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BACKGROUND: Mitochondrial transplantation (MTx) has emerged as a novel therapeutic strategy, particularly effective in diseases characterized by mitochondrial dysfunction. This review synthesizes current knowledge on MTx, focusing on its role in modulating immune responses and explores its potential in treating post-cardiac arrest syndrome (PCAS). METHODS: We conducted a comprehensive narrative review of animal and human studies that have investigated the effects of MTx in the context of immunomodulation. This included a review of the immune responses following critical condition such as ischemia reperfusion injury, the impact of MTx on these responses, and the therapeutic potential of MTx in various conditions. RESULTS: Recent studies indicate that MTx can modulate complex immune responses and reduce ischemia-reperfusion injury post-CA, suggesting MTx as a novel, potentially more effective approach. The review highlights the role of MTx in immune modulation, its potential synergistic effects with existing treatments such as therapeutic hypothermia, and the need for further research to optimize its application in PCAS. The safety and efficacy of autologous versus allogeneic MTx, particularly in the context of immune reactions, are critical areas for future investigation. CONCLUSION: MTx represents a promising frontier in the treatment of PCAS, offering a novel approach to modulate immune responses and restore cellular energetics. Future research should focus on long-term effects, combination therapies, and personalized medicine approaches to fully harness the potential of MTx in improving patient outcomes in PCAS.
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Paro Cardíaco , Hipotermia Inducida , Daño por Reperfusión , Animales , Humanos , Terapia Combinada , Medicina de Precisión , Paro Cardíaco/terapia , Inmunomodulación , Daño por Reperfusión/terapiaRESUMEN
The human brain possesses three predominate phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS), which account for approximately 35-40%, 35-40%, and 20% of the brain's phospholipids, respectively. Mitochondrial membranes are relatively diverse, containing the aforementioned PC, PE, and PS, as well as phosphatidylinositol (PI) and phosphatidic acid (PA); however, cardiolipin (CL) and phosphatidylglycerol (PG) are exclusively present in mitochondrial membranes. These phospholipid interactions play an essential role in mitochondrial fusion and fission dynamics, leading to the maintenance of mitochondrial structural and signaling pathways. The essential nature of these phospholipids is demonstrated through the inability of mitochondria to tolerate alteration in these specific phospholipids, with changes leading to mitochondrial damage resulting in neural degeneration. This review will emphasize how the structure of phospholipids relates to their physiologic function, how their metabolism facilitates signaling, and the role of organ- and mitochondria-specific phospholipid compositions. Finally, we will discuss the effects of global ischemia and reperfusion on organ- and mitochondria-specific phospholipids alongside the novel therapeutics that may protect against injury.
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Encéfalo , Paro Cardíaco , Mitocondrias , Fosfolípidos , Humanos , Fosfolípidos/metabolismo , Mitocondrias/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/patología , Paro Cardíaco/metabolismo , Transducción de Señal , Membranas Mitocondriales/metabolismo , Dinámicas MitocondrialesRESUMEN
BACKGROUND: Mitochondrial transplantation (MTx) is an emerging but poorly understood technology with the potential to mitigate severe ischemia-reperfusion injuries after cardiac arrest (CA). To address critical gaps in the current knowledge, we test the hypothesis that MTx can improve outcomes after CA resuscitation. METHODS: This study consists of both in vitro and in vivo studies. We initially examined the migration of exogenous mitochondria into primary neural cell culture in vitro. Exogenous mitochondria extracted from the brain and muscle tissues of donor rats and endogenous mitochondria in the neural cells were separately labeled before co-culture. After a period of 24 h following co-culture, mitochondrial transfer was observed using microscopy. In vitro adenosine triphosphate (ATP) contents were assessed between freshly isolated and frozen-thawed mitochondria to compare their effects on survival. Our main study was an in vivo rat model of CA in which rats were subjected to 10 min of asphyxial CA followed by resuscitation. At the time of achieving successful resuscitation, rats were randomly assigned into one of three groups of intravenous injections: vehicle, frozen-thawed, or fresh viable mitochondria. During 72 h post-CA, the therapeutic efficacy of MTx was assessed by comparison of survival rates. The persistence of labeled donor mitochondria within critical organs of recipient animals 24 h post-CA was visualized via microscopy. RESULTS: The donated mitochondria were successfully taken up into cultured neural cells. Transferred exogenous mitochondria co-localized with endogenous mitochondria inside neural cells. ATP content in fresh mitochondria was approximately four times higher than in frozen-thawed mitochondria. In the in vivo survival study, freshly isolated functional mitochondria, but not frozen-thawed mitochondria, significantly increased 72-h survival from 55 to 91% (P = 0.048 vs. vehicle). The beneficial effects on survival were associated with improvements in rapid recovery of arterial lactate and glucose levels, cerebral microcirculation, lung edema, and neurological function. Labeled mitochondria were observed inside the vital organs of the surviving rats 24 h post-CA. CONCLUSIONS: MTx performed immediately after resuscitation improved survival and neurological recovery in post-CA rats. These results provide a foundation for future studies to promote the development of MTx as a novel therapeutic strategy to save lives currently lost after CA.
