RESUMO
Cancer cells produce vast quantities of reactive oxygen species, leading to the accumulation of toxic nucleotides as 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP). The human MTH1 protein catalyzes the hydrolysis of 8-oxo-dGTP, and cancer cells are dependent on MTH1 for their survival. MTH1 inhibitors are possible candidates for a class of anticancer drugs; however, a reliable screening system using live cells has not been developed. Here we report a visualization method for 8-oxo-dGTP and its related nucleotides in living cells. Escherichia coli MutT, a functional homologue of MTH1, is divided into the N-terminal (1-95) and C-terminal (96-129) parts (Mu95 and 96tT, respectively). Mu95 and 96tT were fused to Ash (assembly helper tag) and hAG (Azami Green), respectively, to visualize the nucleotides as fluorescent foci formed upon the Ash-hAG association. The foci were highly increased when human cells expressing Ash-Mu95 and hAG-96tT were treated with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and 8-oxo-dGTP. The foci formation by 8-oxo-dG(TP) was strikingly enhanced by the MTH1 knockdown. Moreover, known MTH1 inhibitors and oxidizing reagents also increased foci. This is the first system that visualizes damaged nucleotides in living cells, provides an excellent detection method for the oxidized nucleotides and oxidative stress, and enables high throughput screening for MTH1 inhibitors.
Assuntos
Nucleotídeos de Desoxiguanina , Pirofosfatases , Humanos , Nucleotídeos de Desoxiguanina/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/antagonistas & inibidores , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Nucleotídeos de Guanina/metabolismo , Oxirredução , Monoéster Fosfórico Hidrolases/metabolismo , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/antagonistas & inibidoresRESUMO
DNA oxidation is a serious threat to genome integrity and is involved in mutations and cancer initiation. The G base is most frequently damaged, and 8-oxo-7,8-dihydroguanine (GO, 8-hydroxyguanine) is one of the predominant damaged bases. In human cells, GO causes a G:CâT:A transversion mutation at the modified site, and also induces untargeted substitution mutations at the G bases of 5'-GpA-3' dinucleotides (action-at-a-distance mutations). The 5'-GpA-3' sequences are complementary to the 5'-TpC-3' sequences, the preferred substrates for apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3) cytosine deaminases, and thus their contribution to mutagenesis has been considered. In this study, APOBEC3B, the most abundant APOBEC3 protein in human U2OS cells, was knocked down in human U2OS cells, and a GO-shuttle plasmid was then transfected into the cells. The action-at-a-distance mutations were reduced to ~25% by the knockdown, indicating that GO-induced action-at-a-distance mutations are highly dependent on APOBEC3B in this cell line.
Assuntos
DNA , Guanina , Guanina/análogos & derivados , Humanos , Mutação , Mutagênese , Guanina/metabolismo , Citidina Desaminase/genética , Antígenos de Histocompatibilidade Menor/genéticaRESUMO
The generation of DNA damage causes mutations and consequently cancer. Reactive oxygen species are important sources of DNA damage and some mutation signatures found in human cancers. 8-Oxo-7,8-dihydroguanine (GO, 8-hydroxyguanine) is one of the most abundant oxidized bases and induces a GâT transversion mutation at the modified site. The damaged G base also causes untargeted base substitution mutations at the G bases of 5'-GpA-3' dinucleotides (action-at-a-distance mutations) in human cells, and the cytosine deaminase apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3) is involved in the mutation process. The deaminated cytosine, i.e., uracil, bases are expected to be removed by uracil DNA glycosylase. Most of the substitution mutations at the G bases of 5'-GpA-3' might be caused by abasic sites formed by the glycosylase. In this study, we expressed the uracil DNA glycosylase inhibitor from Bacillus subtilis bacteriophage PBS2 in human U2OS cells and examined the effects on the GO-induced action-at-a-distance mutations. The inhibition of uracil DNA glycosylase increased the mutation frequency, and in particular, the frequency of GâA transitions. These results indicated that uracil DNA glycosylase, in addition to APOBEC3, is involved in the untargeted mutation process induced by GO.
