Interleukin-1 family cytokines and soluble receptors in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic skin disease, characterized by clinical inflammation of the hair follicle with the recurrence of abscesses, nodules, and tunnels. Recently, several studies suggested a role of IL-1 family (IL-1F) cytokines in eliciting and sustaining the disease. The aim of this work is to perform a comprehensive analysis of IL-1F cytokines, soluble inhibitors and receptors in a cohort of HS patients not treated with biological agents. Sixteen patients affected by HS and 16 healthy controls were recruited; clinical data were collected and disease severity evaluated by means of the International HS Severity Score System (IHS4). Serum levels of IL-1F cytokines, inhibitors and receptors were measured using a Multiplex Assays. IL-18 and free IL-18 levels were significantly higher in patients vs controls. Among soluble inhibitors, IL-1Ra, IL-1R2 and ST2/IL-1R4 were significantly increased. IL-18, free IL-18 and IL-33 levels are strongly correlated with IHS4. Also the inhibitors IL-1Ra and IL-18BP show a correlation with IHS4. The data obtained in this study confirm the involvement of IL-1F cytokines in mediating the disease and determining its severity and suggest a possible role for IL-18 as novel serum biomarker of active disease.

Identifying Differences between Semiclassical and Full-Quantum Descriptions of Plexcitons.

Strong light-matter coupling between molecules and plasmonic nanoparticles gives rise to new hybrid eigenstates of the coupled system, commonly referred to as polaritons or, more precisely, plexcitons. Over the past decade, it has been amply shown that molecular electron dynamics and photophysics can be drastically affected by such interactions, thus paving the way for light-induced control of molecular excited state properties and reactivity. Here, by combining the ab initio molecular description and classical or quantum modeling of arbitrarily shaped plasmonic nanostructures within the stochastic Schrödinger equation, we present two approaches, one semiclassical and one full-quantum, to follow in real time the electronic dynamics of plexcitons while realistically taking plasmonic dissipative losses into account. The full-quantum theory is compared with the semiclassical analogue under different interaction regimes, showing (numerically and theoretically) that even in the weak-field and weak-coupling limit a small-yet-observable difference arises.

Cord Blood Serum Levels of IL-31 and CCL17, Cutaneous Markers, and Development of Atopic Dermatitis.

Importance: Atopic dermatitis (AD) is the most prevalent chronic skin condition characterized by inflammation and itching. Currently, there is no reliable method for identifying which newborns might have an increased risk of developing AD. Objective: To evaluate the predictive value of serological biomarkers, such as CCL17/thymus- and activation-regulated chemokine, CCL18, CCL22, CCL27, IL-31, and thymus stromal lymphopoietin, with transepidermal water loss (TEWL) and hydration rate and the development of AD in infants. Design, Setting, and Participants: This observational prospective study included 40 consecutive full-term newborns from a single university hospital in Pisa, Italy. The cutaneous markers of infants were assessed at 1, 6, and 12 months of age, while the biomarkers from the 10-mL sample of cord blood taken at birth were measured after delivery. Data were collected from March to December 2018 and analyzed from January to April 2019. Main Outcomes and Measures: Level of serological biomarkers associated with TEWL and hydration rate, as well as the emergence of AD during the first 12 months of life. Results: All 40 included infants (27 male [68%]) completed the study. At 6 months, 16 infants presented symptoms and signs of AD (AD group) and 24 did not (non-AD group). Infants with AD signs had statistically significant anterior cubital fossa TEWL values at 1, 6, and 12 months of age compared to those without AD signs. No statistically significant correlations were observed between the TEWL measured at the anterior part of knee and hydration rate at the anterior cubital fossa at first month in the 2 groups. With regard to the blood biomarkers, at birth those in the AD group vs the non-AD group had statistically significant higher levels of CCL17/thymus- and activation-regulated chemokine (median [IQR], 716 [509-951] pg/mL vs 419 [24-566] pg/mL; P = .003) and IL-31 (median [IQR], 212 [114-409] pg/mL vs 97 [52-277] pg/mL; P = .04); in contrast, no statistically significant serum level differences were registered for thymus stromal lymphopoietin (median [IQR], 105 [66-295] pg/mL vs 88 [43-187] pg/mL), CCL18 (median [IQR], 1236 [1115-1605] pg/mL vs 1255 [1188-1677] pg/mL), CCL22 (median [IQR], 1032 [936-1454] pg/mL vs 1096 [932-1536] pg/mL), and CCL27 (median [IQR], 172 [122-251] pg/mL vs 120 [90-265] pg/mL). Conclusions and Relevance: In this observational study, the analysis of TEWL at the anterior cubital fossa area occurred prior to and correlated with the clinical signs of AD. Quantification of cytokines indicated that assessing cord blood serum levels of CCL17 and IL-31 could offer new perspectives in identifying newborns who might be susceptible to AD. Larger studies are needed to validate these findings.

