Short-, mid- and long-term efficacy of dupilumab in moderate to severe atopic dermatitis: a real life multicenter Italian study on 2576 patients.

BACKGROUND: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long term treatment outcomes are currently available to inform clinical decisions. OBJECTIVES: to describe long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD. METHODS: a multicenter, retrospective, dynamic cohort study was conducted to assess long term effectiveness and safety of dupilumab in patients with moderate to severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria (defined as the simultaneous achievement of EASI90, itch NRS score ≤1, sleep NRS score ≤1 and DLQI ≤1) were investigated. RESULTS: 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506 (21.91%), 769 (40.63%), 628 (50.36%), 330 (55.37%) and 58 (54.72%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AE) were mild and were observed in 373 (15.78%), 166 (7.02%), 83 (6.43%), 27 (4.50%) and 5 (4.55%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AE led to treatment discontinuation in <1% of patients during the evaluated time periods. CONCLUSION: High long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate to severe AD, regardless of clinical phenotype and course at baseline. Further research will be needed to investigate the effect of Th2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD.

Surgical Management of Patients with Parotid Involvement from Non-Melanoma Skin Cancer of the Head and Neck.

We conducted a retrospective, longitudinal study on a single-center series of patients who underwent parotidectomy in the management of advanced head and neck non-melanoma skin cancer (hnNMSC). The aim of this study was to identify prognostic factors associated with worse outcomes. Forty-one men and nine women were included. The mean age at the time of surgery was 78.9 years. The 5-year overall survival, disease-specific survival, locoregional recurrence-free survival, and distant metastasis-free survival calculated with Kaplan-Meier curves were 39.9%, 56.3%, 58.6%, and 82.1%, respectively. A univariate analysis showed that the status of the margins, facial nerve direct involvement, lymph vascular invasion, and histological grading were associated with worse outcomes (p < 0.05). Positive margins were associated with worse disease-specific survival also in a multivariate analysis (p = 0.001, HR = 32.02, and CIs 4.338 to 351.3). Because the resection in free margins is the most important prognostic factor, early diagnosis or, in the case of advanced disease, extensive surgical resection with concomitant reconstruction is needed. Adjuvant therapy is indicated in selected cases.

Treatment of psoriasis with different classes of biologics reduces the likelihood of peripheral and axial psoriatic arthritis development.

OBJECTIVE: To assess the potential role of biological treatment for psoriasis (PsO) in reducing the likelihood of psoriatic arthritis (PsA), through a detailed analysis that considered the different historical phases in the PsA management, the different biologics classes, and the different patterns of articular involvement. METHODS: A monocentric cohort of 1023 PsO patients underwent a rheumatologic assessment in which clinical and therapeutic data were recorded. Chi-squared test and multivariate logistic regression analysis (adjusted for the main PsA risk factors) were performed to compare the likelihood of PsA development in different treatment groups. RESULTS: The PsA prevalence in PsO patients treated at least once with biologics was significantly lower than in patients never treated with biologics (8.9% vs 26.1%, p< 0.001). In multivariate analysis, a significantly (p< 0.01) lower likelihood of PsA development in biologic-treated patients was confirmed in the whole cohort (adjOR 0.228), as well as in the subgroups of patients with PsO onset after 2005 (adjOR 0.264) and after 2014 (adjOR 0.179). Separately analysing the different biologics classes, both the TNF (adjOR 0.206), IL-17 (adjOR 0.051) and IL-23 or 12/23 (adjOR 0.167) inhibitors were significantly (p< 0.01) associated with a lower likelihood of PsA development. Finally, patients treated with biologics had a significantly (p< 0.04) lower prevalence of both pure peripheral PsA (adjOR 0.182) and peripheral PsA with axial involvement (adjOR 0.115). CONCLUSIONS: This study provides meaningful and concordant evidence supporting the significant role of different classes of biologics in reducing the likelihood of peripheral and axial PsA development.

Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study.

BACKGROUND: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. OBJECTIVE: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes. METHODS: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. RESULTS: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. CONCLUSIONS: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research.

The Challenging Differentiation of Psoriatic Arthritis from Other Arthropathies and Nonspecific Arthralgias in Patients with Psoriasis: Results of a Cross-Sectional Rheumatologic Assessment of a Large Dermatologic Cohort.

Aiming to identify the potential challenges in the classification of musculoskeletal manifestations in patients with psoriasis (PsO), this study analyzed the outcomes of a cross-sectional rheumatologic assessment of 1057 PsO patients. In total, 209 had a previous diagnosis of psoriatic arthritis (PsA). Out of the remaining 848 subjects, 293 (35%) were classified as suspected PsA cases according to the rheumatologist's judgment and/or Early PsA Screening Questionnaire score (EARP) ≥ 3. However, only 14% received a PsA diagnosis, 49% had a PsA-alternative diagnosis, and the remaining 37% had nonspecific arthralgias. Most of the newly diagnosed PsA patients had a symptoms duration ≥1 year (72%) and moderate disease activity (55%) with active oligoarthritis (85%), dactylitis, or enthesitis (35%) as the most frequent clinical pattern. The most frequent PsA-alternative diagnoses were osteoarthritis and fibromyalgia (44% and 41%). The only factors with significant (p < 0.05) utility in discriminating PsA from other diseases and nonspecific arthralgias were young age and EARP score with a history of morning stiffness, swollen joints, or dactylitis. These results demonstrated a high prevalence of suspected musculoskeletal symptoms in PsO patients, with, however, only a small proportion due to PsA. Close collaboration between the dermatologist and rheumatologist plays a crucial role in the differential diagnosis of PsA, as well as in monitoring nonspecific arthralgias for the potential transition to overt PsA.

