Treatment of hidradenitis suppurativa with adalimumab in the PIONEER I and II trials reduced indices of systemic inflammation, recognised risk factors for cardiovascular disease.

BACKGROUND: Hidradenitis suppurativa (HS) is associated with increased cardiovascular disease (CVD) risk. Systemic immune inflammation index (SII), neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR) and monocyte/lymphocyte ratios (MLR) are biomarkers of systemic inflammation and CVD. One small study identified a lower NLR and PLR in patients treated with adalimumab. OBJECTIVES: Our aim was to assess changes in SII, NLR, PLR and MLR in a larger cohort, and to evaluate their association with disease severity and treatment response. METHODS: This was a post-hoc analysis of PIONEER I and PIONEER II, two phase 3 randomised placebo-controlled clinical trials of adalimumab for HS. SII, NLR, PLR and MLR were log10-transformed and linear mixed model was used to estimate treatment effect. RESULTS: SII, NLR, PLR and MLR reduced from baseline levels with adalimumab treatment by week 12, when the primary response endpoint was assessed. Significant changes first appeared at week 4 and were maintained to week 36. In contrast, no significant changes were observed in placebo-treated patients. In patients re-randomised at week 12 from placebo to adalimumab, SII, NLR, PLR and MLR also reduced within 4 weeks. In patients re-randomised from adalimumab to placebo, these biomarkers returned to baseline by week 36. In addition, SII, NLR and PLR correlated with draining fistula count (r=0.26-0.43, p<0.001). Adalimumab non-responders in PIONEER I had a higher SII, NLR and PLR at baseline and week 12, but this was not significant when adjusted for draining fistulae. CONCLUSIONS: Treatment of HS patients with adalimumab results in rapid sustained reduction in systemic inflammation measured by SII, NLR, PLR and MLR which correlate with CVD risk. SII, NLR and PLR may predict adalimumab response, although dependent on their interaction with the number of draining fistulae.

GRAPPA Point-Counterpoint: Should Biologics Be Used for Mild Psoriasis?

Psoriasis (PsO) is commonly classified as mild, moderate, or severe, usually based on body surface area (BSA) or other validated measures. Although most dermatologists agree that mild PsO should be treated with topical therapies, there are circumstances where mild or limited PsO should be treated with biologics, even as first line. A debate about use of topical vs biologic therapy was presented at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting. Arguments in favor of using biologics when patients have mild disease on limited BSA included presence of psoriatic arthritis (PsA) and symptoms on special sites (ie, scalp, face, body folds, genitals, nails, palms, soles). New data suggest that treating limited or early PsO may decrease the risk of developing PsA. Arguments against using biologics for mild PsO focused on the definition of mild PsO, citing that limited BSA with PsA and significant quality of life impact should not be defined as mild. Truly mild PsO should be treated with topical agents, given their safety and relative low cost. The availability of newer agents like roflumilast and tapinarof have expanded therapeutic choice and have data supporting their use for treatment of special sites.

Standardized Protocols for Clinical and Histopathological Characterization of Hidradenitis Suppurativa Tissue Specimens.

Methods for describing and reporting the clinical and histologic characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. In this study, we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens. This study was conducted from May 2023 to August 2023. Experts in clinical care, dermatopathology, and translational research were recruited, and a modified Delphi technique was used to develop a protocol for histologic reporting and clinical characterization of submitted tissue specimens from patients with HS. A total of 27 experts participated (14 dermatologists, 3 fellowship-trained dermatopathologists, 3 plastic surgeons, 3 general surgeons, and 4 research scientists) in creating and reviewing protocols for the clinical and histopathological examination of HS tissue specimens. The protocols were formatted as a synoptic report and will help to consistently classify specimens in biobanks on the basis of histologic features and more accurately report and select samples used in translational research projects.

An update on topical therapies for psoriasis.

PURPOSE OF REVIEW: Topical therapies are a mainstay of treatment for mild psoriasis and may be a useful adjunct in treatment of moderate-to-severe psoriasis. This review summarizes recent advances in topical therapies for psoriasis and currently available treatments. RECENT FINDINGS: Topical aryl hydrocarbon receptor modulators (tapinarof) and topical phosphodiesterase-4 inhibitors (roflumilast) have been proven effective in randomized controlled trials for psoriasis. Although topical JAK inhibitors have also been studied, none are currently licensed for treatment of psoriasis. Topical corticosteroids and vitamin D analogues remain the most commonly used and widely available topical treatments for psoriasis. Cost may limit use of novel topical agents. SUMMARY: Although the novel topical agents tapinarof and roflumilast are licensed for treatment of psoriasis by the FDA in the United States, they have not yet been licensed in Europe, and it remains to be seen whether they will be limited by cost.

Reduction-Induced Magnetic Behavior in LaFeO3-δ Thin Films.

The effect of oxygen reduction on the magnetic properties of LaFeO3-δ (LFO) thin films was studied to better understand the viability of LFO as a candidate for magnetoionic memory. Differences in the amount of oxygen lost by LFO and its magnetic behavior were observed in nominally identical LFO films grown on substrates prepared using different common methods. In an LFO film grown on as-received SrTiO3 (STO) substrate, the original perovskite film structure was preserved following reduction, and remnant magnetization was only seen at low temperatures. In a LFO film grown on annealed STO, the LFO lost significantly more oxygen and the microstructure decomposed into La- and Fe-rich regions with remnant magnetization that persisted up to room temperature. These results demonstrate an ability to access multiple, distinct magnetic states via oxygen reduction in the same starting material and suggest LFO may be a suitable materials platform for nonvolatile multistate memory.

