A 20-Year Analysis of Ruptured Abdominal Aortic Aneurysm Outcomes and Associated Factors in Korea.

BACKGROUND: Unlike western countries, which have reported distinct decreases in incidence of ruptured abdominal aortic aneurysm (rAAA) over the last few decades, epidemiologic studies in Korea have not shown significant changes in incidence or mortality of rAAA. The purpose of this study was to analyze the changes in rAAA treatment outcomes and various associated risk factors over the past 2 decades. METHODS: A 20-year retrospective multicenter review for rAAA cases from the period of January 2000 to December 2020 was undertaken. Preoperative, intraoperative and postoperative clinical data were extracted for patients diagnosed with rAAA. For analysis, outcomes from the early era, defined as patients treated between January 1, 2000, and December 31, 2010, were compared with outcomes from the late era, defined as patients treated between January 1, 2011, and December 31, 2020. RESULTS: The total in-hospital mortality was 34.1% in the early era compared to 44.8% in the late era. Patients in the late era were older than those in the early era (75.2 ± 10.3 years vs. 70.3 ± 8.9 years; P = 0.009). Treatment with rAAA endovascular aneurysm repair increased from 2.3% in early to 13.8% in late era (P = 0.031). In the early era, more patients were operated by experienced surgeons than the late era (78.1% vs. 45.9%; P = 0.002). The emergency room to operating room time did not show improvement over the 20 years. CONCLUSIONS: The results indicate that mortality rate of rAAA in Korea has not changed over the last 2 decades. The study suggests the need for national preventive strategies, improved systemic coordination, and potential centralization of vascular services to enhance survival rates for rAAA.

Tripartite motif-containing protein 26 promotes colorectal cancer growth by inactivating p53.

Tripartite motif-containing protein 26 (TRIM26) is an E3 ubiquitin ligase that exhibits divergent roles in various cancer types (oncogenic and anti-oncogenic). This study investigates the interaction of TRIM26 with the tumor suppressor protein p53 in colorectal cancer (CRC) cells by performing a comprehensive set of biochemical, cell-based assays, and xenograft experiments. As a result, we found that overexpression of TRIM26 significantly enhances CRC cell proliferation and colony formation, while knockdown of TRIM26 suppresses these processes. Xenograft experiments further validated the tumor-promoting role of TRIM26 in CRC. Supporting this is that TRIM26 is highly expressed in human CRC tissues as revealed by our analysis of the TCGA database. Biochemically, TRIM26 directly bound to the C-terminus of p53 and facilitated its ubiquitination, resulting in proteolytic degradation and attenuated p53 activity independently of MDM2. Also, TRIM26 increased the MDM2-mediated ubiquitination of p53 by binding to MDM2's C-terminus. This study uncovers the oncogenic potential of TRIM26 in CRC by inhibiting p53 function. Through its ubiquitin ligase activity, TRIM26 destabilizes p53, consequently promoting CRC cell proliferation and tumor growth. These findings shed light on the complex involvement of TRIM26 in cancer and identify this ubiquitin ligase as a potential therapeutic target for future development of CRC treatment.

Activin Suppresses the Inflammatory Response of TNF-α -stimulated Human Umbilical Vein Endothelial Cells.

Activins belong to the transforming growth factor (TGF)-ß superfamily and are involved in the regulation of homeostasis, proliferation, differentiation, and inflammation. In the present study, we examined the mechanism by which activin regulates the transcription of tumor necrosis factor-α (TNF-α)-stimulated cytokines, chemokines, toll-like receptors (TLRs), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in human umbilical vein endothelial cells (HUVECs), and the involvement of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Cell viability was analyzed using MTS/PES solution, mRNA expression was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and protein expression was measured by immunoblotting. TNF-α increased the mRNA expression of cytokines (IL-1ß and IL-6), chemokines (IL-8 and MCP-1), and TLR2, as well as the mRNA and protein expression of iNOS and COX-2. Activin decreased TNF-α-induced cytokine, chemokine, and TLR mRNA expression as well as TNF-α-induced iNOS and COX-2 mRNA and protein expression. In addition, activin suppressed the phosphorylation of NF-κB p65 in TNF-α-stimulated HUVECs and reduced TNF-α-induced phosphorylation of AKT, JNK, ERK, and p38 MAPK. Our results demonstrate that the anti-inflammatory effects of activin are mediated by inflammatory response genes through the inhibition of NF-κB and AKT/JNK/MAPK signaling.

Vein Graft Aneurysm after Aorto-Renal Bypass for Childhood Renovascular Hypertension Due to Fibromuscular Dysplasia.

