Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study.

Purpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks. Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts. Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6-positive and HLA-Cw6-negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLA-Cw6-positive and HLA-Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings. Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile.

RNAscope in situ hybridization and RT-PCR for detection of SARS-CoV-2 in chilblain-like lesions: A clinical, laboratory and histopathological study.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, an increasing number of chilblain-like lesions (ChLL) have been increasingly reported worldwide. To date, the causal link between ChLL and SARS-CoV-2 infection has not been unequivocally established. METHODS: In this case series, we present demographic, clinical, laboratory, and histopathological information regarding 27 young patients with a clinical diagnosis of ChLL who referred to the Dermatology Unit of Papa Giovanni XXIII Hospital, Bergamo, Italy, from 1 April 2020 to 1 June 2020. RESULTS: The mean age was 14.2 years, and 21 patients (78%) experienced mild systemic symptoms a median of 28 days before the onset of cutaneous lesions. ChLL mostly involved the feet (20 patients - 74%). Among acral lesions, we identified three different clinical patterns: (i) chilblains in 20 patients (74%); (ii) fixed erythematous macules in 4 children (15%); (iii) erythrocyanosis in 3 female patients (11%). Blood examinations and viral serologies, including parvovirus B19, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and coxsackievirus were normal in all. Three patients (11%) underwent nasopharyngeal swab for RT-PCR for SARS-CoV-2 showing only 1 positive. Histopathological examinations of 7 skin biopsies confirmed the clinical diagnosis of chilblains; vessel thrombi were observed only in 1 case. Our findings failed to demonstrate the direct presence of SARS-CoV-2 RNA in skin biopsies, both with real-time polymerase chain reaction (RT-PCR) and RNAscope in situ hybridization (ISH). LIMITATIONS: Limited number of cases, unavailability of laboratory confirmation of COVID-19 in all patients, potential methodological weakness, and latency of skin biopsies in comparison to cutaneous lesions onset. CONCLUSIONS: These observations may support the hypothesis of an inflammatory pathogenesis rather than the presence of peripheral viral particles. Although, we could not exclude an early phase of viral endothelial damage followed by an IFN-I or complement-mediated inflammatory phase. Further observations on a large number of patients are needed to confirm this hypothesis.

Italian expert-based recommendations on the use of photo(chemo)therapy in the management of mycosis fungoides: Results of an e-Delphi consensus.

BACKGROUND: Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule. AIMS: The primary aim of this study was to establish the first structured, expert-based consensus regarding the indications and technical schedules of NB-UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item. MATERIALS & METHODS: E-delphi study. Item-specific expert consensus was defined as the number of "Totally Agree" results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic. RESULTS: Overall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7). CONCLUSIONS: Items related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB-UVB and PUVA in MF.

Who Are the Subjects with Gambling-Related Problems Requiring Treatment? A Study in Northern Italy.

BACKGROUND: This study analyzes data related to Hospital (HOS), Public Treatment Service Dedicated to Drug Addicts (SERD), or Community Mental Health Center (CMHC) clients with a first diagnosis of Pathological Gambling (PG) in the period 2000/2016 in Northern Italy. The aims were to describe trends and characteristics of pathological gamblers (PGs) and to estimate the prevalence of other diagnoses before or after the diagnosis of PG. METHODS: Participants aged over 17 years with an ICD-9 or ICD-10 PG diagnosis were selected. RESULTS: 680 PGs were identified, mean age 47.4 years, 20% female, 13% non-natives, 30% had other mental disorders diagnoses, 9% had alcohol dependence syndrome, and 11% had drug dependence. Most participants with comorbid disorders were diagnosed before PG, with a more elevated prevalence regarding mental disorders. Almost seven years had elapsed on average between the first admission and the diagnosis of PG. CONCLUSIONS: The results of this study highlight a growing demand for PG treatment addressed not only to SERD, but also to psychiatric and hospital services, based on the increase in SERD attendance from 2013. Many of them had already been treated for mental health problems before, but their percentage remained costant over time.

Dermatomyositis: clinicopathological correlations.

