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.
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.
Introduction: At our institution, we perform off-pump coronary artery bypass (OPCAB) as a standard procedure. Moreover, patients with favorable coronary anatomy and condition are selected for minimally invasive cardiac surgery (MICS)-OPCAB. We retrospectively compared early outcomes, focusing on safety, between MICS-OPCAB and conventional off-pump techniques for multivessel coronary artery bypass grafting (CABG). Methods: From August 2017 to September 2022, 1,220 patients underwent multivessel coronary artery grafting at our institution. They were divided into the MICS-OPCAB group (MICS group = 163 patients) and the conventional OPCAB group (MS group = 1057 patients). Propensity score matching (1 : 1 ratio) was applied to the MICS-OPCAB and MS groups (149 patients per group) based on 23 preoperative clinical characteristics. Results: After matching, there were no significant differences in preoperative characteristics between the groups. The MICS group had a lower total graft number (2.3 ± 0.6 vs. 2.9 ± 0.8, p < 0.001) and fewer distal anastomoses (2.7 ± 0.8 vs. 3.2 ± 0.9, p < 0.001). There were no significant differences in hospital stay, intensive care unit stay, postoperative complications, and 30-day mortality. The MICS group had less drain output (MICS 350â ml [250-500], MS 450â ml [300-550]; p = 0.013). Kaplan-Meier analysis revealed no significant differences in postoperative MACCE (major adverse cardiac or cerebrovascular events)-free and survival rates between the groups (MACCE-free rate p = 0.945, survival rate p = 0.374). Conclusion: With proper patient selection, MICS-OPCAB can provide good short to mid-term results, similar to those of conventional OPCAB.
Introduction: The procedure called the "aorta no-touch" (NT) or anaortic technique in off-pump coronary artery bypass grafting (OPCAB) is designed to reduce the perioperative risk of stroke. We have observed an increased frequency of anaortic OPCAB procedures at our institution. The main purpose of the present study is to investigate the effectiveness of anaortic OPCAB in reducing the perioperative risk of stroke. Methods: From April 2011 to July 2023, a total of 2,236 patients underwent isolated OPCAB at our single center. The patients were divided into the anaortic group (NT, n = 762) and the aortic group (A, n = 1,474). The NT group was propensity score-matched (PSM) with the A group at a 1:1 ratio (NT n = 640; A n = 640), and matching was performed based on 26 covariates with preoperative clinical characteristics. Results: In both the unmatched and matched cohorts of the NT and A groups, there were no significant differences observed in new stroke rates (NT vs. A; unmatched, 1.0% vs. 1.2%, p = 0.624; matched, 0.9% vs. 1.3%, p = 0.789). The univariable logistic analysis did not identify the anaortic technique as an independent factor negatively associated with new stroke events (OR = 0.81, 95% CI = 0.35-1.86, p = 0.624). Conclusion: The present study did not find the anaortic technique to reduce the perioperative risk of stroke in OPCAB. Hence, further large studies are needed to identify patient cohorts in which anaortic OPCAB is significantly beneficial.
We report the case of a 76-year-old woman with an incomplete atrioventricular septal defect and severe congestive heart failure who underwent surgical repair. Surgical intervention involved mitral valve repair and patch closure of the ostium primum defect, resulting in a favorable postoperative course. Successful outcomes support surgery as a reasonable treatment option owing to its significant improvement in postoperative quality of life, even in elderly patients with left atrioventricular valve degeneration.
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.