Secukinumab in the Treatment of Psoriasis: A Narrative Review on Early Treatment and Real-World Evidence.

Psoriasis is a chronic, immune-mediated, inflammatory skin disease, associated with multiple comorbidities and psychological and psychiatric disorders. The quality of life of patients with this disease is severely compromised, especially in moderate-to-severe plaque psoriasis. Secukinumab, a fully humanized monoclonal antibody, was the first anti-interleukin (IL)-17 biologic approved for treating psoriasis. Secukinumab demonstrated long-lasting efficacy and a good safety profile in individuals with plaque psoriasis, and it is associated with an improvement in health-related quality of life. While there is evidence that early treatment with systemic therapy can affect disease progression and improve long-term outcomes in other autoimmune diseases, evidence is limited in psoriasis, especially in real-world settings. This review provides an overview of studies describing the effectiveness of secukinumab in the treatment of psoriasis summarizing the literature and focusing on real-world evidence and early intervention.

Evaluation of post-surgical complications of hidradenitis suppurativa lesions explored with presurgical ultra-high frequency ultrasound mapping.

OBJECTIVE: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicle. Its treatment often requires a surgical approach. The aim of our study was to evaluate the occurrence of post-surgical complications following a new standard of surgical management. This included presurgical lesion mapping by ultra-high frequency ultrasound (UHFUS) with a 70MHz probe. Postoperative management was based on the principles of HS-TIME (time, inflammation/infection, moisture, edges). METHOD: A single-centre, retrospective study was conducted by the Department of Dermatology of the University of Pisa. Patients with moderate and severe HS, refractory to previous medical and surgical therapies, were enrolled. All of the patients were treated with wide surgical excision of lesions, previously explored through a UHFUS evaluation with VEVO MD (Fujifilm VisualSonics, Inc., Canada) using a 48MHz and a 70MHz ultrasound probe. Following surgery, all patients were treated with secondary intention healing following the principles of HS-TIME. For each patient, we assessed the occurrence of post-surgical complications at follow-up visit six months after surgery. For each patient we assessed the occurrence of early post-surgical complications at every follow-up visit after surgery until complete wound healing. The occurrence of delayed complications was then assessed in all patients with an observation time after complete healing of >3 months (n=23). RESULTS: A total of 26 patients were enrolled in the study. There were no reported cases of post-surgical bleeding or haematoma occurrence, while three (11.5%) patients developed minor surgical site infection. The average severity of pain decreased from a numerical rating scale of 5.3 immediately after surgery to 1.3 after four weeks. The average healing time was 33.3±16.8 days, and only five (19.2%) patients reported a complete wound healing time of >6 weeks. Focusing on delayed complications: 1/23 (4.3%) patient had hypertrophic scarring; 2/23 (8.7%) patients reported dysaesthesia; and 2/23 (8.7%) cases of clinical relapse were reported. No cases of limited mobility at the surgery site were registered. CONCLUSION: The findings of the study demonstrated the efficacy of a novel surgical protocol, including a preoperative ultrasound evaluation and appropriate postoperative wound management. Further prospective studies are needed to validate the observed results; however, we conclude that the low recurrence rates and post-surgical complications confirmed that our proposed protocol would represent an effective strategy for the management of patients with HS eligible for surgical therapy.

Wound area severity index (WASI): A novel tool for assessing and predicting healing times in hidradenitis suppurativa postsurgical wounds.

Hidradenitis suppurativa (HS) presents challenges in management due to its chronic nature and high risk of recurrence. Post-surgical wound care plays a crucial role in treatment, even if standardized methods for assessing and predicting healing times are lacking. The aim of the study is to introduce the Wound Area Severity Index (WASI) as a novel tool to guide clinicians in assessing postsurgical wound progression and predicting potential healing times. A team of wound healing experts assessed 93 post-surgical HS wounds resulting from wide excision and secondary intention healing. For each wound healing time, wound area, wound bed score (WBS), and WASI were evaluated. WASI includes four parameters: area, temperature, depth and wound Bed, each with four severity levels. The total WASI score ranges from 4 to 16. Spearman correlation and Kruskal-Wallis tests were employed for statistical analysis. WASI strongly correlated with wound healing time (rho: 0.813, p < 0.001). Higher WASI scores were associated with prolonged healing, while lower scores indicated almost healed wounds. The WASI score has proven to be more highly predictive of healing times when compared to the individual parameter of the Area (moderate positive correlation, r: 0.77) and the WBS (negative correlation, r: -0.72). A total WASI score of 4 corresponded to a median healing time of 7 days, while a score exceeding 9 suggested a median healing time of 56 days. WASI has proven to be a valuable tool for assessing and predicting healing times in post-surgical HS wounds. Its simplicity, cost-effectiveness, and ability to integrate multiple parameters make it a promising addition to wound care practice.