Dermatomyositis (DM) is a chronic autoimmune disease affecting primarily the skeletal muscle and the skin. Although the diagnosis is usually based upon clinical and laboratory findings, histopathology is helpful for confirmation purposes and is mandatory in amiopathic DM where there is only skin involvement. Histologically, the typical cases are characterized by subtle vacuolar interface alterations with epidermal atrophy, mild capillary ectasia and sparse perivascular lymphocytic infiltrate; these findings are similar to those seen in other connective tissue diseases, especially lupus erythematosus. This review deals with the specific histological findings that can be found in the different presentations of the disease and discuss the most common differential diagnoses. As for many other inflammatory skin diseases, the diagnosis of DM is based on a strict interaction between the dermatologist and the dermatopathologist.

Mortality risk in a cohort of Italian alcoholic individuals treated for alcohol dependence.

INTRODUCTION AND AIMS: The aim of this study was to investigate the mortality risk and to explore the presence of subjects more at risk of dying in a cohort of alcoholic individuals treated for alcohol dependence over a lengthy follow-up period. DESIGN AND METHODS: A total of 2363 subjects attending 10 centres for addiction treatment for alcohol dependence were recruited. RESULTS: During the 17 year follow-up period, 14.7% of the entire cohort died. Total standardised mortality rates (SMR) were higher in women (SMR = 5.94) as compared with men (SMR = 4.65). Higher SMRs were found for several diseases, for traumatic episodes (SMR = 6.65) and in younger patients (18-44 age group) (SMR = 8.16). Alcoholic women showed a higher survival rate as compared with men. In addition, a higher risk of death for men and unemployed subjects, with a progressive increase of risk in line with the increase of the age of admission to treatment, and with a progressive decrease of risk after 1 year from the beginning of the treatment, was also found. DISCUSSION AND CONCLUSIONS: This study confirms that mortality risk in alcoholic individuals in treatment is higher in comparison with the general population. Moreover, alcoholics men, unemployed, >40 years at time of admission and during the first year of treatment are more at risk to die. Thus, much more attention to patients with these characteristics should be planned by the professional staff working in centres for addiction treatment. [ Pavarin R M, Caputo F, Zoli G, Domenicali M, Bernardi M, Gambini D. Mortality risk in a cohort of Italian alcoholic individuals treated for alcohol dependence Drug Alcohol Rev 2017;36:186-191].

Emergency department presentation and mortality rate due to overdose: A retrospective cohort study on nonfatal overdoses.

BACKGROUND: The aims of this retrospective cohort study are to describe the presentation characteristics for nonfatal overdose-related complaints at the emergency departments (EDs) of the metropolitan area of Bologna (northern Italy), to estimate the subsequent risk of mortality by overdose, and to identify the profiles of the subjects most at risk. METHODS: Records of patients admitted to 10 EDs for overdose between January 2004 and December 2012 were retrospectively evaluated. The International Classification of Diseases was used to ascertain the cause of death. RESULTS: A total of 294 episodes of overdose involving 218 individuals were identified. The total time at risk was 1048 person-years (PY). The mortality rate for all causes was 35.48 per 1000 PY for males and 20.61 per 1000 PY for females. The mortality rate for overdose was 16.6 per 1000 PY for males and 13.74 per 1000 PY for females. In the multivariate regression analysis, the time from first ED overdose access (less than 1 year risk ratio [RR]: 7.07, 95% confidence interval [CI]: 5.32-9.39) was significantly associated with death by overdose. Males, subjects aged >30 years at presentation, patients who refused ED treatment, and those having previously contacted mental health services showed an increased mortality risk due to overdose. CONCLUSIONS: Experiencing a nonfatal overdose within the past 12 months increases the risk of mortality compared with an overdose more than 12 months earlier. Nonfatal overdose patients presenting to an ED form a specific target for prevention projects.

Let It "B"? The role of Hepatitis B universal vaccination among italian problematic drug users.

Hepatitis B virus (HBV) hepatitis is extremely common among problematic drug users (DUs). As of 2012, 47 of the 53 European countries had implemented a universal hepatitis B vaccination programme, a scenario that could radically change its spread. Even so, drug users are still one of the main groups at risk of being infected by HBV, exposing the fact that universal vaccination still has not managed to reach an optimal level of contagion protection. In order to evaluate the role of universal HBV vaccination in protecting against risk behaviour related to the use of illicit drugs, a group of 748 DUs, 511 male and 237 female, was tested for HBV markers, at their first access to public addiction clinics in the metropolitan area of Bologna, Italy. 487 were born after 1981, so they were eligible to have received HBV vaccination in adolescence or at birth; in these subjects antibodies against HBV core antigen had the significant prevalence of 6.2%. Universal HBV vaccination has shown evidence of protecting against infection in the general population. These results, amongst the first to evaluate actual protection in DUs vaccinated at birth or during adolescence, show that compulsory universal vaccination does not solve the problem of HBV transmission in the most at risk groups and that additional strategies must be studied and implemented to address this issue.