A 52-week multicenter retrospective real-world study on effectiveness and safety of dupilumab in children with atopic dermatitis aged from 6 to 11 years.

Background: Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years.Methods: All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled.Results: Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52.Conclusions: Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time.

Recurrent nasal basal cell carcinoma treated with standard surgery excision: evaluation of volume ratio.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignant skin tumor. Although it rarely evolves into a metastatic disease, BCC can lead to a significant morbidity due to local invasion. The risk of lesion recurrence depends on clinical and histopathological factors as described by the Nation Comprehensive Cancer Network (NCCN). The surgical excision margins have a well-known role: there is a close relationship between high recurrence rate of BCC and the tumor proximity to the surgical margins. Aim of our study was to assess whether there is a significative correlation between recurring BCC and volume ratio (VRb/t), defined as ratio between excisional biopsy volume and tumor volume, and if VRb/t is a useful parameter to assess the risk of recurrence of BCC. METHODS: Retrospective case-control study in 80 patients with history of recurrent basal cell carcinoma of the nose (cases), and 43 patients with history of basal cell carcinoma of the nose with no evidence of relapse (controls) in the following 8 years. RESULTS: Surgical excision margins, histological subtype, ulceration, depth of invasion and volume ratio (VRb/t) were evaluated in case and controls. The evaluation of VRb/t evidenced a significant difference between recurrent BCC and non-recurrent BCC. The mean values of VRb/t were 6.17 for cases and 11.94 for controls. The Binomial Logistic Regression has displayed, for values of VRb/t around 7, a probability of 75% to identify BCCs belonging to the recurrent group. CONCLUSIONS: Our data show a significant correlation between recurrent BCCs and VRb/t. VRb/t can help in the assessment of recurrence risk, used together with others prognostic factor. For values of VRb/t close to 7 it should be recommended a close follow-up to promptly identify a possible recurrence.

Non-surgical treatment of hidradenitis suppurativa: the role of cryotherapy.

Background: Hidradenitis suppurativa is a chronic and recurrent inflammatory disease with a great impact on a patient's quality of life, due to the painful involvement of very sensitive areas, such as the groin, mammary area, and genitals, with malodourous discharge. Multiple treatment options are available; however, no single treatment is effective for all patients, and usually, a combination of medical therapy with various surgical and physical procedures is provided. Cryotherapy is not a routine technique to treat HS, although usually available in the majority of medical clinics, and is cheaper than laser and surgical treatments. The aim of this study was to evaluate the effectiveness of cryotherapy on persistent HS nodules, to reduce the burden of local disease. Materials and methods: Retrospective observational study in all patients treated with liquid nitrogen cryotherapy for persistent nodules of hidradenitis suppurativa in the last 2 years, with at least 6 months of follow-up after the procedure. Disease severity was assessed with Hurley staging and sonographic staging according to SOS-HS (18 MHz probe, Esaote-MyLab™). The results were scored with a 0-3 points scale, as complete remission (3), partial response (2 to 1), or no response (0), after one session of treatment. Local cleansing and antiseptic treatment after the procedure was the same as previously performed in each patient, not to influence recovery. Results: In total, 23 patients were included, with a total of 71 persistent nodules treated with a single cryotherapy session. The treatment has been effective in 63 out of 71 nodules treated (88.7%), and the patients attested that they recommend the treatment, the discomfort during recovery was minimal, and the management was not different from daily routine. Persistence was considered as having a failure rate (11.3% overall) and occurred in 7.5% of the nodules of the axillary region, 18.2% on the groin, and 11.2% for nodules of the gluteal region. Conclusion: Cryotherapy is a simple and effective procedure for the treatment of persistent nodules of HS not responding to medical therapy, and it is a valid alternative to local surgery or laser ablation.

Clinicopathologic features among different viral epidemic outbreaks involving the skin.

The current coronavirus disease 2019 pandemic has exceeded any epidemiologic prevision, but increasing information suggests some analogies with the major viral outbreaks in the last century, and a general warning has been issued on the possibility that coinfections can make the differential diagnosis and treatment difficult, especially in tropical countries. Some reports have noted that the presence of high dengue antibodies can give a false-negative result when testing for severe acute respiratory syndrome coronavirus 2. Mucocutaneous manifestations are very frequent, with an apparent overlap among different pathogens. However, strong clinicopathologic correlation might provide some clues to address differentials. Waiting for laboratory and instrumental results, the timing and distribution of skin lesions is often pathognomonic. Histopathologic findings characterize certain reaction patterns and provide insights on pathogenetic mechanisms. Unfortunately, skin assessment, especially invasive examinations such as biopsy, takes a back seat in severely ill patients. A literature retrieval was performed to collect information from other epidemics to counteract what has become the most frightening disease of our time.