Monoclonal Antibodies in the Management of Inflammation in Wound Healing: An Updated Literature Review.

Chronic wounds pose a significant clinical challenge due to their complex pathophysiology and the burden of long-term management. Monoclonal antibodies (mAbs) are emerging as a novel therapeutic option in managing difficult wounds, although comprehensive data on their use in wound care are lacking. This study aimed to explore existing scientific knowledge of mAbs in treating chronic wounds based on a rationale of direct inhibition of the main molecules involved in the underlying inflammatory pathophysiology. We performed a literature review excluding primary inflammatory conditions with potential ulcerative outcomes (e.g., hidradenitis suppurativa). mAbs were effective in treating wounds from 16 different etiologies. The most commonly treated conditions were pyoderma gangrenosum (treated with 12 different mAbs), lipoid necrobiosis, and cutaneous vasculitis (each treated with 3 different mAbs). Fourteen mAbs were analyzed in total. Rituximab was effective in 43.75% of cases (7/16 diseases), followed by tocilizumab (25%, 4/16 diseases), and both etanercept and adalimumab (18.75%, 3/16 conditions each). mAbs offer therapeutic potential for chronic wounds unresponsive to standard treatments. However, due to the complex molecular nature of wound healing, no single target molecule can be identified. Therefore, the use of mAbs should be considered as a translational approach for limited cases of multi-resistant conditions.

Presurgical Mapping With Ultra-high Frequency Ultrasound of Hidradenitis Suppurativa Lesions Treated With Wide Local Excision and Secondary Intention Healing.

BACKGROUND: Hidradenitis suppurativa (HS) is a challenging chronic inflammatory condition often requiring surgical intervention, such as wide local excision. Preoperative mapping with ultra-high frequency ultrasound (UHFUS) enables detailed assessment of lesion extension, particularly identifying tunnels and fistulas, facilitating surgical planning. OBJECTIVE: This study aimed to analyze recurrence rates of HS lesions previously mapped with UHFUS and treated with wide excision and secondary intention healing. MATERIALS AND METHODS: A retrospective single-center study enrolled 40 patients with HS undergoing wide excision surgery after UHFUS mapping. Patients were assessed weekly until complete healing and then every 3 months, evaluating clinical and sonographic signs of relapse and pain using the visual analogue scale. RESULTS: Results showed a population predominantly composed of women (65%) with a mean age of 39 years and a medium HS-Hurley score of 2.5. Over a 22-month follow-up, only 10% experienced clinical relapse, achieving an 90% total remission rate. Pain scores decreased significantly from Week 0 to Week 4. CONCLUSION: The study highlights the clinical challenge of HS management, particularly regarding surgical planning and lesion margin definition. The remission rate observed in this study suggests the effectiveness of UHFUS-guided surgical approaches. Future studies should extend observation periods to further validate these findings.

Age affects drug survival rates of interleukin (IL)-17 and IL-23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi-country, cohort study.

BACKGROUND: Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available. OBJECTIVES: To evaluate the drug survival of interleukin (IL)-23 or the IL-17 inhibitors approved for the treatment of moderate-to-severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival. METHODS: This retrospective multicentric cohort study included adult patients with moderate-to-severe psoriasis, dissecting two-patient subcohorts based on age: elderly versus younger adults. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log-rank p < 0.006). This difference was significant for treatment courses involving IL-23 inhibitors (p < 0.001) but not for those with IL-17 inhibitors (p = 0.2). According to both uni- and multi-variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062-1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010-1.422; p = 0.0377). Anti-IL-23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368-0.735; p < 0.001). Being previously treated with IL-17 inhibitors increased the probability of discontinuation. CONCLUSION: Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL-23 inhibitors. However, in stratified analyses conducted in elderly patients, IL-23 inhibitors showed higher drug survival rates than IL-17 inhibitors.

A Vision for the Future of Multiscale Modeling.

