FOXO3 is a member of the FOXO transcription factors thought to play a tumor-suppressor role in gastrointestinal cancer, while tumor-promoting function of FOXO3 has also been reported. These results ...suggest a context-dependent function of FOXO3 in tumor development. However, the relationship between the FOXO3 expression pattern and its role in tumorigenesis has not been elucidated. We examined the FOXO3 expression in 65 human primary gastric cancer and patient-derived xenograft tissues by immunohistochemistry and identified three subtypes according to subcellular localization: FOXO3-nuclear accumulated (FOXO3-Nuc), FOXO3-nuclear/cytoplasmic or cytoplasmic distributed (FOXO3-Cyt), and FOXO3-negative. In the FOXO3-Cyt gastric cancer cells, the expression of the constitutive active mutant FOXO3 (Act-ER FOXO3) induced the nuclear accumulation of FOXO3 and significantly suppressed colony formation and proliferation. The inhibition of the PI3K-AKT pathway by inhibitor treatment also suppressed the proliferation of FOXO3-Cyt gastric cancer cells, which was associated with the nuclear accumulation of endogenous FOXO3. Furthermore, the expression of Act-ER FOXO3 by an endogenous promoter significantly suppressed gastric tumorigenesis in Gan mice, a model of gastric cancer. Finally, treatment of FOXO3-Cyt human gastric cancer-derived organoids with an AKT inhibitor significantly suppressed the survival and proliferation. These results indicate that FOXO3 is a latent tumor suppressor for FOXO3-Cyt-type gastric cancer cells and that activation of the PI3K-AKT pathway protects this type of gastric cancer cell from FOXO3-mediated growth suppression via constitutive nuclear export. Thus, the inhibition of the PI3K-AKT pathway and nuclear translocation of endogenous FOXO3 may have therapeutic applications in the treatment of FOXO3-positive and cytoplasmic-type gastric cancer.
The present study aimed to determine whether aortic cross-clamp duration (ACCD) was directly related to postoperative morbidity and mortality rates and to identify the inflection point of ACCD for ...increased mortality and morbidity rates in patients who had undergone isolated aortic valve replacement (AVR) for aortic stenosis.
From the Japan Cardiovascular Surgery Database, we extracted data from 16,272 patients with AS who underwent isolated AVR between January 2008 and December 2012. We evaluated postoperative mortality and morbidity rates after stratifying patients into five groups based on ACCD (<60 minutes, ≥60 to <90 minutes, ≥90 to <120 minutes, ≥120 to <150 minutes, and ≥150 minutes).
The overall hospital mortality rate was 2.8%. Multivariate logistic analysis revealed that the odds ratio for operative mortality increased as ACCD incrementally increased and was markedly higher for ACCD of 150 minutes or longer (odds ratio, 2.68; 95% confidence interval, 1.66 to 4.32; p < 0.001). There were significant increases in risks of reoperation for bleeding for ACCD of120 minutes or longer, stroke for ACCD of 60 minutes or longer, deep sternal infection for ACCD of 120 minutes or longer, ventilation for more than 24 hours for ACCD of 90 minutes or longer, and new requirement for dialysis for ACCD of 150 minutes or longer.
Prolonged ACCD offers an independent predictor of postoperative morbidity and mortality after isolated AVR for AS despite recent technologic advances and surgical refinements.
Abstract Background Following an acute myocardial infarction (AMI), surgery for left ventricular free wall rupture (LVFWR) and ventricular septal rupture (VSR) has a high in-hospital mortality rate, ...which has not improved significantly over time. Unloading the LV is critical to preventing excessive stress on the repair site and avoiding problems such as bleeding, leaks, patch dehiscence, and recurrence of LVFWR and VSR because the tissue is so fragile. We present two cases of patients who used Impella 5.5 for LV unloading following emergency surgery for AMI mechanical complications. Case presentation A 76-year-old male STEMI patient underwent fibrinolysis of the distal right coronary artery. Three days later, he passed out and went into shock. Echocardiography revealed a cardiac tamponade. We found an oozing-type LVFWR on the posterolateral wall and treated it with a non-suture technique using TachoSil. Before the patient was taken off CPB, Impella 5.5 was inserted into the LV via a 10 mm synthetic graft connected to the right axillary artery. We kept the flow rate above 4.0 to 4.5 L/min until POD 3 to reduce LV wall tension while minimizing pulsatility. On POD 6, we weaned the patient from Impella 5.5. A postoperative cardiac CT scan showed no contrast leakage from the LV. However, a cerebral hemorrhage on POD 4 during heparin administration complicated his hospitalization. Case 2: A diagnosis of cardiogenic shock caused by STEMI occurred in an 84-year-old male patient, who underwent PCI of the LAD with IABP support. Three days after PCI, echocardiography revealed VSR, and the patient underwent emergency VSR repair with two separate patches and BioGlue applied to the suture line between them. Before weaning from CPB, we implanted Impella 5.5 in the LV and added venoarterial extracorporeal membrane oxygenation (VA-ECMO) support for right heart failure. The postoperative echocardiography revealed no residual shunt. Conclusions Patients undergoing emergency surgery for mechanical complications of AMI may find Impella 5.5 to be an effective tool for LV unloading. The use of VA-ECMO in conjunction with Impella may be an effective strategy for managing VSR associated with concurrent right-sided heart failure.
Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder, and a genetic analysis is important to make a definitive diagnosis. A comprehensive genetic analysis using next generation ...sequencing (NGS) and whole exome sequencing (WES) is feasible. However, the application of NGS in the assessment of genomic structural variations is generally limited, and a substantial number of control samples are needed for such assessments. Thus, NGS alone is unlikely to detect genomic structural variations in a "singleton." We present the case of a patient with compound HeFH (heterozygous FH), whose causative mutations in the LDLR gene could not be identified by WES, necessitating the application of the multiplex ligation-dependent probe amplification (MLPA) technique.
Background:Intimal hyperplasia (IH) is a major cause of graft failure. Hemodynamic factors such as stagnation and disturbed blood flow are involved in IH formation. The aim of this study is to ...perform a comparative analysis of distal-end side-to-side (deSTS) and end-to-side (ETS) anastomoses using computational fluid dynamics (CFD) after validating the results via particle image velocimetry (PIV).Methods and Results:We investigated the characteristics of our target flow fields using CFD under steady and pulsatile flows. CFD via PIV under steady flow in a 10-times-actual-size model was validated. The CFD analysis revealed a recirculation zone in the heel region in the deSTS and ETS anastomoses and at the distal end of the graft, and just distal to the toe of the host artery in the deSTS anastomoses. The recirculation zone sizes changed with the phase shift. We found regions of low wall shear stress and high oscillating shear index in the same areas. The PIV and CFD results were similar.Conclusions:It was demonstrated that the hemodynamic characteristics of CFD and PIV is the difference between the deSTS and ETS anastomoses; that is, the deSTS flow peripheral to the distal end of the graft, at the distal end and just distal to the toe of the host artery is involved in the IH formation.
The selection of artificial valve for the hemodialysis patients is still controversial. Initially ACC/AHA guideline recommended using mechanical valve because of concern on the durability of ...bioprosthesis after replacement on the dialysis patients; however, revised guideline deleted that recommendation. Although many reports recognized rapid deterioration of bioprosthesis mainly due to calcification after valve replacement, there is no difference on survival between both types of valve. The recently conducted meta-analysis reported the same conclusions. Actually the long-term survival of the dialysis patients is poorer than that of non-dialysis people; however, it differs according to the etiology of renal failure. For example, the long-term survival of the non-diabetic patients seems longer than that of diabetic patients requiring longer durability of artificial valve. According to ACC/AHA guideline and the meta-analysis, surgeon should not hesitate to use bioprosthetic valve; however, surgeon should consider stratification of the dialysis patients by prediction for the long survival of each patient.
Spontaneous isolated visceral artery dissection (SIVAD) involving the celiac artery or superior mesenteric artery is rare, but it can be fatal. Given its rare incidence, the clinical characteristics ...of SIVAD are not fully understood. Therefore, the aim of this study was to investigate the clinical characteristics and prognosis of SIVAD.
We retrospectively reviewed 39 consecutive patients diagnosed with SIVAD from January 2007 to December 2016. Demographic characteristics, symptoms, vital signs, blood examination results, and computed tomography findings were retrieved through medical record review.
The median age of the patients was 52 years; 94.9% were male, and 64.1% were symptomatic. Median follow-up duration was 11 months. Overall, hypertension (48.7%) and smoking (79.5%) were frequently observed. There were significant differences between symptomatic and asymptomatic patients in white blood cell count and creatine kinase level but not in fibrin degradation products or D-dimer level. There was a significant correlation between symptoms and length of dissection on computed tomography (P < .01). Conservative treatment was performed in 32 patients (82.1%), and only 7 patients required open surgery or intravascular intervention. Notably, the diameter of affected vessels decreased spontaneously with no rupture or symptom recurrence during follow-up, and mortality was 0% at both 30 days and 1 year.
The utility of blood examination, especially for fibrin degradation products and D-dimer levels, for diagnosis of SIVAD is limited. A high index of suspicion is warranted in patients presenting with persistent severe abdominal pain. Conservative treatment should be considered first-line therapy in patients without any signs of bowel ischemia or rupture.
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