Disorders of skin pigmentation exist across a broad spectrum and include manifestations of hypopigmentation and hyperpigmentation in a variety of benign and malignant contexts. Ultraviolet (UV) radiation is arguably one of the best-understood carcinogens and carries the dubious distinction of being one the most common carcinogenic exposures for man. UV also functions as a significant modulator of

Background/Aims: There is limited data regarding trimethoprim (TMP)/sulfamethoxazole (SMX) continuous renal replacement therapy (CRRT) dosing. We aimed to estimate TMP/SMX transmembrane clearance (CLtm) during continuous hemofiltration (CH) and continuous hemodialysis (CD) to guide dosing. Methods: Using an in vitro model, TMP/SMX sieving coefficients (SC) and saturation coefficients (SA) were determined with high-flux polyarylethersulfone and polyacrylonitrile-sodium methallyl sulfonate copolymer hemodiafilters at ultrafiltration/dialysate rates of 1, 2, 3, and 6 l/h. TMP/SMX CLtm was calculated using measured SC and SA. TMP/SMX CRRT doses were modeled using CLtm and published TMP/SMX pharmacokinetic parameters. Results: TMP SC/SA during CH/CD were significantly higher than SMX SC/SA. During modeling, TMP 10 mg/kg/day and its corresponding SMX dose, 50 mg/kg/day, resulted in steady state TMP/SMX peak concentrations associated with efficacy against Pneumocystis jirovecii. Conclusions: CRRT resulted in greater TMP CLtm than SMX. TMP 10 mg/kg/day divided q12h may be an appropriate initial dose to consider in patients undergoing CRRT.

In an effort to understand the difference between melanomas diagnosed in Australia (New South Wales) and Canada, where the incidence in New South Wales is almost three times greater than in Canada, and mortality is twice as high although survival is slightly more favorable, we had one pathologist review 1,271 melanomas from British Columbia and Ontario, Canada, to compare these to melanomas in New South Wales, Australia. We hypothesized that histopathologic characteristics might provide insight into divergent pathways to melanoma development. We found a number of differences in risk factors and tumor characteristics between the two geographic areas. There were higher mole counts and darker phenotypes in the Canadian patients, while the Australian patients had greater solar elastosis, more lentigo maligna melanomas, and more tumor infiltrating lymphocytes. We hypothesize that the differences observed may illustrate different etiologies e the cumulative exposure pathway among Australian patients and the nevus pathway among Canadian patients. This is one of the largest studies investigating the divergent pathway hypothesis and is particularly robust due to the evaluation of all lesions by one dermatopathologist.

At the start of the COVID-19 pandemic, the Centers for Disease Control and Prevention issued recommendations to decrease the spread of SARS-CoV-2 and optimize the use of personal protective equipment (PPE) for frontline workers. 1 In the field of dermatologic surgery, the American College of Mohs Surgery, the National Comprehensive Cancer Network, the American Society for Dermatologic Surgery, and the American Academy of Dermatology made recommendations to postpone nonessential and nonurgent procedures. [2][3][4] The initial guidelines of the American College of Mohs Surgery advised cancellation of all elective surgeries and deferred treatment of most cases of basal cell carcinoma for as long as 3 months; low-risk squamous cell carcinoma (SCC) and melanoma in situ treatment was deferred for as long as 2 or 3 months. 3 Additional recommendations were made to reserve inpatient visits for

Breslow thickness and histopathologic subtype in a large international population-based study of melanoma To the Editor: As of 2019 National Cancer Institute data show that melanoma is the fifth most common cancer in the United States. 1 There has been a recent push to include the histopathologic subtype of nodular melanoma as an independent prognostic classifier due to the identification of associated aggressive histopathologic characteristics and shorter recurrence-free times. 2,3 We used the population-based, Genes, Environment, and Melanoma (GEM) study, 4 to assess the levels of agreement between community pathologists, those who originally diagnosed the melanoma, and expert study dermatopathologists, who reviewed the lesion for complete histology, histopathologic subtype, and Breslow thickness. The salient components of the GEM study were that it was population-based, multi-country size, and included disease-specific mortality data and rereview of hematoxylin-eosinestained tissues by dermatopathologists. We evaluated how histopathologic subtype misclassification might impact the reported disease-specific mortality.Our study included 1957 individuals with a first primary melanoma diagnosed in the year 2000, at centers of the GEM study in Australia, Canada, Italy, and the United States. The Institutional Review Board approval was obtained, and the subjects signed written consent. Each patient had their hematoxylin-eosinestained slides read initially by a community pathologist, who reported Breslow thickness and histopathologic subtype followed by an independent review by a dermatopathologist, blinded to the community pathologist report. The vital status was obtained at an average of 7.4 years.Within the study population and lethal melanoma cases, descriptive statistics were calculated and the frequency tables that compared the kappa value for the readings of community pathologists and