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Reanimación Cardiopulmonar , Paro Cardíaco , Ratas , Animales , Reanimación Cardiopulmonar/métodos , Paro Cardíaco/terapia , Mitocondrias , Encéfalo/metabolismo , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/farmacología , Adenosina Trifosfato/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. METHODS: We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. RESULTS: Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI-associated myocardial dysfunction after cardiac surgery. CONCLUSION: The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.
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Daño por Reperfusión , Animales , Muerte Celular , Niño , Humanos , Mitocondrias , Daño por Reperfusión/terapiaRESUMEN
MAIN CONCLUSION: The histone acetyltransferase GCN5 and associated transcriptional coactivator ADA2b are required to couple endoreduplication and trichome branching. Mutation of ADA2b also disrupts the relationship between ploidy and leaf cell size. Dynamic chromatin structure has been established as a general mechanism by which gene function is temporally and spatially regulated, but specific chromatin modifier function is less well understood. To address this question, we have investigated the role of the histone acetyltransferase GCN5 and the associated coactivator ADA2b in developmental events in Arabidopsis thaliana. Arabidopsis plants with T-DNA insertions in GCN5 (also known as HAG1) or ADA2b (also known as PROPORZ1) display pleiotropic phenotypes including dwarfism and floral defects affecting fertility. We undertook a detailed characterization of gcn5 and ada2b phenotypic effects in rosette leaves and trichomes to establish a role for epigenetic control in these developmental processes. ADA2b and GCN5 play specific roles in leaf tissue, affecting cell growth and division in rosette leaves often in complex and even opposite directions. Leaves of gcn5 plants display overall reduced ploidy levels, while ada2b-1 leaves show increased ploidy. Endoreduplication leading to increased ploidy is also known to contribute to normal trichome morphogenesis. We demonstrate that gcn5 and ada2b mutants display alterations in the number and patterning of trichome branches, with ada2b-1 and gcn5-1 trichomes being significantly less branched, while gcn5-6 trichomes show increased branching. Elongation of the trichome stalk and branches also vary in different mutant backgrounds, with stalk length having an inverse relationship with branch number. Taken together, our data indicate that, in Arabidopsis, leaves and trichomes ADA2b and GCN5 are required to couple nuclear content with cell growth and morphogenesis.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Histona Acetiltransferasas/metabolismo , Hojas de la Planta/crecimiento & desarrollo , Factores de Transcripción/metabolismo , Tricomas/crecimiento & desarrollo , Arabidopsis/enzimología , Arabidopsis/genética , Arabidopsis/metabolismo , Citometría de Flujo , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Microscopía de Interferencia , Ploidias , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: Blood transfusions are a common and costly intervention for cardiac surgery patients. Evidence suggests that a more restrictive transfusion strategy may reduce costs and transfusion-related complications without increasing perioperative morbidity and mortality. STUDY DESIGN AND METHODS: A transfusion-limiting protocol was developed and implemented in a cardiovascular surgery unit. Over a 5-year period, data were collected on patient characteristics, procedures, utilization of blood products, morbidity, and mortality, and these were compared before and after the protocol was implemented. RESULTS: After the protocol was put in place, fewer patients required transfusions (38.2% vs. 45.5%, p = 0.004), with the greatest reduction observed in postoperative blood use (29.1% vs. 37.2%, p = 0.001). In-hospital morbidity and mortality did not increase. When patients who received transfusions were stratified by procedure, the protocol was most effective in reducing transfusions for patients undergoing isolated coronary artery bypass grafting (CABG; 4.09 units vs. 2.51 units, p = 0.009) and CABG plus valve surgery (10.32 units