Assuntos
Guanina , Mutação , Uracila-DNA Glicosidase , Humanos , Guanina/análogos & derivados , Guanina/metabolismo , Uracila-DNA Glicosidase/metabolismo , Uracila-DNA Glicosidase/genética , Linhagem Celular Tumoral , Dano ao DNA , Bacillus subtilis/genética , Bacteriófagos/genéticaRESUMO
BACKGROUND: This study explored if long-distance transfer was safe for patients suffering from acute aortic dissection type A (AADA) and also analyzed the effectiveness of helicopter transfer and cloud-type imaging transfer systems for such patients in northern Hokkaido, Japan. METHODS AND RESULTS: The study included 112 consecutive patients who underwent emergency surgical treatment for AADA from April 2014 to September 2020. The patients were divided into two groups according to the location of referral source hospitals: the Asahikawa city group (group A, n = 49) and the out-of-the-city group (group O, n = 63). Use of helicopter transfer (n = 13) and cloud-type telemedicine (n = 20) in group O were reviewed as subanalyses.Transfer distance differed between groups (4.2 ± 3.5 km in group A vs 107.3 ± 69.2 km in group O; p = 0.0001), but 30-day mortality (10.2% in group A vs 7.9% in group O; p = 0.676) and hospital mortality (12.2% in group A vs 9.5% in group O; p = 0.687) did not differ. Operative outcomes did not differ with or without helicopter and cloud-type telemedicine, but diagnosis-to-operation time was shorter with helicopter (240.0 ± 70.8 vs 320.0 ± 78.5 minutes; p = 0.031) and telemedicine (242.0 ± 75.2 vs 319.0 ± 83.8 minutes; p = 0.007). CONCLUSION: We found that long-distance transfer did not impair surgical outcomes in AADA patients, and both helicopter transfer and cloud-type telemedicine system could contribute to the reduction of diagnosis-to-operation time in the large Hokkaido area. Further studies are mandatory to investigate if both the systems will improve clinical outcomes.
Assuntos
Dissecção Aórtica , Humanos , Resultado do Tratamento , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aeronaves , Japão , Estudos RetrospectivosRESUMO
Neuron-specific-enolase is used as a marker of neurological prognosis after cardiopulmonary resuscitation. It is also present in red blood cells and platelets. It is not known whether hemolysis increases the values of neuron-specific-enolase enough to clinically affect its interpretation in critically ill patients who are to be introduced to veno-arterial extracorporeal oxygenation. In this study, we examined the relationships among neuron-specific-enolase and hemolysis indicators such as free hemoglobin and lactate dehydrogenase after the introduction of veno-arterial extracorporeal oxygenation. Of the 91 patients who underwent veno-arterial extracorporeal membrane oxygenation in our hospital from January 1, 2018, to February 24, 2021, 68 patients survived for more than 24 h. Of these, 14 patients who were categorized into the better cerebral performance categories (1-3) and 19 patients who were categorized into the poor neurological prognosis category (4) were included. After the introduction of veno-arterial extracorporeal membrane oxygenation, neuron-specific-enolase was markedly higher in the poor neurological prognosis group than in the good neurological prognosis group (41.6 vs. 92.0, p = 0.04). A significant positive correlation was revealed between neuron-specific-enolase and free hemoglobin in the good neurological prognosis group (rs = 0.643, p = 0.0131). A similar relationship was observed for lactate dehydrogenase and neuron-specific-enolase in both the conscious (rs = 0.737, p = 0.00263) and non-conscious groups (rs = 0.544, p = 0.0176). When neuron-specific-enolase is used as a marker for neuroprognostic evaluation, an abnormally high value is likely to indicate the lack of consciousness, whereas a lower elevation should be interpreted with caution, taking into account the effects of hemolysis.
