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.

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.

Guidelines How to Integrate Surgery and Targeted Therapy with Biologics for the Treatment of Hidradenitis Suppurativa: Delphi Consensus Statements from an Italian Expert Panel.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent and painful nodules and abscesses in intertriginous skin areas, which can progress to sinus tract formation, tissue destruction, and scarring. HS is highly debilitating and severely impairs the psychological well-being and quality of life of patients. The therapeutic approach to HS is based on medical therapy and surgery. First-line medical therapy includes topical antibiotics, systemic antibiotics, and biologics. Main surgical procedures include deroofing, local excision, and wide local excision. Despite the availability of multiple therapeutic options, the rates of disease recurrence and progression continue to be high. In recent years, the possibility of combining biologic therapy and surgery has raised considerable interest. In a clinical trial, the perioperative use of adalimumab has been associated with greater response rates and improved inflammatory load and pain, with no increased risk of postoperative infectious complications. However, several practical aspects of combined biologic therapy and surgery are poorly defined. In June 2022, nine Italian HS experts convened to address issues related to the integration of biologic therapy and surgery in clinical practice. To this purpose, the experts identified 10 areas of interest based on published evidence and personal experience: (1) patient profiling (diagnostic criteria, disease severity classification, assessment of response to treatment, patient-reported outcomes, comorbidities); (2) tailoring surgery to HS characteristics; (3) wide local excision; (4) presurgery biologic treatment; (5) concomitant biologic and surgical treatments; (6) pre- and postsurgery management; (7) antibiotic systemic therapy; (8) biologic therapy after radical surgery; (9) management of adverse events to biologics; and (10) management of postoperative infectious complications. Consensus between experts was reached using the Estimate-Talk-Estimate method (Delphi Method). The statements were subsequently presented to a panel of 27 HS experts from across Italy, and their agreement was assessed using the UCLA Appropriateness Method. This article presents and discusses the consensus statements.

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.

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.

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.

Non-invasive imaging techniques in presurgical margin assessment of basal cell carcinoma: Current evidence.

BACKGROUND: The diagnosis of basal cell carcinoma (BCC) is based on clinical and dermoscopical features. In uncertain cases, innovative imaging techniques, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), have been used. The main limitation of these techniques is the inability to study deep margins. HFUS (high-frequency ultrasound) and the most recent UHFUS (ultra-high-frequency ultrasound) have been used in various applications in dermatology, but they are not yet routinely used in the diagnosis of BCC. A key point in clinical practice is to find an imaging technique that can help to reduce post-surgical recurrences with a careful presurgical assessment of the lesional margins. This technique should show high sensitivity, specificity, reproducibility and simplicity of execution. This concept is very important for the optimal management of patients who are often elderly and have many comorbidities. The aim of the paper is to analyse the characteristics of current imaging techniques and the studies in the literature on this topic. MATERIALS AND METHODS: The authors independently searched the MEDLINE, PubMed, Embase, Scopus, ScienceDirect and Cochrane Library databases for studies looking for non-invasive imaging techniques for the presurgical margin assessment of BCC. RESULTS: Preoperative study of the BCC subtype can help to obtain a complete excision with free margins. Different non-invasive imaging techniques have been studied for in vivo evaluation of tumour margins, comparing the histologic evaluation with a radical surgery. The possibility to study the lateral and deep margins would allow a reduction of recurrences and sparing of healthy tissue. CONCLUSION: HFUS and UHFUS represent the most promising, non-invasive techniques for the pre-operative study of BCC facilitating the characterization of vascularization, deep lateral margins and high-risk subtypes, although they are limited by insufficient literature unlike RCM and OCT.

Real-life effectiveness and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: A 104-week multicenter retrospective study - IL PSO (ITALIAN LANDSCAPE PSORIASIS).