Atrial Fibrillation , Cardiac Surgical Procedures , Catheter Ablation , Humans , Atrial Fibrillation/surgery , Retrospective Studies , Treatment Outcome , Heart Atria/surgery , Catheter Ablation/methods
The leukemoid reaction (LR) is reported to be caused by severe stress conditions such as infection, malignancies, intoxication, severe hemorrhage, or acute hemolysis; this condition is attributed to a very severe prognosis. Some reports have suggested that the LR was associated with a systemic stress response. A 36-year-old man who required mechanical circulatory support (MCS), including veno-arterial extracorporeal membrane oxygenation and Impella 5.5 due to severe heart failure, was transferred to our hospital. He showed a markedly elevated WBC count and died of multiple organ failure. The autopsy revealed the possibility that leukocytosis might have been due to an LR; however, the cause of the cardiac failure was unknown. To the best of our knowledge, this study is the first to report a rare case of LR in a patient with severe heart failure requiring MCS.
Introduction: The minimally invasive cardiac surgery off-pump coronary artery bypass (MICSOPCAB) is technically difficult; therefore, previous studies have indicated that MICSOPCAB should be contraindicated in patients with impaired left ventricular (LV) function. In this study, we investigated the feasibility of MICSOPCAB in patients with impaired LV function. Methods: The 226 patients underwent MICSOPCAB between August 2017 and September 2022. Our study defined impaired LV function as ejection fraction (EF) in echocardiography 40% or less. The patients were divided into Low EF group (n = 39) and Normal EF group (n = 187). Results: The Low EF group was in a more critical preoperative condition than Normal EF group (41.0% in the Low EF group vs. 14.4% in the Normal EF group; p < 0.001). For preoperative transthoracic echocardiography, LV end-diastolic diameter (5.5 ± 0.9â cm in the Low EF group vs. 5.0 ± 0.8â cm in the Normal EF group; p < 0.001) and LV end-systolic diameter (4.4 ± 1.0â cm in the Low EF group vs. 3.4 ± 1.0â cm in the Normal EF group; p < 0.001) were significantly larger in the Low EF group. No differences were found in the operative time (180 [160-240] min in the Low EF group vs. 205 [165-253] min in the Normal EF group; p = 0.231) and the median number of distal anastomoses (2 [1-2] in the Low EF group vs. 2 [1-3] in the Normal EF group; p = 0.073). Intensive care unit stay was longer in the Low EF group than in the Normal EF group (2 [1-2] in the Low EF group vs. 1 [1-2] in the Normal EF group; p = 0.010). Perioperative transfusion was more common in the Low EF group than in the Normal EF group (69.7% vs. 49.2%; p = 0.023). There were no differences in major complications, hospital stay, and 30-day mortality. The Kaplan-Meier curve showed no significant difference in postoperative major adverse cardiac or cerebrovascular events rates between the two groups (p = 0.185). Conclusion: In this study, MICSOPCAB can be performed in patients with low EF having short- and mid-term outcomes similar to patients with normal EF. Therefore, low EF should not be contraindicated in MICSOPCAB.
Inadvertent renal artery obstruction during endovascular aortic repair is a rare but serious complication. In such cases, endovascular recanalization is typically attempted; however, it can be challenging, leading to many severe cases. Moreover, if treatment is delayed, the blockage time of the renal artery poses a problem. We encountered a case of inadvertent renal artery occlusion during endovascular aortic repair. In this case, bailout stent implantation through a gap between the aortic wall and a stent graft made by a balloon catheter was effective in reducing the renal ischemia time and facilitating the revascularization procedure.