RESUMO
It is believed that a lower temperature setting of hypothermic circulatory arrest (HCA) in thoracic aortic surgery causes coagulopathy, resulting in excessive bleeding. However, experimental studies that eliminate clinical factors are lacking. The objective of this study is to investigate the influence of the temperature setting of HCA on coagulation in a pig model. Ten pigs were divided into the following two groups: moderate temperature at 28 °C (group M, n = 5) or lower temperature at 20 °C (group L, n = 5). Two hours of HCA during a total of 4 h of cardiopulmonary bypass (CPB) were performed. Blood samples were obtained at the beginning (T1) and the end (T2) of the surgery, and coagulation capability was analyzed through standard laboratory tests (SLTs) and rotational thromboelastometry (ROTEM). In SLTs, hemoglobin, fibrinogen, platelet count, prothrombin time, and activated partial thromboplastin time were analyzed. In ROTEM analyses, clotting time and clot formation time of EXTEM, maximum clot firmness (MCF), and maximum clot elasticity (MCE) of EXTEM and FIBTEM were analyzed. Fibrinogen decreased significantly in both groups (group M, p = 0.008; group L, p = 0.0175) at T2, and FIBTEM MCF and MCE also decreased at T2. There were no differences regarding changes in parameters of SLTs and ROTEM between groups. CPB decreases coagulation capacity, contributed by fibrinogen. However, a lower temperature setting of HCA at 20 °C for 2 h did not significantly affect coagulopathy compared to that of HCA at 28 °C after re-warming to 37 °C.
RESUMO
BACKGROUND: This study investigates short-term outcomes following surgical interventions for atrial fibrillation (Af), including the Cox-maze â £ procedure (maze procedure) and pulmonary vein isolation (PVI), performed concurrently with other cardiac surgeries. Additionally, we aim to determine the indications for surgical intervention for Af. METHOD: We retrospectively studied a total of 1,580 patients, out of which 274 had preoperative Af, that underwent cardiac surgery between January 2015 and April 2023. Patients who underwent emergency surgery, died in the hospital postoperatively, or received pacemaker implantation were excluded. Patients were first divided into two groups:the intervention group (n=135, 53.6%) and the non-intervention group( n=117, 46.4%), further categorized by whether they were in sinus rhythm at discharge. The intervention group was then subdivided into the maze procedure group( n=54), and the PVI group (n=76). RESULTS: Within the maze procedure group, significant differences were observed between the sinus rhythm and non-sinus rhythm groups in terms of age, preoperative Af duration, and aortic valve intervention status. In the PVI group, patients with persistent Af, longer preoperative Af duration, and larger left atrium diameter( LAD) were less likely to return to sinus rhythm. Smaller LAD was also a significant factor for returning to sinus rhythm in the non-intervention group. Multivariate analysis for all patients revealed that an LAD smaller than 50 mm was the strongest predictor for returning to sinus rhythm post operation( p<0.01). CONCLUSION: For patients with persistent Af, the maze procedure is favored over PVI as a surgical intervention. When LAD exceeds 50 mm, the likelihood of returning to sinus rhythm is diminished.
Assuntos
Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Ablação por Cateter , Humanos , Fibrilação Atrial/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Átrios do Coração/cirurgia , Ablação por Cateter/métodosRESUMO
Neuron-specific enolase (NSE) is one of the biomarkers used as an indicator of brain disorder, but since it is also found in blood cell components, there is a concern that a spurious increase in NSE may occur after cardiovascular surgery, where cardiopulmonary bypass (CPB) causes hemolysis. In the present study, we investigated the relationship between the degree of hemolysis and NSE after cardiovascular surgery and the usefulness of immediate postoperative NSE values in the diagnosis of brain disorder. A retrospective study of 198 patients who underwent surgery with CPB in the period from May 2019 to May 2021 was conducted. Postoperative NSE levels and Free hemoglobin (F-Hb) levels were compared in both groups. In addition, to verify the relationship between hemolysis and NSE, we examined the correlation between F-Hb levels and NSE levels. We also examined whether different surgical procedures could produce an association between hemolysis and NSE. Among 198 patients, 20 had postoperative stroke (Group S) and 178 had no postoperative stroke (Group U). There was no significant difference in postoperative NSE levels and F-Hb levels between Group S and Group U (p = 0.264, p = 0.064 respectively). F-Hb and NSE were weakly correlated (r = 0.29. p < 0.01). In conclusion, NSE level immediately after cardiac surgery with CPB is modified by hemolysis rather than brain injury, therefore it would be unreliable as a biomarker of brain disorder.
RESUMO
For patients with cardiogenic shock, delaying surgery with mechanical circulatory support is reported to yield better outcomes than emergency surgery. We report on an 82-year-old man diagnosed with vertebral osteomyelitis with concomitant infective endocarditis. Chest radiographs revealed a growing abscess, which resulted in an aorto-right ventricular fistula. Providing Impella support allowed for hemodynamic stabilization prior to surgery. The patient had an uneventful postoperative course and reported to be well in a follow-up 1 year later. Impella support can be used as a bridge to surgery for repairing fistulous tract formation in patients in cardiogenic shock.
