative stress, and neuronal death, contributing to disease progression. As a direct consequence, specific miRNA signatures may serve as potential biomarkers for the early detection and monitoring of AD and PD progression. This review aims to elucidate the complex interrelationships between the gut microbiota, trimethylamine-N-oxide (TMAO), microRNAs (miRNAs), and the central nervous system, and the implications of these connections in neurodegenerative diseases. In this context, an overview of the current neuroradiology techniques available for studying neuroinflammation and of the animal models used to investigate these intricate pathologies will also be provided. In summary, a bulk of evidence supports the concept that modulating the gut-brain communication pathway through dietary changes, the manipulation of the microbiome, and/or miRNA-based therapies may offer novel approaches for implementing the treatment of debilitating neurological disorders.
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Trimethyl-N-oxide (TMAO) has been linked to peripheral artery disease (PAD). Taurisoloâ is a natural, balanced phytocomplex containing resveratrol, quercetin, catechins, procianidins, gallic acid, and caffeic acid. Numerous studies have shown that Taurisoloâ reduces the damage of TMAO and exerts a protective effect on endothelial cells (ECs). The aim of this randomized, double-blind, single-center study was to evaluate the effects of Taurisoloâ on claudication in patients with PAD (Rutheford grade I, category II, Fontaine Classification: Stage IIA, American Medical Association Whole Person Impairment Classification: Class 0-WPI 0%) in two parallel groups of 31 patients. The primary outcomes were an increase in the pain-free walking distance and the ankle/brachial pressure index at the beginning and at the end of the treatment with Taurisolo. The secondary endpoint was the serum TMAO changes. The claudication distance improved by 14.1% in the Taurisolo group and by 2.0% in the placebo group, while the maximal distance increased by 15.8% and 0.6% only, respectively (both p < 0.05). The TMAO plasma levels decreased from 3.97 ± 2.13 micromole/L to 0.87 ± 0.48 (p < 0.0001) in the treated group. All these changes were highly significant both in univariate mixed models as well as in the adjusted model. Ultimately, Taurisoloâ might be an effective intervention to ameliorate intermittent claudication.
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Given the recent evidence in the clinical application of regenerative medicine, mostly on integumentary systems, we focused our interests on recent bladder regeneration approaches based on mesenchymal stem cells (MSCs), platelet-rich plasma (PRP), and hyaluronic acid (HA) in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) in humans. IC/BPS is a heterogeneous chronic disease with not-well-understood etiology, characterized by suprapubic pain related to bladder filling and urothelium dysfunction, in which the impairment of immunological processes seems to play an important role. The histopathological features of IC include ulceration of the mucosa, edema, denuded urothelium, and increased detection of mast cells and other inflammatory cells. A deeper understanding of the molecular mechanism underlying this disease is essential for the selection of the right therapeutic approach. In fact, although various therapeutic strategies exist, no efficient therapy for IC/BPS has been discovered yet. This review gives an overview of the clinical and pathological features of IC/BPS, with a particular focus on the molecular pathways involved and a special interest in the ongoing few investigational therapies in IC/BPS, which use new regenerative medicine approaches, and their synergetic combination. Good knowledge of the molecular aspects related to stem cell-, PRP-, and biomaterial-based treatments, as well as the understanding of the molecular mechanism of this pathology, will allow for the selection of the right and best use of regenerative approaches of structures involving connective tissue and epithelia, as well as in other diseases.
