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Purpose Tildrakizumab is a selective inhibitor of IL-23 approved for the treatment of moderate-to-severe plaque psoriasis in two dosages. We conducted a 16-week multicenter retrospective study to compare the effectiveness and safety of tildrakizumab 200 mg versus tildrakizumab 100 mg in patients with a high disease burden or high body weight.Materials and methods Our retrospective study included 134 patients treated with tildrakizumab 200 mg and 364 patients treated with tildrakizumab 100 mg from 28 Italian Dermatology Units affected by moderate-to-severe plaque psoriasis. The patients had a body weight above 90 kg or a high disease burden (Psoriasis Area and Severity Index [PASI] ≥ 16 or the involvement of difficult-to-treat areas). We evaluated the effectiveness of tildrakizumab at the week-16 visit in terms of PASI90, PASI100 and absolute PASI ≤ 2.Results After 16 weeks of treatment with tildrakizumab 200 mg, PASI90 was reached by 57.5% of patients and PASI100 by 39.6% of patients. At the same time point, 34.3% and 24.2% of patients treated with tildrakizumab 100 mg achieved PASI90 and PASI100, respectively.Conclusions Our data suggest that tildrakizumab 200 mg has better effectiveness than tildrakizumab 100 mg in patients with a body weight ≥ 90 kg and a high disease burden.

Abstract Introduction The introduction of biological therapies has revolutionized the treatment of moderate-to-severe plaque psoriasis. In particular, ixekizumab, an inhibitor of interleukin-17A, has shown great results in terms of efficacy and safety in both clinical trials and real-world experiences. However, there is a lack of long-term real-world data available for ixekizumab. Methods We conducted a multicenter real-life study to evaluate the effectiveness and safety of ixekizumab in patients with moderate-to-severe plaque psoriasis. Psoriasis Area and Severity Index score (PASI) was collected at baseline and after 1, 2, 3, 4, and 5 years. The occurrence of any adverse events was recorded at each time point. Results We enrolled 1096 patients treated with ixekizumab for at least 1 year. At week 52, the percentages of PASI 90 and PASI 100 were 85.04% and 69.07%, respectively. After 5 years of treatment with ixekizumab, out of 145 patients, a PASI 90 response was achieved by 86.90% of patients, while complete skin clearance was reached by 68.28% of patients. We did not observe any new significant safety findings throughout the study period. Conclusion This study supports the long-term effectiveness and safety of ixekizumab in a real-world setting.

Introduction: Psoriasis and hidradenitis suppurativa (HS) are chronic inflammatory diseases with significant overlap in their immunologic pathways, which involve cytokines such as tumor necrosis factor-alfa, interleukin (IL)-17, and IL-23. Current treatment options for HS are limited, as only adalimumab and secukinumab are approved for severe cases. Given the overlapping pathogenetic features between HS and psoriasis, anti-IL-17 and anti-IL-23 drugs could represent valuable treatments for the management of HS. Objectives: We sought to evaluate the effectiveness and safety of anti-IL-17 and anti-IL-23 drugs in patients with HS and concomitant moderate-to-severe plaque psoriasis. Methods: We conducted a multicenter retrospective study in 11 Italian Dermatology Units. The effectiveness of the drugs was evaluated by assessing the percentage of patients achieving HS Clinical Response (HiSCR) each week. Results: We enrolled 41 patients with at least 16 weeks of follow-up, with 17 of them completing 52 weeks of treatment. The most commonly prescribed anti-IL drug was secukinumab (27 patients), followed by ixekizumab (5) and guselkumab (5). The HiSCR was achieved by 39%, 74.3%, and 77.8% of patients after 16, 32, and 52 weeks, respectively. No severe adverse events (AEs) or AEs leading to discontinuation were observed during the study. The most common AE was nasopharyngitis (4 patients). Conclusion: In this real-world study, we highlight the effectiveness of anti-IL-23 and anti-IL-17 drugs in the treatment of concomitant plaque psoriasis and severe HS. Longer and larger studies are needed to further evaluate the long-term effectiveness and safety of these treatments in patients affected by HS.