vs. 4.77 units, p = 0.014). A small group of patients were disproportionate recipients of transfusions, with approximately 6% of all patients receiving approximately half of the blood products. CONCLUSION: A protocol to limit transfusions decreased the proportion of cardiothoracic surgery patients who received blood products. A very small group of patients received a large number of transfusions, and within that group the observed mortality was significantly higher than in the general patient population. Current protocols cannot possibly account for these patients, and this should be considered when analyzing the performance of protocols designed to reduce unnecessary transfusions.
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Transfusión Sanguínea/estadística & datos numéricos , Procedimientos Quirúrgicos Cardíacos/economía , Protocolos Clínicos , Transfusión Sanguínea/economía , Comorbilidad , Puente de Arteria Coronaria , Mortalidad Hospitalaria , Humanos , Cuidados Posoperatorios/métodosRESUMEN
PURPOSE OF REVIEW: Bilateral internal thoracic arteries (BITAs) have demonstrated their superiority over all other types of graft in terms of patency and survival benefit. BITA implementation requires the surgeon's evaluation of the patient's coronary anatomy and demographics. There is no single ideal approach to BITA utilization, but instead a variety of configurations that can be implemented based on the patient characteristics. RECENT FINDINGS: This article details the advantages and disadvantages of several BITA configurations in the setting of left-sided myocardial revascularization and right-sided myocardial revascularization. Different BITA configurations will be described and will ultimately serve as a guide to avoiding technical difficulties and helping surgeons construct decision-making trees to direct the implementation of BITA grafts. SUMMARY: BITA grafting provides long-term clinical benefit over conventional grafting. Efforts should be directed toward a more efficient use of internal thoracic arteries, reducing the need for a third complementary graft, and toward identification of the best alternative to the saphenous vein graft as the third graft material for complete revascularization. Surgeons should ask their cardiologists to be as accurate as possible regarding the severity of the coronary lesion. If the severity of the lesion is not obvious upon an informal qualitative assessment, a functional flow reserve of the lesion should be performed, in order to identify the optimal graft.
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Puente de Arteria Coronaria , Arterias Mamarias , Revascularización Miocárdica , Humanos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Ascending aortic dissections (AADs) require prompt diagnosis and surgical treatment. We present the results of implementing a multidisciplinary aortic dissection protocol on the outcomes of AAD treatment at a nonteaching hospital. METHODS: From January 2002-December 2013, 54 patients with the diagnosis of AAD were treated at our institution. Thirty-seven (68.5%) were male with a mean age of 62.3 y. Cardiogenic shock was present in 25.9% of patients. An AAD protocol, focused on educating physicians on presenting signs and symptoms, adequate triaging, and the need for immediate surgical intervention, was implemented, alongside the standardization of surgical treatment. We divided the cohort into two eras, based on AAD program's implementation in 2006, to better assess the impact of this protocol. RESULTS: Patients from the early era had significantly longer time from Emergency Department to the operating room, more postoperative occurrence of prolonged ventilation, and a longer postoperative hospital stay at 8.7 ± 8 versus 3.1 ± 2.6 h (P = 0.002), 63% versus 18% (P = 0.002), and 63% versus 18% (P = 0.002), respectively. The overall mortality for the cohort was 9.3%, decreasing from 12.5% before 2006 to 7.9% after 2006. CONCLUSIONS: The implementation of a multidisciplinary aortic dissection protocol has resulted in faster diagnosis and transport of AAD cases from the emergency room to the operating room, improving outcomes. Our data support the concept that nonteaching institutions can deliver excellent care to patients with acute aortic emergencies.
