Real-life experience with ixekizumab in plaque psoriasis: a multi-center, retrospective, 3-year study.

BACKGROUND: Confirmatory data on the long-term effectiveness and safety of ixekizumab in psoriatic patients from real-world studies are needed. OBJECTIVES: The primary aim was to evaluate the 3-year drug survival of ixekizumab in the treatment of patients with moderate-to-severe plaque psoriasis, in a multicenter real-world setting. The secondary aim was to assess the influence of predictive factors on the drug survival of ixekizumab. METHODS: A retrospective analysis was performed on a cohort of patients with chronic plaque psoriasis, who received at least one dose of ixekizumab before December 2018. The drug survival analysis was performed and descriptively analyzed using Kaplan-Meier survival curves. Multivariable Cox regression analyses were carried out including variables considered to be of clinical importance. RESULTS: A total of 306 patients were enrolled. The overall drug survival at 12, 24, and 36 months of treatment with ixekizumab was 92.11%, 83.85%, and 80.19%, respectively. A higher probability (HR 2.34) of drug withdrawal was found among patients who had already received an anti-IL-17 agent compared with bio-naive patients (p 0.017). CONCLUSIONS: We found that ixekizumab is a biological agent characterized by long-term effectiveness, not influenced by several clinical factors and associated with a good safety profile.

Evidence for a 'window of opportunity' in hidradenitis suppurativa treated with adalimumab: a retrospective, real-life multicentre cohort study.

BACKGROUND: The anti-tumour necrosis factor (TNF)-α adalimumab is the only licenced biologic for moderate-to-severe hidradenitis suppurativa (HS). No predictors of response have been identified so far. OBJECTIVES: To identify clinical parameters predicting response to adalimumab and confirm its efficacy/safety. METHODS: The data of 389 patients with HS treated with adalimumab in 21 Italian centres were reviewed. Sex, age at onset/diagnosis/baseline, body mass index, smoking, phenotype, previous treatments, concomitant antibiotics and 'therapeutic delay', defined as the time from HS onset to adalimumab initiation, were assessed. Response to adalimumab and its impact on quality of life (QoL) were evaluated using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the Dermatology Life Quality Index (DLQI) or the Visual Analogue Scale for pain (VAS pain), respectively. Logistic regression analysis was performed. RESULTS: The therapeutic delay correlated to lack of response to adalimumab at week 16 [odds ratio (OR) 1·92 for therapeutic delay > 10 years; 95% confidence interval (CI) 1·28-2·89; P = 0·0016). HiSCR was achieved in 43·7% and 53·9% patients at week 16 and 52, respectively. Significant reductions in both DLQI and VAS pain were found between week 16 vs. baseline (P < 0·0001 for both) and week 52 vs. baseline (P < 0·0001 for both). Previous immunosuppressants inversely correlated to HiSCR at week 52 (OR = 1·74, 95% CI 1·04-2·91, P = 0·0342). CONCLUSIONS: Inverse correlation between therapeutic delay and clinical response was found, supporting early adalimumab use and providing evidence for a 'window of opportunity' in HS treatment. Adalimumab efficacy and safety were confirmed, along with patients' QoL improvement. Immunosuppressants could negatively influence the response to adalimumab inducing a switch to non-TNF-α-driven pathways.

Creation of a severity index for hidradenitis suppurativa that includes a validated quality-of-life measure: the HIDRAscore.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, debilitating disease with a considerable effect on patient quality of life. Its clinical severity can be measured using different scoring systems; however, few of them include patient-centred parameters. OBJECTIVE: To create a new scoring system for HS that includes a quality-of-life instrument, the HIDRAdisk. METHODS: This post hoc analysis was carried out within the framework of a multicentre, longitudinal, epidemiologic study conducted over 9 months on quality-of-life aspects of HS. The new severity score was created using as reference a question from the Subject Satisfaction Questionnaire (SSQ) concerning the severity of HS as evaluated by the patient. Associated variables were selected using univariable and multivariable logistic regression models. The discriminant capabilities of the final model and of the final score were evaluated by the area under the receiver operating characteristic curve and the Hosmer-Lemeshow test. RESULTS: The study population included 308 patients with HS of any severity grade. According to the results of the regression models, the variables associated with the reference SSQ measure were number of inflammatory nodules, abscesses and draining fistulas; the HIDRAdisk score; and the number of subumbilical lesions. The HIDRAscore is obtained by the sum of the scores associated with the number of these parameters. Possible scores range from 0 to 10. CONCLUSION: The HIDRAscore is a new scoring system for HS severity which, in addition to the clinical evaluation by the physician, includes a validated patient-reported outcome measure, the HIDRAdisk.