BACKGROUND: Guselkumab is a fully human monoclonal antibody that binds selectively to the p19 subunit of interleukin-23, which has shown efficacy in patients with previous incomplete response to ustekinumab in the NAVIGATE clinical trial. [Correction added on [28-02-2023], after first online publication: 'humanized monoclonal antibody' has been changed to 'fully human monoclonal antibody' in the preceding sentence.] OBJECTIVES: We conducted a 104-week multicenter retrospective study to assess the effectiveness and safety of guselkumab in patients affected by plaque psoriasis with an inadequate response to ustekinumab in a real-life setting. METHODS: Our retrospective study included 233 adults affected by moderate-to-severe plaque psoriasis, enrolled in 14 different Italian centres, and treated with guselkumab after failing therapy with ustekinumab. Patient characteristics and PASI (Psoriasis Area and Severity Index) score at each visit (baseline, weeks 16, 52 and 104) were recorded. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI, compared with baseline, were registered. RESULTS: At week 52, PASI 75 was reached by 89.88% of patients, PASI 90 by 71.43%, PASI 100 by 58.83% and absolute PASI ≤2 by 90.48%. At week 104, similar effectiveness results were observed. Compared to the NAVIGATE trial, we observed higher rates of PASI 75/90/100. Patients with the involvement of difficult-to-treat areas were significantly less likely to achieve PASI90 and PASI100 at week 16. Obese patients had significantly lower rates of PASI75 and PASI ≤2 at week 52. At week 104, comparable responses were observed among all patients' subgroups, regardless of BMI status, involvement of difficult-to-treat areas, presence of cardiometabolic comorbidities and concomitant psoriatic arthritis. No significant safety findings were reported throughout the study. CONCLUSION: Our data suggest that the efficacy of guselkumab in patients with inadequate response to ustekinumab for plaque psoriasis in 'real-life' clinical practice is comparable with NAVIGATE study with higher percentages of patients achieving PASI90 and PASI100 at weeks 16, 52 and 104.

Real-life effectiveness of tildrakizumab in chronic plaque psoriasis: A 52-week multicentre retrospective study-IL PSO (Italian landscape psoriasis).

BACKGROUND: Tildrakizumab is a humanized monoclonal antibody that binds selectively the p19 subunit of interleukin-23. It is approved for treatment of moderate-severe chronic plaque psoriasis. OBJECTIVES: We conducted a 52-week retrospective study to assess the effectiveness and safety of tildrakizumab in a real-life setting. METHODS: Our retrospective study included 237 consecutive adults with moderate-to-severe plaque psoriasis, enrolled in 10 different Italian centres, treated with tildrakizumab up to Week 52. Patient characteristics, comorbidities, previous treatments and the PASI (Psoriasis Area and Severity Index) score at each visit (baseline, Week 16, Week 28 and Week 52) were retrieved from the electronic medical records. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI with respect to baseline PASI were registered. RESULTS: At Week 52, 90.91%, 73.55% and 58.68% of patients achieved a PASI reduction ≥75% (PASI 75), PASI 90 and PASI 100, respectively. An absolute PASI ≤ 2 was reached by 85.95% at Week 52. Compared with Phase 3 clinical trials, we observed similar rates of PASI 75/90 responses and higher percentages of patients achieving PASI 100. Patients who had not responded to previous biologic treatments and patients with cardio-metabolic comorbidities were significantly more likely to achieve PASI 100 at Week 28 and PASI 90 at Week 52. The higher body mass index did not interfere with the odds of reaching PASI 75/90/100 at each time point. No significant safety findings were recorded throughout the study, and none of the patients had to interrupt the treatment because of adverse events. CONCLUSION: Our data suggest that the efficacy of tildrakizumab for plaque psoriasis in 'real-life' clinical practice is comparable with Phase 3 clinical trials with higher percentages of patients achieving complete skin clearance (PASI 100) at Weeks 16, 28 and 52.

Ultra-High Frequency Ultrasound in Melanoma Management: A New Combined Ultrasonographic-Histopathological Approach.

