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BACKGROUND. Actinic keratosis is a precursor to cutaneous squamous cell carcinoma. Long treatment durations and severe side effects have limited the efficacy of current actinic keratosis treatments. Thymic stromal lymphopoietin (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity in barrier-defective skin. Here, we investigated the efficacy of calcipotriol, a topical TSLP inducer, in combination with 5-fluorouracil (5-FU) as an immunotherapy for actinic keratosis. METHODS. The mechanism of calcipotriol action against skin carcinogenesis was examined in genetically engineered mouse models. The efficacy and safety of 0.005% calcipotriol ointment combined with 5% 5-FU cream were compared with Vaseline plus 5-FU for the field treatment of actinic keratosis in a randomized, double-blind clinical trial involving 131 participants. The assigned treatment was self-applied to the entirety of the qualified anatomical sites (face, scalp, and upper extremities) twice daily for 4 consecutive days. The percentage of reduction in the number of actinic keratoses (primary outcome), local skin reactions, and immune activation parameters were assessed. RESULTS. Calcipotriol suppressed skin cancer development in mice in a TSLP-dependent manner. Four-day application of calcipotriol plus 5-FU versus Vaseline plus 5-FU led to an 87.8% versus 26.3% mean reduction in the number of actinic keratoses in participants (P < 0.0001). Importantly, calcipotriol plus 5-FU treatment induced TSLP, HLA class II, and natural killer cell group 2D (NKG2D) ligand expression in the lesional keratinocytes associated with a marked [CD4.sup.+] T cell infiltration, which peaked on days 10-11 after treatment, without pain, crusting, or ulceration. CONCLUSION. Our findings demonstrate the synergistic effects of calcipotriol and 5-FU treatment in optimally activating a [CD4.sup.+] T cell-mediated immunity against actinic keratoses and, potentially, cancers of the skin and other organs. TRIAL REGISTRATION. ClinicalTrials.gov NCT02019355. FUNDING. Not applicable (investigator-initiated clinical trial)., Introduction Thymic stromal lymphopoietin (TSLP) has emerged as a potent inducer of antitumor immunity in barrier-defective skin, as it has the potential to significantly improve the treatment of skin cancers [...]

Advances in the field of cancer immunology, including studies on tumor-infiltrating [CD8.sup.+] cytotoxic T lymphocytes (CTLs), have led to new immunotherapeutics with proven efficacy against late-stage cancers. However, the antitumor potential of the immune system in targeting early-stage cancers remains uncertain. Here, we demonstrated that both genetic and chemical induction of thymic stromal lymphopoietin (TSLP) at a distant site leads to robust antitumor immunity against spontaneous breast carcinogenesis in mice. Breast tumors exposed to high circulating levels of TSLP were arrested at an early adenoma-like stage and were prevented from advancing to late carcinoma and metastasis. Additionally, [CD4.sup.+] Th2 cells mediated the antitumor effects of TSLP, challenging the notion that Th2 cells only promote cancer. We also discovered that TSLP is expressed by the breast tumor cells themselves and acts to block breast cancer promotion. Moreover, TSLP-induced immunity also blocked early stages of pancreatic cancer development. Together, our findings demonstrate that TSLP potently induces immunity directed against early stages of breast cancer development without causing inflammation in the normal breast tissue. Moreover, our results highlight a previously unappreciated function of the immune system in controlling the early development of cancer and establish a fundamental role for TSLP and Th2 cells in tumor immunity against early-stage cancers., Introduction Studies of the immune response to late-stage cancers including the role of tumor-infiltrating [CD8.sup.+] cytotoxic T lymphocytes (CTLs) in attacking cancer cells have led to promising new cancer immunotherapeutics [...]

