Brodalumab for the Treatment of Moderate-to-Severe Psoriasis: An Expert Delphi Consensus Statement.

Brodalumab is a recombinant, fully human immunoglobulin IgG2 monoclonal antibody specifically targeted against interleukin-17RA that has been approved for the treatment of moderate-to-severe psoriasis in Europe. We developed a Delphi consensus document focused on brodalumab for the treatment of moderate-to-severe psoriasis. Based on published literature and their clinical experience a steering committee drafted 17 statements covering 7 domains specific to the treatment of moderate-to-severe psoriasis with brodalumab. A panel of 32 Italian dermatologists indicated their level of agreement using a 5-point Likert scale (from 1 = "strongly disagree" to 5 = "strongly agree") using an online modified Delphi method. After the first round of voting (32 participants), positive consensus was reached for 15/17 (88.2%) of the proposed statements. Following a face-to-face virtual meeting, the steering committee decided that 5 statements would form "main principles" and 10 statements formed the final list. After a second round of voting, consensus was reached in 4/5 (80%) of the main principles and 8/10 (80%) for consensus statements. The final list of 5 main principles and 10 consensus statements identify key indications specific to the use of brodalumab in the treatment of moderate-to-severe psoriasis in Italy. These statements aid dermatologists in the management of patients with moderate-to-severe psoriasis.

Real-World Experience of Methotrexate in the Treatment of Skin Diseases: an Italian Delphi Consensus.

BACKGROUND: After decades of use, methotrexate displays an established safety and efficacy profile in both in-hospital and outpatient settings. Despite its widespread use, there is surprisingly little clinical evidence to guide daily practice with methotrexate in dermatology. OBJECTIVES: To provide guidance for clinicians in daily practice for areas in which there is limited guidance. METHODS: A Delphi consensus exercise on 23 statements was carried out on the use of methotrexate in dermatological routine settings. RESULTS: Consensus was reached on statements that cover six main areas: (1) pre-screening exams and monitoring of therapy; (2) dosing and administration in patients naïve to methotrexate; (3) optimal strategy for patients in remission; (4) use of folic acid; (5) safety; and (6) predictors of toxicity and efficacy. Specific recommendations are provided for all 23 statements. CONCLUSIONS: In order to optimize methotrexate efficacy, it is essential to optimize treatment using appropriate dosages, carrying out a rapid drug-based step-up on a treat-to-target strategy and preferably using the subcutaneous formulation. To manage safety aspects appropriately, it is essential to evaluate patients' risk factors and carry out proper monitoring during the course of treatment.

Efficacy of Secukinumab in Psoriasis: Post Hoc Gender-Wise Analysis of the SUPREME Study.

Purpose: Psoriasis, a common systemic inflammatory disorder, presents with gender-related differences in the quality of life (QoL) and treatment outcomes. This post hoc analysis from the Phase 3b SUPREME study explored gender-related differences in patient characteristics and efficacy of secukinumab 300 mg on Psoriasis Area and Severity Index (PASI) 75/90/100 and impact on QoL using the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis through week 24. Patients and Methods: The proportion of patients achieving PASI 75/90/100 was computed using a nonresponder imputation approach. Differences between cohorts were analyzed using a logistic regression model. The mean change from baseline in DLQI was computed using the Wilcoxon test. Results: Among the 433 patients (males: 71.6%), females had a higher DLQI than males at baseline (13.1 vs 9.5; P<0.0001). Males had a slightly higher response for PASI 90 than females at week 16 (80.7% vs 78.1%; P=0.0779) and 24 (83.2% vs 79.7%; P=0.0319). No differences were observed between genders in PASI 100/75 responses at week 24. Both genders showed an improvement in DLQI with secukinumab at week 24 (-10.9 vs -8.1, respectively, in females vs males; P=0.0004). Conclusion: In summary, secukinumab was effective in the treatment of psoriasis, irrespective of gender.

Efficacy and Safety of Quadrivalent Conjugate Meningococcal Vaccines: A Systematic Review and Meta-Analysis.