OBJECTIVES: The main aim of this study is to evaluate the correspondence between the ultrasonographic thickness and the Breslow thickness in melanoma using ultra-high frequency ultrasound and the intra- and inter-operator repeatability in the ultrasonographic measurements of melanoma depth. Moreover, we propose a new protocol based on a combined ultrasonographic-histopathological approach. METHODS: We analyzed 27 melanomas in a population consisted of 27 patients (mean age 57.6 years, 51.8% males), who came at the Department of Dermatology (University of Pisa, Pisa, Italy) from April 2016 to March 2018 and had an ultrasonographic examination of a suspected lesion before the surgical removal using ultra-high frequency ultrasound (Vevo®MD, Fujifilm, Visualsonics, Toronto, Canada; 70 MHz probe). B-mode images were analyzed by two skilled and blinded operators, and the maximum depth of the lesions was measured using a dedicated graphical user interface developed in Matlab R2016b (MathWorks Inc., Natick, MA), to obtain repetitive measurements. RESULTS: All melanomas appeared as band-like or oval/fusiform shaped hypoechoic inhomogeneous lesions. We observed an excellent agreement between the Breslow thickness of melanomas and the ultrasonographic thickness, as well as a reduced intra- and inter-operator variability in the ultrasonographic measurements of melanoma depth. CONCLUSIONS: We propose a ultrasonographic-histopathological protocol which may help clinicians to reduce the diagnostic delay, improve prognosis and survival rates, perform a surgical excision with negative margins, and reduce the variability in the assessment of Breslow thickness.

Effectiveness of Flattening-Filter-Free versus Flattened Beams in V79 and Glioblastoma Patient-Derived Stem-like Cells.

Literature data on the administration of conventional high-dose beams with (FF) or without flattening filters (FFF) show conflicting results on biological effects at the cellular level. To contribute to this field, we irradiated V79 Chinese hamster lung fibroblasts and two patient-derived glioblastoma stem-like cell lines (GSCs-named #1 and #83) using a clinical 10 MV accelerator with FF (at 4 Gy/min) and FFF (at two dose rates 4 and 24 Gy/min). Cell killing and DNA damage induction, determined using the γ-H2AX assay, and gene expression were studied. No significant differences in the early survival of V79 cells were observed as a function of dose rates and FF or FFF beams, while a trend of reduction in late survival was observed at the highest dose rate with the FFF beam. GSCs showed similar survival levels as a function of dose rates, both delivered in the FFF regimen. The amount of DNA damage measured for both dose rates after 2 h was much higher in line #1 than in line #83, with statistically significant differences between the two dose rates only in line #83. The gene expression analysis of the two GSC lines indicates gene signatures mimicking the prognosis of glioblastoma (GBM) patients derived from a public database. Overall, the results support the current use of FFF and highlight the possibility of identifying patients with candidate gene signatures that could benefit from irradiation with FFF beams at a high dose rate.

Reusable Cavitand-Based Electrospun Membranes for the Removal of Polycyclic Aromatic Hydrocarbons from Water.

The removal of toxic and carcinogenic polycyclic aromatic hydrocarbons (PAHs) from water is one of the most intractable environmental problems nowadays, because of their resistance to remediation. This work introduces a highly efficient, regenerable membrane for the removal of PAHs from water, featuring excellent filter performance and pH-driven release, thanks to the integration of a cavitand receptor in electrospun polyacrylonitrile (PAN) fibers. The role of the cavitand receptor is to act as molecular gripper for the uptake/release of PAHs. To this purpose, the deep cavity cavitand BenzoQxCav is designed and synthetized and its molecular structure is elucidated via X-Ray diffraction. The removal efficiency of the new adsorbent material toward the 16 priority PAHs is demonstrated via GC-MS analyses at ng L-1 concentration. A removal efficiency in the 32%, to 99% range is obtained. The regeneration of the membrane is performed by exploiting the pH-driven conformational switching of the cavitand between the vase form, where the PAHs uptake takes place, to the kite one, where the PAHs release occurs. The absorbance and regeneration capability of the membrane are successfully tested in four uptake/release cycles and the morphological stability.