We elucidated the efficacy of gut microbiome-altering drugs on pembrolizumab efficacy in patients with metastatic urothelial carcinoma (mUC). Clinical data were analyzed retrospectively from 133 patients with mUC who received second-line pembrolizumab therapy between January 2018 and January 2021, following failed platinum-based chemotherapy. We evaluated the effects of gut microbiome-altering drugs (proton pump inhibitors [PPI]/potassium-competitive acid blockers [P-CAB], H2 blockers, antibiotics, non-steroidal anti-inflammatory drugs [NSAIDs], metformin, antipsychotics, steroids, and opioids), taken by patients within 30 days before/after pembrolizumab treatment, on progression-free survival (PFS) and overall survival (OS). Fifty-one patients received PPI/P-CAB (37/14, respectively); H2 blockers, 7; antibiotics, 35; NSAIDs, 22; antipsychotics, 8; metformin, 3; steroids, 11; and opioids, 29. Kaplan-Meier curves revealed PPI or P-CAB users showed shorter PFS than non-PPI-P-CAB users (p = 0.001, p = 0.005, respectively). Multivariate analysis highlighted PPI/P-CAB use as the only independent prognostic factor for disease progression (hazards ratio: 1.71, 95% confidence interval: 1.14-2.07, p = 0.010) but not death (p = 0.177). Proton pump inhibitors/potassium-competitive acid blockers may decrease the efficacy of pembrolizumab therapy for mUC, possibly via gut microbiome modulation.
Antibodies, Monoclonal, Humanized , Carcinoma, Transitional Cell , Metformin , Urinary Bladder Neoplasms , Humans , Proton Pump Inhibitors/pharmacology , Proton Pump Inhibitors/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Retrospective Studies , Urinary Bladder Neoplasms/pathology , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Steroids/therapeutic use , Metformin/therapeutic use
Germline and somatic mutations cause various diseases, including cancer. Clinical applications of genome editing are keenly anticipated, since it can cure genetic diseases. Recently, we reported that a 5'-tailed duplex (TD), consisting of an approximately 80-base editor strand oligodeoxyribonucleotide and a 35-base assistant strand oligodeoxyribonucleotide, could edit a target gene on plasmid DNA and correct a single-base substitution mutation without an artificial nuclease in human cells. In this study, we assessed the ability of the TD to correct base substitution mutations located consecutively or separately, and deletion and insertion mutations. A TD with an 80-base editor strand was co-introduced into human U2OS cells with plasmid DNA bearing either a wild-type or mutated copepod green fluorescent protein (copGFP) gene. Among the mutations, three-base consecutive substitutions were efficiently repaired. The correction efficiencies of deletion mutations were similar to those of substitution mutations, and two to three times higher than those of insertion mutations. Up to three-base substitution, deletion, and insertion mutations were excellent targets for correction by TDs. These results suggested that the TDs are useful for editing disease-causing genes with small mutations.
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.
Aortic Dissection , Humans , Treatment Outcome , Aortic Dissection/diagnostic imaging , Aortic Dissection/surgery , Aircraft , Japan , Retrospective Studies
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.
DNA , Guanine , Guanine/analogs & derivatives , Humans , Mutation , Mutagenesis , Guanine/metabolism , Cytidine Deaminase/genetics , Minor Histocompatibility Antigens/genetics
Although total arch replacement would be performed in a patient with acute type A aortic dissection and concomitant aortic aneurysm in the distal aortic arch, total arch replacement may be too invasive in elderly patients with significant morbidities. A 92-year-old female with acute type II DeBakey aortic dissection and concomitant distal aortic arch aneurysm was successfully treated with hemi-arch replacement followed by thoracic endovascular aortic repair. Hybrid two-stage repair of DeBakey type II aortic dissection complicated by distal arch aneurysm using thoracic endovascular aortic repair after hemi-arch replacement may be effective.
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.
Cardiac Output, Low , Cardiac Surgical Procedures , Humans , Cardiac Surgical Procedures/adverse effects , Reperfusion Injury/prevention & control , Perioperative Period
Acute coronary syndrome with cardiogenic shock is a life-threatening condition, but with planned staged treatment combined with coronary revascularization and mechanical circulatory supports its management is increasingly possible. Here, we present our successful life-saving case. A 76-year-old male patient was diagnosed with ST-elevation myocardial infarction with cardiogenic shock due to severe stenosis of the left main coronary artery based on the severe triple vessel disease. We initially introduced Impella CP and performed a percutaneous coronary intervention without stenting on the patient. We maintained hemodynamics with Impella CP and performed coronary artery bypass grafting after a week. Intraoperatively, Impella CP was left to function as a left ventricular vent. The patient required upgrading to Impella 5.5 plus veno-arterial extracorporeal membrane oxygenation postoperatively, but his condition gradually improved, all mechanical circulatory supports could be weaned off, and he eventually survived.