Tuscan consensus on the diagnosis and treatment of hidradenitis suppurativa.

BACKGROUND: A rationalized model of clinical and therapeutic management of hidradenitis suppurativa (HS) should place the patients at the heart of the process, facilitating their access to diagnostic tests and treatments, providing the appropriate care for each grade of disease severity and optimizing the use of healthcare resources, both in economic and human terms. MATERIAL AND METHODS: This paper reports the results of a Consensus of the Tuscany HS working group for a rationalized model of diagnosis and management of HS. RESULTS: The diagnostic and therapeutic protocols, the available technological equipments and the management models, are presented in the light of today's scientific evidence. CONCLUSION: The goal of the Consensus is to bring the issue of HS management to the attention of the Tuscan regional government, in order to create unanimously accepted diagnostic and therapeutic protocols.

Ultrasonography in the pathway to an optimal standard of care of hidradenitis suppurativa: the Italian Ultrasound Working Group experience.

BACKGROUND: Ultrasound (US) is a real-time non-invasive technique that has been demonstrated to support an early diagnosis and a more precise assessment of hidradenitis suppurativa (HS). OBJECTIVES: To compare the clinical and US evaluation of a series of HS patients. METHODS: 434 HS patients (259 F, 175 M; mean age 33.82 ±13.31 years) observed across 19 Italian dermatology centres [members of the Italian Ultrasound Working Group (IUWG)] were enrolled in a retrospective study. Clinical staging was obtained by the Hidradenitis Suppurativa Physician's Global Assessment score (HS-PGA), while the ultrasonographic staging was determined by the US HS-PGA, based on the same scores as clinical HS-PGA but performed with the aid of US. RESULTS: At the end of the study, the mean clinical and US HS-PGA scores were 2.70 and 2.92, respectively. Direct comparison of clinical and ultrasonographic assessment revealed that a higher proportion of patients was classified as having moderate and very severe disease by US. In particular, 117 patients (26.96%) had a worse classification by US HS-PGA compared to clinical assessment. CONCLUSION: Our findings confirm that the use of clinical grading only to assess HS severity may underestimate the real disease severity. US examination can be considered an essential non-invasive imaging tool available to dermatologists for a more accurate diagnosis, staging, treatment planning and monitoring of HS and should be included in the pathway to an optimal standard of care of HS.

HIDRAdisk: validation of an innovative visual tool to assess the burden of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease characterized by painful inflamed nodules, recurrent abscesses and fistulas located in apocrine gland-bearing body sites. The negative impact of HS on patient's quality of life (QoL) has been reported to be greater than other dermatologic conditions as psoriasis and atopic eczema, and its improvement is an important goal in disease management. Nowadays, there are no specific validated QoL instruments available for HS and generic dermatologic questionnaires are used. OBJECTIVE: The objective of this study was to demonstrate the validity, reliability and responsiveness of HIDRAdisk, a new innovative tool designed for rapid assessment of HS burden and, at the same time, an intuitive graphic visualization of the measurement outcome. METHODS: A multicentre, longitudinal, observational study was conducted to validate the HIDRAdisk compared with other validated questionnaires [Skindex-16, Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment-General Health (WPAI:GH)] and to evaluate its correlation with disease severity in Italian patients with any degree of HS severity, as measured by Hurley stage and HS Physician Global Assessment (HS-PGA). RESULTS: A total of 140 patients (59% women; mean age 34.9 ± 11.0 years) were enrolled in 27 dermatologic centres. HIDRAdisk showed a strong correlation with Skindex-16 and DLQI, and a good one with WPAI:GH (correlation coefficient: 0.7568, 0.6651 and 0.5947, respectively) and a statistically significant correlation with both Hurley stage and HS-PGA. Very good internal consistency (Cronbach coefficient >0.80; intraclass correlation coefficient >0.6), with correlation between the 10 items, good test-retest reliability (Spearman correlation coefficient, 0.8331; P < 0.0001) and responsiveness to changes were demonstrated. CONCLUSION: Our study shows that HIDRAdisk, a short and innovative visual HS QoL instrument, has been psychometrically validated in Italian language and it may help improve the management of HS once implemented in routine clinical practice.

Sex-related differences of clinical features in hidradenitis suppurativa: analysis of an Italian-based cohort.