Abstract Background Monoclonal antibodies (mAbs) directed against tumour necrosis factor alpha (TNF‐α) and interleukin (IL)‐17 and ‐23 represent the ultimate therapeutic strategy in treating psoriasis patients, but scientific literature still does not provide conclusive results regarding the possible influence of previous biological therapies on real‐life therapeutic response. Objectives The objective of our work was to investigate any putative difference in the achievement and maintenance of PASI 75, 90 and 100, as well as the probability to achieve absolute PASI ≤ 1 and ≤3, between 305 bio‐naïve and bio‐experienced patients treated with anti‐IL mAbs. Methods A comparison between previous biologic and clinical factors, including relative and absolute PASI, was carried out through chi square test. Survival curves for the achievement of PASI 75, 90 and 100 and their differences were evaluated, performing a multivariate analysis (confidence interval 95%; p

(1) Background/Objectives: Nail psoriasis (NP) is a chronic and difficult-to-treat disease, which causes significant social stigma and impairs the patients’ quality of life. Moreover, nail psoriasis is a true therapeutic challenge for clinicians. The presence of nail psoriasis can be part of a severe form of psoriasis and can have predictive value for the development of psoriatic arthritis. Our real-world-evidence multicenter study aims to evaluate the efficacy of bimekizumab in nail psoriasis. (2) Methods: A retrospective analysis of a multicenter observational study included 834 patients affected by moderate-to-severe psoriasis, in 33 Dermatologic Units in Italy, treated with bimekizumab from December 2022 to September 2023. Clinimetric assessments were based on Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Physician’s Global Assessment of Fingernail Psoriasis (PGA-F) for the severity of nail psoriasis at 0, 12, 24, and 36 weeks. (3) Results: Psoriatic nail involvement was present in 27.95% of patients. The percentage of patients who achieved a complete clearance of NP in terms of PGA-F 0 was 31.7%, 57%, and 88.5% at week 4, 16, and 36, respectively. PASI 100 was achieved by 32.03% of patients at week 4, by 61.8% at week 16, and by 78.92% of patients at week 36. The mean baseline PASI was 16.24. The mean DLQI values for the entire group of patients at baseline, at week 4, at week 16, and at week 36 were 14.62, 3.02, 0.83, and 0.5, respectively. (4) Conclusions: Therapies that promote the healing of both the skin and nails in a short time can also ensure a lower risk of subsequently developing arthritis which is disabling over time. Bimekizumab proved to be particularly effective to treat NP, with a fast response in terms of complete clearance, with over 88.5% of patients free from NP after 36 weeks. The findings of our real-world study showed that patients with moderate-to-severe PsO and concomitant NP had significantly faster and more substantial improvements in NP up to 36 weeks with respect to previous research findings. Considering the rapid healing of the nail, the dual inhibition of IL17 A and F might have a great value in re-establishing the dysregulation of keratin 17 at the nail level.

Introduction: Genital involvement is observed in approximately 60% of patients with psoriasis, presenting clinicians with formidable challenges in treatment. While new biologic drugs have emerged as safe and effective options for managing psoriasis, their efficacy in challenging-to-treat areas remains inadequately explored. Intriguingly, studies have shown that interleukin (IL)-17 inhibitors exhibit effectiveness in addressing genital psoriasis. Objectives: We aimed to determine the effectiveness profile of bimekizumab in patients affected by moderate-to-severe plaque psoriasis with involvement of genitalia. Methods: Bimekizumab, a dual inhibitor of both IL-17A and IL-17F, was the focus of our 16-week study, demonstrating highly favorable outcomes for patients with genital psoriasis. The effectiveness of bimekizumab was evaluated in terms of improvement in Static Physician's Global Assessment of Genitalia (sPGA-G) and Psoriasis Area and Severity Index. Results: Sixty-five adult patients were enrolled. Remarkably, 98.4% of our participants achieved a clear sPGA-G score (s-PGA-g=0) within 16 weeks. Moreover, consistent improvements were observed in PASI scores, accompanied by a significant reduction in the mean Dermatology Life Quality Index (DLQI), signifying enhanced quality of life. Notably, none of the patients reported a severe impairment in their quality of life after 16 weeks of treatment. In our cohort of 65 patients, subgroup analyses unveiled that the effectiveness of bimekizumab remained unaffected by prior exposure to other biologics or by obesity. Conclusions: Our initial findings suggest that bimekizumab may serve as a valuable treatment option for genital psoriasis. Nevertheless, further research with larger sample sizes and longer-term follow-up is imperative to conclusively validate these results.

IntroductionThe development of several effective biological drugs for moderate-to-severe plaque psoriasis has dramatically changed the lives of patients. Despite the wide use of interleukin (IL) inhibitors, limited data are available to date regarding long-term treatment persistence.MethodThis multicenter retrospective real-world study evaluated 5932 treatment courses across 5300 patients, all treated with interleukin inhibitors. Drug survival was expressed by using the Kaplan-Meier estimator for each biological drug at 6, 12, 24, 36 and 48 months. We also stratified by discontinuation associated with primary or secondary ineffectiveness.ResultsIn our study, the most prescribed drugs were secukinumab (1412), ixekizumab (1183), and risankizumab (977). After four years of follow-up, risankizumab emerged as the treatment with the highest drug survival overall, as 91.6% of patients were still on treatment. The overall probability of drug survival at four years was comparable for tildrakizumab (83.5%), ixekizumab (82.6%), guselkumab (82.4%) and brodalumab (81.8%). When evaluating only patients who discontinued the treatment because of ineffectiveness, once again risankizumab was the molecule with the highest drug survival at 4 years (93.4%), this time followed by ixekizumab (87%). Our study, in which all IL inhibitors were adequately represented, confirmed a slightly better treatment persistence for IL-23 inhibitors, consistent with other real-world studies.ConclusionOur experience showed that IL-23 inhibitors, and risankizumab in particular, had a higher probability of drug survival overall during a 4-year follow-up. Risankizumab and ixekizumab were less likely to be discontinued because of ineffectiveness after four years.