Ultra-high frequency ultrasound detection of the dermo-epidermal junction: Its potential role in dermatology.

Traditional high-frequency ultrasound (HFUS; 20 MHz) is a non-invasive method used to study skin in vivo but is not able to measure skin thickness accurately and to identify the dermal-epidermal junction (DEJ). Ultra-high frequency ultrasound (UHFUS; 70-100 MHz) has sub-millimetre resolution comparable to histology. The aim of this study was to identify, by UHFUS, the DEJ and to describe skin differences in healthy individuals by providing a measure of skin thickness, based on age and gender. We also described the bullous pemphigoid lesion. We enrolled 42 patients divided into 2 groups: A and B. Group A included 32 healthy volunteers aged 22-74 years. Group B consisted of 10 patients with bullous pemphigoid. For each patient in group A, 8 ultrasound (US) clips by 70 MHz probe were performed at forehead, cheek, nose, forearm, abdomen, chest, back and leg. For each patient in group B, 5 US images were acquired at blisters roofs and edges. In each US image, we measured thickness of stratum corneum (α-ß), epidermis (α-γ) and epidermis plus dermis (α-δ). In both groups, we found the presence of 4 lines delimiting: the stratum corneum (the layer between α-line and ß-line), the epidermis (distance between α- and γ-line), and the boundary between dermis and subcutis (δ-line). The γ-line corresponds to the point of detachment of the bullae. The abdominal α-ß layer was thicker in males (p = 0.019) and α-δ thickness at cheeks (p < 0.001), chest (p = 0.007), back (p = 0.025) and forearm (p < 0.001). In females, α-γ thickness of the back was greater (p = 0.005). In old people compared to young, we noticed an increase of α-ß layer at forehead and chest (p = 0.014), an increase of α-γ layer at forearm (p = 0.001), back (p = 0.024) and leg (p = 0.010) and an increase of α-δ layer at forehead (p = 0.001) and nose (p = 0.049). UHFUS is an advanced imaging technique that can detect both the DEJ and the boundary between dermis and subcutaneous tissue so that epidermal and dermal thickness can be measured with good accuracy. Regarding gender and age, skin differences obtained with UHFUS were comparable to other non-invasive methods.

Impact of psychiatric comorbidities in psoriasis, hidradenitis suppurativa and atopic dermatitis: The importance of a psychodermatological approach.

BACKGROUND: There is a strong interaction between the immunological and nervous system in the skin. Lesions that are physically disfiguring and chronically relapsing have a high impact on quality of life (QoL) and can result in the emergence of psychiatric disorders. The literature data confirm a higher prevalence of psychiatric disorders in patients with psoriasis, hidradenitis suppurativa (HS) and atopic dermatitis (AD), but such data are compromised by low-quality evidence due to methodological heterogeneity. OBJECTIVES: The primary aim was to analyse the prevalence of psychiatric comorbidities in a group of psoriasis, AD and HS patients compared with a control group. The secondary aims were to evaluate the impact of psychiatric comorbidities on the disease development, severity, flare-ups and QoL. METHODS: A total of 59 cases and 64 controls were included. RESULTS: Generalized anxiety disorder and depressive disorder with anxious distress were found to be risk factors for AD. Age, smoking and substance-related disorder showed a specific association with HS. Major depressive disorder showed a specific association with dermatology life quality index (DLQI) and all the above disease flare-ups. CONCLUSIONS: Atopic dermatitis, psoriasis and HS are associated with psychiatric disorders. A psychodermatological approach improves outcomes in terms of QoL, disease flare-ups and long-term management.

Ultra-high-frequency ultrasound and machine learning approaches for the differential diagnosis of melanocytic lesions.

