Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration

Background: Stressed and hospitalized goats are at risk of developing abomasal (gastric) ulceration, but there is a paucity of pharmacokinetic studies for proton pump inhibiting drugs, such as, esomeprazole in goats. Objectives: The objectives for this study were to estimate plasma pharmacokinetic parameters for esomeprazole in adult goats after intravenous (IV) and subcutaneous (SQ) administration. A secondary objective was to describe the plasma kinetics of the metabolite esomeprazole sulfone after IV and SC administration in goats. Materials and methods: Esomeprazole was administered to 5 adult goats in a crossover study at doses of 1 mg/kg IV or 2 mg/kg SC. Plasma samples were collected over 36 h and analyzed via reverse phase HPLC to determine concentrations of esomeprazole and esomeprazole sulfone. Pharmacokinetic parameters were derived via non-compartmental analysis. Results: Following IV administration, mean values for plasma clearance (Cl), elimination half-life [T1/2 (λz)], C0, and volume of distribution (Vz) of esomeprazole were estimated at 24.9 mL/min/kg, 6 min, 2.324 μg/mL, and 0.23 L/kg, respectively. After SC administration elimination half-life, maximum concentration (Cmax) and time to maximum concentration (Tmax) of esomeprazole were estimated at 29 min, 1.038 μg/mL, and 22 minutes respectively. Maximum concentrations of the sulfone metabolite were 32 and 18 ng/mL after IV and SC administration. Conclusion: Esomeprazole was rapidly eliminated from plasma after both IV and SC injection in goats. The elimination half-life in goats appears to be shorter than reported in dogs, as well as less than that reported for pantoprazole in goats. The sulfone metabolite was detected and also rapidly eliminated from the plasma after both IV and SC administration. Additional pharmacodynamic investigations are needed to determine the efficacy of esomeprazole on abomasal (gastric) acid suppression in goats and could include larger doses or additional routes of administration

Combination Topical Chemotherapy for the Treatment of an Invasive Cutaneous Squamous Cell Carcinoma

Introduction: Standard of care for squamous cell carcinoma (SCC) is usually surgical, with either excision or Mohs micrographic surgery. However, surgery may not be ideal for elderly patients with numerous lesions, who are poor surgical candidates or who refuse surgery. Topical 5-fluorouracil (5-FU) and imiquimod have been studied off-label as monotherapies in the treatment of SCC in situ with promising results. However, long-term tumor-free survival rates are still less than with surgical management. Methods: We report a case of biopsy-proven invasive SCC in an 86-year-old Caucasian male with history of multiple actinic keratoses and no previous skin cancers. The patient declined surgical treatment due to concerns about cosmetic outcomes. A combination of topical 5% imiquimod cream, 2% 5-FU solution, and 0.1% tretinoin cream was used five nights per week under occlusion for a treatment goal of 30 total applications. The patient was evaluated in clinic every 2 weeks during which the site was treated with cryotherapy. The patient reported burning pain associated with treatment and only completed 24 of the 30 applications. Results: Follow-up biopsy 15 months after completing topical treatment revealed dermal scar with no evidence of residual carcinoma. Conclusion: Topical combination therapy with imiquimod, 5-FU, and tretinoin with intermittent, brief cryotherapy effectively treated a small, invasive SCC in this select patient who deferred surgery. Prospective randomized-controlled clinical trials to assess the role of combination topical treatment for invasive SCCs are warranted. J Drugs Dermatol. 2020;19(2)202-204. doi:10.36849/JDD.2020.222

Malignancy risk of non-biologic immunosuppressive therapies: A review of the literature with evidence-based treatment recommendations

Non-biologic immunosuppressive therapies are a mainstay in the treatment of various dermatologic conditions. However, the use of these therapies has been scrutinized for potentially increasing risk of haematologic or solid-organ malignancies. Currently, there are no evidence-based guidelines stratifying the risk of malignancy in patients receiving these immunosuppressive agents for the treatment of dermatologic disease. In our review, we evaluate the risk of solid organ and haematologic malignancies in patients receiving non-biologic immunosuppressant therapy for dermatologic indications. A literature search was conducted on PubMed/MEDLINE. Search terms included commonly prescribed non-biologic immunosuppressants and common dermatologic conditions for which non-biologic immunosuppressants are typically prescribed. Levels of evidence and grades of recommendation were used for guidelines. All immunosuppressants evaluated, with the exception of cyclophosphamide, demonstrated low solid-organ or haematologic malignancy potential. Co-morbidities may play a role in malignancy risk in the context of immunosuppressant treatment, including autoimmune disease, which have been associated with increased risk of malignancy and confound overall risk. Duration and/or dosage of treatment may influence this risk as well. Limitations of the review include that the majority of studies were of small sample size, retrospective in nature, and there was lack of direct comparison trials