One of the most intriguing and still pending questions in radiobiology is to understand whether and how natural environmental background radiation has shaped Life over millions of years of evolution on Earth. Deep Underground Laboratories (DULs) represent the ideal below-background exposure facilities where to address such a question. Among the few worldwide DULs, INFN-Laboratorio Nazionale del Gran Sasso (LNGS) is one of the largest in terms of size and infrastructure. Designed and built to host neutrino and dark matter experiments, since the 1990 s the LNGS has been one of the first DULs to systematically host radiobiology experiments. Here we present the DISCOVER22 (DNA Damage and Immune System Cooperation in VEry low Radiation environment 2022) experiment recently started at LNGS. DISCOVER22 aims at investigating how the low radiation background modulates the Immune System (IS) response in in vitro and in vivo models. Underground radiobiology experiments are particularly complex and tricky to design and perform. In these studies, the accurate characterization of exposure scenarios is mandatory, but a challenging aspect is to understand how the very few ionizing tracks in the ultra-Low Radiation Environment (LRE) interact with the living matter in space and time in order to trigger different biological responses. In this Perspective, we describe these challenges and how we address them through a microdosimetric and a radiobiological approaches. We aim at linking physical microdosimetric measurements and the corresponding biological radiation responses by using radiation biophysical models that could shed light on many as yet unresolved questions.

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IntroductionBrodalumab is a monoclonal antibody that targets the subunit A of the interleukin-17A receptor (IL17RA), inhibiting the signaling of various isoforms of the IL-17 family. It has been approved for the treatment of moderate-to-severe plaque psoriasis after being evaluated in three Phase-3 trials. However, long-term data on brodalumab in a real-life setting are still limited.MethodsThe aim of this study was to evaluate the long-term effectiveness and safety of brodalumab in psoriasis. We also assessed the drug survival of brodalumab in a 3 years timespan. We conducted a retrospective multicenter study on 606 patients followed up at 14 Italian dermatology units, all treated with brodalumab according to Italian guidelines. Patients’ demographics and disease characteristics were retrieved from electronic databases. At baseline and weeks 12, 24, 52, 104 and 156, we evaluated the psoriasis area and severity index (PASI) score and investigated for adverse events. The proportions of patients reaching 75, 90 and 100% (PASI 75, PASI 90 and PASI 100, respectively) improvement in PASI, compared with baseline, were also recorded.ResultsAt week 12, 63.53% of the patients reached PASI 90 and 49.17% PASI 100. After 3 years of treatment, 65.22% of patients maintained a complete skin clearance, and 91.30% had an absolute PASI of 2 or less. Patients naïve to biological therapies had better clinical responses at weeks 12, 24 and 52. However, after 2 years of treatment, no significant differences were observed. Body mass index did not interfere with the effectiveness of brodalumab throughout the study. No new safety findings were recorded. After 36 months, 85.64% of our patients were still on treatment with brodalumab.ConclusionOur data confirm the effectiveness and the safety of brodalumab in the largest real-life cohort to date, up to 156 weeks.

Background Lidocaine hydrochloride is frequently used for management of painful wounds. This prospective, multicentre study examined the effects of 5% lidocaine cream on wound pain relief. Material and methods The study included 78 patients with painful wounds treated with 5% Lidocaine cream for two weeks in two Italian Hospitals. Patients’ perception of pain was recorded by, using the 5-point Visual Rate Scale and the 11-point Numerical Pain Rating Scale. All medications and adverse events were evaluated in a daily diary. The primary outcome of the study was establishing the wound pain relief based on the results of 5-VRS and pain intensity based on the 11-NPRS testing from baseline to the end of treatment. Clinical aspects and adverse events were also collected. Results Seventy-eight patients had a median age of 67.5 years (range 18-96 years). 62.8% were women. The wounds included traumatic wounds (n = 39), venous ulcers (n = 25), post-surgical wounds (n = 6) pyoderma gangrenosum (n = 6), vasculitis (n = 1) and pressure ulcer (n = 1). The intensity of pain significantly decreased from the baseline level established at the beginning of treatment (mean score 6.7 − 1.90) - to the level at end of treatment (3.0 − 2.23-; p