Malignant melanoma (MM) is one of the most dangerous skin cancers. The aim of this study was to present a potential new method for the differential diagnosis of MM from melanocytic naevi (MN). We examined 20 MM and 19 MN with a new ultra-high-frequency ultrasound (UHFUS) equipped with a 70 MHz linear probe. Ultrasonographic images were processed for calculating 8 morphological parameters (area, perimeter, circularity, area ratio, standard deviation of normalized radial range, roughness index, overlap ratio and normalized residual mean square value) and 122 texture parameters. Colour Doppler images were used to evaluate the vascularization. Features reduction was implemented by means of principal component analysis (PCA), and 23 classification algorithms were tested on the reduced features using histological response as ground-truth. Best results were obtained using only the first component of the PCA and the weighted k-nearest neighbour classifier; this combination led to an accuracy of 76.9%, area under the ROC curve of 83%, sensitivity of 84% and specificity of 70%. The histological analysis still remains the gold-standard, but the UHFUS images processing using a machine learning approach could represent a new non-invasive approach.

A real-life experience as a proof of Guselkumab effectiveness and safety in patients with moderate to severe psoriasis.

Psoriasis is a skin disorder characterized by chronic inflammation driven by different immunologic pathways, among which the IL-23/Th17 axis plays a pivotal role. For this reason, the use of IL23p19 inhibitors in psoriasis treatment has been evaluated over the years. Guselkumab, a totally human IgG1 lambda monoclonal antibody, that selectively blocks the p 19 subunit of IL- 23 has demonstrated high efficacy and safety throughout several, randomized, double-blind phase III trials (VOYAGE 1 and 2, NAVIGATE and ECLIPSE). We designed a single-center retrospective cohort study in a population consisting of 46 patients followed from December 2018 to April 2021. After a diagnosis of moderate to severe psoriasis, all the patients were considered suitable to receive treatment with Guselkumab. In our population, among those who achieved clinical improvement in terms of Psoriasis Area Severity Index (PASI), PASI 75, 90, and 100 were achieved on average on weeks 14, 19, 21 respectively. We then analyzed a subgroup of our population, consisting of 35 patients, who had an identical follow-up time of 28 weeks, thus observing the trend in mean PASI at subsequent assessments and the number of patients who had reached PASI 75, PASI 90, and PASI 100 at week 4 (10; 3; 1), week 12 (12; 13; 11), week 20 (7; 6; 2), and week 28 (1; 4; 6), respectively. The results obtained are in line with those obtained from previous studies, thus confirming that Guselkumab is an excellent choice in terms of security, long-term efficacy, and overall tolerance.

Real life long-term efficacy and safety of ixekizumab in moderate-to-severe psoriasis: A 192 weeks multicentric retrospective study-IL PSO (Italian landscape psoriasis).

Psoriasis is one of the commonest inflammatory skin diseases determining a very high impact on patients' quality of life and daily activities and relationships. Several biologic therapies have been approved through the years for the treatment of moderate-to-severe plaque psoriasis, and efficacy and safety profile have been analyzed in clinical trials. Ixekizumab is an immunoglobulin G subclass 4 monoclonal antibody that selectively targets and binds IL-17A with high specificity and affinity. Inhibiting IL-17A activity, ixekizumab reduces and turns down levels of inflammation, resulting in the clinical improvement of the disease. Long-term efficacy and safety profile of ixekizumab have been investigated and reported in the UNCOVER trials, but in literature there are only few studies based on real life experience. We present the efficacy and safety profile of ixekizumab in a cohort of 779 patients affected by moderate-to-severe plaque psoriasis and treated with ixekizumab in 11 Italian dermatology hospitals, with a follow-up of care until 192 weeks.