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Cistite Intersticial , Humanos , Cistite Intersticial/terapia , Bexiga Urinária/patologia , Ácido Hialurônico , Doença CrônicaRESUMO
Background: Bone marrow (BM)-derived stem cells were implanted to induce angiogenesis in patients with no-option critical limb-threatening ischemia. Considering the potential for this therapy, conflicting results related to BM harvesting methods have been reported that could affect stem cell concentrations and quality. Methods: A total of 75 patients with no-option critical limb-threatening ischemia were treated with BM implantation. For 58 patients, BM was harvested using a BM aspirate concentrate system (Harvest Technologies; group HT) with a standard aspiration needle, followed by an automated centrifugation process, to produce BM aspirate concentrate. For 17 patients, BM was harvested using the Marrow Cellution system (Aspire Medical Innovation; group MC). CD34+ cells/mL, CD117+ cells/mL, CD133+ cells/mL, CD309+ cells/mL, hematocrit, and BM purity were compared between the two BM preparations. Results: The retrospective analysis of a subset group after adjustment for age shows that the quality of BM obtained using the Marrow Cellution system is better, in terms of purity, than the classic harvesting method before centrifugation. Harvested BM before centrifugation is characterized by a higher percentage of CD133+ cells compared with BM after centrifugation. In contrast, the MC aspirate had a larger amount of very small embryonic-like cells, as indicated by the higher percentage of CD133+, CD34+, and CD45- cells. These differences translated into an increased occurrence of leg amputations in group HT than in group MC and an increase in transcutaneous oxygen pressure in patients treated with BM aspirated using MC. Conclusions: BM manipulation, such as centrifugation, affects the quality and number of stem cells, with detrimental consequences on clinical outcomes, as reflected by the different amputation rates between the two groups.
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We evaluated the use of autologus bone marrow stem cells transplantation in patients with critical limb ischaemia (CLI) not eligible for revascularization. Eighty consecutive patients candidate to amputation were enrolled in a single-centre retrospective study. The primary endpoint was defined as the amputation-free rate from stem cells transplantation. Secondary endpoints were the evaluation of transcutaneous oximetry and its predictive potential for probability of amputation and the evaluation of rest pain. Ankle brachial index, transcutaneous oxygen (TcpO2) and radiological imaging were performed at the enrolment and during the follow-up times. All patients were treated with auto transplant of bone marrow stem cells. Two patients died due to acute renal and acute respiratory failures. 19 patients were amputated from the thigh or leg. In total, 59 of 80 patients intended to thigh amputation saved the limb, preserving the plantar support. TcpO2 was found a predictive metric with an AUC equal to .763, and a threshold for a risk of amputation of 10% and 5% at the values ≤22.7 and ≤26.9 mmHg, respectively. Auto transplant of bone marrow stem cells seems to be a safe and an efficient option for CLI not eligible to revascularizzation.
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INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is one of the current public health care challenges. The main strategy adopted to prevent the spread of infection is the rapid identification of COVID-19-positive subjects. The aim of this study was to compare the performance of Lumipulse® antigen immunoassay with the real-time RT-PCR, the gold standard for the diagnosis of SARS-CoV-2 infection, in a strictly selected asymptomatic population. MATERIALS AND METHODS: A total of 392 consecutive oro-nasopharyngeal swabs were collected from patients with no symptoms related to COVID-19 at the Emergency Department of AORN Sant'Anna e San Sebastiano, Caserta, Italy to evaluate the analytical performance of Lumipulse® SARS-CoV-2 antigen compared to qualitative real-time RT-PCR in asymptomatic patients. RESULTS: Lumipulse® SARS-CoV-2 antigen assay shows an overall agreement rate of 97% with a sensitivity of 96% and a specificity of 98%, with a PPV and NPV of 97%. The sensitivity varies according to the cycle threshold (Ct )-value reaching 100% and 86% with 15 < Ct < 25 and Ct ≥ 25, respectively. The ROC analysis yielded an AUC value of 0.98, suggesting that the antigen test may accurately detect SARS-CoV-2. CONCLUSION: Our data showed that Lumipulse® SARS-CoV-2 antigen assay might be an efficient tool in the identification and limitation of SARS-CoV-2 transmission in large asymptomatic populations.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/epidemiologia , Testes Imunológicos , Serviço Hospitalar de Emergência , Curva ROC , Sensibilidade e EspecificidadeRESUMO