Sjögren’s disease (SD) is a chronic autoimmune disease primarily affecting lacrimal and salivary glands. The diagnosis of pediatric SD mostly relies on clinical suspect, resulting in a significant diagnostic delay. Recently, ultrahigh-frequency ultrasound (UHFUS) of labial glands has been proposed as a diagnostic method in adults with suspected SD. Until now, there have been no studies about UHFUS in pediatric diagnostic work-up. The aim of the study was to evaluate the potential role of UHFUS of minor salivary glands in pediatric SD. Consecutive pediatric patients with a diagnosis of pediatric SD seen at AOU Meyer IRCSS were evaluated. Intraoral UHFUS scan of the lip mucosa was performed with Vevo MD equipment, using a 70 MHz probe with a standardized protocol and the images were independently reviewed by two operators. Lip salivary glands were assessed by using a four-grade semiquantitative scoring system for parenchymal alteration and vascularization. Twelve patients were included. When applying UHFUS to this cohort of patients, all patients showed a UHFUS grade of ≥1 with 8/12 showing a mild glandular alteration (i.e., grade 1), 2/12 a moderate glandular alteration (i.e., grade 2) and finally 2/12 a severe glandular alteration (i.e., grade 3). Moderate intraglandular vascularization was seen in 9/12, with only 3/12 showing mild intraglandular vascularization. Due to limited size of the sample, the relationship between histological findings, autoantibodies status and UHFUS grade could not be performed. This preliminary study seems to report UHFUS as feasibility technique to identify salivary gland alterations in children with a clinical suspect of SD.

Psoriatic onychopathy is one of the clinical presentations of psoriasis and a well-known risk factor for the development of psoriatic arthritis. High-frequency ultrasounds (HFUS > 20 MHz) have recently been used to evaluate the nail apparatus of healthy and psoriatic subjects. The aim of our study was to detect by means of ultra-high-frequency ultrasound (UHFUS 70–100 MHz) alterations of the nail bed and matrix in patients with psoriatic onychopathy and to monitor these parameters during the treatment with monoclonal antibody (mAb). We enrolled 10 patients with psoriatic onychopathy and naive to previous biologic therapies. Patients were evaluated at baseline, after 1 month and after 3 months from the beginning of mAb therapy by a complete clinical assessment and US evaluation. A UHFUS examination with a 70 MHz probe was performed on the thumbnail (I), the index fingernail (II) and the nail with greater clinical impairment (W). The following measurements were analyzed: nail plate thickness (A), nail bed thickness (B), nail insertion length (C), nail matrix length (D) and nail matrix thickness (E). Among the various parameters analyzed, some measures showed a statistically significant decrease with p-value < 0.05 (t0 WA = 0.52 mm vs. t2 WA = 0.42 mm; t0 WB = 2.8 mm vs. t2 WB = 2.4 mm; t0 WE = 0.76 mm vs. t2 WE = 0.64 mm; t0 IIA = 0.49 mm vs. t2 IIA = 0.39 mm). In conclusion, UHFUS could represent a viable imaging technique for the real-time evaluation and monitoring of psoriatic onychopathy, thus supporting the clinical parameters and revealing any subclinical signs of early drug response.

Atopic dermatitis (AD) is a chronic multifactorial inflammatory disease characterized by intense itching and inflammatory eczematous lesions. Biological disease-modifying drugs, such as dupilumab are recommended for patients with moderate-to-severe AD, refractory to systemic immunosuppressive therapies. Disease monitoring is performed by clinical scores. Since 1970, however, the use of ultrasound and particularly high-frequency ultrasound (HFUS), has identified alterations in dermal echogenicity, called the subepidermal low-echogenic band (SLEB), that correlates with disease severity and response to treatment. We enrolled 18 patients with moderate-to-severe AD, divided into two groups: twelve patients in the dupilumab treatment (Group A) and six patients in standard treatment, from February 2019 to November 2019. We performed ultra-high frequency ultrasound (UHFUS) evaluation of lesional and non-lesional skin, focusing on SLEB average thicknesses measurement, epidermal thickness, and vascular signal in correlation with objective disease scores (EASI, IGA), patient’s reported scores (Sleep Quality NRS and Itch NRS), and TEWL and corneometry at baseline (T0), after 1 month (T1) and 2 months (T2). The SLEB average thickness measurement, vascular signal, and epidermal thickness showed a statistically significant reduction in lesional skin of the biological treatment group and no significant reduction in non-lesional skin in both groups. In the lesional skin of the standard treatment group, only epidermal thickness showed a statistically significant reduction. Our study demonstrates that SLEB measurement, vascular signals, and epidermal thickness could be used as objective parameters in monitoring the AD treatment response, while the presence of SLEB in non-lesional skin could be used as a marker of subclinical inflammation and could predict development of clinical lesions, suggesting a pro-active therapy. Further follow-up and research are needed to clarify the association of SLEB decrease/disappearance with a reduction of flares/prolongment of the disease remission time.

