Stenting of the ductus arteriosus for ductal‐dependent pulmonary blood flow—current techniques and procedural considerations

The use of prostaglandin‐E1 immediately after birth and subsequent surgical creation of the modified Blalock‐Taussig shunt (BTS) shunt have remarkably improved the prognosis and survival of children with congenital heart disease and ductal‐dependent pulmonary blood flow (PBF). Despite the advancement in surgical techniques, bypass strategies, and postoperative management, significant morbidity and mortality after BTS still remain. Patent ductus arteriosus stenting has been shown to be as an acceptable alternative to BTS placement in select infants with ductal‐dependent PBF. Newer procedural techniques and equipment, along with operator experience have all contributed to procedural refinement associated with improved outcomes over the recent years. In this article, we review the procedural and periprocedural details, with an emphasis on recent advances of this procedure.     

Interferon α2–Thymosin α1 Fusion Protein (IFNα2–Tα1): A Genetically Engineered Fusion Protein with Enhanced Anticancer and Antiviral Effect

Human interferon α2 (IFNα2) and thymosin α1 (Tα1) are therapeutic proteins used for the treatment of viral infections and different types of cancer. Both IFNα2 and Tα1 show a synergic effect in their activities when used in combination. Furthermore, the therapeutic fusion proteins produced through the genetic fusion of two genes can exhibit several therapeutic functions in one molecule. In this study, we determined the anticancer and antiviral effect of human interferon α2–thymosin α1 fusion protein (IFNα2–Tα1) produced in our laboratory for the first time. The cytotoxic and genotoxic effect of IFNα2–Tα1 was evaluated in HepG2 and MDA-MB-231 cells. The in vitro assays confirmed that IFNα2–Tα1 inhibited the growth of cells more effectively than IFNα2 alone and showed an elevated genotoxic effect. The expression of proapoptotic genes was also significantly enhanced in IFNα2–Tα1-treated cells compared to IFNα2-treated cells. Furthermore, the HCV RNA level was significantly reduced in IFNα2–Tα1-treated HCV-infected Huh7 cells compared to IFNα2-treated cells. The quantitative PCR analysis showed that the expression of various genes, the products of which inhibit HCV replication, was significantly enhanced in IFNα2–Tα1-treated cells compared to IFNα2-treated cells. Our findings demonstrate that IFNα2–Tα1 is more effective than single IFNα2 as an anticancer and antiviral agent.     

Surgical e-learning: validation of multimedia web-based lectures

BACKGROUND: Distance learning has been advocated increasingly as a modern efficient method of teaching surgery. Efficiency of knowledge transfer and validity of web-based courses have not been subjected to rigorous study to date. METHODS: An entirely web-based surgical 5-week lecture course was designed. Fifty per cent of the lectures were prepared as HTML slides with voice-over while the other group was presented in the text-only form. Only written material presented was examined. The lectures were presented via an educational web module. The lecture series was balanced specifically to reduce the pre-existent knowledge bias. Web usage was estimated utilising surrogates, including the number of hits as well as log-on timing. Face validity was assessed by a standardised questionnaire. RESULTS: Eighty-eight students took part in the lecture series and subsequent examination and questionnaire. Median multiple choice questionnaire (MCQ) marks were significantly higher in the aural lecture-derived stems versus the non-aural (P = 0.012, Mann-Whitney U-test). There was widespread approval of web-based learning as an adjunct to conventional teaching. Usage rates were augmented significantly in the final week when compared to the previous 4 weeks (mean total hits weeks 1-4 +/- SEM: 100.9 +/- 9.7 and mean total hits week 5: 152.1 +/- 13.1; P < 0.001, Kruskal-Wallis). However, total hits did not correlate with overall examination results (r(2) = 0.16). The aural lectures demonstrated higher face validity than the non-aural for content and presentation (P < 0.05, Kruskal-Wallis). CONCLUSIONS: The addition of aural files to the novel web-based lecture series is face valid and results in significantly increased examination performance.     

CP-31398 restores mutant p53 tumor suppressor function and inhibits UVB-induced skin carcinogenesis in mice

Mutations in the tumor suppressor p53 are detectable in over 50% of all human malignancies. Mutant p53 protein is incapable of transactivating its downstream target genes that are required for DNA repair and apoptosis. Chronic exposure to UVB induces p53 mutations and is carcinogenic in both murine and human skin. CP-31398, a styrylquinazoline compound, restores the tumor suppressor functions of mutant forms of p53 in tumor cells. However, its effectiveness in vivo remains unclear. Here, we demonstrate that CP-31398 blocked UVB-induced skin carcinogenesis and was associated with increases in p53, p21, and BclXs. CP-31398 downregulated Bcl2, proliferating nuclear cell antigen, and cyclin D1. Activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase also occurred in both tumor and perilesional skin following treatment. CP-31398 induced the expression of p53-dependent target proteins, and this was followed by apoptosis in UVB-irradiated wild-type mice but not in their p53-deficient littermates. Similar effects were observed in human skin carcinoma A431 cells expressing mutant p53. In addition, CP-31398 induced mitochondrial translocation of p53, leading to changes in mitochondrial membrane permeability pore transition (MPT) and consequent cytochrome c release in these cells. Blocking MPT diminished p53 translocation and apoptosis. These studies indicate that reconstituting p53 tumor suppressor functions in vivo by small molecular weight compounds may block the pathogenesis and progression of skin cancer.     

Colonic filiform polyposis and a malignant adenomatous polyp

We have reported a case of pseudopolyposis in the unusual form of filiform polyps in the transverse colon with an adenomatous polyp in the sigmoid colon that had a focus of malignant degeneration. The patient did not have any significant past history of inflammatory bowel disease.     

Transcatheter Pulmonary Valve Replacement With the Melody Valve in Small Diameter Expandable Right Ventricular Outflow Tract Conduits

Objectives

This study sought to evaluate the safety, feasibility, and outcomes of transcatheter pulmonary valve replacement (TPVR) in conduits ≤16 mm in diameter.

Percutaneous Pulmonary Valve Implantation‐Associated Ventricular Tachycardia in Congenital Heart Disease

Background

Percutaneous pulmonary valve implantation (PPVI) is utilized for dysfunctional right ventricular outflow tracts (RVOT) to relieve obstruction, regurgitation, and RV dysfunction. PPVI has not been reported to induce arrhythmias. This study is the first to report the incidence of ventricular tachycardia (VT) after PPVI.

Methods

This was a retrospective study of all patients who had PPVI at a single institution. All patients were admitted after PPVI for overnight telemetry monitoring. Patients with no prior history of VT and newly detected VT within 24 hours post‐PPVI were considered to have VT related to PPVI.

Results

In total, 79 patients had PPVI (age 17 ± 9 years, 66% tetralogy of Fallot/pulmonary atresia). PPVI‐related VT was detected in 6 patients (7.5%). These patients had a lower BMI (17.5 ± 2.0 vs. 23.1 ± 6.6, P = 0.04). There was no difference in age, native conduit or percutaneous valve size, or change in the minimum diameter of the RVOT from pre‐ to post‐PPVI. In the 6 patients, VT was non‐sustained and monomorphic at rates between 120 and 170. Five started on β‐blockers. No patient required surgical explantation of the valve. Over a median follow‐up of 2 years, 4 have weaned off medications and all are free of recurrence of VT with normal Holters.

Conclusions

PPVI may be associated with transient VT in the acute peri‐procedural period. Patients of smaller size may be more susceptible. All patients were managed conservatively and none of the patients had a recurrence, which is suggestive of a transient phenomenon.