The role of the foam formulation in improving psoriasis treatment acceptability: a real-life experience and a literature review.

BACKGROUND: Topical therapies represent the first-line treatment for mild-to-moderate psoriasis. Among various topical options, the fixed-dose combination of calcipotriene (Cal) and betamethasone dipropionate (BD) foam (Enstilar®, LEO Pharma, Ballerup, Denmark) showed superior efficacy to Cal and BD monotherapy and ointment and gel formulations. In addition, the Cal/BD foam is the only topical treatment allowed for either reactive treatment of relapse or twice-weekly maintenance use. Since treatment acceptability is crucial to optimize adherence, this paper presents a case series from a multicenter experience using the Cal/BD foam, to further characterize the use of this therapeutic approach. In addition, a narrative review of studies evaluating the acceptability of the Cal/BD foam, even compared with other formulations, is provided. CASE SERIES: The case series involved adult patients with mild-to-moderate psoriasis treated with the Cal/BD foam from October 2021 to June 2022. A clinical and dermoscopic evaluation of plaques was provided for all patients. Data from the clinical practice report complete clinical resolution of plaques in most patients after 4 weeks of active treatment with the Cal/BD foam, and the dermoscopic clearance after a maximum of 8 weeks. Full adherence to treatment was also reported. Literature evidence suggests that the Cal/BD foam is easy to apply and presents high cosmetic acceptance, rapid onset of action, high efficacy, optimal safety, and a high patient preference. The high satisfaction obtained with Cal/BD foam suggests that this formulation is better accepted than others. CONCLUSIONS: The Cal/BD foam represents a valuable approach for managing mild-to-moderate psoriasis, both in short and long-term treatment.

Biosorption of rare earth elements from luminophores by G. sulphuraria (Cyanidiophytina, Rhodophyta).

Lanthanides are indispensable constituents of modern technologies and are often challenging to acquire from natural resources. The demand for REEs is so high that there is a clear need to develop efficient and eco-friendly recycling methods. In the present study, freeze-dried biomass of the polyextremophile Galdieria sulphuraria was employed to recover REEs from spent fluorescent lamps (FL) luminophores by pretreating the freeze-dried biomass with an acid solution to favour ion exchange and enhance the binding sites on the cell surface available for the metal ions. Lanthanides were extracted from the luminophores using sulfuric acid solutions according to standardised procedures, and the effect of biosorbent dosage (0.5-5 mg/ml) and biosorption time (5-60 min) were evaluated. The content of individual REEs in the luminophores and the resulting algal biomass were determined using inductively coupled plasma mass spectrometry (ICP-MS). The most abundant REE in the luminophores was yttrium (287.42 mg/g dm, 91.60% of all REEs), followed by europium (20.98 mg/g, 6.69%); cerium, gadolinium, terbium and lanthanum was in trace. The best biosorption performances were achieved after 5 min and at the lowest biosorbent dosage (0.5 mg/mL). The highest total metal amount corresponded to 41.61 mg/g dried mass, and yttrium was the most adsorbed metal (34.59 mg/g dm, 82.88%), followed by cerium (4.01 mg/g); all other metals were less than 2 mg/g. The rapidity of the biosorption process and the low biosorbent dosage required confirmed this microalga as a promising material for creating an eco-sustainable protocol for recycling REEs.

Role of cardiopulmonary exercise test in the prediction of hemodynamic impairment in patients with pulmonary arterial hypertension.

Periodic repetition of right heart catheterization (RHC) in pulmonary arterial hypertension (PAH) can be challenging. We evaluated the correlation between RHC and cardiopulmonary exercise test (CPET) aiming at CPET use as a potential noninvasive tool for hemodynamic burden evaluation. One hundred and forty-four retrospective PAH patients who had performed CPET and RHC within 2 months were enrolled. The following analyses were performed: (a) CPET parameters in hemodynamic variables tertiles; (b) position of hemodynamic parameters in the peak end-tidal carbon dioxide pressure (PETCO2) versus ventilation/carbon dioxide output (VE/VCO2) slope scatterplot, which is a specific hallmark of exercise respiratory abnormalities in PAH; (c) association between CPET and a hemodynamic burden score developed including mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index, and right atrial pressure. VE/VCO2 slope and peak PETCO2 significantly varied in mPAP and PVR tertiles, while peak oxygen uptake (peak VO2) and O2 pulse varied in the tertiles of all hemodynamic parameters. PETCO2 versus VE/VCO2 slope showed a strong hyperbolic relationship (R 2 = 0.7627). Patients with peak PETCO2 > median (26 mmHg) and VE/VCO2 slope < median (44) presented lower mPAP and PVR (p < 0.005) than patients with peak PETCO2 < median and VE/VCO2 slope > median. Multivariate analysis individuated peak VO2 (p = 0.0158) and peak PETCO2 (p = 0.0089) as hemodynamic score independent predictors; the formula 11.584 - 0.0925 × peak VO2 - 0.0811 × peak PETCO2 best predicts the hemodynamic score value from CPET data. A significant correlation was found between estimated and calculated scores (p < 0.0001), with a precise match for patients with mild-to-moderate hemodynamic burden (76% of cases). The results of the present study suggest that CPET could allow to estimate the hemodynamic burden in PAH patients.