Shear Histories Alter Local Shear Effects on Thrombus Nucleation and Growth.

Our goal was to determine the impact of physiological and pathological shear histories on platelet nucleation and thrombus growth at various local shear rates. We designed and characterized a microfluidic device capable of subjecting platelets to shear histories reaching as high as 6700 s - 1 in a single passage. Time-lapse videos of platelets and thrombi are captured using fluorescence microscopy. Thrombi are tracked, and the degree of thrombosis is evaluated through surface coverage, platelet nucleation maps, and ensemble-averaged aggregate areas and intensities. Surface coverage rates were the lowest when platelets deposited at high shear rates following a pathological shear history and were highest at low shear rates following a pathological shear history. Early aggregate area growth rates were significantly larger for thrombi developing at high shear following physiological shear history than at high shear following a pathological shear history. Aggregate vertical growth was restricted when depositing at low shear following a pathological shear history. In contrast, thrombi grew faster vertically following physiological shear histories. These results show that physiological shear histories pose thrombotic risks via volumetric growth, and pathological shear histories drastically promote nucleation. These findings may inform region-based geometries for biomedical devices and refine thrombosis simulations.

Graded magnetic materials.

Graded magnetic materials represent a promising new avenue in modern material science from both fundamental and application points of view. Over the course of the last few years, remarkable results have been obtained in (epitaxial) heterostructures based on thin alloy films featuring diverse compositional depth profiles. As a result of the precise tailoring of such profiles, the exchange coupling, and the corresponding effective or local Curie temperatures can be controlled over tens of nm with an excellent precision. This topical review article reports the most recent advances in this emerging research field. Several aspects are covered, but the primary focus lies in the study of compositional gradients being transferred into depth dependent magnetic states in ferromagnets, while also reviewing other experimental attempts to create exchange graded films and materials in general. We account for the remarkable progress achieved in each sample and composition geometry by reporting the recent developments and by discussing the research highlights obtained by several groups. Finally, we conclude the review article with an outlook on future challenges in this field.

Thickness dependence of ferrimagnetic compensation in amorphous rare-earth transition-metal thin films.

Magnetic compensation in ferrimagnets plays an important role in spintronic and magnetic recording devices. Experimental results have demonstrated a thickness dependence of the compensation temperature ( T comp ) in amorphous TbFeCo thin films. It was speculated that this thickness dependence originated from a variation in the short-range order. In this work, we have investigated the depth-resolved compositional and magnetization profiles using polarized neutron reflectometry. We find that although the composition is uniform across the film thickness, near the substrate interface, the magnetization exhibits a different temperature dependence from that of the rest of the sample. Monte Carlo simulations show that it is this difference in interfacial magnetization that causes the aforementioned thickness dependence of the compensation. These results demonstrate the critical role of the substrate interface in determining the magnetic properties of amorphous ferrimagnetic thin films for spintronic applications.

Pulsed laser deposition films from a Ba2FeMoO6 target onto SrTiO3[001]: Chemical and magnetic inhomogeneity.

Pulsed laser deposition films from Ba2FeMoO6 (BFMO) targets onto SrTiO3[001] (STO) substrates have been reported previously to have non-zero magnetism at 300 K, a majority of magnetic ordering at 240 K that is less than the 370 K ordering temperature of polycrystalline BFMO, and suppressed saturation magnetization compared to polycrystalline BFMO. To interrogate these previously reported observations of BFMO on STO, we have used a combination of x-ray diffraction, atomic force microscopy, x-ray and neutron reflectivity, and x-ray photoelectron spectroscopy that shows inhomogeneities. The present results show off-stoichiometry on the A-site by incorporation of Sr from the substrate and on the B-site to have %Fe/%Mo > 1 by evolution of BaMoO4. There is an enhanced ordering temperature and magnetic response nearer to the SrTiO3 interface compared to the air interface. Depth dependent strain and microstructure are needed to explain the magnetic response. Holistic considerations and implications are also discussed.

Peak Oxygen Uptake and Physical Activity in 11- to 16-Year-Olds.

The present study examined the relationship between peak V̇O2 and habitual physical activity in 11- to 16-year-old students. The peak V̇O2 of 111 girls and 85 boys was determined using treadmill or cycle ergometry. Habitual physical activity was estimated from minute-by-minute heart rate monitoring over three 12-hr periods during normal school days. Over half of the girls and one third of the boys failed to sustain a single 10-min period with their heart rate at or above 140 bpm. Only one boy sustained a daily 20-minute period with a heart rate at or above 160 bpm. During Saturday monitoring over 90% of the girls and 75% of the boys failed to sustain a single 10-min period with their heart rate at or above 140 bpm, and only one girl and four boys sustained a 20-min period with their heart rate at or above 160 bpm. No significant relationship was detected between peak V̇O2 and heart rate indicators of habitual physical activity. This study suggests that few children have periods of physical activity of sufficient intensity and duration to stress the cardiopulmonary system.