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Algoritmos , Aneurisma de la Aorta , Disección Aórtica , Técnicas de Apoyo para la Decisión , Procedimientos Quirúrgicos Vasculares , Adulto , Anciano , Anciano de 80 o más Años , Disección Aórtica/diagnóstico , Disección Aórtica/mortalidad , Disección Aórtica/cirugía , Aneurisma de la Aorta/diagnóstico , Aneurisma de la Aorta/mortalidad , Aneurisma de la Aorta/cirugía , Protocolos Clínicos , Urgencias Médicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Grupo de Atención al Paciente , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Mitochondrial dysfunction, which is triggered by systemic ischemia-reperfusion (IR) injury and affects various organs, is a key factor in the development of post-cardiac arrest syndrome (PCAS). Current research on PCAS primarily addresses generalized mitochondrial responses, resulting in a knowledge gap regarding organ-specific mitochondrial dynamics. This review focuses on the organ-specific mitochondrial responses to IR injury, particularly examining the brain, heart, and kidneys, to highlight potential therapeutic strategies targeting mitochondrial dysfunction to enhance outcomes post-IR injury. METHODS AND RESULTS: We conducted a narrative review examining recent advancements in mitochondrial research related to IR injury. Mitochondrial responses to IR injury exhibit considerable variation across different organ systems, influenced by unique mitochondrial structures, bioenergetics, and antioxidative capacities. Each organ demonstrates distinct mitochondrial behaviors that have evolved to fulfill specific metabolic and functional needs. For example, cerebral mitochondria display dynamic responses that can be both protective and detrimental to neuronal activity and function during ischemic events. Cardiac mitochondria show vulnerability to IR-induced oxidative stress, while renal mitochondria exhibit a unique pattern of fission and fusion, closely linked to their susceptibility to acute kidney injury. This organ-specific heterogeneity in mitochondrial responses requires the development of tailored interventions. Progress in mitochondrial medicine, especially in the realms of genomics and metabolomics, is paving the way for innovative strategies to combat mitochondrial dysfunction. Emerging techniques such as mitochondrial transplantation hold the potential to revolutionize the management of IR injury in resuscitation science. CONCLUSIONS: The investigation into organ-specific mitochondrial responses to IR injury is pivotal in the realm of resuscitation research, particularly within the context of PCAS. This nuanced understanding holds the promise of revolutionizing PCAS management, addressing the unique mitochondrial dysfunctions observed in critical organs affected by IR injury.
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Background and study aims The COVID-19 pandemic has disrupted routine medical care due to uncertainty regarding the risk of viral spread. One major concern for viral transmission to both patients and providers is performing aerosol-generating procedures such as endoscopy. As such, we performed a prospective study to examine the extent of viral contamination present in the local environment before and after endoscopic procedures on COVID-19 positive patients. Materials and methods A total of 82 samples were collected from 23 surfaces in the procedure area of four COVID-positive patients undergoing upper endoscopic procedures. Samples were collected both before and after the procedure. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was extracted and quantified using reverse transcription quantitative polymerase chain reaction with primers to detect nucleocapsid RNA, and results reported as the number of viral copies per square centimeter of contaminated surface. Results A total of six positive samples were detected from three of the four patients. The floor beneath the patient bed was the most common site of viral RNA, but RNA was also detected on the ventilator monitor prior to the procedure and the endoscope after the procedure. Conclusions The risk of SARS-CoV-2 transmission associated with upper endoscopy procedures is low based on the low rate of surface contamination. Some surfaces in close proximity to the patient and endoscopist may pose a higher risk for contamination. Patient positioning and oxygen delivery methods may influence the directionality and extent of viral spread. Our results support the use of appropriate personal protection to minimize risk of viral transmission.