The frozen elephant trunk (FET) is an effective method for making the distal anastomosis more proximal and facilitating aortic remodeling in acute aortic dissection. However, misdeployment of FET to the false lumen has been reported in several cases. Such cases are usually treated with bail-out thoracic endovascular aortic repair (TEVAR) through the femoral artery or additional FET under direct vision to redirect the blood flow to the true lumen. We encountered a case of misdeployment of FET into the false lumen during open aortic surgery for the treatment of Stanford type A acute aortic dissection. After reconstruction of the aorta and all arch vessels, we performed antegrade bail-out TEVAR through a side branch of the four-arm Dacron graft as main access using a pull-through technique through the right femoral artery, which was perfused from the true lumen. This technique, which uses a Dacron graft branch for stent graft access, enabled us to confirm the true lumen because the distal anastomotic site was definitely the true lumen, and we were also able to avoid access difficulties at the iliac artery.
BACKGROUND: Post-implant right heart failure (RHF) has been recognized as a crucial prognostic factor in patients receiving left ventricular assist devices (LVADs), and its management has long attracted attention from cardiologists and surgeons. CASE PRESENTATION: This report described an 18-year-old female with acutely deteriorating heart failure due to dilated cardiomyopathy who underwent paracorporeal pulsatile-flow LVAD and developed early post-implant RHF. At postoperative day (POD) six, she was almost asymptomatic at rest on 2.5 mg/kg/min of dobutamine; however, the echocardiogram, performed as part of the daily postoperative care, revealed a severely enlarged right ventricle with a decompressed left ventricle, implying the development of post-implant RHF. Bolus infusion of saline and reduction of pump flow (6.0 L/min to 3.0 L/min) led to normalization of both ventricular shapes in 30 s, suggesting that RHF could be managed without surgical interventions. Milrinone was started on POD six, followed by sildenafil administration on POD seven. Fluid balance was strictly adjusted under the close observation of daily echocardiograms. Milrinone and dobutamine were discontinued on PODs 18 and 21, respectively. The patient was listed for a heart transplant on POD 40. Despite reduced right ventricular function (right ventricular stroke work index of 182.34 mmHg*ml/m- 2, body surface area 1.5 m2), she was successfully converted to implantable LVAD on POD 44 with no recurrence of post-implant RHF thereafter for four years. CONCLUSIONS: In post-implant RHF management, early detection, together with proper and prompt medical management, is crucial to avoiding any surgical intervention. Close observation of daily echocardiograms might be helpful in detecting subclinical RHF and is useful for post-implant medical management.
Heart Failure , Heart-Assist Devices , Female , Humans , Adolescent , Milrinone , Heart-Assist Devices/adverse effects , Dobutamine , Retrospective Studies , Heart Failure/etiology , Heart Failure/surgery , Echocardiography
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.
Endocarditis, Bacterial , Endocarditis , Fistula , Heart Valve Prosthesis , Male , Humans , Aged, 80 and over , Shock, Cardiogenic , Fistula/diagnosis , Fistula/etiology , Fistula/surgery
Minimally invasive direct coronary artery bypass is preferred due to its less invasive nature; however, it carries the risk of graft failure owing to inherent technical challenges. We present a case where minimally invasive direct coronary artery bypass grafting was performed and graft failure was detected via coronary angiography 3 days post-operation. Successful percutaneous coronary intervention was subsequently performed on the failed graft itself to salvage myocardial cellular damage. Consequently, the combination of minimally invasive direct coronary artery bypass and percutaneous coronary intervention, both less-invasive revascularization approaches, effectively achieved the primary treatment objective.
