Review of talimogene laherparepvec: A first-in-class oncolytic viral treatment of advanced melanoma.

Talimogene laherparepvec (T-VEC) is an oncolytic virus based on herpes simplex virus type 1 approved for intralesional treatment of advanced melanoma. In this article, we review the clinical literature on T-VEC for advanced melanoma and provide a practical approach to using T-VEC in the dermatologic surgery and oncology clinic. PubMed was used to conduct a systematic literature review of articles describing the structure, basic science, and clinical and therapeutic properties of T-VEC. The national clinical trials database was also searched for T-VEC clinical trials. Phase I to III clinical trials and early real-world experience have shown the efficacy of T-VEC in advanced melanoma as single or combination therapy with tolerable adverse effects. We conclude that with a standardized clinical approach and training, dermatologists can pave the way in using T-VEC and future oncolytic virus therapies in appropriate clinical scenarios.

Idiopathic granulomatous mastitis.

Idiopathic granulomatous mastitis (IGM) is a rare, poorly understood condition that presents as inflammatory nodules of the breast. It is often initially misdiagnosed as furunculosis or cellulitis. Despite the painful, scarring, and debilitating nature of the disease, patients often have a delay in accurate diagnosis and treatment. Even when IGM is considered as a diagnosis, it is one of exclusion, with the differential diagnosis including serious conditions such as breast cancer, sarcoidosis, and cutaneous tuberculosis. Therefore, appropriate workup is important. Given that IGM is a disease of the skin, it is important for dermatologists to be familiar with its presentation. We describe 3 cases of young women with this condition and demonstrate that identification of triggers or methotrexate treatment is highly successful in sparing patients the drastic surgical alternative of mastectomy.

Relationship between subjective and actigraphy-measured sleep in 237 patients with metastatic colorectal cancer.

OBJECTIVE: Patients with cancers frequently experience sleep and circadian dysfunction. To date, only a few studies have used both a questionnaire and actigraphy for concomitant evaluation of sleep and circadian function in patients with cancer. We sought to evaluate objective sleep and circadian parameters in metastatic colon cancer (MCC) patients and their associations with symptoms and quality of life (QOL). METHODS: Patients reported subjective sleep problems on the EORTC QLQ-C30. Sleep and circadian parameters were calculated using a wrist-actigraph that patients wore for 72 h. RESULTS: 237 Patients with MCC (mean age: 60.4 years; range: 20.7-77.6; Male/Female ratio: 1.66) participated in this cross-sectional study. Subjective sleep problems were reported by 63.4% of patients (S+). No differences in any sleep parameters (sleep efficiency, sleep latency, total sleep time, total time in bed, wake after sleep onset, activity bathyphase) were observed between S+ and S- patients. However, S+ patients displayed a significantly worse circadian function than S- patients (96.4 vs 98.1%; p = 0.005). The presence of poor subjective sleep and objective circadian dysfunction negatively affected symptoms and QOL domains (p = 0.038). CONCLUSIONS: Subjective report of sleep problems was not associated with worse objectively measured sleep parameters in patients with MCC although it was associated with disrupted circadian rest-activity rhythm and poorer QOL. These findings coincide with prior research in cancer patients in that an inconsistent relationship exists between subjective and objective sleep measurements on some sleep domains. This study supports the value of coupled evaluation of self-reported and objective measures of sleep and circadian function in cancer patients.

Docosahexaenoic Acid alleviates atopic dermatitis in mice by generating T regulatory cells and m2 macrophages.

Han et al. (this issue) describe a novel mechanism by which docosahexaenoic acid (DHA) may suppress atopic dermatitis symptoms in mice. They find that DHA induces FoxP3 T regulatory cells in vivo, M2 macrophages drive transforming growth factor-ß and IL-10 conversion of CD4 T cells to CD4 FoxP3 T regulatory cells in vitro, and DHA-treated M2 macrophages suppress atopic dermatitis in mice.

Test-retest and interrater reliability of the functional lower extremity evaluation.

STUDY DESIGN: Repeated-measures clinical measurement reliability study. OBJECTIVES: To establish the reliability and face validity of the Functional Lower Extremity Evaluation (FLEE). BACKGROUND: The FLEE is a 45-minute battery of 8 standardized functional performance tests that measures 3 components of lower extremity function: control, power, and endurance. The reliability and normative values for the FLEE in healthy athletes are unknown. METHODS: A face validity survey for the FLEE was sent to sports medicine personnel to evaluate the level of importance and frequency of clinical usage of each test included in the FLEE. The FLEE was then administered and rated for 40 uninjured athletes. To assess test-retest reliability, each athlete was tested twice, 1 week apart, by the same rater. To assess interrater reliability, 3 raters scored each athlete during 1 of the testing sessions. Intraclass correlation coefficients were used to assess the test-retest and interrater reliability of each of the FLEE tests. RESULTS: In the face validity survey, the FLEE tests were rated as highly important by 58% to 71% of respondents but frequently used by only 26% to 45% of respondents. Interrater reliability intraclass correlation coefficients ranged from 0.83 to 1.00, and test-retest reliability ranged from 0.71 to 0.95. CONCLUSION: The FLEE tests are considered clinically important for assessing lower extremity function by sports medicine personnel but are underused. The FLEE also is a reliable assessment tool. Future studies are required to determine if use of the FLEE to make return-to-play decisions may reduce reinjury rates.

Insulin-like growth factor II peptide fusion enables uptake and lysosomal delivery of α-N-acetylglucosaminidase to mucopolysaccharidosis type IIIB fibroblasts.

Enzyme replacement therapy for MPS IIIB (mucopolysaccharidosis type IIIB; also known as Sanfilippo B syndrome) has been hindered by inadequate mannose 6 phosphorylation and cellular uptake of rhNAGLU (recombinant human α-N-acetylglucosaminidase). We expressed and characterized a modified rhNAGLU fused to the receptor-binding motif of IGF-II (insulin-like growth factor 2) (rhNAGLU-IGF-II) to enhance its ability to enter cells using the cation-independent mannose 6-phosphate receptor, which is also the receptor for IGF-II (at a different binding site). RhNAGLU-IGF-II was stably expressed in CHO (Chinese-hamster ovary) cells, secreted and purified to apparent homogeneity. The Km and pH optimum of the fusion enzyme was similar to those reported for rhNAGLU. Both intracellular uptake and confocal microscopy suggested that MPS IIIB fibroblasts readily take up the fusion enzyme via receptor-mediated endocytosis that was inhibited significantly (P<0.001) by the monomeric IGF-II peptide. Glycosaminoglycan storage was reduced by 60% (P<0.001) to near background levels in MPS IIIB cells after treatment with rhNAGLU-IGF-II, with half-maximal correction at concentrations of 3-12 pM. A similar cellular uptake mechanism via the IGF-II receptor was also demonstrated in two different brain tumour-derived cell lines. Fusion of rhNAGLU to IGF-II enhanced its cellular uptake while maintaining enzymatic activity, supporting its potential as a therapeutic candidate for treating MPS IIIB.