Background: Cryoneurolysis uses tissue cooling as an opioid-sparing, long-lasting treatment for peripheral nerve pain. A nerve-selective method for cryoneurolysis by local injection of ice-slurry was developed to allow cryoneurolysis to be performed with a standard needle and syringe, similar to peripheral nerve blocks. Since the treatment of patients with chronic pain may require repeated injections, we investigated the safety and tolerance of repeated treatments in a rat model. Methods: Three repeated ice-slurry treatments, given 6 weeks apart were performed around the rat sciatic nerve. Nerve and surrounding tissues were collected up to 4 months after the third treatment for analysis. Coherent anti-Stokes Raman scattering (CARS) microscopy was used to study effects on myelin sheaths and axon structure. Immunofluorescence (IF) staining was used to study effects on axon density. Hematoxylin and Eosin (H&E) staining was used to examine histologic effects on sciatic nerve and surrounding tissue. Results: Histologic and CARS image analysis of nerve tissue collected months after three injections demonstrated recovery of nerve structure, myelin organization and axon density to baseline levels, without any residual inflammation, scarring or neuroma formation. No inflammation or scarring was detected in surrounding skin and muscle tissues. Conclusion: Repeated ice-slurry injections cause temporary, nerve-selective and reversible changes in the peripheral nerve. There was no histologic damage to surrounding skin and muscle tissues. Repeated treatments with injectable ice-slurry for cryoneurolysis appear to be safe and well tolerated. Clinical studies for patients with chronic pain are warranted. [ABSTRACT FROM AUTHOR]

Background: Adherence to acne medication is poor and is a major reason why treatment plans are ineffective. Recognizing solutions to nonadherence is critical. Objective: The purpose of this study is to describe the hurdles associated with acne nonadherence and to provide mechanisms on how to ameliorate them. Methods: PubMed database was searched. Of the 419 search results, 29 articles were reviewed to identify hurdles to adherence and corresponding solutions. Results: Hurdles to primary nonadherence where the medication is not even started, include lack of knowledge, confusion about usage, weak physician-patient relationship, fear of adverse reactions, and cost. Secondary nonadherence hurdles where the medication is started but is not taken as directed include lack of results, complex regimens, side effects, busy lifestyle, forgetfulness, inconvenience, and psychiatric comorbidity. Solutions to these hurdles include treatment simplification, technology, and dynamic education. Limitations: Adherence is affected by numerous factors, but available literature analyzing acne adherence and interventions to improve adherence to treatment is limited. Conclusion: There are several hurdles in adhering to acne treatment. Recognition of these hurdles and finding appropriate solutions may be as important to treatment outcomes as choosing the right medication to prescribe. [ABSTRACT FROM AUTHOR]

Rosacea is a chronic dermatological disorder with a variety of clinical manifestations localized largely to the central face. The unclear etiology of rosacea fosters therapeutic difficulty; however, subtle clinical improvement with pharmacologic treatments of various drug categories suggests a multifactorial etiology of the disease. Factors that may contribute to disease pathogenesis include immune abnormality, vascular abnormality, neurogenic dysregulation, presence of cutaneous microorganisms, UV damage, and skin barrier dysfunction. The role of ivermectin in the treatment of rosacea may be as an anti-inflammatory and anti-parasitic agent targeting Demodex mites. In comparing topical ivermectin and metronidazole, ivermectin was more effective; this treatment modality boasted more improved quality of life, reduced lesion counts, and more favorable participant and physician assessment of disease severity. Patients who received ivermectin 1% cream had an acceptable safety profile. Ivermectin is efficacious in decreasing inflammatory lesion counts and erythema. [ABSTRACT FROM AUTHOR]

Background: Topical retinoids are first-line treatment options for acne vulgaris. These drugs, however, produce varying degree of cutaneous irritation within the first few weeks of treatment. Objective: Our purpose was to examine differences in tolerability of topical retinoids and assess whether these differences would be clinically meaningful. Methods: A PubMed search was performed for sources on topical retinoids in acne vulgaris treatment. Thirty-four clinical studies were analyzed. Results: Thirteen studies had statistically significant results on tolerability of retinoid based on retinoid, vehicle, concentration, or skin type. All studies classified most of skin reactions as mild-moderate. Large differences in the number of dropouts due to irritation were not identified. Conclusion: Irritation studies did not show a high frequency of clinically significant irritation with topical retinoids. We anticipate that the large variation in patient use of topical retinoids would likely account for more variation in response than differences between drug formulations. [ABSTRACT FROM AUTHOR]

A variety of triggers are thought to exacerbate rosacea. A validated self-assessment tool and survey was used to study the relationship between rosacea severity and triggers. Subjects were adult patients with a clinical diagnosis of rosacea. Increased severity of disease was significantly associated with consumption of many alcoholic beverages in 1 day and employment at a job requiring extensive sun exposure. The authors' findings may inform physician counseling practices; patients may be provided with practical measures for managing their rosacea, such as limiting alcohol consumption over short periods of time and increasing sun protection, especially in the summer., (Copyright © 2017 Elsevier Inc. All rights reserved.)