Over the last decades, different quadrivalent antimeningococcal vaccine formulations (diphteria toxoid conjugate, MenACWY-D; tetanus toxoid conjugate, MenACWY-TT; CRM197 protein conjugate, MenACWY-CRM) have been developed. However, their availability varies, both in terms of authorized formulations and of inclusion in vaccination schedules. Furthermore, several countries include only the monovalent meningococcal C (MenC) vaccine in their immunization programmes. Finally, there is currently no updated systematic review that directly compares the MenACWY formulations. Thus, we summarized the evidence on efficacy and safety through four parallel, independent systematic literature reviews with meta-analysis which included randomized controlled trials comparing the abovementioned vaccines. A total of 16 studies have been included. In terms of efficacy, MenACWY-TT outperformed MenACWY-D and MenACWY-CRM for A, W-135, and Y serogroups, while no significant difference was found for serogroup C. Furthermore, we did not find significant differences in efficacy between MenC and MenACWY-TT. Regarding the safety, we were able to perform a quantitative analysis only between MenACWY-TT and MenC, finding no significant differences. Similarly, among the different MenACWY formulations no relevant differences were identified. These findings suggest that MenACWY-TT could be preferable to other formulations to improve current vaccination programs and to better develop future immunization policies.

Resolving the intrinsic short-range ordering of K+ ions on cleaved muscovite mica.

Muscovite mica, KAl2(Si3Al)O10(OH)2, is a common layered phyllosilicate with perfect cleavage planes. The atomically flat surfaces obtained through cleaving lend themselves to scanning probe techniques with atomic resolution and are ideal to model minerals and clays. Despite the importance of the cleaved mica surfaces, several questions remain unresolved. It is established that K+ ions decorate the cleaved surface, but their intrinsic ordering - unaffected by the interaction with the environment - is not known. This work presents clear images of the K+ distribution of cleaved mica obtained with low-temperature non-contact atomic force microscopy (AFM) under ultra-high vacuum (UHV) conditions. The data unveil the presence of short-range ordering, contrasting previous assumptions of random or fully ordered distributions. Density functional theory (DFT) calculations and Monte Carlo simulations show that the substitutional subsurface Al3+ ions have an important role for the surface K+ ion arrangement.

Does psoriasis influence female sexual dysfunction? A multicentric Italian case-control study.

BACKGROUND: Psoriasis has a significant impact on quality of life and affects the sexual sphere in 25-70% of patients. The aim of this study is to determine the prevalence of sexual dysfunction in female patients with psoriasis and to assess the possible correlation of sexual dysfunction with disease severity, genital involvement, age and some comorbidities. METHODS: In this prospective case-control study, all female patients with psoriasis followed at three Psoriasis Outpatient Services were divided into two groups depending on psoriasis severity assessed by the Psoriasis Area Severity Index. Both psoriatic patients and female controls without psoriasis were given the Female Sexual Function Index (FSFI) questionnaire. RESULTS: One hundred forty female patients with psoriasis were evaluated, 70 with mild disease and 70 with moderate-severe disease, and compared with 70 female controls without psoriasis. According to FSFI Score, prevalence of sexual dysfunctions was significantly higher in moderate-severe psoriatic patients compared to controls. Psoriatic women under the age of 46 presented lower FSFI scores than women over 46. No correlation between genital localization of psoriasis and worsening of sexual health was found. Diabetes mellitus and hypertension were significantly associated with sexual dysfunction, whereas the smoking habit did not significantly affect the sexual sphere of these patients. CONCLUSIONS: Sexual dysfunction should be routinely investigated in female patients with psoriasis in the case of moderate-severe disease due to its negative impact on quality of life, especially in younger women and in presence of diabetes mellitus and hypertension.

Secukinumab in Patients with Psoriasis and a Personal History of Malignancy: A Multicenter Real-Life Observational Study.