Beta-blockers in pulmonary arterial hypertension: Time for a second thought?

Pulmonary arterial hypertension (PAH) is a heart failure syndrome characterized by right ventricular (RV) to pulmonary circulation uncoupling, counteracted by the sympathetic nervous system activation leading to ß1-receptors and α-myosin heavy chain downregulation, downregulation of the sarcoplasmic reticulum Ca2+ATPase, and ß-myosin heavy chain upregulation. Increased ventilation (VE) associated with VE inefficiency further characterizes PAH, as shown by an elevated VE versus carbon dioxide relationship slope during exercise, reflecting a specific behavior with progressive increase of dead space (VD) VE. The sympathetic system interacts with chemoreceptor-mediated VE control with increased VD leading to VE/perfusion mismatch. Growing evidence in the experimental models shows beneficial effects of different adrenoreceptor blockers on both right heart and pulmonary artery morphology and function. These effects can significantly change among ß-blockers according to their different pharmacokinetic and pharmacodynamic profiles. Since the first observation in the clinical setting, showing improvement associated with ß-blocker withdraw in PAH patients, recent studies suggest that the effects of ß-blockers in PAH might be related to the ß1-adrenergic receptors selectivity and α1- and ß3-related ancillary properties. While in the advanced stages of PAH ß-blockers may result deleterious as counteract the compensatory adrenergic-mediated effects of low cardiac output, in the early stages the modulation of the adrenergic system could ultimately improve VE efficiency and promote beneficial effects on heart failure gene expression and RV remodeling, particularly ß1-selective blockers and those associated with α- or ß3-activities. At present, all the above are physiologically sound but clinically unproven suggestions, and need to be tested in future randomized controlled trials.

Bone marrow mesenchymal stem cells offer an immune-privileged niche to Cutibacterium acnes in case of implant-associated osteomyelitis.

Considered as some of the most devastating complications, Cutibacterium acnes (C. acnes)-related osteomyelitis are among the hardest infections to diagnose and treat. Mesenchymal stem cells (MSCs) secrete number of immunomodulatory and antimicrobial soluble factors, making them an attractive treatment for bacterial infection. In this study, we examined MSCs/C. acnes interaction and analyzed the subsequent MSCs and bacteria's behaviors. Human bone marrow-derived MSCs were infected by C. acnes clinical strain harvested from non-infected bone site. Following 3 h of interaction, around 4% of bacteria were found in the intracellular compartment. Infected MSCs increased the secretion of prostaglandin E2 and indolamine 2,3 dioxygenase immunomodulatory mediators. Viable intracellular bacteria analyzed by infrared spectroscopy and atomic force microscopy revealed deep modifications in the wall features. In comparison with unchallenged bacteria, the viable intracellular bacteria showed (i) an increase in biofilm formation on orthopaedical-based materials, (ii) an increase in the invasiveness of osteoblasts and (iii) persistence in macrophage, suggesting the acquisition of virulence factors. Overall, these results showed a direct impact of C. acnes on bone marrow-derived MSCs, suggesting that blocking the C. acnes/MSCs interactions may represent an important new approach to manage chronic osteomyelitis infections. STATEMENT OF SIGNIFICANCE: The interaction of bone commensal C. acnes with bone marrow mesenchymal stem cells induces modifications in C. acnes wall characteristics. These bacteria increased (i) the biofilm formation on orthopaedical-based materials, (ii) the invasiveness of bone forming cells and (iii) the resistance to macrophage clearance through the modification of the wall nano-features and/or the increase in catalase production.

Mechanisms of checkpoint inhibition-induced adverse events.

