Management of ostium secundum atrial septal defect in the era of percutaneous trans-catheter device closure: 7-Year experience at a single institution

AbstractObjectivesThis study aimed to review the single institutional experience of the repair of secundum atrial septal defect (ASD) after the initiation of percutaneous trans-catheter device closure, to confirm the current management strategy and outcomes.MethodsFrom August 2005 to December 2012, a total of 1026 (659 females, age 27±21 years) consecutive patients underwent the repair of ASD. Including eight patients who converted to surgical repair, 317 patients (31%) underwent surgical repair and 709 (69%) underwent trans-catheter device closure.ResultsAn embolized device into the left atrium was surgically retrieved in one patient soon after trans-catheter device closure without any postoperative complications. The other patient developed left atrium to aorta fistula due to late erosion, and required the removal of implanted device and patch closure of fistula and ASD 3 months after trans-catheter device closure. Whereas serious central nerve system complications occurred in three patients after the surgical repair including a 75-year-old patient with postoperative transient atrial fibrillation who subsequently developed aspiration pneumonia and died; there were no mortalities and no morbidities associated with cranial nerve function after trans-catheter device closure. A number of patients approached through partial sternotomy with limited skin incision have increased per year, and the length of skin incision was 5.1±1.2cm in pediatric patients weighing less than 15kg (n=40), 6.9±1.9cm in the remaining pediatric patients (n=91), and 10.0±2.5cm in young adult females (n=10).ConclusionPercutaneous trans-catheter ASD closure was safely performed under the support of a surgical team. The cosmetic outcome of surgical closure is improving after initiation of partial sternotomy via limited skin incision for the pediatric population and young adult females. Prior to the treatment, the physicians must thoroughly inform patients and families of the advantages and disadvantages of both treatment options

Impact of glycemic control with sitagliptin on the 2‑year progression of arterial stiffness : a sub‑analysis of the PROLOGUE study

Background: No conclusive evidence has been obtained yet on the significance of the effects of dipeptidyl peptidase-4 (DPP-4 inhibitor) treatment on the arterial stiffness in clinical settings. In addition, the effects of good glycemic control on the arterial stiffness have also not been clarified yet. As a sub-analysis of the PROLOGUE study, we examined the effect of a DPP-4 inhibitor (sitagliptin) on the 2-year progression of the arterial stiffness and also to determine the effect of good glycemic control on the rate of progression of the arterial stiffness. Methods: In the PROLOGUE study, the study participants were either allocated to add-on sitagliptin treatment or to continued treatment with conventional anti-diabetic agents. Among the 463 participants of the PROLOGUE study, we succeeded in measuring the brachial-ankle pulse wave velocity (baPWV) at least two times during the 2-year study period in 96 subjects. Results: The changes in the baPWV during the study period were similar between the both groups (i.e., with/without staglipitin), overall. On the other hand, when the study subjects were divided into two groups according to the glycemic control status during the study period {good glycemic control group (GC) = hemoglobin (Hb)A1c <7.0 at both 12 and 24 months after the treatment randomization; poor glycemic control group (PC) = HbA1c ≥7.0 at either 12 months, 24 months, or both}, the 2-year increase of the baPWV was marginally significantly larger in the PC group (144 ± 235 cm/s) as compared to that the GC group (−10 ± 282 cm/s) (p = 0.036). Conclusion: While the present study could not confirm the beneficial effect of sitagliptin per se on the arterial stiffness, the results suggested that good glycemic control appears to be beneficial for delaying the annual progression of the arterial stiffness

Increased expression of PHD3 represses the HIF-1 signaling pathway and contributes to poor neovascularization in pancreatic ductal adenocarcinoma