Renovascular hypertension (RVHT) is a major cause of surgically correctable secondary hypertension. Refractory hypertension despite multiple antihypertensive drugs requires angioplasty, surgical revascularization, or even nephrectomy. Herein, we report a pediatric patient who had been treated with angioplasty, nephrectomy, and aortorenal bypass surgery for RVHT due to fibromuscular dysplasia and re-do endoaneurysmal graft replacement for a vein graft aneurysm. This case highlights the various treatment modalities for RVHT and the recurrent nature of the disease with a rare presentation of a vein graft aneurysm after aortorenal bypass.

Effects of tacrolimus intrapatient variability and CYP3A5 polymorphism on the outcomes of pediatric kidney transplantation.

BACKGROUND: The intrapatient variability (IPV) of tacrolimus (Tac) is associated with the long-term outcome of kidney transplantation. The CYP3A single-nucleotide polymorphism (SNP) may affect the IPV of Tac. We investigated the impact of IPV and genetic polymorphism in pediatric patients who received kidney transplantation. METHODS: A total of 202 pediatric renal transplant recipients from 2000 to 2016 were analyzed retrospectively. The IPV was calculated between 6 and 12 months after surgery. Among these patients, CYP3A5 polymorphism was analyzed in 67 patients. RESULTS: The group with high IPV had a significantly higher rate of de novo donor-specific human leukocyte antigen antibodies (dnDSA) development (35.7% vs. 16.7%, p = .003). The high IPV group also had a higher incidence of T-cell-mediated rejection (TCMR; p < .001). The high IPV had no significant influence on Epstein-Barr virus, cytomegalovirus, and BK virus viremia but was associated with the incidence of posttransplant lymphoproliferative disorders (p = .003). Overall, the graft survival rate was inferior in the high IPV group (p < .001). The CYP3A5 SNPs did not significantly affect the IPV of Tac. In the CYP3A5 expressor group, however, the IPV was significantly associated with the TCMR-free survival rate (p < .001). CONCLUSION: The IPV of Tac had a significant impact on dnDSA development, occurrence of acute TCMR, and graft failure in pediatric patients who received renal transplantation. CYP3A5 expressors with high IPV of Tac showed worse outcomes, while the CYP3A5 polymorphism had no impact on IPV of Tac.

Efficacy of Nitric Oxide-Releasing Nanofibers in Reducing Renal Ischemia-Reperfusion Injury in a Rat Model.

BACKGROUND This study aimed to analyze the preventive effect of nitric oxide (NO)-releasing nanofibers against ischemia-reperfusion injury (IRI) and to determine the mechanism of action as a novel NO delivery system in a rat model. MATERIAL AND METHODS Eight-week-old male Sprague-Dawley rats, weighing 250 to 280 g, were divided into 3 groups: sham, untreated (n=5); control, renal ischemia injury for 55 min (n=4); and NO24, renal ischemia injury for 55 min with kidney wrapping of NO-releasing nanofiber for 24 h (n=6). mRNA expression was measured by real-time polymerase chain reaction (PCR), whereas protein expression was assessed by immunohistochemistry and western blot analysis. RESULTS Serum creatinine levels in the sham, control, and NO24 groups were 0.48±0.08, 4.66±0.33, and 2.60±1.00 mg/dL, respectively (P=0.002). Anti-apoptotic Bcl-2 protein expression differed significantly between the control and the NO24 groups (Bcl-2/ß-actin; control, 0.50±0.12; NO24, 1.56±0.56; P=0.024). mRNA expression level of the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) was significantly higher in the control group (23.24±11.32, P=0.016) than in the sham group (1.00±1.21), and mRNA expression of TNF-alpha in the NO24 group (1.28±1.16, P=0.010) was significantly lower than in the control group. Histological analysis revealed decreased atrophy and necrosis in the NO24 group compared to those in the control group. CONCLUSIONS This study demonstrated that kidney wrapping of NO-releasing nanofibers had a protective effect against kidney IRI through anti-apoptotic and anti-inflammatory mechanisms.

Methylation and mutation of the inhibin­α gene in human melanoma cells and regulation of PTEN expression and AKT/PI3K signaling by a demethylating agent.