Assuntos
Endocardite Bacteriana , Endocardite , Fístula , Próteses Valvulares Cardíacas , Masculino , Humanos , Idoso de 80 Anos ou mais , Choque Cardiogênico , Fístula/diagnóstico , Fístula/etiologia , Fístula/cirurgiaRESUMO
Minimally invasive mitral valve surgery (MIMVS) is widespread and has become a standard procedure in cardiac surgery [Chitwood 1997; Carpentier 1996]. Therefore, MIMVS is a common procedure for patients with degenerative disease [Raanani 2010; Iribarne 2010] as well. However, the safety of MIMVS in patients with rheumatic heart disease (RHD) has not thoroughly been investigated, due to the low prevalence of RHD in developed countries, where MIMVS is standardized [Miceli 2015]. Here, we investigated the safety of MIMVS for patients with RHD at Lampang Hospital in Thailand.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Doenças Reumáticas , Cardiopatia Reumática , Humanos , Valva Mitral/cirurgia , Resultado do Tratamento , Tailândia/epidemiologia , Cardiopatia Reumática/complicações , Cardiopatia Reumática/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos RetrospectivosRESUMO
Cases that are inoperable owing to poor preoperative conditions are sometimes encountered. However, there are some cases that are led to radical treatment by performing bridge therapy. Here, we presented a case of a patient with complex cardiac disease in an inoperable state who underwent bridging therapy that led to successful surgical treatment. A 73-year-old male who received hemodialysis treatment and had severe aortic valve stenosis and coronary artery disease planned surgical treatment. However, he was deemed inoperable owing to his low cardiac function and hemodynamic instability. Therefore, to escape from a fatal condition, we first performed balloon aortic valvuloplasty and percutaneous coronary intervention as palliative procedures. Subsequently, his cardiac function and hemodynamic stability remarkably improved; therefore, after 1 month, we performed a successful radical surgical treatment. Even in inoperable patients, bridging therapy leading to radical treatment is possible.
Assuntos
Estenose da Valva Aórtica , Procedimentos Cirúrgicos Cardíacos , Masculino , Humanos , Idoso , Função Ventricular Esquerda , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Terapia Ponte , Resultado do TratamentoRESUMO
Low cardiac output syndrome (LOS) is a condition that causes low perfusion and perfusion failure of the entire body's tissues due to a decline in heart contractile strength, posing a significant challenge in cardiothoracic surgical perioperative management. Appropriate myocardial protection is crucial to prevent ischemia-reperfusion injury during open-heart surgery and prevent LOS. The integrated myocardial protection method, proposed by Buckberg et al., is one technique employed for this purpose. In the treatment of LOS, interventions are made in the parameters of stroke volume and heart rate, structural abnormalities are excluded and dealt with, and mechanical assistance is utilized when necessary. With the aging and increasing severity of surgical patients, the risk of postoperative LOS is on the rise. Therefore, the application of appropriate myocardial protection and treatment methods leads to improved prognosis. It's worth noting that ensuring optimal myocardial protection during surgery and the correct application of medication and devices for intervention can significantly improve patient outcomes. With the rise in high-risk surgical cases due to aging and an increase in severe conditions, the importance of these interventions cannot be overstated.
Assuntos
Baixo Débito Cardíaco , Procedimentos Cirúrgicos Cardíacos , Humanos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Traumatismo por Reperfusão/prevenção & controle , Período PerioperatórioRESUMO
BACKGROUND: The objective of this study was to develop a method to evaluate the effects of an aortic dissection on hemodynamic parameters by conducting a comparison with that of a healthy (nondissected) aorta. Open-source software will be implemented, no proprietary software/application will be used to ensure accessorily and repeatability, in all the data analysis and processing. Computed tomography (CT) images of aortic dissection are used for the model geometry segmentation. Boundary conditions from literature are implemented to computational fluid dynamics (CFD) to analyze the hemodynamic parameters. METHODS: A numerical simulation model was created by obtaining accurate 3-dimensional geometries of aortae from CT images. In this study, CT images of 8 cases of aortic dissection (Stanford type-A and type-B) and 3 cases of healthy aortae are used for the actual aorta model geometry segmentation. These models were exported into an open-source CFD software, OpenFOAM, where a simplified pulsating flow was simulated by controlling the flow pressure. Ten cycles of the pulsatile flow (0.50 sec/cycle) conditions, totaling 5 sec, were calculated. RESULTS: The pressure distribution, wall shear stress (WSS) and flow velocity streamlines within the aorta and the false lumen were calculated and visualized. It was found that the flow velocity and WSS had a high correlation in high WSS areas of the intermittent layer between the true and false lumen. Most of the Stanford type-A dissections in the study showed high WSS, over 38 Pa, at the systole phase. This indicates that the arterial walls in type-A dissections are more likely to be damaged with pulsatile flow. CONCLUSIONS: Using CFD to estimate localized high WSS areas may help in deciding to treat a type-A or B dissection with a stent graft to prevent a potential rupture.