PURPOSES: Radiomics is a quantitative method able to analyze a high-throughput extraction of minable imaging features. Herein, we aim to develop a CT angiography-based radiomics analysis and machine learning model for carotid plaques to discriminate vulnerable from no vulnerable plaques. MATERIALS AND METHODS: Thirty consecutive patients with carotid atherosclerosis were enrolled in this pilot study. At surgery, a binary classification of plaques was adopted ("hard" vs "soft"). Feature extraction was performed using the R software package Moddicom. Pairwise feature interdependencies were evaluated using the Spearman rank correlation coefficient. A univariate analysis was performed to assess the association between each feature and the plaque classification and chose top-ranked features. The feature predictive value was investigated using binary logistic regression. A stepwise backward elimination procedure was performed to minimize the Akaike information criterion (AIC). The final significant features were used to build the models for binary classification of carotid plaques, including logistic regression (LR), support vector machine (SVM), and classification and regression tree analysis (CART). All models were cross-validated using fivefold cross validation. Class-specific accuracy, precision, recall and F-measure evaluation metrics were used to quantify classifier output quality. RESULTS: A total of 230 radiomics features were extracted from each plaque. Pairwise Spearman correlation between features reported a high level of correlations, with more than 80% correlating with at least one other feature at |ρ|> 0.8. After a stepwise backward elimination procedure, the entropy and volume features were found to be the most significantly associated with the two plaque groups (p < 0.001), with AUCs of 0.92 and 0.96, respectively. The best performance was registered by the SVM classifier with the RBF kernel, with accuracy, precision, recall and F-score equal to 86.7, 92.9, 81.3 and 86.7%, respectively. The CART classification tree model for the entropy and volume features model achieved 86.7% well-classified plaques and an AUC of 0.987. CONCLUSION: This pilot study highlighted the potential of CTA-based radiomics and machine learning to discriminate plaque composition. This new approach has the potential to provide a reliable method to improve risk stratification in patients with carotid atherosclerosis.
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Doenças das Artérias Carótidas , Placa Aterosclerótica , Algoritmos , Artérias Carótidas , Doenças das Artérias Carótidas/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Humanos , Projetos Piloto , Placa Aterosclerótica/diagnóstico por imagemRESUMO
Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, metformin therapy reducing the metabolic distress and the inflammatory burden could reduce MACE in ACAS patients with pre-diabetes. In this setting, the microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture, and worse prognosis in normoglycemics (NG) versus pre-diabetics metformin users (PDMU) versus pre-diabetics non-metformin users (PDNMU). However, our study aimed to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG versus PDMU versus PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy. The study included 234 patients with ACAS divided into NG (n = 125), PDNMU (n = 73), and PDMU (n = 36). The miRs' expression profiles of circulating exosomes were determined at baseline and at 2 years of follow-up by Affymetrix microarrays from the patients' plasma samples from any study cohort. Then we collected and analyzed MACE at 2 years of follow-up in NG versus PDMU versus PDNMU. Prediabetics versus NG had over-inflammation (p < 0.05) and over expressed miR-24 and miR-27 at baseline. At 2 years of follow-up, PDNMU versus NG, PDMU versus NG, and PDNMU versus PDMU over-expressed inflammatory markers and miR-24, miR-27, miR-100, miR-126, and miR-133 (p < 0.05). Finally, at the end of follow-up, we observed a significant difference about MACE comparing PDNMU versus NG (n = 27 (36.9%) versus n = 8 (6.4%); p < 0.05), PDNMU versus PDMU (n = 27 (36.9%) versus n = 6 (16.6%); p < 0.05); and PDMU versus NG (n = 6 (16.6%) versus n = 8 (6.4%); p < 0.05). Admission glucose values (HR (hazard ratio) 1.020, CI (confidence of interval) 95% (1.001-1.038), p = 0.029), atheromatous carotid plaque (HR 5.373, CI 95% (1.251-11.079), p = 0.024), and miR-24 (HR 3.842, CI 95% (1.768-19.222), p = 0.011) predicted MACE at 2 years of follow-up. Specific circulating miRs could be over-expressed in pre-diabetics and specifically in PDNMU versus PDMU after endarterectomy. MiR24, hyperglycemia, and atheromatous plaque could predict MACE at 2 years of follow-up.