Hidradenitis Suppurativa in a Large Cohort of Italian Patients: Evaluation of the Burden of Disease.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually occurs after puberty with painful, deep-seated, inflamed nodules and sinus tracts in the apocrine gland-bearing areas of the body, most commonly the axillae and inguinal and anogenital regions, with a relevant impact on patients' quality of life (QoL). OBJECTIVE: To evaluate how the burden of HS disease impacts on patient well-being and working activities in a large Italian population over a period of 9 months. METHODS: A multicenter, prospective, epidemiologic cohort study was conducted in adult Italian patients with HS. HS severity was assessed through Hurley stage and HS Physician's Global Assessment (HS-PGA), clinical improvement by HS Clinical Response (HiSCR) and partial response, and disease burden through QoL questionnaires (HIDRAdisk, Skindex-16, Dermatology Life Quality Index [DLQI]), and Work Productivity and Activity Impairment - General Health (WPAI:GH). RESULTS: A total of 308 patients (56.2% women; mean age 35.2 ± 12.9 years) were enrolled in 27 dermatologic clinics. Men were older (37.4 years vs. 33.5), more smoking addicted (74.1% vs. 60.1%), and alcohol consumer (34.1% vs. 13.9%), while more women were obese (34.10% vs. 22.22%). At baseline, most patients had a Hurley severity stage of 2 (43.9%), a moderate HS-PGA score (57.1%), and poor QoL (HIDRAdisk: 65.7 ± 23.3, Skindex-16: 60.3 ± 26.9, and DLQI: 10.8 ± 8.1). Patients with more severe disease showed worse QoL. Mean values for the variables related to HS severity decreased during the study period. The achievement of HiSCR and partial response increased during the study. CONCLUSION: This study offers insight into the disease burden of HS in an Italian population. Our results underline the impact of QoL evaluation, also with the use of the HIDRAdisk, in clinical routine as a support to validated severity clinical and instrumental indexes for a "360-degree" assessment of HS patient's burden of disease.

Changes in Radiosensitivity to Gamma-Rays of Lymphocytes from Hyperthyroid Patients Treated with I-131.

This study investigated the peripheral blood lymphocytes (PBL) response to a dose of γ-rays in patients treated with radioiodine (I-131) for hyperthyroidism vs. healthy controls, to gain information about the individual lymphocytes' radio-sensitivity. Blood samples were taken from 18 patients and 10 healthy donors. Phosphorylated histone variant H2AX (γ-H2AX) and micronuclei (MN) induction were used to determine the change in PBL radio-sensitivity and the correlations between the two types of damage. The two assays showed large inter-individual variability in PBL background damage and in radio-sensitivity (patients vs. healthy donors). In particular, they showed an increased radio-sensitivity in 36% and 33% of patients, decrease in 36% and 44%, respectively. There was a scarce correlation between the two assays and no dependence on age or gender. A significant association was found between high radio-sensitivity conditions and induced hypothyroidism. PBL radio-sensitivity in the patient group was not significantly affected by treatment with I-131, whereas there were significant changes inter-individually. The association found between clinical response and PBL radio-sensitivity suggests that the latter could be used in view of the development of personalized treatments.

Evaluation of neutrophil extracellular trap deregulated formation in pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic dermatose (ND) characterized by a dense neutrophilic infiltrate in the affected tissue. Neutrophil extracellular traps (NETs) are web-like structures released by neutrophils and composed of cytosolic and granule proteins assembled on a scaffold of decondensed chromatin. Very little is known about the role of NETosis in PG. Here, we assessed the possible implication of NETosis in the pathogenesis of PG by investigating the NETosis in the ulcers of 26 PG patients. We demonstrated that neutrophils in the PG skin lesions undergo an aberrant level of NETosis in 100% of the analysed cases (N = 26). All control and abscess biopsies were instead negative for the NETosis. In addition, neutrophils from peripheral blood of PG patients showed a significantly higher rate of spontaneous, but not induced, NETosis. Overall, this study suggests that the NETosis may contribute to systemic inflammation and tissue destruction in PG, thus representing a possible novel therapeutic target.