Assuntos
Aorta/fisiopatologia , Aneurisma Aórtico/fisiopatologia , Dissecção Aórtica/fisiopatologia , Hemodinâmica , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/terapia , Aorta/diagnóstico por imagem , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/terapia , Aortografia , Estudos de Casos e Controles , Tomada de Decisão Clínica , Angiografia por Tomografia Computadorizada , Humanos , Hidrodinâmica , Análise Numérica Assistida por Computador , PrognósticoRESUMO
OBJECTIVES: The aims of the present study were to evaluate and compare the safety and feasibility, including hospitalization, intensive care unit (ICU) stay, frequency of conversion to general anesthesia (GA), pH, PaCO2, and PaO2, of selected patients who underwent minimally invasive mitral valve surgery (MIMVS) via a right minithoracotomy under conscious sedation (CS) to avoid GA. The authors also aimed to evaluate the perioperative management of spontaneous breathing. DESIGN: A retrospective, observational study. SETTING: Single-center. PARTICIPANTS: This study enrolled 101 patients who underwent MIMVS under CS or GA. INTERVENTIONS: The patients who underwent MIMVS were managed under CS or GA according to indication criteria. MEASUREMENTS AND MAIN RESULTS: ICU stay (p = 0.010), postoperative time until first fluid intake (p < 0.0001), and duration of mechanical ventilation (p = 0.004) were shorter in the CS group than in the GA group. No patients converted to GA from CS. PaCO2 during cardiopulmonary bypass (CPB) in the CS group was significantly lower than that in the GA group. However, PaCO2 at the termination of CPB in the CS group was significantly higher than that in the GA group. CONCLUSIONS: In the CS group, advanced-age patients with comorbidities underwent mitral surgery without postoperative complications. The authors' findings suggested that MIMVS under CS could be a potentially less-invasive method, providing a quicker recovery than MIMVS under GA.
Assuntos
Anestesia por Condução , Valva Mitral , Anestesia Geral , Sedação Consciente , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Valva Mitral/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Hypothermic circulatory arrest (HCA) is an essential procedure during aortic surgery to protect organs; however, hypothermia is believed to cause coagulopathy, which is a major fatal complication. This study aimed to clarify the impact of hypothermia on coagulation by eliminating clinical biases in vitro. In the hypothermic storage study, blood samples from five healthy volunteers were stored at 37 â (group N) for 3 h or at 20 â for 2 h, followed by 1 h of rewarming at 37 â (group H). Thromboelastography was performed before and after 3 h of storage. In the mock circulation loop (MCL) study, blood samples were placed in the MCL and (a) maintained at 37 â for 4 h (group N, n = 5), or (b) cooled to 20 â to simulate HCA with a 0.1 L/min flow rate for 3 h and then rewarmed to 37 â (group H, n = 5). The total MCL duration was 4 h, and the flow rate was maintained at 1 L/min, except during HCA. Blood samples collected 15 min after the beginning and end of MCL were subjected to standard laboratory tests and rotational thromboelastometry analyses. Hypothermia had no impact on coagulation in both the hypothermic storage and MCL studies. MCL significantly decreased the platelet counts and clot elasticity in the INTEM and EXTEM assays; however, there was no effect on fibrinogen contribution measured by FIBTEM. Hypothermia does not cause irreversible coagulopathy in vitro; however, MCL decreases coagulation due to the deterioration of platelets.