The rise of modern computer science enabled physical chemistry to make enormous progresses in understanding and harnessing natural and artificial phenomena. Nevertheless, despite the advances achieved over past decades, computational resources are still insufficient to thoroughly simulate extended systems from first principles. Indeed, countless biological, catalytic and photophysical processes require ab initio treatments to be properly described, but the breadth of length and time scales involved makes it practically unfeasible. A way to address these issues is to couple theories and algorithms working at different scales by dividing the system into domains treated at different levels of approximation, ranging from quantum mechanics to classical molecular dynamics, even including continuum electrodynamics. This approach is known as multiscale modeling and its use over the past 60 years has led to remarkable results. Considering the rapid advances in theory, algorithm design, and computing power, we believe multiscale modeling will massively grow into a dominant research methodology in the forthcoming years. Hereby we describe the main approaches developed within its realm, highlighting their achievements and current drawbacks, eventually proposing a plausible direction for future developments considering also the emergence of new computational techniques such as machine learning and quantum computing. We then discuss how advanced multiscale modeling methods could be exploited to address critical scientific challenges, focusing on the simulation of complex light-harvesting processes, such as natural photosynthesis. While doing so, we suggest a cutting-edge computational paradigm consisting in performing simultaneous multiscale calculations on a system allowing the various domains, treated with appropriate accuracy, to move and extend while they properly interact with each other. Although this vision is very ambitious, we believe the quick development of computer science will lead to both massive improvements and widespread use of these techniques, resulting in enormous progresses in physical chemistry and, eventually, in our society.

Risankizumab as a Therapeutic Approach for Recalcitrant Pyoderma Gangrenosum.

ABSTRACT: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that is challenging to diagnose and treat. Clinicians frequently use fast-acting corticosteroids, which are subsequently combined with slower-acting immunosuppressants to progressively taper the corticosteroid dosage. Current research is focused on the use of monoclonal antibodies (mAbs) directed against target molecules involved in the pathogenesis of PG. However, available data on their efficacy are based on sporadic case reports and clinical experiences, so the authors aimed to evaluate the efficacy of risankizumab, an anti-interleukin-23 mAb, in the management of two complex PG cases. The authors enrolled two patients with PG who were already treated with immunosuppressive therapies. Their management was based on the off-label use of an mAb directed against the p19 subunit of interleukin-23: risankizumab. Patients received subcutaneous injections of 150 mg at the start of treatment, at week 4, and then every 10 weeks thereafter. Systemic therapy was combined with local management of ulcers, based on the principles of TIME (tissue, infection, moisture balance, and epithelialization) applied to the inflammatory and noninflammatory phases of PG. Clinical resolution was obtained at week 24 for patient 1 and week 16 for patient 2 and was maintained until week 40, without adverse effects or disease recurrence. These clinical cases demonstrate that risankizumab is a valid tool in terms of efficacy and safety for complicated cases of multirefractory PG when provided in parallel with local personalized wound management.

Unique combination of hyaluronic acid and amino acids in the management of patients with a range of moderate-to-severe chronic wounds: Evidence from international clinical trials.

Chronic wounds present a prolonged burden to patients, their families and healthcare systems. There is evidence that the unique combination of hyaluronic acid (HA) and amino acids (Vulnamin®) promotes re-epithelialization of wounds and stimulates activation and proliferation of fibroblasts with a significant increase in the regeneration of epithelial cells. Tissue regeneration and tissue repair are considered to be the fundamental activities of this unique combination of HA and amino acids that distinguishes it from other wound healing products. A review of trials over the last 15 years indicates distinct advantages of the unique combination of HA and amino acids, in terms of healing rate and induction of granulation tissue production compared with HA alone.

Unique combination of hyaluronic acid and amino acids in the management of patients with a wide range of moderate-to-severe chronic wounds: Evidence from international clinical practice.

The availability of new products and strategies to manage wounds has taken a quantum leap in recent years. Healthcare professionals now have an extensive range of products to choose from, but while positive this also raises dilemmas in real-world clinical practice to decide on the most appropriate treatment for a given patient. Clinical trials confirm the effectiveness of the unique combination of hyaluronic acid and amino acids (Vulnamin®) in a range of wounds, but are these results replicated in real-world clinical practice? International experts presented their clinical experience with the use of the combination in difficult-to-treat wounds. The objective was to reach a consensus on how and when to use the unique combination products to provide a cost-effective, convenient option, in all healthcare settings that improves QoL for patients and their carers.

Unraveling the mechanism of tip-enhanced molecular energy transfer.

Electronic Energy Transfer (EET) between chromophores is fundamental in many natural light-harvesting complexes, serving as a critical step for solar energy funneling in photosynthetic plants and bacteria. The complicated role of the environment in mediating this process in natural architectures has been addressed by recent scanning tunneling microscope experiments involving EET between two molecules supported on a solid substrate. These measurements demonstrated that EET in such conditions has peculiar features, such as a steep dependence on the donor-acceptor distance, reminiscent of a short-range mechanism more than of a Förster-like process. By using state of the art hybrid ab initio/electromagnetic modeling, here we provide a comprehensive theoretical analysis of tip-enhanced EET. In particular, we show that this process can be understood as a complex interplay of electromagnetic-based molecular plasmonic processes, whose result may effectively mimic short range effects. Therefore, the established identification of an exponential decay with Dexter-like effects does not hold for tip-enhanced EET, and accurate electromagnetic modeling is needed to identify the EET mechanism.