Differences in lethality and diffusion of Covid-19 in countries using different kinds of vaccines.

To verify if lethality and diffusivity of Covid-19 correlated with percentage of people vaccinated in different countries and whether results on these indicators were comparable under different types of vaccines. A linear regression analysis was conducted between vaccines/inhabitant, new cases/inhabitants and ratio deaths/cases. A comparison between the three indicators was carried out in countries subdivided by kind of vaccine. The proportion of vaccinations/inhabitants correlates negatively with proportion of deaths × 100 cases (R = -3.90, p < 0.0001), but didn't on incidence of new cases. Countries with prevalence of mRNA vaccines were similar to others on incidence of new cases; but a lower lethality of Sars-Cov2 was found than in countries with prevalence of viral vehicle vaccines (F = 6.064, p = 0.0174) but didn't against countries with prevalence of inactivated vaccines. The higher is the proportion of vaccine/inhabitant in a given country, the less is the fraction of infected people who die.

The perception of professionals and users of the quality of care and respect for human rights in four outpatient care facilities of an Italian hospital during the Covid-19 pandemic.

Background: During the Covid-19 pandemic, delays in providing medical services, dissatisfaction, criticism toward health workers (HW) and the risk of burnout of HW in Italy have been documented. No studies have contrasted the point of view of HW and users on the quality of care and respect for human rights in health facilities. Objective: To compare the perception of users of their satisfaction with the care provided with the perception of HW of their satisfaction with work as well as the perception of the respect of HW "s and users" human rights. Methods: The "Well-Being at work and respect for human rights questionnaire" (WWRR) was administered on a sample of users (142) and HW (154) in four outpatient health care facilities of a hospital in Sardinia, Italy. Results: Users showed higher scores than HW on their satisfaction with the care received (p < 0.0001), the perception of respect for their human rights (p < 0.0001), and availability of resources for care (p < 0.0001). The HW scores were higher than 50% of the maximum in all items, but a relatively low score was reported on the HW's satisfaction of the resources and the respect for their rights. Conclusion: The satisfaction for care and respect for human rights in the outpatient health services was higher than expected. The relatively low score by the HWs in relation to the satisfaction with the resources and perception of respect for their human rights could be a wake-up call. The study does not involve emergency rooms, wards, or Covid units.

Why Was the Perception of Human Rights Respect and Care Satisfaction So High in Users of Italian Mental Health Services during the COVID-19 Pandemic?

The aim of this study was to compare users' and mental health workers' (MHW) perception of respect of human rights and job/care satisfaction in mental health services in Italy during the COVID-19 pandemic. A sample of users and MHW of Sardinia, Italy, fulfilled the "Well-Being at work and respect for human rights questionnaire" (WWRR). The study included 240 MHW and 200 users. Users showed a higher level of satisfaction of care than MHW of work, and a higher perception of the satisfaction of users and human rights respected for health workers. Both user and MHW responses were about 85% of the maximum score, except for satisfaction with resources. Responses were higher for users, but users and MHW both showed high levels of satisfaction. In previous surveys, MHW of Sardinia showed higher scores in all items of WWRR, except for satisfaction with resources, compared with workers from other health sectors of the same region, and with MHW from other countries. The low score for satisfaction with resources (in users and staff) is consistent with a progressive impoverishment of resources for mental health care in Italy. The study, although confirming the validity of the Italian model, fully oriented towards community, sets off an alarm bell on the risks resulting from the decrease in resources.

Exercise in Older Adults to Prevent Depressive Symptoms at the Time of Covid-19: Results of a Randomized Controlled Trial with Follow-Up.

Background: This study aimed to verify, through a randomized controlled trial, whether a medium-intensity mixing/aerobic/anaerobic exercise (accessible to older adults even with mild chronic diseases) can effectively counteract depressive episodes. A characteristic of the trial was that the follow-up coincided (unscheduled) with the lockdown due to Covid-19. Methods: Participants (N=120) were randomized into an intervention group, performing physical exercise, and a control group. Participants, aged 65 years and older, belonged to both genders, living at home, and cleared a medical examination, were evaluated with a screening tool to detect depressive episodes, the PHQ9, at pre-treatment, end of the trial (12-week), and follow-up (48-week). Results: A decrease in the frequency of depressive episodes after the trial (T1) was found in both groups; however, a statistically significant difference was observed only in the control group (p=0.0039). From T1 to follow-up (conducted during the lockdown), the frequency of depressive episodes increased in the control group, reaching a frequency equal to the time of study entry (p=0.788). In the experimental group, the frequency of depressive episodes did not change at the end of the trial but reached a statistically significant difference compared to the start of the study (p = 0.004) and was higher than the control group (p=0.028). Conclusion: Moderate-intensity physical exercise can be conducted safely, benefitting older adults even suffering from mild chronic disorders. Physical exercise seems to guarantee a long-term preventive effect towards depressive symptoms, especially in serious stressful situations such as the lockdown due to the Covid-19 pandemic.