Assuntos
Transtornos da Coagulação Sanguínea , Parada Cardíaca , Hipotermia , Humanos , Hipotermia/etiologia , Transtornos da Coagulação Sanguínea/etiologia , Tromboelastografia/métodos , Coagulação Sanguínea , FibrinogênioRESUMO
BACKGROUND: No study has examined the association of the calcification of abdominal artery orifices with nonocclusive mesenteric ischemia (NOMI) in dialysis patients undergoing cardiac surgery. Thus, this study aimed to determine whether calcification of abdominal blood vessel orifices in hemodialysis patients may be a risk factor for NOMI and examine the long-term survival of dialysis patients after undergoing cardiac surgery. METHODS: From April 2014 to September 2020, 100 dialysis patients underwent cardiac surgery at our hospital. The calcification of the celiac artery (CA) and superior mesenteric artery (SMA) was evaluated by computed tomography, and the degree of orifice stenosis was graded as follows: patent, 0; partial occlusion, 1; and complete occlusion, 2. RESULTS: Eight patients experienced NOMI, and all of them died. SMA calcification scores were not significantly different between the NOMI and non-NOMI groups (1.38±0.52 vs. 1.13±0.69; P = 0.247). However, the average CA orifice calcification score was significantly greater in the NOMI group than in the non-NOMI group (1.63±0.52 vs. 1.15±0.65; P = 0.039), and the SMA+CA orifice calcification scores were significantly different between the groups (3.00±0.76 vs. [non-NOMI] 2.25±1.18; P = 0.028). In all patients, the 30-day and in-hospital mortality rates were 13% and 18%, respectively. All patients were completely followed up with a mean follow-up period of 604±585 days. Kaplan-Meier survival curves showed that patients with SMA and CA calcification tended to have a shorter overall survival than patients without calcification; however, no significant difference was noted. CONCLUSIONS: The calcification of CA and/or SMA orifices was associated with postoperative NOMI and poor long-term survival among dialysis patients undergoing cardiac surgery.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Isquemia Mesentérica , Humanos , Isquemia Mesentérica/complicações , Isquemia Mesentérica/cirurgia , Diálise Renal , Fatores de Risco , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: It still remains unclear the depth of influence of left ventricular dysfunction on the recovery of patients' physical conditions in the early and midterm period following off-pump coronary artery bypass grafting (OPCAB). METHODS: From April 2011 to May 2018, 851 patients underwent OPCAB in our center. All were grouped into two groups: Those whose ejection fraction (EF) was under 35% were defined as the Low EF group (N = 158) and those who maintained EF over 35% were defined as the Faired EF group (N = 693). Preoperatively, there was significant difference in NYHA class (P < 0.001), CCS class (P = 0.038), level of creatinine (P < 0.001), and rate of establishment of IABP (P < 0.001). RESULTS: Regarding all-cause death in the early postoperative period, low EF was a not a risk factor in patients (P = 0.52) or in the matched cohort (P = 0.398); however, in the midterm, it was a significant risk factor in patients (HR 2.07, P = 0.016) and in the matched cohort (HR 2.72, P = 0.029). Overall survival at 5 years in the Low EF group was significantly inferior to that of the Faired EF group in all (67.4±4.1% and 86.1±2.9%, P = 0.001) and in the matched cohort (66.5±6.4% vs. 86.5±4.5%, P = 0.008). CONCLUSION: OPCAB seems beneficial for patients with LV dysfunction considering the early outcome, however, low EF is a significant risk factor for overall death in the midterm period.
Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Disfunção Ventricular Esquerda , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Humanos , Pontuação de Propensão , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/cirurgia , Função Ventricular EsquerdaRESUMO
G:C sites distant from 8-oxo-7,8-dihydroguanine (GO, 8-hydroxyguanine) are frequently mutated when the lesion-bearing plasmid DNA is replicated in human cells with reduced Werner syndrome (WRN) protein. To detect the untargeted mutations preferentially, the oxidised guanine base was placed downstream of the reporter supF gene and the plasmid DNA was introduced into WRN-knockdown cells. The total mutant frequency seemed higher in the WRN-knockdown cells as compared to the control cells. Mutation analyses revealed that substitution mutations occurred at the G:C pairs of 5'-GpA-3'/5'-TpC-3' sites, the preferred sequence for the apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3)-family cytosine deaminases, in the supF gene in both control and knockdown cells. These mutations were observed more frequently at G sites than C sites on the DNA strand where the GO base was originally located. This tendency was promoted by the knockdown of the WRN protein. The present results imply the possible involvement of APOBEC3-family cytosine deaminases in the action-at-a-distance (untargeted) mutations at G:C (or G) sites induced by GO and in cancer initiation by oxidative stress.