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Cardiac arrest (CA) induces whole-body ischemia resulting in mitochondrial dysfunction. We used isolated mitochondria to examine phospholipid alterations in the brain, heart, kidney, and liver post-CA. Our data shows that ischemia/reperfusion most significantly alters brain mitochondria phospholipids, predominately after resuscitation. Furthermore, the alterations do not appear to be a function of dysregulated importation of phospholipids, but caused by impaired intra-mitochondrial synthesis and/or remodeling of phospholipids. Our data demonstrates only brain mitochondria undergo significant alterations in phospholipids, providing a rationale for the high vulnerability of the brain to ischemia/reperfusion. Furthermore, analyzing this pathophysiologic state provides insight into physiologic mitochondrial phospholipid metabolism.
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Encéfalo/metabolismo , Paro Cardíaco/metabolismo , Mitocondrias/metabolismo , Miocardio/metabolismo , Fosfolípidos/metabolismo , Animales , Riñón/metabolismo , Hígado/metabolismo , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Background: Health care systems in the United States are continuously expanding and contracting spaces to treat patients with coronavirus disease 2019 (COVID-19) in intensive care units (ICUs). As a result, hospitals must effectively decontaminate and contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in constructed and deconstructed ICUs that care for patients with COVID-19. We assessed decontamination of a COVID-19 ICU and examined the containment efficacy of combined contact and droplet precautions in creating and maintaining a SARS-CoV-2-negative ICU "antechamber". Methods: To examine the efficacy of chemical decontamination, we used high-density, semi-quantitative environmental sampling to detect SARS-CoV-2 on surfaces in a COVID-19 ICU and COVID-19 ICU antechamber. Quantitative real-time polymerase chain reaction was used to measure viral RNA on surfaces. Viral location mapping revealed the distribution of viral RNA in the COVID-19 ICU and COVID-19 ICU antechamber. Results were further assessed using loop-mediated isothermal amplification. Results: We collected 224 surface samples pre-decontamination and 193 samples post-decontamination from a COVID-19 ICU and adjoining COVID-19 ICU antechamber. We found that 46% of antechamber objects were positive for SARS-CoV-2 pre-decontamination despite the construction of a swinging door barrier system, implementation of contact precautions, and installation of high-efficiency particulate air filters. The object positivity rate reduced to 32.1% and viral particle rate reduced by 95.4% following decontamination. Matched items had an average of 432.2 ± 2729 viral copies/cm2 pre-decontamination and 19.2 ± 118 viral copies/cm2 post-decontamination, demonstrating significantly reduced viral surface distribution (p < 0.0001). Conclusions: Environmental sampling is an effective method for evaluating decontamination protocols and validating measures used to contain SARS-CoV-2 viral particles. While chemical decontamination effectively removes detectable viral RNA from surfaces, our approach to droplet/contact containment with an antechamber was not highly effective. These data suggest that hospitals should plan for the potential of aerosolized virions when creating strategies to contain SARS-CoV-2.
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COVID-19 , SARS-CoV-2 , Descontaminación , Humanos , Unidades de Cuidados Intensivos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificación de Ácido NucleicoRESUMEN
Cardiac arrest remains a significant cause of death and disability throughout the world. However, as our understanding of cardiac arrest and resuscitation physiology has developed, new technologies are fundamentally altering our potential to improve survival and neurologic sequela. Some advances are relatively simple, requiring only alterations in current basic life support measures or integration with pre-hospital organization, whereas others, such as extra-corporeal membrane oxygenation, require significant time and resource investments. When combined with consistent rescuer and patient-physiologic monitoring, these innovations allow an unprecedented capacity to personalize cardiac arrest resuscitation to patient-specific pathophysiology. However, as more extensive options are established, it can be difficult for providers to incorporate novel resuscitation techniques into a cardiac arrest protocol which can fit a wide variety of cases with varying complexity. This article will explore recent advances in our understanding of cardiac arrest physiology and resuscitation sciences, with particular focus on the metabolic phase after significant ischemia has been induced. To this end, we establish a practical consideration for providers seeking to integrate novel advances in cardiac arrest resuscitation into daily practice.
