Spesolimab, A Novel Interleukin-36 Inhibitor for Generalized Pustular Psoriasis Flares in Adult Patients.

Generalized pustular psoriasis (GPP) is a rare, immune-mediated inflammatory disease with characteristic cutaneous and systemic manifestations. Mutations in the interleukin-36 receptor antagonist (IL36RN) gene have been implicated in its pathogenesis. Spesolimab is a novel systemic biologic therapy that selectively inhibits interleukin-36. It was recently approved by Health Canada and the US FDA for the treatment of GPP flares in adults. Results from phase 1 and 2 studies have been promising. Herein, we review the efficacy and safety of spesolimab for the treatment of GPP flares, as demonstrated in clinical trials.

Tralokinumab for Moderate-to-Severe Atopic Dermatitis in Adults.

Atopic dermatitis (AD) is a common, chronic, recurrent, immune-mediated inflammatory skin disease. Targeted treatment options remain limited. Tralokinumab (Adtralza®) is a promising, new systemic therapy that inhibits interleukin-13. It was recently approved by Health Canada and the US FDA for the treatment of moderate-to-severe AD in adults and may be used alone or with topical corticosteroids. Herein, we review the efficacy and safety of tralokinumab in adults, as demonstrated in clinical trials.

Halobetasol Propionate 0.01% Lotion for Plaque Psoriasis and Corticosteroid-Responsive Dermatoses.

A novel topical corticosteroid, halobetasol propionate (HP) 0.01% lotion (Bryhali™), has recently been introduced for the treatment of plaque psoriasis and corticosteroid-responsive dermatoses in adults. Once daily application of HP 0.01% lotion is indicated for use up to 8 weeks. Treatment success for plaque psoriasis in the pivotal phase 3 clinical trials (defined as an Investigator Global Assessment [IGA] of clear/almost clear [IGA 0/1] with ≥2-grade improvement from baseline) occurred in over one-third of patients by week 8. Treatment-emergent adverse events were typically mild-to-moderate in intensity and usually limited to the application site(s). No treatment-related cases of skin atrophy have been reported from the studies. Counselling should be considered to optimize treatment outcomes.

Diversification dynamics of mammalian clades during the K-Pg mass extinction.

The Cretaceous/Palaeogene (K-Pg) episode is an iconic mass extinction, in which the diversity of numerous clades abruptly declined. However, the responses of individual clades to mass extinctions may be more idiosyncratic than previously understood. Here, we examine the diversification dynamics of the three major mammalian clades in North America across the K-Pg. Our results show that these clades responded in dramatically contrasting ways to the K-Pg event. Metatherians underwent a sudden rise in extinction rates shortly after the K-Pg, whereas declining origination rates first halted diversification and later drove the loss of diversity in multituberculates. Eutherians experienced high taxonomic turnover near the boundary, with peaks in both origination and extinction rates. These findings indicate that the effects of geological episodes on diversity are context dependent and that mass extinctions can affect the diversification of clades by independently altering the extinction regime, the origination regime or both.

The extended Price equation quantifies species selection on mammalian body size across the Palaeocene/Eocene Thermal Maximum.

Species selection, covariation of species' traits with their net diversification rates, is an important component of macroevolution. Most studies have relied on indirect evidence for its operation and have not quantified its strength relative to other macroevolutionary forces. We use an extension of the Price equation to quantify the mechanisms of body size macroevolution in mammals from the latest Palaeocene and earliest Eocene of the Bighorn and Clarks Fork Basins of Wyoming. Dwarfing of mammalian taxa across the Palaeocene/Eocene Thermal Maximum (PETM), an intense, brief warming event that occurred at approximately 56 Ma, has been suggested to reflect anagenetic change and the immigration of small bodied-mammals, but might also be attributable to species selection. Using previously reconstructed ancestor-descendant relationships, we partitioned change in mean mammalian body size into three distinct mechanisms: species selection operating on resident mammals, anagenetic change within resident mammalian lineages and change due to immigrants. The remarkable decrease in mean body size across the warming event occurred through anagenetic change and immigration. Species selection also was strong across the PETM but, intriguingly, favoured larger-bodied species, implying some unknown mechanism(s) by which warming events affect macroevolution.

Case report of hidradenitis suppurativa localized to the face in an HIV patient.

Hidradenitis suppurativa is a chronic, debilitating inflammatory skin disease. Case reports of individuals with hidradenitis suppurativa presenting exclusively on the face, as well as reports of individuals with HIV and hidradenitis suppurativa, are rare. Here, we present the case of an HIV-positive man who presented with hidradenitis suppurativa localized only on his face. We also review facial hidradenitis suppurativa and hidradenitis suppurativa in HIV patients.

Retrospective Analysis of Cardiovascular Disease Risk Parameters in Participants of a Preventive Health and Wellness Program.

Lifestyle, dietary, and nutritional choices are important influencing parameters of cardiovascular disease (CVD) risk, the number one cause of morbidity and mortality globally. Our aims were to i) characterize CVD risk parameters using data from 7939 participants enrolled in a preventive health and wellness program between March 2010 and January 2017; and ii) evaluate intervention effects in 3,020 participants who returned for follow-up. Blood measurements (nutrient markers), CVD risk parameters (abdominal obesity, hypertension, hyperglycemia, hypertriglyceridemia, low high-density lipoprotein (HDL), insulin resistance, and inflammation), glycemic status (HbA1c), and insulin resistance (HOMA-IR) were assessed. Framingham and Reynold's risk scores were also calculated. After approximately one year of treatment (n = 3 020), mean arachidonic acid:eicosapentaenoic acid (AA:EPA) ratio, homocysteine, and HbAlc concentrations were significantly reduced; other risk parameters did not improve but mean values remained within reference ranges. Excluding participants taking related medications, 38.8%, 37.2%, 38.0%, 42.5%, and 59.7% of those with hyperglycemia, hypertriglyceridemia, low HDL, insulin resistance, or prediabetes, respectively, at baseline no longer had the condition at follow-up. In contrast, of individuals within the reference range at baseline, new cases at follow-up were found for 10.1%, 12.2%, 6.3%, 8.2%, and 7.6% (as above, respectively). Regression models revealed a significant association between serum 25-hydroxyvitamin D concentrations ≥100 nmol/L and reductions in many CVD risk parameters after adjustment for confounding variables. These findings suggest that a preventive approach to health and wellness focused on nutrients, optimal serum 25-hydroxyvitamin D concentrations, and lifestyle changes has the potential to reduce the risk of CVD.