Assuntos
Guanina , Mutação , Helicase da Síndrome de Werner/genética , Síndrome de Werner/genética , Sequência de Bases , Linhagem Celular , Técnicas de Silenciamento de Genes , Ordem dos Genes , Guanina/metabolismo , Humanos , Taxa de Mutação , Plasmídeos/genética , Síndrome de Werner/metabolismo , Helicase da Síndrome de Werner/metabolismoRESUMO
BACKGROUND: Coagulopathy and following massive bleeding are complications of cardiovascular surgery, particularly occurring after procedures requiring prolonged cardiopulmonary bypass (CPB). Reliable and rapid tests for coagulopathy are desirable for guiding transfusion. Measuring multiple coagulation parameters may prove useful. The purpose of this study is to determine the laboratory parameters predicting massive bleeding. METHODS: In a prospectively collected cohort of 48 patients undergoing cardiovascular surgery, markers of coagulation and fibrinolysis were measured using automated analyzer and their correlations with bleeding volume were determined. RESULTS: Operation time was 318 (107-654) min. CPB time was 181 (58-501) min. Bleeding volume during surgery was 2269 (174-10,607) ml. Number of transfusion units during surgery were packed red blood cells 12 (0-30) units, fresh frozen plasma 12 (0-44) units, platelets 20 (0-60) units and intraoperative autologous blood collection 669 (0-4439) ml. Post-surgery activities of coagulation factors II (FII), FV, FVII, FVIII, FIX, FX, FXI and FXII were decreased. Values of fibrinogen, antithrombin, α2 plasmin inhibitor (α2PI) and FXIII were also decreased. Values of thrombin-antithrombin complex (TAT) were increased. Values of FII, FIX, FXI and α2PI before surgery were negatively correlated with bleeding volume (FII, r = - 0.506: FIX, r = - 0.504: FXI, r = - 0.580; α2PI, r = - 0.418). Level of FIX after surgery was negatively correlated with bleeding volume (r = - 0.445) and level of TAT after surgery was positively correlated with bleeding volume (r = 0.443). CONCLUSIONS: These results suggest that several clinical and routine laboratory parameters of coagulation were individually associated with bleeding volume during cardiovascular surgery. Determining the patterns of coagulopathy may potentially help guide transfusion during cardiovascular surgery.
RESUMO
BACKGROUND: The aim of the present study was to validate safety of total arch replacement (TAR) using a novel frozen elephant trunk device, operated by trainees as surgical education. METHODS: Sixty-four patients including 19 patients (29.6%) with acute aortic dissection type A (AADA) underwent TAR in our institute between April 2014 and March 2019 were retrospectively analyzed. Twenty-nine patients were operated by trainees (group T) and 35 patients were operated by attending surgeons (group A). RESULTS: Patient characteristics did not differ between groups. Operative time (409.4 ± 87.8 vs. 468.6 ± 129.6 minutes, p = 0.034), cardiopulmonary bypass time (177.7 ± 50.4 vs. 222.9 ± 596.7 minutes, p = 0.019), and hypothermic circulatory arrest time (39.5 ± 13.4 vs. 54.5 ± 18.5 minutes, p = 0.001) were significantly shorter in group A than in group T, but aortic clamping time did not differ between groups (115.3 ± 55.7 vs. 114.2 ± 35.0 minutes, p = 0.924) because the rate of concomitant surgery was higher in group A (37.1 vs. 10.3%, p = 0.014). Thirty-day mortality was 3.1% in the entire cohort. Although operation time was longer in group T, there were no significant difference in postoperative results between the groups, and the experience levels of the main operator were not independent predictors for in-hospital mortality + major postoperative complications. There was no difference in late death and aortic events between groups. CONCLUSIONS: The present study demonstrated that TAR can be safely performed by trainees, and suggests TAR as a possible and safe educational operation.