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Reanimación Cardiopulmonar/métodos , Paro Cardíaco/terapia , Humanos , Medicina de PrecisiónRESUMEN
Increased detection of plasma lysophosphatidic acid (LPA) has been proposed as a potential diagnostic biomarker in ovarian cancer, but inconsistency exists in these reports. It has been shown that LPA can undergo an artificial increase during sample processing and analysis, which has not been accounted for in ovarian cancer research. The aim of this study is to provide a potential explanation about how the artificial increase in LPA may have interfered with previous LPA analysis in ovarian cancer research. Using an established LC-MS method, we measured LPA and other lysophospholipid levels in plasma obtained from three cohorts of patients: non-cancer controls, patients with benign ovarian tumors, and those with ovarian cancer. We did not find the LPA level to be higher in cancer samples. To understand this inconsistency, we observed that LPA content changed more significantly than other lysophospholipids as a function of plasma storage time while frozen. Additionally, only LPA was found to be adversely impacted by incubation time depending on the Ethylenediaminetetraacetic acid (EDTA) concentration used during blood drawing. We also show that the inhibition of autotaxin effectively prevented artificial LPA generation during incubation at room temperature. Our data suggests that the artificial changes in LPA content may contribute to the discrepancies reported in literature. Any future studies planning to measure plasma LPA should carefully design the study protocol to consider these confounding factors.
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Ovarian cancer remains a highly lethal disease due to its late clinical presentation and lack of reliable early biomarkers. Protein-based diagnostic markers have presented limitations in identifying ovarian cancer. We tested the potential of phospholipids as markers of ovarian cancer by utilizing inter-related regulation of phospholipids, a unique property that allows the use of ratios between phospholipid species for quantitation. High-performance liquid chromatography mass spectrometry was used to measure phospholipid, lysophospholipid, and sphingophospholipid content in plasma from patients with benign ovarian masses, patients with ovarian cancer, and controls. We applied both absolute and relative phospholipid ratios for quantitation. Receiver operating characteristic analysis was performed to test the sensitivity and specificity. We found that utilization of ratios between phospholipid species greatly outperformed absolute quantitation in the identification of ovarian cancer. Of the phospholipids analyzed, species in phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and sphingomyelin (SM) were found to have great biomarker potential. LPC(20:4)/LPC(18:0) carried the greatest capacity to differentiate cancer from control, SM(d18:1/24:1)/SM(d18:1/22:0) to differentiate benign from cancer, and PC(18:0/20:4)/PC(18:0/18:1) to differentiate benign from control. These results demonstrate the potential of plasma phospholipids as a novel marker of ovarian cancer by utilizing the unique characteristics of phospholipids to further enhance the diagnostic power.
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Phospholipids content in cellular and mitochondrial membranes is essential for maintaining normal function. Previous studies have found a lower polyunsaturated fatty acid (PUFA) content in mitochondria than whole tissue, theorizing decreased PUFA protects against oxidative injury. However, phospholipids (PPLs) are uniquely difficult to quantify without class separation and, as prior approaches have predominately used reverse-phase HPLC or shotgun analysis, quantitation of PPL classes may have been complicated due to the existence of numerous isobaric and isomeric species. We apply normal-phase HPLC with class separation to compare whole tissue and mitochondrial PPL profiles in rat brain, heart, kidney, and liver. In addition, we establish a novel method to ascertain PPL origin, using cardiolipin as a comparator to establish relative cardiolipin /PPL ratios. We report a higher PUFA content in tissue mitochondria driven by increased phosphatidylcholine unsaturation, suggesting mitochondria purposefully incorporate higher PUFA PPLs.