INTRODUCTION: There is limited evidence to guide clinicians on the treatment of psoriasis with biologics in patients with a history of malignancy who are often excluded from clinical trials investigating biologics. The aim of this work is to report a multicenter real-life experience of secukinumab treatment in patients with psoriasis and a personal history of cancer. METHODS: This retrospective observational study included adult patients with moderate-to-severe plaque psoriasis treated with secukinumab for at least 24 weeks and a previous diagnosis of cancer at 15 Italian referral centers. The primary endpoint of the study was tumor recurrence or progression and new cancer diagnosis during treatment. Secondary outcome assessment of secukinumab effectiveness (reduction of Psoriasis Area and Severity Index [PASI] score, improvement of Dermatology Life Quality Index [DLQI], itch and pain). RESULTS: Forty-two patients (27 male) were included. Malignancy was diagnosed in the previous 5 years in 21 (56.8%) and in the previous 10 years in 37 (88.1%). The mean interval between cancer diagnosis and the start of secukinumab treatment was 3.5 ± 3.3 years. No tumor recurrence nor progression occurred over a mean of 56 ± 31.7 weeks of treatment. Three patients developed a new malignancy not related to the previous cancer. At week 48, PASI 90 was reached by 64.7% of patients and PASI 100 by 38.2%. Mean DLQI, itch, and pain VAS scores significantly improved during treatment. CONCLUSIONS: Our multicenter real-life experience is the largest reported to date focusing on a specific biologic and adds evidence to the safety of secukinumab in psoriatic patients with a personal history of cancer.

Burden of Colovesical Fistula and Changing Treatment Pathways: A Systematic Literature Review.

PURPOSE: Colovesical fistula (CVF) is a rare complication of sigmoid diverticulitis causing significant morbidity and quality of life impairment. Aim of this study was to analyze contemporary literature data to appraise the current standard of care and changes of treatment algorithms over time. MATERIALS AND METHODS: A systematic review of the literature on surgical management of CVF was conducted through PUBMED, EMBASE, and COCHRANE databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guidelines. RESULTS: Fourteen papers published between 2014 and 2020 and including 1061 patients were analyzed. One-stage colonic resection with primary anastomosis, with or without loop ileostomy, was the most common surgical procedure. A laparoscopic or robotic approach was attempted in 39.5% of patients, and conversion rate to open surgery was 7.8%. Clavien-Dindo grade ≥3 complication rate, 30-day mortality, and recurrence rate were 7.4%, 1.5%, and 0.5%, respectively. CONCLUSIONS: Minimally invasive sigmoidectomy with primary anastomosis is safe and should be the first-choice approach for CVF. Bladder repair is not necessary after a negative intraoperative leak test. A standardized perioperative care can improve clinical outcomes and reduce the length of hospital stay and the duration of Foley catheterization.

Implementation of the South African Triage Scale (SATS) in a New Ambulance System in Beira, Mozambique: A Retrospective Observational Study.

In 2019, an urban ambulance system was deployed in the city of Beira, Mozambique to refer patients from peripheral health centres (HCs) to the only hospital of the city (Beira Central Hospital-HCB). Initially, the system worked following a first-in-first-out approach, thus leading to referrals not based on severity condition. With the aim of improving the process, the South African Triage Scale (SATS) has been subsequently introduced in three HCs. In this study, we assessed the impact of SATS implementation on the selection process and the accuracy of triage performed by nurses. We assessed 552 and 1608 referral charts from before and after SATS implementation, respectively, and we retrospectively calculated codes. We compared the expected referred patients' codes from the two phases, and nurse-assigned codes to the expected ones. The proportion of referred orange and red codes significantly increased (+12.2% and +12.9%) while the proportion of green and yellow codes decreased (-18.7% and -5.8%). The overall rates of accuracy, and under- and overtriage were 34.2%, 36.3%, and 29.5%, respectively. The implementation of SATS modified the pattern of referred patients and increased the number of severe cases receiving advanced medical care at HCB. While nurses' accuracy improved with the routine use of the protocol, the observed rates of incorrect triage suggest that further research is needed to identify factors affecting SATS application in this setting.

Work-Related Stress among a Cohort of Italian Long-Term Care Workers during the COVID-19 Pandemic: An Observational Study.

Despite long-term care (LTC) workers having been identified as particularly subject to chronic stress, only a few studies evaluated the impact of the COVID-19 pandemic on stress in this population. As far as the authors know, no studies have investigated the relationship between work-related stress and chronic stress in the LTC setting. This retrospective observational study aimed to assess the level of chronic stress in LTC workers, to identify some possible predictors and vulnerability factors, and to measure the impact of the COVID-19 pandemic on work-related stress. The study was based on the information gathered from two different questionnaires administered before and one year after the beginning of the pandemic, to a cohort of Italian LTC workers. We found that chronic stress was associated with lower resilience to stress scores (57.42 vs. 60.66) and with higher work-related stress scores (30.48 vs. 20.83). Interestingly, the overall level of work-related stress did not differ between the two questionnaires (27.84 vs. 29.08). However, the main components of the questionnaires changed; fatigue and burnout symptoms became more relevant after the pandemic. Results of this study suggests deepening knowledge of the components of stress to develop and implement effective stress mitigation interventions.

