The Australasian Registry for Severe Cutaneous Adverse Reactions (AUS-SCAR) - Providing a roadmap for closing the diagnostic, patient, and healthcare gaps for a group of rare drug eruptions.

Background: Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR. Methods: Prospective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites. Results: we report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%). Conclusion: In the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro/in vivo diagnostic strategies to ascertain drug causality. Trial registration: ANZCTR ACTRN12619000241134. Registered 19 February 2019.

Topical Calcipotriol Plus 5-Fluorouracil in the Treatment of Actinic Keratosis, Bowen's Disease, and Squamous Cell Carcinoma: A Systematic Review.

BACKGROUND/OBJECTIVES: Actinic keratoses (AK) are premalignant skin lesions caused by chronic sun exposure, topically managed by 5-fluorouracil (5-FU), diclofenac 3% gel, and imiquimod. Despite their effectiveness, long treatment duration and severe adverse local skin reactions have limited patient concordance. Calcipotriol has recently been used as a combination agent for existing topical AK treatments. A systematic review was performed to determine the clinical efficacy of 5-FU and calcipotriol for the treatment of AK, Bowen's disease, and squamous cell carcinoma (SCC). METHODS: A systematic literature search was conducted on Medline, Embase, and Cochrane Library. Among the 84 records screened, 12 were retrieved for full-text review and 8 were included in the final analysis. RESULTS: Among the 8 studies, there were 214 control patients and 288 patients who received the intervention. The combination 5% 5-FU with calcipotriol resulted in a significant reduction in the number of AKs on the face, scalp, right upper extremity, and left upper extremity for all sites at 8 weeks (P < .0001). No significant difference in SCC incidence was observed at 1 or 2 years, but there was a significant reduction observed at 3 years for SCC on face and scalp. No study assessed the combination for Bowen's disease. CONCLUSIONS: Combination 5% 5-FU with calcipotriol is an effective treatment for Aks; however, future trials may consider longer treatment and follow-up periods for the treatment and prevention of AK, SCC in situ, and SCC.

Sulfonic-acid-based lyotropic bicontinuous cubic polymer network for molecular-size-selective heterogeneous catalysis.

A nanoporous, bicontinuous cubic, lyotropic liquid crystal polymer resin with sulfonic acid groups is presented that exhibits high catalytic activity and is capable of molecular-size-selective heterogeneous acid catalysis.

Correction: Cross-linkable, phosphobetaine-based, zwitterionic amphiphiles that form lyotropic bicontinuous cubic phases.

Correction for 'Cross-linkable, phosphobetaine-based, zwitterionic amphiphiles that form lyotropic bicontinuous cubic phases' by Lauren N. Bodkin et al., Soft Matter, 2023, 19, 3768-3772, https://doi.org/10.1039/D3SM00269A.

Cross-linkable, phosphobetaine-based, zwitterionic amphiphiles that form lyotropic bicontinuous cubic phases.

The design, synthesis, and lyotropic liquid crystal phase behaviour of six cross-linkable, phosphobetaine-based, zwitterionic amphiphiles are described. Two form a QII phase with aq. NH4Cl solution, giving 3D-nanoporous membrane materials that can be used for water desalination and are not susceptible to ion exchange like traditional ionic analogues.

Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients.

BACKGROUND: Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B3) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life. RESULTS: A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups. CONCLUSIONS: In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.).

Study protocol: Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR).

INTRODUCTION: Severe cutaneous adverse reactions (SCAR) are a group of T cell-mediated hypersensitivities associated with significant morbidity, mortality and hospital costs. Clinical phenotypes include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP). In this Australasian, multicentre, prospective registry, we plan to examine the clinical presentation, drug causality, genomic predictors, potential diagnostic approaches, treatments and long-term outcomes of SCAR in Australia and New Zealand. METHODS AND ANALYSIS: Adult and adolescent patients with SCAR including SJS, TEN, DRESS, AGEP and another T cell-mediated hypersensitivity, generalised bullous fixed drug eruption, will be prospectively recruited. A waiver of consent has been granted for some sites to retrospectively include cases which result in early mortality. DNA will be collected for all prospective cases. Blood, blister fluid and skin biopsy sampling is optional and subject to patient consent and site capacity. To develop culprit drug identification and prevention, genomic testing will be performed to confirm human leukocyte antigen (HLA) type and ex vivo testing will be performed via interferon-γ release enzyme linked immunospot assay using collected peripheral blood mononuclear cells. The long-term outcomes of SCAR will be investigated with a 12-month quality of life survey and examination of prescribing and mortality data. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Austin Health Human Research Ethics Committee (HREC/50791/Austin-19). Results will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12619000241134).