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Extracellular vesicles (EVs) have become a key tool in the biotechnological landscape due to their well-documented ability to mediate intercellular communication. This feature has been explored and is under constant investigation by researchers, who have demonstrated the important role of EVs in several research fields ranging from oncology to immunology and diagnostics to regenerative medicine. Unfortunately, there are still some limitations to overcome before clinical application, including the inability to confine the EVs to strategically defined sites of interest to avoid side effects. In this study, for the first time, EV application is supported by 3D bioprinting technology to develop a new strategy for applying the angiogenic cargo of human umbilical vein endothelial cell-derived EVs in regenerative medicine. EVs, derived from human endothelial cells and grown under different stressed conditions, were collected and used as bioadditives for the formulation of advanced bioinks. Afterin vivosubcutaneous implantation, we demonstrated that the bioprinted 3D structures, loaded with EVs, supported the formation of a new functional vasculaturein situ, consisting of blood-perfused microvessels recapitulating the printed pattern. The results obtained in this study favour the development of new therapeutic approaches for critical clinical conditions, such as the need for prompt revascularization of ischaemic tissues, which represent the fundamental substrate for advanced regenerative medicine applications.
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Bioimpressão , Vesículas Extracelulares , Impressão Tridimensional , Comunicação Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Medicina RegenerativaRESUMO
BACKGROUND: This study examined the quality of bone marrow aspirates extracted using a novel, FDA cleared method to optimally target cells from the inner cortical iliac bone surface without the need for centrifugation. This method employs small draws from a single puncture that promote only lateral flow from multiple sites (SSLM method). The study utilized the Marrow Cellutions bone marrow aspiration system (MC system) which is based on the SSLM method and compared the MC system directly to bone marrow concentrates (BMAC) generated by centrifugation of aspirates harvested with a standard aspiration needle. METHODS: Three direct comparisons were conducted evaluating the SSLM draws and BMACs derived from the same patient from contralateral iliac crests. The levels of TNCs/mL, CD34+ cells/mL, CD117+ cells/mL, and CFU-f/mL were compared between the various bone marrow preparations. The cellular content of a series of SSLM draws was also analyzed to determine the total nucleated cell (TNC) count and the concentration of mesenchymal stem/progenitor cells as measured by colony forming unit fibroblasts (CFU-f). RESULTS: In direct comparisons with BMAC systems, SSLM draws yielded significantly higher CFU-f concentrations and comparable concentrations of CD34+ and CD117+ cells. In addition, the average quantity of TNCs/mL in a series of 30 patients utilizing the SSLM draw was 35.2 × 106 ± 17.1 × 106 and the average number of CFU-f/mL was 2885 ± 1716. There were small but significant correlations between the TNCs/mL and the CFU-fs/mL using the SSLM method as well as between the age of the patient and the CFU-fs/mL. CONCLUSIONS: The MC Device, using the SSLM draw technique, produced concentrations of CFU-fs, CD34+ cells and CD117+ cells that were comparable or greater to BMACs derived from the same patient. Given the rapid speed and simplicity of the MC Device, we believe this novel system possesses significant practical advantages to other currently available centrifugation based systems.
