Value of ultrasonography in laryngeal and laryngopharyngeal cancers

High-resolution sonography has improved in the past few years and has become a very valuable tool in the diagnosis of diseases of the head and neck. Ultrasonography (US) is commonly the first imaging modality after clinical examination. It is inexpensive, noninvasive and is easily tolerated by patients. It provides valuable diagnostic information with a high degree of diagnostic accuracy. This article provides the most up-to-date information about the indications, findings and limitations of high-resolution sonography in the evaluation of laryngeal and laryngopharyngeal cancers.     

Epstein–Barr virus patterns in US Burkitt lymphoma tumors from the SEER residual tissue repository during 1979–2009

Burkitt lymphoma (BL) occurs at all ages, but the patterns of Epstein–Barr virus (EBV) positivity in relation to human immunodeficiency virus (HIV), immunoprofiles and age have not been fully explored. BL tissues from residual tissue repositories, and two academic centers in the United States were examined by expert hematopathologists for morphology, immunohistochemistry, MYC rearrangement, EBV‐encoded RNA (EBER), and diagnosed according to the 2008 WHO lymphoma classification. Analysis was done using frequency tables, Chi‐squared statistics, and Student's t‐test. Of 117 cases examined, 91 were confirmed as BL. The age distribution was 26%, 15%, 19%, and 29% for 0–19, 20–34, 35–59, 60+ years, and missing in 11%. MYC rearrangement was found in 89% and EBER positivity in 29% of 82 cases with results. EBER positivity varied with age (from 13% in age group 0–19 to 55% in age group 20–34, and fell to 25% in age group 60+ years, p = 0.08); with race (56% in Blacks/Hispanics vs 21% in Whites/Asians/Pacific Islanders, p = 0.006); and by HIV status (64% in HIV positive vs 22% in HIV negative cases, p = 0.03). EBER positivity was demonstrated in about one‐third of tumors and it was strongly associated with race and HIV status, and marginally with age‐group.     

Value of ultrasonography in laryngeal and laryngopharyngeal cancers

High-resolution sonography has improved in the past few years and has become a very valuable tool in the diagnosis of diseases of the head and neck. Ultrasonography (US) is commonly the first imaging modality after clinical examination. It is inexpensive, noninvasive and is easily tolerated by patients. It provides valuable diagnostic information with a high degree of diagnostic accuracy. This article provides the most up-to-date information about the indications, findings and limitations of high-resolution sonography in the evaluation of laryngeal and laryngopharyngeal cancers.     

Sifalimumab,a Human Anti–Interferon‐α Monoclonal Antibody,in Systemic Lupus Erythematosus: A Phase I Randomized,Controlled, Dose‐Escalation Study

Objective

To evaluate the safety and tolerability of multiple intravenous (IV) doses of sifalimumab in adults with moderate‐to‐severe systemic lupus erythematosus (SLE).

Methods

In this multicenter, double‐blind, placebo‐controlled, sequential dose‐escalation study, patients were randomized 3:1 to receive IV sifalimumab (0.3, 1.0, 3.0, or 10.0 mg/kg) or placebo every 2 weeks to week 26, then followed up for 24 weeks. Safety assessment included recording of treatment‐emergent adverse events (AEs) and serious AEs. Pharmacokinetics, immunogenicity, and pharmacodynamics were evaluated, and disease activity was assessed.