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Ácidos Grasos Insaturados/análisis , Membranas Mitocondriales/química , Fosfatidilcolinas/análisis , Fosfolípidos/análisis , Animales , Química Encefálica , Cardiolipinas/análisis , Cromatografía Líquida de Alta Presión , Ácidos Grasos Insaturados/química , Riñón/química , Hígado/química , Miocardio/química , Especificidad de Órganos , Fosfatidilcolinas/química , Fosfolípidos/química , RatasRESUMEN
OBJECTIVES: Utilization of bilateral internal mammary arteries (BIMAs) has been shown to improve long-term outcomes in patients undergoing coronary artery bypass grafting. To achieve complete revascularization, BIMAs may be used as either sole conduits for revascularization through a Y-graft configuration (BIMA-Y) or deployed with additional grafts used in conjunction with BIMAs. The purpose of this study was to compare the long-term outcomes of two institutions that predominantly used either the BIMA-Y configuration or BIMA plus additional grafts to achieve optimal revascularization. METHODS: From 1 January 2000 to 31 December 2010, 436 patients were revascularized using a non-sequential BIMA grafting at one institution (Group A), with veins being used for additional targets. At the second institution (Group B), 771 patients were revascularized using a BIMA-Y graft for all distal targets. KaplanMeier analysis was used to compare unadjusted survival between the groups. Cox proportional hazards regression modelling was used to provide an adjusted comparison of survival between the groups. RESULTS: There was no statistically significant difference between the average number of anastomotic sites used in Group A and Group B (A = 4.0 ± 0.7 vs B = 4.0 ± 0.7; P = 0.24). Group A did not have a significantly greater in-hospital mortality (0.7% vs 1.0% P = 0.39), stroke (0.5% vs 0.8% P = 0.40), deep sternal wound infection (0.0% vs 0.6% P = 0.11) or reoperation for bleeding (1.6% vs 0.6% P = 0.10) than Group B. Cox proportional hazards analyses demonstrated that at 14 years, Group B had a significantly improved survival compared to Group A (Group B = 88% vs Group A = 81%) with an overall reduction in mortality (adjusted hazard ratio 0.780, 95% confidence interval 0.4480.849; P = 0.043). CONCLUSION: Utilization of the BIMA-Y configuration was associated with improved survival when compared to BIMA grafting with additional vein grafts. Further studies are necessary to evaluate the efficacy of BIMA-Y grafting against other means of providing complete arterial revascularization.
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Anastomosis Interna Mamario-Coronaria/métodos , Anciano , Bélgica/epidemiología , Femenino , Mortalidad Hospitalaria , Humanos , Anastomosis Interna Mamario-Coronaria/efectos adversos , Anastomosis Interna Mamario-Coronaria/mortalidad , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , New Jersey/epidemiología , Modelos de Riesgos Proporcionales , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Vena Safena/trasplante , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Resultado del TratamientoRESUMEN
Performing a reoperative root replacement in cases of prosthetic valve endocarditis (PVE) can often be challenging due to significant inflammation and scarring. During these cases, surgeons may decide to utilize an interpositional graft when mobilization of the coronary ostia becomes too hazardous. The authors describe their experience performing a reoperative root replacement on a patient with PVE. In this case, the authors utilize a segment of the homograft left subclavian artery as an interpositional graft to provide an infection-resistant bioprosthetic graft that maintains coronary anatomy.