Background: Pancreatic ductal adenocarcinoma (PDAC) is known as one of the most malignant potential diseases with poor neovascularization. By comparing PDAC to hepatocellular carcinoma (HCC), which is well vascularized, we investigated the mechanisms and tumor biological significance of the poor neovascularization in PDAC. Methods: Surgical specimens from primary PDAC and HCC patients were immunohistologically stained to detect the expressions of CD105, CD44, HIF-1α, PHD3, and Siah2. We also used two PDAC and two HCC cell lines to compare the expressions of HIF-1α, PHD3, and CD44, as well as the production of VEGF in hypoxic condition. The role of PHD3 in regulating HIF-1α expression was further confirmed by siRNA knockdown in a PDAC cell line that highly expressed PHD3. Results: There were significantly fewer microvessels but more cancer stem cells in PDAC specimens compared to HCC specimens. The expression of CD105 was reversely related to the expression of CD44 in PDAC and HCC specimens. PDAC specimens also showed higher expressions of PHD3 but lower expressions of HIF-1α. Similarly, the expression of PHD3 was observed clearly in PDAC cell lines, but was almost completely negative in HCC cell lines. Hypoxic stimulation clearly enhanced HIF-1α expression and VEGF secretion in both HCC cell lines, but did not significantly change in PDAC cell lines. The knockdown of PHD3 in PDAC cells restored the hypoxic-induced HIF-1α expression, which accordingly stimulated the cells’ VEGF secretion. Conclusions: The enhanced expression of PHD3 might likely contribute to the poor neovascularization and affect the biological characterization in PDAC cancer cells

Advances in Early Detection of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. PDAC is the fourth leading cause of death in the United States and Japan based on epidemiological data. Early detection of PDAC is very important to improve the prognosis of PDAC. Early detection of pancreatic ductal adenocarcinoma (PDAC) requires further examination after selecting cases with risk factors for the condition, such as family history, hereditary pancreatic carcinoma syndrome, intraductal papillary mucinous neoplasms, or chronic pancreatitis. The Japan Study Group on the Early Detection of Pancreatic Cancer has investigated and clarified the clinicopathological features for the early diagnosis of PDAC. In Japan, an algorithm for the early diagnosis of PDAC, which utilized the cooperation of local clinics and regional general hospitals, has been a breakthrough in the detection of early-stage PDAC. Further approaches for the early diagnosis of PDAC are warranted

Shoseiryuto Ameliorated TDI-Induced Allergic Rhinitis by Suppressing IL-33 Release from Nasal Epithelial Cells

Toluene diisocyanate (TDI) is a major cause of occupational asthma and rhinitis. Shoseiryuto (SST) is one of the traditional herbal medicines (Kampo medicine) and has long been used as a natural medicine for allergic diseases such as allergic rhinitis (AR) and asthma. Recent studies have shown that the expression and release of IL-33, which regulates the TH2 cytokine response in epithelial cells, is an important step in developing the inflammatory response of the nasal mucosa. In this study, we investigated whether SST may ameliorate the TDI-induced AR-related symptoms in rats and inhibit IL-33 release from nasal epithelial cells. An AR rat model was generated by sensitization and induction with TDI. SST was administered during the sensitization period. AR-related symptoms in rats were evaluated, and IL-33 release was measured both in vivo and in vitro. SST suppressed symptoms appearing in TDI-induced AR model rats, such as elevated serum histamine and IL-33 levels in nasal lavage fluid (NLF)/serum, which were suppressed by SST administration. TDI-induced IL-33 release from the nasal epithelial cell nuclei was also observed and suppressed in SST-treated rats and cultured nasal epithelial cells. These results suggest that SST ameliorates the symptoms of TDI-induced AR at least partially by inhibiting IL-33 release from nasal epithelial cells

Click Chemistry of Melamine Dendrimers: Comparison of &ldquo;Click-and-Grow&rdquo; and &ldquo;Grow-Then-Click&rdquo; Strategies Using a Divergent Route to Diversity

Dendrimers are attractive macromolecules for a broad range of applications owing to their well-defined shapes and dimensions, highly branched and globular architectures, and opportunities for exploiting multivalency. Triazine dendrimers in particular offer advantages such as ease of synthesis, stability, well-defined spherical structure, multivalency, potential to achieve acceptable drug loadings, and low polydispersity. In this study, the potential utility of alkyne-azide &ldquo;click&rdquo; cycloadditions of first-, second-, and third-generation triazine dendrimers containing three or six alkynyl groups with benzyl azide was examined using copper catalysts. &ldquo;Click-and-grow&rdquo; and &ldquo;grow-then-click&rdquo; strategies were employed. For the first- and second- generation dendrimers, the desired triazole derivatives were obtained in high yields and purified by simple reprecipitation without column chromatography; however, some difficulties were observed in the preparation of third-generation dendrimers. The desired reaction proceeded under microwave irradiation as well as with simple heating. This click chemistry can be utilized for various melamine dendrimers that are fabricated with other amine linkers