Dermal hyaluronic acid (HA) fillers are used for nasolabial fold correction, but no study is still available on the use of ultra-high-frequency ultrasound (UHFUS) with 70 MHz probes for the evaluation of HA distribution and wrinkle amelioration. We selected 13 patients who received HA filler, evaluated before (Time (T) 0) and after injection (T1), and after 24 weeks (T2). The dermal thickness and distribution of HA were registered, as well as the Wrinkle Severity Rating Scale (WSRS), Global Aesthetic Improvement Scale (GAIS), and wrinkle 3D fullness. The UHFUS dermal thickness was increased by 11% for both sides at T1 and by 7.4% and 6.8% for the right and left side, respectively, at T2 (p < 0.01). The 3D wrinkle fullness showed a T1 increase (+0.59 cc and +0.79 cc for the right and left side, respectively) with a T2 maintenance of 45% of the T1 fullness (p-value < 0.001). The only clinical score significantly modified was WSRS, with a reduction of 56% at T1 and of 47.1% at T2 (p-value < 0.001). Our study then demonstrated the efficacy of UHFUS in the assessment of nasolabial fold correction, representing also the first multi-modal evaluation of HA persistence and its visual subsequent aesthetic results.

Pyoderma gangrenosum (PG) is a neutrophilic dermatological disease, whose pathogenesis is still poorly clarified. Because of the lack of validated criteria for diagnosis and response, PG treatment is still challenging and should be differentiated in the inflammatory and non-inflammatory phases. Our study aimed to provide a new semi-quantitative approach for PG diagnosis and monitoring, identifying ultra-high-frequency ultrasound (UHFUS) early biomarkers associated with the transition between the two phases. We enrolled 13 patients affected by painful PG lesions evaluated during the inflammatory phase (T0) and during the non-inflammatory phase (T1): pain was measured by the Visual Analogue Scale (VAS); clinical features were recorded through digital photography; epidermis and dermis ultrasound (US) characteristics were evaluated by UHFUS examination with a 70 MHz probe (Vevo MD® FUJIFILM VisualSonics). In T1 UHFUS examination, the presence of hyperechoic oval structures was lower compared to T0 (p value < 0.05). An hyperechogenic structure within the oval structure, suggestive of a hair tract, was evident in T0 and absent in T1 (p value < 0.05). In T0, blood vessels appear as U-shaped and V-shaped anechoic structures with a predominance of U-shaped vessels (p value < 0.05) compared to the more regular distribution found in T1. Finding early biomarkers of the transition from the inflammatory to the non-inflammatory phase could provide new insight in terms of therapeutic decision making and response monitoring. The differences found by this study suggest a potential use of UHFUS for the development of an objective standardized staging method. Further investigations will be necessary to confirm our preliminary results, thus providing a turning point in PG early detection, differential diagnosis and treatment monitoring.

Abstract Background 223Ra is currently used for treatment of metastatic castration resistant prostate cancer patients (mCRPC) bone metastases with fixed standard activity. Individualized treatments, based on adsorbed dose (AD) in target and non-target tissue, are absolutely needed to optimize efficacy while reducing toxicity of α-emitter targeted therapy. This is a pilot first in human clinical trial aimed to correlate dosimetry, clinical response and biological side effects to personalize 223Ra treatment. Methods Out of 20 mCRPC patients who underwent standard 223Ra treatment and dosimetry, in a subset of 5 patients the AD to target and non-target tissues was correlated with clinical effects and radiation-induced chromosome damages. Before each 223Ra administrations, haematological parameters, PSA and ALP values were evaluated. Additional blood samples were obtained baseline (T0), at 7 days (T7), 30 days (T30) and 180 days (T180) to evaluate chromosome damage. After administration WB planar 223Ra images were obtained at 2–4 and 18–24 h. Treatment response and toxicity were monitored with clinical evaluation, bone scan, 18F-choline-PET/CT, PSA value and ALP while haematological parameters were evaluated weekly after 223Ra injection and 2 months after last cycle. Results 1. a correlation between AD to target and clinical response was evidenced with threshold of 20 Gy as a cut-off to obtain tumor control; 2. the AD to red marrow was lower than 2 Gy in all the patients with no apparently correlation between dosimetry and clinical toxicity. 3. a high dose dependent increase of the number of dicentrics and micronuclei during the course of 223Ra therapy was observed and a linear correlation has been found between blood AD (BAD) and number of dicentrics. Conclusions This study provides some interesting preliminary evidence to be further investigated: dosimetry may be useful to identify a more appropriate 223Ra administered activity predicting AD to target tissue; a dose dependent complex chromosome damage occurs during 223Ra administration and this injury is more evident in heavily pre-treated patients; dosimetry could be used for radioprotection purpose. Trial registration The pilot study has been approved from the Ethics Committee of Regina Elena National Cancer Institute (N:RS1083/18–2111).