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Células da Medula Óssea/citologia , Separação Celular/métodos , Células-Tronco Mesenquimais/citologia , Contagem de Células , Núcleo Celular/metabolismo , Centrifugação , Ensaio de Unidades Formadoras de Colônias , Humanos , SucçãoAssuntos
Anestesia Geral/métodos , Anestesia Intravenosa/métodos , Barorreflexo/fisiologia , Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Idoso , Idoso de 80 Anos ou mais , Bradicardia/induzido quimicamente , Bradicardia/diagnóstico , Bradicardia/prevenção & controle , Eletrodos Implantados , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Hematopoiesis as the only essential function of bone marrow cells has been challenged for several decades through basic science (in vitro and in vivo) and clinical data. Such work has shed light on two other essential functions of bone marrow cells: osteopoiesis and angio-genesis/vasculogenesis. Clinical utility of autologous concentrated bone marrow aspirate (CBMA) has demonstrated both safety and efficacy in treating bone defects. Moreover, CBMA has been shown to be comparable to the gold standard of iliac crest bone graft (ICBG), or autograft, with regard to being osteogenic and osteoinductive. ICBG is not considered an advanced therapy medicinal product (ATMP), but CBMA may become regulated as an ATMP. The European Medicines Agency Committee for Advanced Therapies (EMA:CAT) has issued a reflection paper (20 June 2014) in which reversal of the 2013 ruling that CBMA is a non-ATMP has been proposed. We review bone marrow cell involvement in osteopoiesis and angiogenesis/vasculogenesis to examine EMA:CAT 2013 decision to use CBMA for treatment of osteonecrosis (e.g, of the femoral head) should be considered a non-ATMP. This paper is intended to provide discussion on the 20 June 2014 reflection paper by reviewing two non-hematopoietic essential functions of bone marrow cells. Additionally, we provide clinical and scientific rationale for treating osteonecrosis with CBMA.
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OBJECTIVE: Postoperative atrial fibrillation is a major cause of morbidity and mortality for stroke after cardiac surgery. Both systemic inflammation and oxidative stress play a role in the initiation of postoperative atrial fibrillation after cardiac surgery. The possible association between long-term intake of antioxidant-rich foods and postoperative atrial fibrillation incidence was examined in patients undergoing cardiac surgery. METHODS: A total of 217 consecutive patients (74% were men; median age, 68.4 years) undergoing cardiac surgery, mainly coronary artery bypass grafting and valve replacement or repair, were recruited from January 2010 to September 2012. Total antioxidant capacity was measured in foods by the Trolox equivalent antioxidant capacity assay. The European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire was used for dietary total antioxidant capacity assessment. The association among tertiles of dietary total antioxidant capacity and postoperative atrial fibrillation incidence was assessed using multivariable logistic analysis. RESULTS: The overall incidence of total arrhythmias and postoperative atrial fibrillation was 42.4% and 38.2%, respectively. In multivariable analysis, after adjustment for age, gender, use of hypoglycemic drugs, physical activity, education, previous diagnosis of atrial fibrillation, and total energy intake, patients in the highest tertile of dietary total antioxidant capacity had a lower risk of postoperative atrial fibrillation than patients in the 2 lowest tertiles (odds ratio, 0.46; 95% confidence interval, 0.22-0.95; P = .048). A restricted cubic spline transformation confirmed the nonlinear relationship between total antioxidant capacity (in continuous scale) and postoperative atrial fibrillation (P = .023). When considering only coronary artery bypass grafting, valve replacement/repair, and combined surgeries, the protective effect on postoperative atrial fibrillation of a diet rich in antioxidants was confirmed. CONCLUSIONS: Long-term consumption of antioxidant-rich foods is associated with a reduced incidence of postoperative atrial fibrillation in patients undergoing cardiac surgery.
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Antioxidantes/administração & dosagem , Fibrilação Atrial/prevenção & controle , Ponte de Artéria Coronária/efeitos adversos , Dieta , Implante de Prótese de Valva Cardíaca/efeitos adversos , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/fisiopatologia , Comportamento Alimentar , Feminino , Humanos , Incidência , Itália/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação Nutricional , Estado Nutricional , Razão de Chances , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
Mitral valve repair for ischaemic mitral incompetence has a 10% rate of failure at ten year follow-up. Progressive annular dilation could play an important role. We have implanted the enCor(SQ)(TM) mitral valve repair system. This system can be downsized during follow-up with the appropriate activation via the lead passed through the left atrium suture line, in order to restore mitral leaflet coaptation.
