A randomized, phase 1, placebo-controlled trial of APG-157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor-associated microbes.

BACKGROUND: Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target. METHODS: A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity. RESULTS: Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1ß, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment. CONCLUSIONS: The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy. LAY SUMMARY: Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.

Low-dose amitriptyline for treatment of persistent arm pain due to repetitive use.

Amitriptyline is sometimes used to treat arm pain related to repetitive use, but rigorous evidence of its benefit is lacking. This randomized controlled trial investigated whether amitriptyline provided greater pain relief or improved arm function than a placebo pill in adults with arm pain associated with repetitive use that had persisted for at least 3 months. Participants (N=118) were randomly assigned to receive 25mg of amitriptyline or a placebo pill for 6 weeks. The primary outcome was intensity of pain (10-point numerical rating scale) and secondary outcomes were arm symptoms, arm function, grip strength, mood, and sleep. Assessments were done at baseline, 3 and 6 weeks of treatment, and 1 month after the treatment ended. Changes in arm pain were not statistically significant. However, the amitriptyline group improved more than the placebo group in arm function (p=0.023) and sense of well being (p=0.034). In a longitudinal analysis, the amitriptyline group's arm function score improved 0.45 points per week faster than placebo after adjusting for subject characteristics (p=0.015). At the treatment's midpoint, the amitriptyline group reported more "troublesome side-effects" than the placebo group (52.5% vs. 27.1%, p=0.005), but this difference decreased by the end of the treatment (30.5% vs. 22.0%, p=0.30). The most frequent side effect was drowsiness. In conclusion, this study found that low-dose amitriptyline did not significantly decrease arm pain among these participants but did significantly improve arm function and well being. Future research is needed to explore the effects of higher doses and longer duration of treatment.

Latex paint-gun injuries of the hand: are the outcomes better?

This study aims to present the functional outcome in patients who sustained paint-gun injuries to the hand with latex paint and review the current trends, recommendations, and pitfalls of surgical treatment in contemporary literature. Five male patients with an average age of 35 years were treated between 2000 and 2003 after sustaining a paint-gun injury with latex paint. All wounds were located volarly on the digits of the nondominant hand. Preoperative radiographs were obtained in every patient. All patients underwent debridement of the affected digit. Despite delayed presentation, more than 24 h post injury, our patients recovered substantial function at an average follow-up of 12 months. Every patient returned to his previous occupation and there were no amputations. Paint-gun injuries with latex paint appear to be associated with an outcome that is superior to the poor outcome traditionally associated with oil-based paints.

Closed traumatic rupture of the extensor digitorum communis and extensor indicis proprius at the musculo-tendinous junction.

This report describes a closed rupture of the entire extensor digitorum communis and extensor indicis proprius.

Volar open reduction of complex metacarpophalangeal dislocation of the index finger: a pictorial essay.

Dislocations of the metacarpophalangeal joint are uncommon and usually caused by significant trauma. The distinction between subluxations and dislocations is critical. Complex dislocations require surgical reduction. The need for surgical reduction is primarily due to the anatomy of this region, which contributes to the complexity of this injury and to the degree of difficulty in its reduction. This pictorial essay aims to highlight the clinical, radiographic, and surgical features of this uncommon yet complex injury.