Immune checkpoint inhibition has revolutionized the treatment of several solid cancers, most notably melanoma and non-small-cell lung cancer (NSCLC). Drugs targeting cytotoxic T lymphocyte antigen (CTLA)-4 and programmed cell death 1 (PD-1) have made their way into routine clinical use; however, this has not been without difficulties. Stimulation of the immune system to target cancer has been found to result in a reduction of self-tolerance, leading to the development of adverse effects that resemble autoimmunity. These adverse effects are erratic in their onset and severity and can theoretically affect any organ type. Several mechanisms for immune-related toxicity have been investigated over recent years; however, no consensus on the cause or prediction of toxicity has been reached. This review seeks to examine reported evidence for possible mechanisms of toxicity, methods for prediction of those at risk and a discussion of future prospects within the field.

Interaction of Cutibacterium acnes with human bone marrow derived mesenchymal stem cells: a step toward understanding bone implant- associated infection development.

Crosstalk between mesenchymal stem cells (MSCs) and bacteria plays an important role in regulating the regenerative capacities of MSCs, fighting infections, modulating immune responses and maintaining tissue homeostasis. Commensal Cutibacterium acnes (C. acnes) bacterium becomes an opportunistic pathogen causing implant-associated infections. Herein, we examined MSCs/C. acnes interaction and analysed the subsequent bacteria and MSCs behaviours following infection. Human bone marrow derived MSCs were infected by two clinical and one laboratory C. acnes strains. Following 3h of interaction, all bacterial strains were able to invade MSCs. Viable intracellular bacteria acquired virulence factors by increasing biofilm formation and/or by affecting macrophage phagocytosis. Although the direct and indirect (through neutrophil stimulation) antibacterial effects of the MSCs secretome were not enhanced following C. acnes infection, ELISA analysis revealed that C. acnes clinical strains are able to license MSCs to become immunosuppressive cell-like by increasing the secretion of IL-6, IL-8, PGE-2, VEGF, TGF-ß and HGF. Overall, these results showed a direct impact of C. acnes on bone marrow derived MSCs, providing new insights into the development of C. acnes during implant-associated infections. STATEMENT OF SIGNIFICANCE: The originality of this work relies on the study of relationship between human bone marrow derived mesenchymal stem cells (MSCs) phenotype and C. acnes clinical strains virulence following cell infection. Our major results showed that C. acnes are able to invade MSCs, inducing a transition of commensal to an opportunistic pathogen behaviour. Although the direct and indirect antibacterial effects were not enhanced following C. acnes infection, secretome analysis revealed that C. acnes clinical strains were able to license MSCs to become immunosuppressive and anti-fibrotic cell-like. These results showed a direct impact of C. acnes on bone marrow derived MSCs, providing new insights into the development of C. acnes during associated implant infections.

Diet Modulation Restores Autophagic Flux in Damaged Skeletal Muscle Cells.

OBJECTIVES: Autophagy is a physiological and highly regulated mechanism, crucial for cell homeostasis maintenance. Its impairment seems to be involved in the onset of several diseases, including muscular dystrophies, myopathies and sarcopenia. According to few papers, chemotherapeutic drug treatment is able to trigger side effects on skeletal muscle tissue and, among these, a defective autophagic activation, which leads to the persistence of abnormal organelles within cells and, finally, to myofiber degeneration. The aim of this work is to find a strategy, based on diet modulation, to prevent etoposide-induced damage, in a model of in vitro skeletal muscle cells. METHODS: Glutamine supplementation and nutrient deprivation have been chosen as pre-treatments to counteract etoposide effect, a chemotherapeutic drug known to induce oxidative stress and cell death. Cell response has been evaluated by means of morpho-functional, cytofluorimetric and molecular analyses. RESULTS: Etoposide treated cells, if compared to control, showed dysfunctional mitochondria presence, ER stress and lysosomal compartment damage, confirmed by molecular investigations. CONCLUSIONS: Interestingly, both dietary approaches were able to rescue myofiber from etoposide-induced damage. Glutamine supplementation, in particular, seemed to be a good strategy to preserve cell ultrastructure and functionality, by preventing the autophagic impairment and partially restoring the normal lysosomal activity, thus maintaining skeletal muscle homeostasis.

Bullous pemphigoid associated with ipilimumab therapy for advanced metastatic melanoma.

Immunotherapy is now being routinely used in the management of many cancers. It is therefore vital that all clinicians are aware of the diverse array of cutaneous manifestations that can result from their use, which can vary from mild to life threatening.