Knowledge Gaps and Research Priorities on the Health Effects of Heatwaves: A Systematic Review of Reviews.

Although extreme weather events have played a constant role in human history, heatwaves (HWs) have become more frequent and intense in the past decades, causing concern especially in light of the increasing evidence on climate change. Despite the increasing number of reviews suggesting a relationship between heat and health, these reviews focus primarily on mortality, neglecting other important aspects. This systematic review of reviews gathered the available evidence from research syntheses conducted on HWs and health. Following the PRISMA guidelines, 2232 records were retrieved, and 283 reviews were ultimately included. Information was extracted from the papers and categorized by topics. Quantitative data were extracted from meta-analyses and, when not available, evidence was collected from systematic reviews. Overall, 187 reviews were non-systematic, while 96 were systematic, of which 27 performed a meta-analysis. The majority evaluated mortality, morbidity, or vulnerability, while the other topics were scarcely addressed. The following main knowledge gaps were identified: lack of a universally accepted definition of HW; scarce evidence on the HW-mental health relationship; no meta-analyses assessing the risk perception of HWs; scarcity of studies evaluating the efficacy of adaptation strategies and interventions. Future efforts should meet these priorities to provide high-quality evidence to stakeholders.

Oligometastatic Prostate Cancer: A Comparison between Multimodality Treatment vs. Androgen Deprivation Therapy Alone.

BACKGROUND: We compared multimodality treatment (MMT, defined as robot-assisted radical prostatectomy (RARP) with androgen deprivation therapy (ADT), with or without adjuvant radiotherapy (RT)) vs. ADT alone in oligometastatic prostate cancer (OPC) patients. METHODS: From 2010 to 2018, we identified 74 patients affected by cM1a-b OPC (≤5 metastases). Kaplan-Meier (KM) plots depicted cancer-specific mortality (CSM), disease progression, metastatic castration-resistant PC (mCRPC), and time to second-line systemic therapy rates. Multivariable Cox regression models (MCRMs) focused on disease progression and mCRPC. RESULTS: Forty (54.0%) MMT and thirty-four (46.0%) ADT patients were identified. On KM plots, higher CSM (5.9 vs. 37.1%; p = 0.02), mCRPC (24.0 vs. 62.5%; p < 0.01), and second-line systemic therapy (33.3 vs. 62.5%; p < 0.01) rates were recorded in the ADT group. No statistically significant difference was recorded for disease progression. ForMCRMs adjusted for the metastatic site and PSA, a higher mCRPC rate was recorded in the ADT group. No statistically significant difference was recorded for disease progression. Treatment-related adverse events occurred in 5 (12.5%) MMT vs. 15 (44.1%) ADT patients (p < 0.01). CONCLUSIONS: MMT was associated with lower CSM, mCRPC, and second-line therapy rates. A lower rate of treatment-related adverse events was recorded for the MMT group.

Guselkumab for the treatment of psoriasis: a 60-week real-life multicenter retrospective experience.

BACKGROUND: Real-world data for guselkumab, the first interleukin-23 inhibitor approved to treat moderate-to-severe psoriasis, are scarce. This study represents the first 60-week, real-life, multicenter, retrospective experience to investigate the effectiveness, safety, tolerability, and drug retention of guselkumab in psoriatic patients. RESEARCH DESIGN AND METHODS: Clinical information was collected at baseline and at weeks 12, 24, 36, 48, and 60. RESULTS: The mean baseline Psoriasis Activity Severity Index (PASI) reduced from 14.2 to 3.1 at week 12 and decreased to around 0 at weeks 36, 48, and 60. PASI 75, PASI 90, and PASI 100 were 100%, 96.8%, and 83.9% at week 60, respectively. Multiple logistic regression analysis showed that neither body mass index >30, smoking, ≥3 comorbidities, difficult-to-treat areas, nor a failure to ≥2 prior biologic treatments significantly influenced PASI reduction (p > 0.05). CONCLUSIONS: Our findings confirm guselkumab as an appropriate therapeutic option in routine clinical practice, especially when dealing with complex patients with comorbidities or previous failure to biologic treatments.