Stable cross-linked lyotropic gyroid mesophases from single-head/single-tail cross-linkable monomers.

A single-head/single-tail surfactant with a polymerizable group at each end is presented as a new simplified motif for intrinsically cross-linkable, gyroid-phase lyotropic mesogens. The resulting nanoporous polymer networks exhibit excellent structural stability in various solvents and are capable of molecular size discrimination.

Effects of structural modification of (alkyldiene-imidazolium bromide)-based gemini monomers on the formation of the lyotropic bicontinuous cubic phase.

Seven homologues of an amphiphilic gemini monomer were synthesized and screened for the ability to form a bicontinuous cubic (Q) lyotropic liquid crystal phase. Four of these homologues form a Q phase with glycerol or water that can be cross-linked with retention of the nanoporous structure, with one exhibiting a well-ordered Q phase with a wider phase window than the parent monomer.

Upper airway involvement in Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life-threatening hypersensitivity conditions associated with epidermal detachment and mucositis. The indication for flexible nasoendoscopy (FNE) and overall predictive factors for early intubation are unclear. OBJECTIVES: To describe the incidence of airway involvement and the key indicators for intubation in our SJS or TEN patient cohort. To determine the association between FNE findings and early intubation. METHODS: A retrospective review of 45 patients with biopsy proven SJS or TEN admitted to an Australian tertiary burns centre from 2010 to 2017. RESULTS: Thirty-five patients were diagnosed with TEN (77.8%), followed by overlap syndrome (SJS-TEN) (n = 6, 13.3%) and SJS (n = 4, 8.9%). Twenty (44.4%) patients were intubated; and all 20 had a diagnosis of TEN (100.0%) (p < 0.05). Intubated patients had a higher increase in total body surface area percentage(%) from day 1-3 [10.0% (IQR 0.0-23.8%)] and a longer length of stay [26.0 days (IQR 12.5-34.0)], compared to non-intubated patients [0.0% (IQR 0.0-4.0%)], [10.0 days (IQR 6.0-14.0)] (p < 0.05) respectively. The main indications for intubation were to facilitate operative and dressing management (47.4%) followed by airway involvement (26.3%). FNE was performed on 32 patients (71.1%), however FNE findings did not significantly influence intubation rates. CONCLUSION: More than half (n = 20, 57.1%) of the 35 patients diagnosed with TEN underwent intubation, mainly to facilitate operative and dressing management. FNE was performed on most patients, however there was no clear association between FNE findings and early intubation.

System for Living ROMP of a Paramagnetic FeCl4--Based Ionic Liquid Monomer: Direct Synthesis of Magnetically Responsive Block Copolymers.

Direct, living ring-opening metathesis polymerization of a highly paramagnetic, norbornene-based imidazolium FeCl4- ionic liquid monomer was achieved using the Grubbs third-generation catalyst and starting the polymerization off with an uncharged, nonparamagnetic norbornene monomer in a sequential block copolymerization. Preparing the paramagnetic norbornene imidazolium FeCl4- monomer in high purity was found to be crucial for enabling living polymerization behavior and generating paramagnetic diblock copolymers with predictable block lengths and compositions.

Single crystal texture by directed molecular self-assembly along dual axes.

Creating well-defined single-crystal textures in materials requires the biaxial alignment of all grains into desired orientations, which is challenging to achieve in soft materials. Here we report the formation of single crystals with rigorously controlled texture over macroscopic areas (>1 cm2) in a soft mesophase of a columnar discotic liquid crystal. We use two modes of directed self-assembly, physical confinement and magnetic fields, to achieve control of the orientations of the columnar axes and the hexagonal lattice along orthogonal directions. Field control of the lattice orientation emerges in a low-temperature phase of tilted discogens that breaks the field degeneracy around the columnar axis present in non-tilted states. Conversely, column orientation is controlled by physical confinement and the resulting imposition of homeotropic anchoring at bounding surfaces. These results extend our understanding of molecular organization in tilted systems and may enable the development of a range of new materials for distinct applications.

Disseminated cutaneous-only histoplasmosis in a patient with AIDS.

Histoplasmosis is an opportunistic fungal infection that occurs predominantly in immunocompromised patients. Cutaneous lesions in histoplasmosis are rare and typically occur in the absence of extra-cutaneous manifestations. We present a rare case of disseminated cutaneous-only histoplasmosis in a patient with recently diagnosed AIDS.

Cyclosporine for moderate-to-severe alopecia areata: A double-blind, randomized, placebo-controlled clinical trial of efficacy and safety.