The clinical characteristics associated with hidradenitis suppurativa (HS) severity are poorly understood. In this study, 124 patients with HS from 6 Italian dermatology centres participated in this study. Disease severity was assessed using the Hidradenitis Suppurativa Physician's Global Assessment score (HS-PGA) and Hurley score. The impact of clinical characteristics on disease severity was assessed by logistic regression. Clinical characteristics were similar between men (n = 53) and women (n = 71). Disease severity was also similar; 75% of the patients had Hurley stage II or III disease, and > 60% had moderate, severe or very severe HS as judged by HS-PGA. Lesions were more frequent in the gluteal region in men (32.3% in men vs. 8.7% in women, P < 0.001) and more frequent on the breast in women (16.3% in women vs. 4.6% in men, P = 0.02). Obesity was associated with increased disease severity as measured by HS-PGA (OR: 3.28, 95% CI 1.55-6.95, P < 0.01) and Hurley classification (OR: 3.22, 95% CI 1.34-7.31, P < 0.01). Although severity of HS is similar between the sexes, the localization of lesions is different.

Potential correlation of wound bed score and biomarkers in chronic lower leg wounds: an exploratory study.

OBJECTIVE: The wound bed score is a validated tool to monitor wound healing in chronic wounds, and depends on visual examination by trained personnel. This study describes the feasibility of adding some biochemical and immunohistochemical parameters to increase the objectivity and specificity of the wound bed score Method: Patients with chronic wounds on the lower leg with different durations were enrolled to assess the correlation between the wound bed score and specific wound-related biomarkers, namely MMP-9, MMP-2, NGAL, albumin, integrin α2/ß1, and other histochemical (CD68, PK1, CD32, fractalkine, periostin) and immunocytochemical markers from biopsies and smears taken from wound edges and bed. RESULTS: The study examined samples from 10 patients. Patients with an unfavourable wound bed score had a low expression of periostin and fractalkine in the wound bed tissue. CD68 PK1 showed a low or negative expression in the majority of the samples. Patients negative for CD68 PK1 were also negative for CD32. Principal component analysis revealed that the albumin level and the amount of proteins were associated with a high wound bed score. Two different subsets of patients could be discriminated either by integrin α2/ß1 and albumin percentages or the MMP-9 and MMP-2 activities Conclusion: These preliminary results pave the way towards an improved wound status diagnosis and an advanced quality of wound care and management. These findings need confirming with a large number of patients and at different time points.

Temperature and pH sensors based on graphenic materials.

Point-of-care applications and patients' real-time monitoring outside a clinical setting would require disposable and durable sensors to provide better therapies and quality of life for patients. This paper describes the fabrication and performances of a temperature and a pH sensor on a biocompatible and wearable board for healthcare applications. The temperature sensor was based on a reduced graphene oxide (rGO) layer that changed its electrical resistivity with the temperature. When tested in a human serum sample between 25 and 43°C, the sensor had a sensitivity of 110±10Ω/°C and an error of 0.4±0.1°C compared with the reference value set in a thermostatic bath. The pH sensor, based on a graphene oxide (GO) sensitive layer, had a sensitivity of 40±4mV/pH in the pH range between 4 and 10. Five sensor prototypes were tested in a human serum sample over one week and the maximum deviation of the average response from reference values obtained by a glass electrode was 0.2pH units. For biological applications, the temperature and pH sensors were successfully tested for in vitro cytotoxicity with human fibroblast cells (MRC-5) over 24h.

Contact dermatitis in patients with chronic leg ulcers: a common and neglected problem: a review 2000-2015.

OBJECTIVE: Contact allergies can occur frequently in patients with chronic leg ulcers (CLUs), even in those with a short duration of ulcerative disease. The wide spectrum of therapeutic products promotes development of the delayed type of hypersensitivity and continuous changes in the allergens pattern, which make the diagnosis and treatment extremely difficult in many cases. A prompt diagnosis and treatment of allergic contact dermatitis (ACD) in patients suffering from CLUs is very important for a best clinical outcome of these two common diseases. Thus, this review aims to highlight a common, challenging and often neglected problem. METHOD: The search included all studies published between 2000 and September 2015. Keyword used were: 'allergic contact dermatitis leg ulcer', 'contact dermatitis leg ulcers' 'contact dermatitis wound care' 'contact dermatitis non-healing wounds' 'contact sensitisation non-healing wounds'. RESULTS: Contact allergy and polysensitisation are very frequent in patients suffering from CLUs. Although it is believed modern dressings have a lower potential for inducing cutaneous sensitisation, positive patch test reactions to modern dressing are becoming common: hydrogels, followed by hydrocolloid and the ionic silver-containing wound dressing seem to be the principal causes of ACD. CONCLUSION: This review wanted to highlighted ACD in CLUs as a common and neglected disease whose economic and social burden has not previously been estimated, giving new insights for clinical and therapeutic management.

A D-optimal design to model the performances of dressings and devices for negative pressure wound therapy.