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Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Anuloplastia da Valva Mitral/instrumentação , Insuficiência da Valva Mitral/cirurgia , Humanos , Desenho de Prótese , Técnicas de Sutura , Resultado do TratamentoRESUMO
BACKGROUND: The purpose of this research was to investigate the in vivo morphofunctional changes induced in the radial artery (RA) by its use as coronary artery bypass conduit by comparing the morphological features and vasoreactivity of the native RA versus the coronary RA graft in the same patient. METHODS AND RESULTS: Ten years after surgery, 10 patients were submitted to intravascular ultrasound examination of the RA graft of the controlateral (in situ) RA and of the internal thoracic artery (ITA) graft and to vasoactive challenges with acetylcholine and serotonin. Quantitative angiographic assessment showed that the mean diameter of the RA coronary grafts was significantly larger than that of the in situ RA and of the ITA (2.89+/-0.40 mm RA grafts, 2.14+/-0.52 mm in situ RA, 2.25+/-0.53 mm ITA grafts; P<0.001). The in situ RA demonstrated a typical muscular architecture, whereas RA coronary grafts showed a clear reduction of the thickness of the medial layer and had a less well-defined muscular component of the media with interposition of elastic tissue. Serotonin endovascular infusion elicited a strong spastic reaction in in situ RAs; the same challenge induced only moderate constriction in RA and ITA coronary grafts. CONCLUSIONS: Implantation in the coronary circulation leads to major anatomic and vasoreactive modifications of the RAs that tend to lose the morphofunctional features of a muscular conduit and assume those of an elastomuscular artery, such as the ITA.
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Ponte de Artéria Coronária , Tecido Elástico/ultraestrutura , Músculo Liso Vascular/ultraestrutura , Artéria Radial/transplante , Acetilcolina , Prótese Vascular , Angiografia Coronária , Tecido Elástico/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Anastomose de Artéria Torácica Interna-Coronária , Dinitrato de Isossorbida/farmacologia , Masculino , Artéria Torácica Interna/diagnóstico por imagem , Artéria Torácica Interna/efeitos dos fármacos , Artéria Torácica Interna/ultraestrutura , Pessoa de Meia-Idade , Músculo Liso Vascular/diagnóstico por imagem , Artéria Radial/diagnóstico por imagem , Artéria Radial/efeitos dos fármacos , Artéria Radial/ultraestrutura , Serotonina , Transplante Heterotópico , Ultrassonografia de Intervenção , Vasoconstritores/farmacologia , Vasodilatadores/farmacologiaRESUMO
BACKGROUND: This study was aimed at evaluating the determinants of postoperative dialysis-requiring acute renal failure and at identifying eventual correlations between the different etiologic mechanisms and postoperative prognosis. METHODS: We evaluated the preoperative and intraoperative features of the 69 out of 6,542 consecutive cardiac surgery patients who developed postoperative dialysis-requiring acute renal failure at our Institution during a 10-year period. RESULTS: Age, valvular and aortic surgery, hypertension, extracardiac vasculopathy, timing of surgery, cardiopulmonary bypass time, and preoperative creatinine level greater than 2.0 mg/dL were identified as predictors by multivariate analysis. In a second analysis, patients were divided in two groups according to the preoperative creatinine level: group A (preoperative creatinine 2.0 mg/dL or less; 38 cases) and group B (preoperative creatinine 2.1 mg/dL or more; 31 cases). The two groups significantly differed in preoperative and intraoperative characteristics and in postoperative outcome: group A patients were younger, had a lower incidence of cardiac and vascular risk factors and comorbidities, were mainly operated on urgent or emergent basis for valvular or aortic pathologies, had longer cardiopulmonary bypass and cross-clamp time, and worse in-hospital outcome but higher midterm survival. Group B patients were older, had a higher prevalence of comorbidities, required more often in-hospital or after-discharge dialysis, had lower in-hospital mortality, but reduced midterm survival. CONCLUSIONS: Postoperative dialysis-requiring acute renal failure can be the result of two different pathophysiological pathways: complicated perioperative course due to urgent-emergent surgery or main intraoperative technical complications in patients with preoperative normal renal function and uncomplicated perioperative course associated with reduced preoperative kidney function. The two patient groups significantly differ in baseline preoperative features, as well as in in-hospital and in midterm outcome.
