Current management of generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a rare subset of psoriasis involving episodes of sterile pustules accompanied by inflammation and, often, systemic involvement. The inflammatory nature of GPP has potential for severe multisystem complications including high-output cardiac failure, infections, digestive system issues, and disfiguring or lethal acute flare episodes. The disease tends to have higher prevalence in females and Asians. The IL-1/IL-36 inflammatory pathway is a critical facet of GPP's pathology. Genetic mutations that are associated with GPP include modifications of Interleukin 36 Receptor Antagonist (IL36RN), Caspase Recruitment Domain Family Member 14 (CARD14), Adaptor Related Protein Complex 1 Subunit Sigma 3 (AP1S3), Myeloperoxidase (MPO) and Serpin Peptidase Inhibitor Clade A Member 3 (SERPINA3) genes. Treatment guidelines for GPP are not well-entrenched. Currently, only one GPP-specific treatment, the interleukin-36 receptor antagonist (IL-36Ra) spesolimab, has been approved for use in the United States. Additional anti-IL-36 pathway therapies are currently being developed. Other treatment options include other biologic therapies such as IL-17 inhibitors, IL-23 inhibitors and TNFα inhibitors. Non-biologic therapeutic options include retinoids, cyclosporine and methotrexate. Treatment options differ throughout the world; most countries utilize retinoids, cyclosporine and methotrexate as first-line non-biologic options. China and United Kingdom have no GPP-specific biologic therapies approved for use, while several biologic therapies are approved for use in Japan. This review aims to serve as an update on the current global management of GPP while also including relevant aspects of disease pathogenesis, diagnosis, clinical presentation, histopathology, aetiology and epidemiology.

Assessing melanoma prognosis: the interplay between patient profiles, survival, and BRAF, NRAS, KIT, and TWT mutations in a retrospective multi-study analysis.

The incidence and prevalence of melanoma are increasing globally, presenting a significant public health concern. The main genetic drivers of melanoma include BRAF, NRAS, KIT and triple wild-type (TWT) mutations. Little is known about the effects of these mutations on outcomes in terms of demographics and patient characteristics. We examined differences in melanoma mortality risk and mutation count across mutation type and patient disease profile. We extrapolated primary melanoma patient data from 14 studies via the cBioportal database. Patients were divided into demographic groups and classified according to BRAF, NRAS, KIT and TWT mutation status. Analyses included two-sample Student t-test and two-way analysis of variance tests analysis with Tukey's post hoc test. Survival outcomes were compared via Kaplan-Meier curve and Cox regression. NRAS-mutated patients exhibited decreased overall survival compared to BRAF-mutated patients. Male patients had higher mutation counts across all gene groups than females, with the fewest TWT mutations in comparison to BRAF, NRAS and KIT mutations. Males also exhibited increased mortality risk for NRAS, KIT and TWT mutations compared to BRAF mutations. An unknown primary melanoma was associated with increased mortality risk across all gene groups. NRAS-mutated acral melanoma patients had an increased mortality risk compared to NRAS-mutated cutaneous melanoma patients. Older patients had a higher mortality risk than younger patients. Patients with heavier versus lower weights had lower mortality risk, which was more pronounced for BRAF-mutated patients. These relationships highlight the importance of demographic and pathologic relationships to aid in risk assessment and personalize treatment plans.

PET Radiotracers in Atherosclerosis: A Review.

Traditional atherosclerosis imaging modalities are limited to late stages of disease, prior to which patients are frequently asymptomatic. Positron emission tomography (PET) imaging allows for the visualization of metabolic processes underscoring disease progression via radioactive tracer, allowing earlier-stage disease to be identified. 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG) uptake largely reflects the metabolic activity of macrophages, but is unspecific and limited in its utility. By detecting areas of microcalcification, 18F-Sodium Fluoride (18F-NaF) uptake also provides insight into atherosclerosis pathogenesis. Gallium-68 DOTA-0-Tyr3-Octreotate (68Ga-DOTATATE) PET has also shown potential in identifying vulnerable atherosclerotic plaques with high somatostatin receptor expression. Finally, 11-carbon (11C)-choline and 18F-fluoromethylcholine (FMCH) tracers may identify high-risk atherosclerotic plaques by detecting increased choline metabolism. Together, these radiotracers quantify disease burden, assess treatment efficacy, and stratify risk for adverse cardiac events.

Acrophialophora: A Comprehensive Review of Clinical Guidelines and Diagnosis.

Acrophialophora is a saprotrophic genus of fungi found in both temperate and tropical regions. The genus is comprised of 16 species, with the subspecies A. fusispora and A. levis necessitating the most clinical concern. Acrophialophora is an opportunistic pathogen with a broad range of clinical manifestations; the fungus has been implicated in cases of fungal keratitis, lung infection, and brain abscess. Acrophialophora infection is particularly of concern for immunocompromised patients, who often present with a more severe disease course involving disseminated infection and may not exhibit typical symptoms. Early diagnosis and therapeutic intervention are critical to the successful clinical management of Acrophialophora infection. Guidelines for antifungal treatment have yet to be established, partially due to the lack of documented cases. Aggressive use of antifungal agents and long-term treatment is required, especially in immunocompromised patients and patients with systemic involvement, due to the potential for morbidity and mortality. In addition to outlining the rarity and epidemiology of the disease, this review provides an overview of the diagnosis and clinical management of Acrophialophora infection to facilitate an early diagnosis and appropriate interventions.