Low-energy electrons (Auger electrons) can be produced via the interaction of photons with gold atoms in gold nanorods (AuNRs). These electrons are similar to those emitted during the decay of technetium-99m (99mTc), a radioactive nuclide widely used for diagnostics in nuclear medicine. Auger and internal conversion (IC) electron emitters appropriately targeted to the DNA of tumors cells may, therefore, represent a new radiotherapeutic approach. 99mTc radiopharmaceuticals, which are used for diagnosis, could indeed be used in theragnostic fields when loaded on AuNRs and delivered to a tumor site. This work aims to provide a proof of concept (i) to evaluate AuNRs as carriers of 99mTc-based radiopharmaceuticals, and (ii) to evaluate the efficacy of Auger electrons emitted by photon-irradiated AuNRs in inducing radio-induced damage in T98G cells, thus mimicking the effect of Auger electrons emitted during the decay of 99mTc used in clinical settings. Data are presented on AuNRs’ chemical characterization (with an aspect ratio of 3.2 and Surface Plasmon Resonance bands at 520 and 680 nm) and the loading of pharmaceuticals (after 99mTc decay) on their surface. Spectroscopic characterizations, such as UV-Vis and synchrotron radiation-induced X-ray photoelectron (SR-XPS) spectroscopies, were performed to investigate the drug–AuNR interaction. Finally, preliminary radiobiological data on cell killing with AuNRs are presented.

Background: To assess skin involvement in a cohort of patients with systemic sclerosis (SSc) by comparing results obtained from modified Rodnan skin score (mRSS), durometry and ultra-high frequency ultrasound (UHFUS). Methods: SSc patients were enrolled along with healthy controls (HC), assessing disease-specific characteristics. Five regions of interest were investigated in the non-dominant upper limb. Each patient underwent a rheumatological evaluation of the mRSS, dermatological measurement with a durometer, and radiological UHFUS assessment with a 70 MHz probe calculating the mean grayscale value (MGV). Results: Forty-seven SSc patients (87.2% female, mean age 56.4 years) and 15 HC comparable for age and sex were enrolled. Durometry showed a positive correlation with mRSS in most regions of interest (p = 0.025, ρ = 0.34 in mean). When performing UHFUS, SSc patients had a significantly thicker epidermal layer (p < 0.001) and lower epidermal MGV (p = 0.01) than HC in almost all the different regions of interest. Lower values of dermal MGV were found at the distal and intermediate phalanx (p < 0.01). No relationships were found between UHFUS results either with mRSS or durometry. Conclusions: UHFUS is an emergent tool for skin assessment in SSc, showing significant alterations concerning skin thickness and echogenicity when compared with HC. The lack of correlations between UHFUS and both mRSS and durometry suggests that these are not equivalent techniques but may represent complementary methods for a full non-invasive skin evaluation in SSc.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon angioproliferative benign disorder. A 24- year-old Caucasian female patient presented with multiple itchy reddish pearly nodule.

This study aimed to compare adalimumab originator vs. biosimilar in HS patients, and to evaluate the effect of a switch to a biosimilar, or a switch back to the originator, in terms of treatment ineffectiveness. Patients with a diagnosis of HS were enrolled from 14 Italian sites. Treatment ineffectiveness was measured using Hurley score. The major analyses were 1) comparison between the two treatment groups (non-switcher analysis), and 2) the cross-over trend of Hurley score between treatment switchers (switcher analysis). Cox and Poisson regression models were used to compare the treatment ineffectiveness between groups. A total of 326 patients were divided into four groups: 171 (52.5%) taking originator; 61 (18.7%) patients taking biosimilar; 66 (20.2%) switchers; 28 (8.6%) switchers from originator to biosimilar and switched. A greater loss of efficacy was observed in the group allocated to the biosimilar than the originator group. The switcher analysis showed an effectiveness loss in the biosimilar compared to the originator. These results seem to indicate that a switch from one drug to the other may lead to a greater risk of inefficacy. A return to the previous treatment also does not ensure efficaciousness.

A very rare variant of MPD is the Pigmented Mammary Paget Disease (PMPD), first described by Culberson et al. in 1956. It is very difficult to distinguish this variant from melanoma both clinically and dermoscopically. The diagnosis is confirmed by histopathology and immunohistochemistry. Correct diagnosis is crucial for surgical treatment, which is different for these two diseases. We report the case of a 92-year-old woman, who presented an asymptomatic pigmented lesion of the right nipple and areola. The lesion was arisen for about 6 months and was suspected for melanoma because of clinical and dersmoscopic characteristics. Incisional biopsy revealed tumor cells, that proliferate in the major mammary ducts, and tumor cells in the overlying epidermis of the nipple, thus diagnosing pigmented mammary Paget disease (PMPD). The patient underwent radical mastectomy.