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Aorta Torácica/cirugía , Implantación de Prótesis Vascular/métodos , Vasos Coronarios/cirugía , Infecciones Relacionadas con Prótesis/cirugía , Anciano , Válvula Aórtica/cirugía , Bioprótesis/efectos adversos , Endocarditis Bacteriana/cirugía , Prótesis Valvulares Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Masculino , Reoperación/métodos , Infecciones Estafilocócicas/cirugíaRESUMEN
OBJECTIVES: Recent studies have demonstrated the superiority of bilateral internal mammary arteries (BIMAs) as conduit material for coronary artery bypass grafting (CABG) surgery. However, there is limited research on the effects of other graft conduits used in patients who require additional bypasses. The goal of this study was to evaluate the impact of the radial artery (RA) when used in conjunction with the BIMAs. METHODS: From the beginning of 2000 to the end of 2013, 4370 patients underwent CABG for three or more vessels at our institution. There were 568 and 183 patients who received BIMA + saphenous vein graft (SVG) and BIMA + radial ± SVG, respectively. Propensity matching was used to create a balanced cohort from these patients, which resulted in two groups of 183 patients. Thirty-day outcomes and long-term survival were compared between the two groups. Long-term follow-up was generated using the Social Security Death Index. RESULTS: There were no significant differences in preoperative characteristics. For 30-day outcomes, the BIMA + radial ± SVG group had more postoperative atrial fibrillation (24.6 vs 12.0%; P = 0.001) and a longer median postoperative length of stay (6 vs 5 days; interquartile range = 2; P = 0.016) than BIMA + SVG patients. There was no significant difference in long-term survival between the two groups over the 14-year period. However, before year 10, the BIMA + SVG group had a trend towards higher survival, whereas on follow-up after 10 years, there was a trend that favoured the BIMA + radial ± SVG patients. Cox regression analysis using a time-dependent covariate demonstrated that when the groups were split at 10 years, there was a statistically significant improvement in survival of the BIMA + radial ± SVG group [adjusted hazard ratio 0.254 95% confidence interval (CI) 0.062-0.977; P = 0.048] over BIMA + SVG patients between 10 and 14 years. CONCLUSIONS: Overall, there were no statistically significant differences in survival between the BIMA + SVG and BIMA + radial ± SVG groups over the 14 years. However, further analysis demonstrated that while the BIMA + radial ± SVG group had a trend towards decreased survival before 10 years, use of the RA in conjunction with BIMAs was associated with significantly increased survival in the later years. A larger cohort of patients with longer follow-up is needed to assess the outcomes of CABG using BIMA + radial ± SVG.
Asunto(s)
Puente de Arteria Coronaria/métodos , Enfermedad de la Arteria Coronaria/cirugía , Arterias Mamarias/trasplante , Arteria Radial/trasplante , Adulto , Anciano , Enfermedad de la Arteria Coronaria/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVES: Bilateral internal thoracic artery (BITA) bypass provides long-term survival benefits over strategies that use single internal mammary arteries during coronary artery bypass grafting (CABG). However, the rate of adoption of this strategy remains very low. Moreover, optimal BITA configuration and the use of cardiopulmonary bypass still remain a matter of debate. We investigated the long-term results of a coronary revascularization strategy, utilising exclusively BITA-Y composite grafts using off-pump platform and sequential anastomoses. METHODS: From March 2000 to November 2010, all isolated CABGs (n = 2057 patients) were performed using an off-pump platform. Of these, 1240 patients had three-vessel coronary disease (60.3%), with severe coronary disease defined as >70% stenosis and three-vessel disease defined as the presence of 3 vessels with >70% stenosis, of which 784 (63.2%) were treated with two internal thoracic artery grafts in a composite fashion with a no-touch technique avoiding any manipulation of the ascending aorta. The primary end-point was the long-term survival and freedom from major adverse cerebral and cardiovascular events (MACCEs). The follow-up was completed using the annual anniversary method. RESULTS: The mean number of anastomoses per patient was 4.0. Hospital mortality occurred in 8 patients (1%). Ninety-day stroke, myocardial infarction and repeat revascularization rates were respectively 0.7, 0.6 and 0.3%. The mean follow-up was 6.6 ± 3.2 years and was obtained for 99% of the patients. The 5- and 10-year survival rates were 93.1 ± 1.6 and 83.8 ± 3.2%, respectively. Freedom from major adverse cardiac and cardiovascular event (MACCE) at 5 and 10 years was: cardiovascular event: 98.7 ± 1.6 and 96.1 ± 1.7%, documented ischaemia: 90.5 ± 2 and 80.2 ± 3.8%, revascularization: 94.0 ± 1.5 and 89.7 ± 2.5%, infarction: 98.1 ± 0.8 and 96.0 ± 1.6%. The patency of left and right internal thoracic artery in a BITA-Y configuration was 91.1 and 88.8% at 5 ± 3 years, respectively. CONCLUSION: Performance of an exclusive composite BITA off-pump revascularization strategy optimal and sustained long-term protection from MACCE.