Results

Of 161 patients, 121 received sifalimumab (26 received 0.3 mg/kg; 25, 1.0 mg/kg; 27, 3.0 mg/kg; and 43, 10 mg/kg) and 40 received placebo. Patients were predominantly female (95.7%). At baseline, patients had moderate‐to‐severe disease activity (mean SLE Disease Activity Index score 11.0), and most (75.2%) had a high type I interferon (IFN) gene signature. In the sifalimumab group versus the placebo group, the incidence of ≥1 treatment‐emergent AE was 92.6% versus 95.0%, ≥1 serious AE was 22.3% versus 27.5%, and ≥1 infection was 67.8% versus 62.5%; discontinuations due to AEs occurred in 9.1% versus 7.5%, and death occurred in 3.3% (n = 4) versus 2.5% (n = 1). Serum sifalimumab concentrations increased in a linear and dose‐proportional manner. Inhibition of the type I IFN gene signature was sustained during treatment in patients with a high baseline signature. No statistically significant differences in clinical activity (SLEDAI and British Isles Lupus Assessment Group score) between sifalimumab and placebo were observed. However, when adjusted for excess burst steroids, SLEDAI change from baseline showed a positive trend over time. A trend toward normal complement C3 or C4 level at week 26 was seen in the sifalimumab groups compared with baseline.

Conclusion

The observed safety/tolerability and clinical activity profile of sifalimumab support its continued clinical development for SLE.

     

Adding ultralow-dose naltrexone to oxycodone enhances and prolongs analgesia: a randomized, controlled trial of Oxytrex.

Oxytrex is a novel drug that combines oxycodone with ultralow-dose naltrexone, an opioid antagonist. Ultralow-dose opioid antagonists have been demonstrated to enhance and prolong opiate analgesia and alleviate opioid tolerance and withdrawal in rodents. This 3-week, Phase II clinical trial assessed safety and analgesic efficacy of Oxytrex in patients with moderate to severe pain from osteoarthritis. Patients with a pain score > or =5 received placebo, oxycodone 4 times a day (qid), Oxytrex qid, or Oxytrex twice a day (bid). All active treatment groups received the same total daily dose and dose escalation of oxycodone starting at 10 and ending at 40 mg/day. Importantly, the Oxytrex bid group received a lower daily dose of naltrexone than Oxytrex qid (0.002 vs 0.004 mg/day). Oxytrex bid produced a 39% reduction in pain intensity, which was significantly greater than that of placebo (P < .001), oxycodone qid (P = .006), and Oxytrex qid (P = .003). Oxytrex bid was also superior to placebo in quality of analgesia (P = .002), duration of pain control each day (P = .05), patients' global assessments (P = .04), and the Western Ontario and MacMaster Universities Osteoarthritis Index total score (P = .03). The incidence of side effects was comparable between active treatments. In this Phase II dose-ranging study, Oxytrex bid demonstrated greater pain relief with a more convenient dosing schedule compared to oxycodone qid. PERSPECTIVE: Preclinical data have shown ultralow-dose opioid antagonists to enhance and prolong opioid analgesia while reducing analgesic tolerance and physical dependence. Recent molecular pharmacology data show a mechanism of action to be the prevention of aberrant G protein coupling by opioid receptors that underlies opioid tolerance and dependence.     

Examining the relationship between bone mineral density and fracture risk reduction during pharmacologic treatment of osteoporosis

Osteoporosis is a skeletal disorder characterized by compromised bone strength that predisposes the patient to an increased risk for fracture. Elements of bone strength include bone mineralization, architecture, turnover, size, and bone mineral density (BMD). Measurement of BMD is the most readily available, noninvasive method for assessing osteoporotic fracture risk and is used by the World Health Organization for diagnostic purposes. Because low BMD is predictive of increased fracture risk, it was believed that changes in BMD during pharmacologic therapy for osteoporosis would strongly predict observed fracture risk reductions. We examined the relationship between changes in BMD and reduction in fracture risk during pharmacologic therapy in postmenopausal women with osteoporosis. The correlation between BMD increases and fracture risk reduction during treatment is not consistent; larger increases in BMD do not necessarily correlate with greater reductions in fracture risk. Multiple factors, in addition to BMD, appear to contribute to the increased bone strength and decreased fracture risk achieved with approved drug therapies for osteoporosis. Until the exact relationship of these factors is fully understood, clinicians should continue to evaluate drug efficacy for osteoporosis based on the fracture risk reductions from well-designed clinical trials.