BACKGROUND: Despite widespread use of steroid-sparing agents, particularly cyclosporine, for treatment of alopecia areata (AA), there are no clinical trials investigating the efficacy of these agents. OBJECTIVE: To evaluate the efficacy of cyclosporine compared with placebo at 3 months in patients aged 18 to 65 years with moderate-to-severe AA. METHODS: A double-blind, randomized, placebo-controlled trial was conducted. Adults aged 18 to 65 years of age with moderate-to-severe AA were randomized in a 1:1 ratio to receive 3 months of cyclosporine (4 mg/kg/d) or matching placebo. Blinded assessments included physical examination, blood biochemistry, photography, quality of life measurements, and efficacy evaluation using Severity of Alopecia Tool score and eyelash and eyebrow assessment scales. RESULTS: The results obtained for 32 participants (16 who received cyclosporine and 16 who received placebo) were analyzed. Compared with the placebo group, the cyclosporine group had a greater proportion of participants achieving at least a 50% reduction in Severity of Alopecia Tool score (31.3% vs 6.3% [P = .07]) and greater proportion of participants achieving a 1-grade improvement in eyelash (18.8% vs 0% [P = .07]) and eyebrow (31.3% vs 0% [P = .02]) scale score. LIMITATIONS: Small sample size and single-institution trial may limit interpretation and generalizability of these results. CONCLUSION: Response approached but did not reach a statistically significant difference between cyclosporine and placebo.

Understanding the Nanoscale Structure of Inverted Hexagonal Phase Lyotropic Liquid Crystal Polymer Membranes.

Periodic, nanostructured porous polymer membranes made from the cross-linked inverted hexagonal phase of self-assembled lyotropic liquid crystals (LLCs) are a promising class of materials for selective separations. In this work, we investigate an experimentally characterized LLC polymer membrane using atomistic molecular modeling. In particular, we compare simulated X-ray diffraction (XRD) patterns with experimental XRD data to quantify and understand the differences between simulation and experiment. We find that the nanopores are likely composed of five columns of stacked LLC monomers which surround each hydrophilic core. Evidence suggests that these columns likely move independently of each other over longer time scales than accessible via atomistic simulation. We also find that wide-angle X-ray scattering structural features previously attributed to monomer tail tilt are likely instead due to ordered tail packing. Although this system has been reported as dry, we show that small amounts of water are necessary to reproduce all features from the experimental XRD pattern because of asymmetries introduced by hydrogen bonds between the monomer head groups and water molecules. Finally, we explore the composition and structure of the nanopores and reveal that there exists a composition gradient rather than an abrupt partition between the hydrophilic and hydrophobic regions. A caveat is that the time scales of the dynamics are extremely long for this system, resulting in simulated structures that appear too ordered, thus requiring careful examination of the metastable states observed in order to draw any conclusions. The clear picture of the nanoscopic structure of these membranes provided in this study will enable a better understanding of the mechanisms of small-molecule transport within these nanopores.

Systemic treatments for alopecia areata: A systematic review.

A range of systemic treatments are used for alopecia areata with variable evidence supporting efficacy. In this systematic review, we evaluated the evidence surrounding systemic treatments for alopecia areata, alopecia totalis and alopecia universalis. A systematic search was conducted of the peer-reviewed literature published between 1946 and March 2018 via Medline, Embase, Amed, the Cochrane Central Register of Controlled Trials, PsychINFO and Lilacs. All randomised controlled trials (RCTs) that evaluated the effectiveness of systemic treatments for individuals with alopecia areata, totalis or universalis were included. Sixteen studies were included with a total of 768 participants. We found eight placebo-controlled RCTs, three RCTs comparing two systemic treatments and five RCTs comparing three treatments. A total of 15 different systemic therapies were investigated. The most frequently investigated therapy was oral prednisolone pulse therapy and oral inosiplex. There was significant variability in the definition of treatment success. No study evaluated the impact of pharmacotherapy on quality of life using complete quantitative quality of life instruments. Adverse events were reported in 13 studies and were corticosteroid related or otherwise well tolerated. Relapse rates were considerable in the four studies that reported this outcome. There is currently no specific systemic therapy that is supported by robust body of evidence from RCTs. The current evidence suggests efficacy of oral prednisolone pulse therapy and oral inosiplex. Evidence does not support the use of oral zinc sulphate, alefacept and efalizumab. Future RCTs should be adequately powered and employ clearly defined clinical response endpoints to allow future meta-analyses.

Ordered nanoporous lyotropic liquid crystal polymer resin for heterogeneous catalytic aerobic oxidation of alcohols.

An ordered, nanoporous, TEMPO-based polymer resin formed from lyotropic liquid crystal monomers catalyzes the hetereogeneous oxidation of alcohols with high activity and substrate size selectivity under transition-metal-free, aerobic conditions.