Review of diagnostic,prognostic, and predictive biomarkers in melanoma

Melanoma is an aggressive cutaneous malignancy with rapidly rising incidence. Diagnosis of controversial melanocytic lesions, correct prognostication of patients, selection of appropriate adjuvant and systemic therapies, and prediction of response to a given therapy remain very real challenges. Despite these challenges, multiple high throughput, nucleic-acid based biomarkers have been developed that can be assayed from histologic tissue specimens. FISH, CGH, Decision-Dx, and other multi-marker assays have been combined to improve overall predictability. This review discusses some of the most promising nucleic acid based assays that can be obtained from tissue specimens to assist with diagnosis, prognostication, and prediction of treatment response.     

The First Reported Case of Anti-Dob Causing an Acute Hemolytic Transfusion Reaction

The antibodies of the Dombrock blood group system have only rarely been encountered in transfusion practice, and anti-Do^b has not previously been implicated in an acute hemolytic transfusion reaction. We have encountered the first such case involving a chronically transfused black female with hemoglobin SS disease and multiple antibodies in her serum. During a previous admission for sickle cell crisis, the patient received 3 units of compatible blood with no untoward effects. Serum obtained 21 days later contained, in addition to the known antibodies, anti-S plus an unidentified antibody showing characteristics of HTLA. Blood lacking the E, K1, Fy(a), Jk(b) and S antigens was obtained, and 2 least incompatible units were transfused. While administering the second unit, the patient complained of fever and low back pain, and hemoglobinemia was detected. Anti-Do^b was identified in the post-reaction samples by absorption-elution tests, and the patient was confirmed to be Do(a+b–). The first unit transfused during this hemolytic episode tested Do (b+). This case, and a similar case involving anti-Do^a reported in 1986, strengthens the belief that Dombrock antibodies are clinically significant and illustrates the need for their differentiation, prior to transfusion from less clinically significant HTLA antibodies.     

Oritavancin for acute bacterial skin and skin structure infections

Introduction: Inpatient treatment of acute bacterial skin and skin structure infections (ABSSSIs) exerts a significant economic burden on the healthcare system. Oritavancin is a concentration-dependent, rapid bactericidal agent approved for the treatment of ABSSSIs. Its prolonged half-life with one-time intravenous (i.v.) dosing offers a potential solution to this burden. In addition, oritavancin represents an alternative therapy for Streptococci and multidrug-resistant Gram-positive bacteria including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Animal models have also shown promising results with oritavancin for other disease states including those that require long courses of i.v. therapy.

Areas covered: This review covers oritavancin’s basic chemistry, spectrum of activity, pharmacodynamics/pharmacokinetics and efficacy in clinical trials, and provides expert opinion on future directions. To compose this review, a search of PubMed was performed, and articles written in the English language were selected based on full text availability.

Expert opinion: If oritavancin is proven to be a cost-effective strategy for outpatient treatment and prevents complications of prolonged i.v. therapy, it will be sought as an alternative antibiotic therapy for ABSSSIs. In addition, further clinical data demonstrating efficacy in Gram-positive infections requiring prolonged therapy such as endocarditis and osteomyelitis could support oritavancin’s success in the current market.     

A critical appraisal of daclizumab use as emerging therapy in multiple sclerosis

Introduction: Daclizumab (DAC) is a mAb that binds to CD25, a receptor on the surface of lymphocytes for IL-2, a chemical messenger in the immune system. This prevents activation and proliferation of lymphocytes, which are involved in the immune attack in multiple sclerosis (MS).

Areas covered: In this review, we will focus on newly emerging DAC-high-yield process (HYP) therapy for MS. Based on published original articles and citable meeting abstracts, we will discuss its mode of action as well as data on efficacy and safety.

Expert opinion: DAC has been observed to have multiple (biological) effects, which may contribute to beneficial effects in immune-related disease and particularly in relapsing-remitting MS. The positive results in the clinical studies represent achievement of an important milestone in the development of DAC-HYP as a potential new treatment option for MS patients. The benefit/risk ratios of this new biological agent in MS therapy are still being evaluated. Soon, DAC-HYP might qualify as MS therapy. A safety monitoring program is recommended in the clinical practice.     

Prevalence and risk of colorectal neoplasia in consumers of alcohol in a screening population

BACKGROUND AND AIMS: Although studies suggest a positive association between alcohol consumption and risk for colorectal neoplasia, the impact on screening has not been fully examined. It is also unclear whether all types of alcohol are associated with an increased risk. We performed a cross-sectional study to examine the impact of regular alcohol consumption on the detection of significant colorectal neoplasia in a screening population. METHODS: Data collected for 2,291 patients presenting for screening colonoscopy: known risk factors for colorectal neoplasia and alcohol drinking pattern. Our outcome was the endoscopic detection of significant colorectal neoplasia, which included adenocarcinoma, high-grade dysplasia, villous tissue, adenomas 1 cm or greater and multiple (>2) adenomas of any size. RESULTS: When compared to abstainers, we found an increased risk for significant neoplasia in those patients who consumed more than eight drinks of spirits alcohol (26.3%; OR = 2.53; 95% CI = 1.10-4.28; p < 0.01) and those who drank more than eight servings of beer per week (21.7%; OR = 2.43; 95% CI = 1.11-5.32; p= 0.02). Consuming one to eight glasses of wine per week was associated with a decreased risk for significant neoplasia (OR = 0.55; 95% CI = 0.34-0.87; p < 0.01). CONCLUSIONS: While there was a more than twofold increased risk of significant colorectal neoplasia in people who drink spirits and beer, people who drank wine had a lower risk. In our sample, people who drank more than eight servings of beer or spirits per week had at least a one in five chance of having significant colorectal neoplasia detected by screening colonoscopy.