A D-optimal design was used to identify and model variables that affect the transit time of wound exudate through an illustrative dressing used for negative pressure wound therapy. Many authors have addressed the clinical benefits of negative pressure wound therapy, but limited information is available on how to assess performances of dressings. In this paper, the transit time of wound exudate through a dressing was chosen as a model parameter to show how experimental design (DOE) can be used for this purpose. Results demonstrated that rate of exudate production, temperature and dressing thickness were the variables with the largest impact on transit time. The DOE approach could be used to model other dressing properties, like for example capability of absorbing excess exudate or breathability.

The use of a collagen matrix in hard-to-heal venous leg ulcers.

OBJECTIVE: The effects of a collagen dressing on hard-to-heal venous leg ulcers (vlUs) were evaluated in this prospective, randomised, controlled study. METHOD: Patients with hard-to-heal vlU were included and divided into two groups using the block randomisation method. The first group was treated with a collagen and an alginate dressing (group A), and the second group with an alginate dressing alone (group b). both groups also had a short-stretch compression system applied at every dressing change. The dressings were changed twice a week for 12 weeks or until the ulcer was healed. Granulation tissue improvement, wound size, overall dressing performance and dressing comfort were evaluated and recorded. RESULTS: A total of 40 patients completed the study evaluation period. Group A had a 65% increase in granulation tissue compared to 38% in group b. The mean ulcer area was reduced to 45% in group A compared to 20% in group b at 12 weeks. no significant side effects were detected in either group. Patients of both groups were satisfied with their treatment and healing progress. CONCLUSION: The results of this study showed the effectiveness and safety of a collagen dressing in hard-to-heal vlUs as an adjunctive therapy with compression bandaging. These encouraging results may positively affect the quality of life of patients with chronic wounds.

Glioblastoma stem cells: radiobiological response to ionising radiations of different qualities.

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumour, with very poor prognosis. The high recurrence rate and failure of conventional treatments are expected to be related to the presence of radio-resistant cancer stem cells (CSCs) inside the tumour mass. CSCs can both self-renew and differentiate into the heterogeneous lineages of cancer cells. Recent evidence showed a higher effectiveness of C-ions and protons in inactivating CSCs, suggesting a potential advantage of Hadrontherapy compared with conventional radiotherapy for GBM treatment. To investigate the mechanisms involved in the molecular and cellular responses of CSCs to ionising radiations, two GBM stem cell (GSC) lines, named lines 1 and 83, which were derived from patients with different clinical outcomes and having different metabolic profiles (as shown by NMR spectroscopy), were irradiated with (137)Cs photons and with protons or C-ions of 62 MeV u(-1) in the dose range of 5-40 Gy. The biological effects investigated were: cell death, cell cycle progression, and DNA damage induction and repair. Preliminary results show a different response to ionising radiation between the two GSC lines for the different end points investigated. Further experiments are in progress to consolidate the data and to get more insights on the influence of radiation quality.

Induction and Repair of DNA DSB as Revealed by H2AX Phosphorylation Foci in Human Fibroblasts Exposed to Low- and High-LET Radiation: Relationship with Early and Delayed Reproductive Cell Death.

The spatial distribution of radiation-induced DNA breaks within the cell nucleus depends on radiation quality in terms of energy deposition pattern. It is generally assumed that the higher the radiation linear energy transfer (LET), the greater the DNA damage complexity. Using a combined experimental and theoretical approach, we examined the phosphorylation-dephosphorylation kinetics of radiation-induced γ-H2AX foci, size distribution and 3D focus morphology, and the relationship between DNA damage and cellular end points (i.e., cell killing and lethal mutations) after exposure to gamma rays, protons, carbon ions and alpha particles. Our results showed that the maximum number of foci are reached 30 min postirradiation for all radiation types. However, the number of foci after 0.5 Gy of each radiation type was different with gamma rays, protons, carbon ions and alpha particles inducing 12.64 ± 0.25, 10.11 ± 0.40, 8.84 ± 0.56 and 4.80 ± 0.35 foci, respectively, which indicated a clear influence of the track structure and fluence on the numbers of foci induced after a dose of 0.5 Gy for each radiation type. The γ-H2AX foci persistence was also dependent on radiation quality, i.e., the higher the LET, the longer the foci persisted in the cell nucleus. The γ-H2AX time course was compared with cell killing and lethal mutation and the results highlighted a correlation between cellular end points and the duration of γ-H2AX foci persistence. A model was developed to evaluate the probability that multiple DSBs reside in the same gamma-ray focus and such probability was found to be negligible for doses lower than 1 Gy. Our model provides evidence that the DSBs inside complex foci, such as those induced by alpha particles, are not processed independently or with the same time constant. The combination of experimental, theoretical and simulation data supports the hypothesis of an interdependent processing of closely associated DSBs, possibly associated with a diminished correct repair capability, which affects cell killing and lethal mutation.