Scientific community and institutions (e. g., ICRP) consider that the Linear No-Threshold (LNT) model, which extrapolates stochastic risk at low dose/low dose rate from the risk at moderate/high doses, provides a prudent basis for practical purposes of radiological protection. However, biological low dose/dose rate responses that challenge the LNT model have been highlighted and important dowels came from radiobiology studies conducted in Deep Underground Laboratories (DULs). These extreme ultra-low radiation environments are ideal locations to conduct below-background radiobiology experiments, interesting from basic and applied science. The INFN Gran Sasso National Laboratory (LNGS) (Italy) is the site where most of the underground radiobiological data has been collected so far and where the first in vivo underground experiment was carried out using Drosophila melanogaster as model organism. Presently, many DULs around the world have implemented dedicated programs, meetings and proposals. The general message coming from studies conducted in DULs using protozoan, bacteria, mammalian cells and organisms (flies, worms, fishes) is that environmental radiation may trigger biological mechanisms that can increase the capability to cope against stress. However, several issues are still open, among them: the role of the quality of the radiation spectrum in modulating the biological response, the dependence on the biological endpoint and on the model system considered, the overall effect at organism level (detrimental or beneficial). At LNGS, we recently launched the RENOIR experiment aimed at improving knowledge on the environmental radiation spectrum and to investigate the specific role of the gamma component on the biological response of Drosophila melanogaster.

Matrix metalloproteinases (MMPs) are a large family of ubiquitously expressed zinc-dependent enzymes with proteolitic activities. They are expressed in physiological situations and pathological conditions involving inflammatory processes including epithelial to mesenchymal transition (EMT), neuronal injury, and cancer. There is also evidence that MMPs regulate inflammation in tumor microenvironment, which plays an important role in healing tissue processes. Looking at both inflammatory and neuronal damages, MMP9 is involved in both processes and their modulation seems to be regulated by two proteins: tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6). However other important genes are involved in molecular regulation of transcription factors, protein-kinase B (AKT), and p65. In addition, Triticum vulgare extract (TVE) modulated the biological markers associated with inflammatory processes, including p65 protein. While there are no evidence that TVE might be involved in the biological modulation of other inflammatory marker as AKT, we would like to assess whether TVE is able to (1) modulate phosphorylation of AKT (pAKT) as an early marker of inflammatory process in vitro and (2) affect MMP9 protein expression in an in vitro model. The BV-2 cells (microglial of mouse) have been used as an in vitro model to simulate both inflammatory and neuronal injury pathologies. Here, MMP9 seems to be involved in cellular migration through inflammatory marker activation. We simulate an inflammatory preclinical model treating BV-2 cells with lipopolysaccharide (LPS) to induce proinflammatory activation affecting pAKT and p65 proteins. TVE is revealed to restore the native expression of AKT and p65. Additionally, TVE extract modulates also the protein concentration of MMP9. Nevertheless, immunofluorescence confocal analyses revealed that both AKT and MMP9 are regulated together, synchronously. This work seems to demonstrate that two important genes can be used to monitor the beginning of an inflammatory process, AKT and MMP9, in which TVE seems able to modulate their expression of inflammation-associated molecules.

Background: The aims of this review are to analyze the current literature regarding the characteristics and pathophysiological mechanisms of itch in chronic wounds, to assess the impact on quality of life and delayed-healing, to focus on the best strategies of prevention and treatment, to highlight the importance of on-going research in order to fully understand the pathophysiology, and to improve the management of target therapies. Methods: A systematic literature review was performed using MEDLINE, PubMed, Embase, Scopus, ScienceDirect, and the Cochrane Library. We included a total of 11 articles written in English with relevant information on the pathophysiology of itch in chronic wounds and on management strategies. Results: Itch in chronic wounds was found to be correlated with xerosis, larger wound areas, necrotic tissue and amount of exudate, peripheral tissue edema, sclerosis, granulation tissue, contact dermatitis, and bacterial burden, as well as with lower quality of life. Conclusions: Although there are several aspecific pharmacological and non-pharmacological approaches, there appears to be no validated prevention or management strategy for itch in chronic wounds. Further studies are needed to clarify the association and pathophysiology of itch in chronic wounds, to evaluate the safety and efficacy of topical treatments on perilesional skin to reduce itch, to characterize multidimensional sensations of itch in chronic wounds, to identify specific cytokine and chemokine expressions that are correlated to a tailored-based approach, and to develop practical guidelines.