Health status of users of the Bologna local health authority drug addiction treatment services: a study of hospital admissions in the period 2004-2013.

The aim of this study was to monitor the health status of the users of the services for drug addiction (SERT) in the metropolitan area of Bologna by analysing the hospital discharge records (SDO). For the period 2004-2013, among the residents of the metropolitan areas aged 15-64, we compared the trend in hospital admissions of SERT users with that of the general population. We calculated the standardised rates of hospitalisation and the likelihood of admission. Over the period in question the standardised hospitalisation rates decreased, with a larger drop among SERT users (330.17 males per 10,000 inhabitants in 2004, 215.91 in 2013; 547.60 females per 10,000 inhabitants in 2004, 283.20 in 2013) as compared with the general population (109.49 males in 2004, 82.16 in 2013; 161.40 females in 2004, 124.38 in 2013). Admission likelihood was always higher for SERT users, but was lower in 2013 than in 2004, especially for infectious diseases and psychic disorders. The results highlight the effectiveness of Bologna's local system of services in taking care of aspects connected to addiction, as well as health-related disorders.

Three cases of primary cutaneous lymphoblastic lymphoma: microarray-based comparative genomic hybridization and gene expression profiling studies with review of literature.

Lymphoblastic lymphoma (LBL) is a neoplasm of precursor B- or T-lymphocytes, and primary skin involvement is uncommon. The aim of the study was to review all reported primary cutaneous (PC)-LBLs and to examine three new cases to better characterize this neoplasm. Two of our patients showed a pre-B phenotype (PC-B-LBL) and one a never-reported pre-T phenotype (PC-T-LBL). The patient with PC-T-LBL showed an aggressive course, while those with PC-B-LBL showed a complete remission (CR) after polychemotherapy. Cytogenetic analysis and gene expression profiling (GEP) were performed on one case of PC-B-LBL and on that of PC-T-LBL. A specimen of PC-B-LBL and two specimens (early and late stage) of PC-T-LBL were investigated by microarray-based comparative genomic hybridization (CGH). All specimens revealed trisomy of chromosome 4. PC-T-LBL showed a gain of 1p36.33-p22.1 in the early stage and multiple chromosome gains/losses in the late stage. Our data suggest that trisomy 4 could be detected early in LBL and gain of 1p36.33-p22.1 could be an interesting marker in PC-T-LBL. LBL is an aggressive disease but, only in B-LBL, the cutaneous presentation seems to be a favorable prognostic factor and polychemotherapy is the best therapeutic approach. We suggest that PC-LBL should be included as a provisional clinicopathologic entity in future cutaneous lymphoma classification.

The clinical spectrum of psoriasis.

The clinical picture of psoriasis is not uniform. Being one of the most common chronic inflammatory skin disorders, psoriasis may present in many different forms and may include extracutaneous manifestations. Classifications have been proposed based on disease onset or the clinical course of psoriasis. Chronic plaque psoriasis occurs in a variety of clinical forms primarily distinguished by size, distribution, and dynamics of psoriatic plaques. In addition, psoriasis inversa, localized and generalized pustular forms, erythrodermic psoriasis, as well as a number of more uncommon forms have been recognized, a distinction on clinical grounds that is relevant for the overall prognosis and impact on the patients' quality of life as well as for the choice of therapy. The broad and rather colorful clinical spectrum of psoriasis as well as implications for clinical practice will be comprehensively reviewed in this article.

Primary cutaneous follicular center cell lymphoma of the nose with maxillary sinus involvement in a pediatric patient.

We report a primary cutaneous follicular center cell lymphoma (PCFCCL) that arose on the nose and the left naso-labial fold, spread to the left cheek, the left maxillary sinus, and the soft palate in a 16-year-old boy. Polychemotherapy was performed and the patient is disease-free after 41 months. This case is unusual because PCFCCL rarely arises on the nose, only occasionally disseminates to extracutaneous sites, and, to our knowledge, has never been described in pediatric patients.