The Potential Impact of Social Genomics on Wound Healing

Significance: Human skin wounds carry an immense epidemiologic and financial burden, and their impact will continue to grow with an aging population and rising incidence of comorbid conditions known to affect wound healing. To comprehensively address this growing clinical issue, physicians should also be aware of how conditions of the human social environment may affect wound healing. Here we provide a review of the emerging field of social genomics and its potential impact on the wound healing. Recent Advances: Multiple studies using human and animal models have correlated social influences and their contributing effects to acute and chronic stress with delays in wound healing. Furthermore, observations between nongenetic factors such as nutrition, socioeconomic, and educational status have also shown to have a direct or indirect impact on clinical outcomes of wound healing. Critical Issues: Nutrition, financial burden, socioeconomic and education status, and acute and chronic stress are variables that have either direct (epigenetic) or indirect impact on wound healing and patients' quality of life. Wound care is costly and remains a challenge placing economic burden on patients. Furthermore, poor clinical outcomes and complications including loss of mobility and disability may lead to job loss, further contributing to socioeconomic related stress. Thus, the economic burden and inadequate wound healing are intertwined, making each other worse. Future Directions: Although some evidence regarding the specific changes in genetic pathways imparted by conditions of the social environment exists, further studies are warranted to identify potential mechanisms, interventions, and prevention approaches

Laser and Light Treatments for Hair Reduction in Fitzpatrick Skin Types IV-VI: A Comprehensive Review of the Literature

Unwanted facial and body hair presents as a common finding in many patients, such as females with hirsutism. With advances in laser and light technology, a clinically significant reduction in hair can be achieved in patients with light skin. However, in patients with darker skin, Fitzpatrick skin types (FST) IV-VI, the higher melanin content of the skin interferes with the proposed mechanism of laser-induced selective photothermolysis, which is to target the melanin in the hair follicle to cause permanent destruction of hair bulge stem cells. Many prospective and retrospective studies have been conducted with laser and light hair-removal devices, but most exclude patients with darkly pigmented skin, considering them a high-risk group for unwanted side effects, including pigmentation changes, blisters, and crust formation. We reviewed the published literature to obtain studies that focused on hair reduction for darker skin types. The existing literature for this patient population identifies longer wavelengths as a key element of the treatment protocol and indicates neodymium-doped yttrium aluminum garnet (Nd:YAG), diode, alexandrite, and ruby lasers as well as certain intense pulsed light sources for safe hair reduction with minimal side effects in patients with FST IV-VI, so long as energy settings and wavelengths are appropriate. Based on the findings in this review, safe and effective hair reduction for patients with FST IV-VI is achievable under proper treatment protocols and energy settings

Efficacy of fractional lasers in treating alopecia: a literature review

Hair loss stemming from different types of alopecia, such as androgenic alopecia and alopecia areata, negatively affects over half the population and, in many circumstances, causes serious psychosocial distress. Current treatment options for alopecia, such as minoxidil, anthralin, and intralesional corticosteroids, vary efficacy and side effect profiles. It is known that low-level laser/light therapies (LLLT), or photobiomodulations, such as the US FDA-cleared HairMax Lasercomb®, He-Ne laser, and excimer laser, are relatively affordable, user-friendly, safe, and effective forms of treatment for hair loss. While less is known about the effectiveness of fractional lasers for combating hair loss, research suggests that by creating microscopic thermal injury zones, fractional lasers may cause an increase in hair growth from a wound healing process, making them potential therapeutic options for alopecia. A literature review was performed to evaluate the effectiveness of fractional lasers on hair regrowth. The specific fractional laser therapies include the 1550-nm nonablative fractional erbium-glass laser, the ablative fractional 2940-nm erbium:YAG laser, and the ablative fractional CO fractional laser. Additional randomized controlled trials are necessary to further evaluate the effectiveness of the lasers, as well as to establish appropriate parameters and treatment intervals

The Role of Completion Lymphadenectomy in Positive Regional Lymph Nodes in Melanoma: A Meta-analysis

The optimal management of melanoma with positive sentinel lymph node (SLN) remains unclear. Completion lymph node dissection (CLND) only yields additional positive non-SLN in 20% of cases and its benefits on survival remains debatable. An online database search of Medline was performed; key bibliographies were reviewed. Studies comparing outcomes after CLND versus observation were included. Odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) by random fixed effects models of pooled data were calculated. The primary endpoints were disease-free survival (DFS), melanoma-specific survival (MSS), and overall survival (OS). Search strategy yielded 117 publications. Twelve studies were selected for inclusion, comprising 7966 SLN-positive patients. Among these patients, 5306 (66.6%) subjects underwent CLND and 2660 (33.4%) patients were observed. Median Breslow thickness and ulceration were similar between groups (2.8 ± 0.6 mm versus 2.5 ± 0.8 mm, P = 0.721; and 38.8% versus 37.2%, P = 0.136, CLND versus observation, respectively). CLND was associated with statistically significant improved 3-y (71.0% versus 66.2%, OR 0.82, 95% CI 0.69-0.97, P = 0.02) and 5-y DFS (48.3% versus 47.8%, OR 0.75, 95% CI 0.59-0.96, P = 0.02) compared with observation. However, no difference was demonstrated in 3-y MSS (83.7% versus 84.7%, OR 1.09, 95% CI 0.88-1.35, P = 0.41), 5-y MSS (68.4% versus 69.8%, OR 1.02, 95% CI 0.88-1.19, P = 0.78), or OS (68.2% versus 78.9%, OR 0.93, 95% CI 0.55-1.57, P = 0.78). Based on this large-scale analysis, CLND improved both 3- and 5-y DFS, possibly because of increased rates of local control; however, this did not translate in improved MSS or OS. Efforts toward the identification of molecular markers associated with poor outcomes in SLN-positive patients who undergo observation are warranted