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Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Injúria Renal Aguda/epidemiologia , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND: Intravascular ultrasound (IVUS) studies have shown that a mechanism of plaque compression/embolization contributes toward the poststenting increase in lumen area. The aim of this IVUS study was to compare the mechanisms of lumen enlargement after coronary stenting in 54 consecutive patients with unstable angina (UA) (group 1) and 56 with stable angina (group 2) to verify whether plaque embolization plays a major role in the former. METHODS AND RESULTS: Both groups underwent the IVUS assessment (speed, 0.5 mm/sec) before the intervention and after stent implantation. The lumen area, the external elastic membrane area, and the plaque+media area (PA) were measured at 0.5-mm intervals. PA reduction in the lesion site was significantly greater in group 1 (-2.50+/-1.97 versus -0.53+/-1.43 mm2, P<0.001). After stenting, 47% of the lumen area increase in group 1 was obtained by means of PA reduction, and 53% was attributable to external elastic membrane area increase; the corresponding figures in group 2 were 13% and 87% (P<0.05). Decrease in PA after stenting was the only significant predictor of the MB fraction of creatinine kinase (CK-MB) release in a multiple regression model (P=0.047). CONCLUSIONS: Serial volumetric IVUS assessment revealed in UA lesions a marked poststenting reduction in plaque volume, which is significantly greater than in stable angina and is associated with postprocedural CK-MB release. The decrease in PA during the procedure predicts CK-MB release in a multiple regression model. These findings suggest that stent deployment is often associated with plaque embolization in patients with UA.
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Angina Instável/cirurgia , Embolia/etiologia , Stents/efeitos adversos , Angina Pectoris/cirurgia , Angina Instável/diagnóstico por imagem , Angina Instável/patologia , Vasos Coronários/diagnóstico por imagem , Creatina Quinase/análise , Creatina Quinase Forma MB , Feminino , Humanos , Isoenzimas/análise , Masculino , Pessoa de Meia-Idade , UltrassonografiaRESUMO
BACKGROUND: As a consequence of plaque accumulation, coronary arteries may undergo both compensatory enlargement and paradoxical constriction. The aim of this study was to address the distribution of the different remodeling patterns in patients with obstructive coronary atherosclerosis. METHODS: Eighty-seven non-branching segments of native coronary arteries with de novo, focal, non-ostial lesions were imaged at intravascular ultrasound (IVUS). Images were acquired with a motorized pull-back at a speed of 0.5 mm/s. The cross-sectional area (CSA) circumscribed by the external elastic membrane (EEM), the plaque + media complex and the lumen area were measured at its narrowest site (CSA with the minimal lumen area) and in the reference segment (average of proximal and distal reference cross-sections, defined as the most normal looking sites). The IVUS index of vessel remodeling (VRI) was calculated using the following formula: (narrowest site EEM CSA--reference EEM CSA)/reference EEM CSA*100. The index was tested for normality using the Kolmogorov-Smirnov goodness-of-fit test. RESULTS: The frequency distribution of VRI was found to have a normal unimodal distribution (p = 0.60). VRI ranged from -60 to +164, with a mean of 9.3 +/- 28.0 and a median of 3.6. Frequency distribution of VRI slightly skewed towards right (skewness index 1.69). None of the analyzed clinical and morphological variables predicted the presence of compensatory enlargement as opposed to paradoxical constriction. CONCLUSIONS: The frequency distribution of the vascular remodeling of de novo coronary lesions is unimodal. Therefore, compensatory enlargement and paradoxical constriction represent the extremes of a continuous spectrum.