In the last decade, many innovative nanodrugs have been developed, as well as many nanoradiocompounds that show amazing features in nuclear imaging and/or radiometabolic therapy. Their potential uses offer a wide range of possibilities. It can be possible to develop nondimensional systems of existing radiopharmaceuticals or build engineered systems that combine a nanoparticle with the radiopharmaceutical, a tracer, and a target molecule, and still develop selective nanodetection systems. This review focuses on recent advances regarding the use of gold nanoparticles and nanorods in nuclear medicine. The up-to-date advancements will be shown concerning preparations with special attention on the dimensions and functionalizations that are most used to attain an enhanced performance of gold engineered nanomaterials. Many ideas are offered regarding recent in vitro and in vivo studies. Finally, the recent clinical trials and applications are discussed.

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Marco Romanelli1, Valentina Dini1, Peter Vowden2, Magnus S Ågren31Department of Dermatology, University of Pisa, Pisa, Italy; 2Vascular Unit, Bradford Royal Infirmary, Bradford, United Kingdom; 3Department of Surgery K, Bispebjerg Hospitals, Copenhagen University Hospital, Copenhagen, DenmarkAbstract: Amelogenins are extracellular matrix proteins that, under physiological conditions, self-assemble into globular aggregates up to micron-sizes. Studies with periodontal fibroblasts indicate that attachment to these structures increases the endogenous secretion of multiple growth factors and cell proliferation. Pre-clinical and clinical studies indicate that cutaneous wounds benefit from treatment with amelogenins. A randomized controlled trial (RCT) involving patients with hard-to-heal venous leg ulcers (VLUs) (ie, ulcers with a surface area ≥10 cm2 and duration of ≥6 months) showed that the application of amelogenin (Xelma®, Molnlycke Health Care, Gothenburg, Sweden) as an adjunct treatment to compression results in significant reduction in ulcer size, improvement in the state of ulcers, reduced pain, and a larger proportion of ulcers with low levels of exudate, compared with treatment with compression alone. Amelogenin therapy was also shown to be safe to use in that there were no significant differences in adverse events noted between patients treated with amelogenin plus compression and those treated with compression alone. Case study evaluations indicate that the benefits of amelogenin therapy demonstrated in the RCT are being repeated in “real life” situations and that amelogenin therapy may also have a role to play in the treatment of other wound types such as diabetic foot ulcers.Keywords: extracellular matrix, amelogenin, venous leg ulcers, diabetic foot ulcers, pyoderma gangrenosum

Wound assessment is usually performed in hospitals or specialized labs. However, since patients spend most of their time at home, a remote real time wound monitoring would help providing a better care and improving the healing rate. This review describes the advances in sensors and biosensors for monitoring the concentration of C-reactive protein (CRP), temperature and pH in wounds. These three parameters can be used as qualitative biomarkers to assess the wound status and the effectiveness of therapy. CRP biosensors can be classified in: (a) field effect transistors, (b) optical immunosensors based on surface plasmon resonance, total internal reflection, fluorescence and chemiluminescence, (c) electrochemical sensors based on potentiometry, amperometry, and electrochemical impedance, and (d) piezoresistive sensors, such as quartz crystal microbalances and microcantilevers. The last section reports the most recent developments for wearable non-invasive temperature and pH sensors suitable for wound monitoring.

Keywords: diabetic foot; nanotechnologies; ulcer; measurements; skin hydration 82 Original ResearchUse of Nanotechnology-Designed Footsock in the Management of Preulcerative Conditions in the Diabetic Foot: Results of a Single, Blind Randomized [...]

Pyoderma gangrenosum (PG) is an inflammatory ulcerative condition of unknown etiology. An autoimmune mechanism including immune complex—mediated neutrophilic vascular reactions has been suggested. The role of tumor necrosis factor (TNF) in PG remains unclear. Evidence supports the idea that TNF plays a role in chronic inflammation and migration of neutrophils to these lesions. PG is frequently associated with various diseases, but up to 50% of cases are idiopathic. There are several reports describing the successful use of infliximabTM (Remicade ®, Centocor, Inc, Horsham, Pa), a chimeric antitumor necrosis factor α monoclonal antibody, in the treatment of inflammatory bowel disease— associated PG, but there have been few reported cases of infliximab in the treatment of idiopathic PG. The authors present a dramatic improvement in 4 cases of idiopathic PG of the lower leg treated with infliximab. [ABSTRACT FROM AUTHOR]

In a previous article, this group described the principles involved in the development of bioengineered skin equivalents that held out much promise. This article has examined some of the uses of such products in treating venous ulcers, diabetic foot ulcers, and skin diseases leaving skin wounds. Data encouraging the use of such products in certain indications are available. The costs of using such products are also appreciated. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)