Inhibin suppresses the pituitary secretion of follicle­stimulating hormone and has been reported to act as a tumor suppressor gene in the gonad in mice. Epigenetic modifications, mutations, changes in the loss of heterozygosity (LOH) of the inhibin­α gene and regulation of gene expression in response to a demethylating agent [5­aza­2'­deoxycytidine (5­Aza­dC)] in human melanoma cells were assessed. In addition, the association between a mutation in the 5'­untranslated region (5'­UTR) of the inhibin­α subunit and the expression of phosphatidylinositol 3,4,5­trisphosphate­dependent Rac exchanger 2 (PREX2) and phosphatase and tensin homolog (PTEN) as well as AKT/PI3K signaling was determined. The methylation status of the CpG sites of the inhibin­α promoter was analyzed by methylation­specific PCR in bisulfite­treated DNA. Cell viability was counted using the trypan blue assay, mRNA expression was examined via reverse transcription­quantitative PCR, and protein expression was examined via western blot analysis. The inhibin­α promoter was hypermethylated in G361, SK­MEL­3, SK­MEL­24 and SK­MEL­28 cells and moderately methylated in SK­MEL­5 cells. Inhibin­α gene mutations were observed in the 5'­UTR exon 1 of G361, SK­MEL­5, SK­MEL­24 and SK­MEL­28 cells as well as in exon 2 of SK­MEL­3 cells. Allelic imbalance, including LOH, in the inhibin­α gene was detected in human melanoma cells. Treatment with 5­Aza­dC increased inhibin­α mRNA and protein levels, inhibited cell proliferation, and delayed the doubling times of surviving melanoma cells. In 5­Aza­dC­treated cells, PREX2 protein expression was slightly increased in G361 and SK­MEL­24 cells and decreased in SK­MEL3, SK­MEL­5 and SK­MEL­28 cells. However, the protein expression of PTEN was decreased in melanoma cells. In addition, AKT and PI3K protein phosphorylation levels increased in all melanoma cells, except of G361 cells, demonstrating decreased PI3K protein phosphorylation. These data provided evidence that methylation, mutation and LOH are observed in the inhibin α­subunit gene and gene locus in human melanoma cells. Furthermore, the demethylating agent reactivated inhibin­α gene expression and regulated PREX2 expression. AKT/PI3K signaling increased as PTEN expression decreased. In addition, mutations in the tumor suppressor inhibin­α, PTEN and p53 genes were not associated with transcriptional silencing, gene expression and cell growth as analyzed through experiments and literature reviews. These data demonstrated that methylation and mutations were associated with the inhibin­α gene in human melanoma cells and indicated the regulation of PTEN expression and AKT/PI3K signaling by a demethylating agent.

Renal transplantation in patients with an augmentation cystoplasty.

Background: The effects of renal transplantation in patients with augmentation cystoplasty are still controversial. We retrospectively analyzed nine patients who underwent renal transplantation after augmentation cystoplasty. Methods: A total of nine patients who underwent augmentation cystoplasty prior to renal transplantation between January 1990 and May 2020 were reviewed. Basic information on augmentation cystoplasty, transplant procedures, and long-term outcomes of renal transplantation were analyzed. Results: The bowel segments utilized for augmentation cystoplasty were the stomach in two patients (one patient needed revision using the ileum), the ileum in four patients, the ileocolic pouch in one patient, the sigmoid in one patient, and the ureter in one patient. All the cystoplasties were performed prior to renal transplantation. The mean follow-up period after transplantation was 161 months (range, 2-341 months). Two patients had an episode of acute rejection each; however, their graft functions were well-maintained. Five patients had recurrent urinary tract infections, and three of these patients progressed to allograft failure. One patient died from bladder cancer with a functioning graft. Five of nine patients showed well-maintained graft function. Conclusions: Renal transplantation after bladder augmentation surgery is a major operation requiring a high level of surgical skill. Based on our long-term experiences, we recommend diligent postoperative monitoring for urinary tract infections, optimal catheter use, and use of appropriate antibiotic prophylaxis to avoid severe complications.

Thrombosis of a Long-Segment Aneurysm from the Iliac to Popliteal Artery Associated with Arteriovenous Malformation and Varicose Veins.

A 58-year-old male patient with severe claudication due to thrombosis of the left ilio-femoro-popliteal artery aneurysm. He also had a venous stasis ulcer with a history of multiple embolotherapy of arteriovenous malformation. Duplex sonography revealed reflux and varicose veins of the left great saphenous vein (GSV). A sequential bypass surgery was performed that consisted of excision of the left external iliac and common femoral artery aneurysm, external iliac to deep femoral interposition with an expanded polytetrafluoroethylene graft, and femoro-posterior tibial artery bypass with the reversed left GSV. Symptoms of claudication were alleviated and the chronic ulcer was healed in time. To our knowledge, this is the first report of successful bypass in a patient with arterial aneurysm, arteriovenous malformation, and venous insufficiency that can be diagnosed as an atypical case of Parkes Weber syndrome. Long-term follow-up is needed to define the fate of aneurysms and varicose vein graft.