Molecular characteristics of young-onset colorectal cancer in Vietnamese patients.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancer globally. Understanding the genetic characteristics of CRC is essential for appropriate treatment and genetic counseling. METHODS: The genetic profile of CRC tumor tissues was identified using next-generation sequencing of 17 target genes (MLH1, MSH2, MSH6, PMS2, EPCAM, APC, SMAD4, BMPR1A, MUTYH, STK11, PTEN, TP53, ATM, CDH1, CHEK2, POLE, and POLD1) in a cohort of 101 Vietnamese patients diagnosed with young-onset CRC. Corresponding germline genetic alterations of determined somatic mutations were subsequently confirmed from patients' blood samples. RESULTS: Somatic mutations were determined in 96 out of 101 CRC patients. Two-thirds of the tumors harbored more than two mutations, and the most prevalent mutated genes were TP53 and APC. Among confirmed germline mutations, 10 pathogenic mutations and 11 variants of unknown significance were identified. CONCLUSIONS: Given the burden of CRC and the gradually reducing cost of genetic testing, multigene panel screening can benefit young-onset CRC patients as well as their relatives.

Economic assessment of different modalities of immunoglobulin replacement therapy.

The delivery (intravenous or subcutaneous), location (home or hospital), and other factors of immunoglobulin replacement therapy are examined for cost effectiveness. Cost-minimization studies from several countries are reviewed and analyzed. A Canadian cost-minimization study is performed. Although common themes emerge, there are cost differences between the various countries.

Meta-analysis of clinical efficacy and bleeding risk with intravenous glycoprotein IIb/IIIa antagonists for percutaneous coronary intervention.

OBJECTIVE: Percutaneous coronary intervention (PCI) has become the most common mode of coronary revascularization. Inhibition of platelet aggregation via glycoprotein (GP) IIb/IIIa receptor blockade significantly reduces the acute ischemic complications associated with PCI, but the risk of bleeding may also be increased with these agents. The purpose of the present study was to provide an up-to-date meta-analysis on the clinical efficacy and safety of intravenous GP IIb/IIIa antagonists in patients undergoing PCI. METHODS: A comprehensive search was undertaken to identify all randomized trials of GP IIb/IIIa antagonists versus control in patients intended to undergo PCI. Medline, Embase, Biosis, HealthStar and hand searches were performed. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), repeat revascularization, thrombocytopenia and bleeding. OR and their 95% CI were calculated using the random effects model. RESULTS: Twenty-one randomized trials were identified, which together included 23,941 patients. The mortality rate at seven days was 0.33% in the GP IIb/IIa group compared with 0.50% in the control group (OR 0.70, 95% CI 0.29 to 1.68); at 30 days, the mortality rate was 0.83% versus 1.21%, respectively (OR 0.72, 95% CI 0.56 to 0.94); at six months, the mortality rate was 1.92% versus 2.33%, respectively (OR 0.85, 95% CI 0.68 to 1.07); and at one year, the mortality rate was 2.61% versus 3.32%, respectively (OR 0.80, 95% CI 0.64 to 1.00). The number needed to treat at 30 days to save one life was 296. The mortality benefit appeared to dissipate by six months and was of borderline significance at one year. The incidence of MI in the treatment group compared with the control group was reduced at seven days (4.31% versus 6.97%, respectively; OR 0.59, 95% CI 0.46 to 0.75), at 30 days (4.54% versus 6.46% respectively; OR 0.63, 95% CI 0.54 to 0.74) and at six months (5.73% versus 8.29%; OR 0.65, 95% CI 0.55 to 0.77). Repeat revascularization procedures were also significantly lower in the GP IIb/IIIa group compared with the control group at seven days (2.47% versus 4.44%, respectively; OR 0.43, 95% CI 0.29 to 0.84), at 30 days (3.44% versus 5.19%, respectively; OR 0.66, 95% CI 0.56 to 0.77) and at six months (15.21% versus 17.40%, respectively; OR 0.86, 95% CI 0.78 to 0.94). Overall, the composite of death, MI and repeat revascularization was reduced at all time points. An assessment of risk revealed that the incidence of thrombocytopenia (OR 1.41, 95% CI 1.10 to 1.81) and minor bleeding (OR 1.80, 95% CI 1.47 to 2.21), but not major bleeding (OR 1.29, 95 CI 0.98 to 1.68), was significantly increased in the GP IIb/IIIa group versus the control group. CONCLUSIONS: Treatment with GP IIb/IIIa inhibitors in the setting of PCI significantly reduces the rates of 30-day mortality, MI and repeat revascularization procedures. These beneficial effects are achieved at an increased risk of thrombocytopenia and minor bleeding, but not major bleeding.

Does skin cholesterol testing provide benefit?

Cholesterol 1,2,3 9 (TM) is being promoted as a non-invasive way to measure cholesterol that has accumulated in a person's skin. The test received a medical device licence from Health Canada in January 2001. It was approved by the U.S. Food and Drug Administration (FDA) in June 2002. This test is not intended to be used as a screening tool for coronary artery disease in the general population. Evidence from non-randomized, non-blinded clinical trials suggests a correlation between higher skin cholesterol levels and the presence of severe coronary arterial lesions. At this point, technical improvements and more robust evidence are required to determine the significance of this technology in clinical practice.

Using a spectral reflectance technique to measure transcutaneous bilirubin in neonates: a new device.

Devices that use a spectral reflectance technique are used to non-invasively measure total bilirubin levels in neonates to monitor the development of hyperbilirubinemia. As a screening technique for the healthy neonate population, these devices provide instantaneous information, may reduce the need of heel-pricks on neonates, and indicate which neonates will need serum bilirubin measurement. Evidence from studies supported by the manufacturer of BiliChek (tm), the newest device using the spectral reflectance technique, suggests that there is a linear correlation between transcutaneous bilirubin measured by BiliChek (tm) and total serum bilirubin as measured by the gold standard technique (i.e. HPLC). The correlation, however, is limited by gestational age of the neonate, as well as certain pathological neonatal conditions. Prospective cohort studies on the effectiveness of the technology in the reduction of hospital readmission, and using the incidence of morbidity and mortality from kernicterus as clinical endpoints, would be useful.