Italian adaptation of EuroGuiDerm guideline on the systemic treatment of chronic plaque psoriasis.

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by moderate to severe plaque psoriasis. The content of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline, suggestions for disease severity grading and treatment goals. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs including acitretin, cyclosporine, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab. Moreover, the guideline provides guidance for specific clinical situations such as patient with concomitant psoriatic arthritis, inflammatory bowel disease, a history of malignancies, a history of depression, diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or those with childbearing potential. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

True congenital multicystic disease of the pancreas in the infant: a very rare case.

The most frequent pancreatic cysts in patients of developmental age are pseudocysts, neoplastic cysts, posttraumatic cysts, and parasitic cysts. Retention cysts, duplication cysts, and congenital cysts are called true cysts. Among the true cysts, congenital cysts are very rare and include 1% of all pancreatic cysts. The finding of true congenital pancreatic cysts in children under 3 years represents a very rare event; less than 30 have been described in the literature. We describe the case of a 3-year-old male who came to our observation for abdominal pain and underwent an abdomen ultrasound examination. The ultrasound examination showed unilocular sub-centimeter cystic lesions, distributed throughout the pancreatic parenchyma. The patient was, therefore, not subjected to any treatment, and after a few days, the symptoms regressed spontaneously. This description probably represents the first case in the literature of "congenital multicystic disease" of the pancreas.

May Thurner syndrome: description of a case with unusual clinical onset.

May-Thurner syndrome (MTS) is a congenital vascular alteration that is part of a restricted category of very rare vascular syndromes that have in common the compression of an arterial or venous vessel. MTS, first described in 1957, is due to compression of the left common iliac vein against the lumbar spine by the adjacent common iliac artery. It can cause chronic thrombosis of the left lower limb and can give edema, pain, claudication, thrombophlebitis, and, in severe cases, pulmonary embolism. Color Doppler and duplex Doppler ultrasound allow us to easily locate the deep vein thrombosis, to measure its extension, and to highlight the vascular changes typical of MTS: compression and consequent hypertension of the left common iliac vein. The therapy depends on the degree of venous stasis and on the presence of venous thrombosis; generally, it consists of the administration of short- or long-term anticoagulant and thrombolytic drugs. In cases of severe stenosis of the left common iliac vein, the first-choice treatment consists of positioning a vascular stent, which resolves compression and significantly reduces chronic thrombotic episodes. We describe a case of MTS with an unusual clinical onset with pulmonary embolism.

Real-world evidence of biologic treatments in moderate-severe psoriasis in Italy: Results of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional longitudinal study of real-life clinical practice) study.

EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional (CANOVA) study was aimed at providing real-world evidence of the effectiveness of biologics in Italian patients with moderate-severe psoriasis. It was an observational, retro-prospective cohort study conducted in 17 Italian dermatology clinics. Adult patients with moderate-severe plaque psoriasis, who started a biologic treatment between 24 weeks and 24 months before enrolment, were included. With a follow-up visit at 6 months after enrolment, each patient had at least 12 months of observation. The primary objective was to describe the clinical response rates (PASI 75) after 16/24/52 weeks from biologic treatment start. Secondary outcomes were sustained response, quality of life, and treatment satisfaction. Of the 669 eligible patients (64% males), 52% were naïve to biologics, though a mean duration of psoriasis since first diagnosis of 18.6 years (SD 13.2). The most frequently prescribed biologics were secukinumab (41%), ustekinumab (25%), TNF-inhibitors (22%) and ixekizumab (12%). PASI 75 was achieved by 86% of patients (95% CI: 82%-89%) at 16 weeks, 90% (87%-93%) at 24 weeks, and 91% (89%-94%) at 52 weeks. Patients achieving PASI 90 and PASI 100 at 52 weeks were 75% (71%-79%) and 53% (49%-57%), respectively. Sustained PASI 75 response after 1 year from treatment start was achieved by 78% (74%-82%) of patients. Mean DLQI total score was 2.3 (SD 3.9) at enrollment and decreased at the final visit to 1.8 (3.6). A high level of treatment satisfaction was expressed by patients over the study period. This large real-world study confirms in the clinical practice the good effectiveness and acceptability of biologics in psoriasis patients.