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Introduction: Treat-to-target strategies are used in several chronic diseases to improve outcomes. Treatment goals have also been suggested for psoriasis, but there is currently no consensus on targets, and guidance is needed to implement this strategy in clinical practice. The project ‘Treat to Target Italia’ was launched by a scientific board (SB) of 10 psoriasis experts to generate expert consensus recommendations. Methods: On the basis of the published literature, their clinical experience, and the results of a survey among Italian dermatologists, the SB identified four relevant topics: (1) clinical remission; (2) quality of life; (3) abrogation of systemic inflammation; (4) safety. They drafted 20 statements addressing these four topics and submitted them to a panel of 28 dermatologists, in a Delphi process, to achieve consensus (greater than 80% agreement). Results: Consensus was reached on all statements. Treatment goals defining clinical remission should include a 90% improvement from baseline in the Psoriasis Area and Severity Index (PASI90 response) or an absolute PASI score of less than or equal to 3. Patient’s quality of life and satisfaction are important targets. If PASI targets are achieved, there should be no or very low impact of psoriasis on quality of life [Dermatology Life Quality Index (DLQI) score less than or equal to 3]. If PASI or DLQI goals are not achieved within 3–4months, treatment should be changed. Abrogation of systemic inflammation may be crucial for preventing or delaying inflammatory comorbidities. Safety is an equally important target as efficacy. Conclusion: These 20 consensus statements define the parameters of a treat-to-target strategy for psoriasis in Italy. It is hoped that use of these in the management of patients with psoriasis will improve treatment outcomes and patient health-related quality of life.

Introduction: Tildrakizumab is a monoclonal antibody that targets the p19 subunit of IL-23, a crucial cytokine for Th17 cells. Tildrakizumab has been assessed in several Phase I, II, and III clinical trials and is approved for treatment of adults with moderate to severe plaque psoriasis who are indicated for systemic therapy. Areas covered: The available evidence on the efficacy, safety, and use of tildrakizumab in special populations was evaluated by 14 experts who critically reviewed the current literature. Expert opinion: Tildrakizumab has good efficacy that lasts for at least 5years in patients with moderate to severe psoriasis, and appears to be safe and well tolerated in the long-term with no apparent dose-related differences in adverse events, a low incidence of discontinuation due to adverse events, and no evidence of increased risk of malignancies. The safety and the efficacy of tildrakizumab has also been confirmed in special populations such as those with inflammatory bowel disease, cardiovascular disease, metabolic syndrome, and advanced age. Early intervention with IL-23-inhibitors, such as tildrakizumab, may help to control symptoms and change the long-term course of the disease in patients affected by plaque psoriasis, while improving the quality of life and potentially minimizing the risk of developing comorbidities.

Hypersensitivity reactions (HRs) to contrast media (CM) can be distinguished in immune-mediated (including allergic reactions) and non-immune-mediated reactions, even if clinical manifestations could be similar. Such manifestations range from mild skin eruptions to severe anaphylaxis, making it important for radiologists to know how to identify and manage them. A panel of experts from the Società Italiana di Radiologia Medica e Interventistica (SIRM) and the Società Italiana di Allergologia, Asma e Immunologia Clinica (SIAAIC) provided a consensus document on the management of patients who must undergo radiological investigations with CM. Consensus topics included: the risk stratification of patients, the identification of the culprit CM and of a safe alternative by an allergy workup, as well as the use of premedication and the correct procedure to safely perform an elective (i.e., scheduled) or urgent examination. The most important recommendations are: (1) in all patients, a thorough medical history must be taken by the prescribing physician and/or the radiologist to identify at-risk patients; (2) in patients with hypersensitivity reactions to CM, the radiologist must consider an alternative, non-contrast imaging study with a comparable diagnostic value, or prescribe a different investigation with another class of CM; (3) if such options are not feasible, the radiologist must address at-risk patients to a reference centre for an allergy evaluation; (4) if timely referral to an allergist is not viable, it is recommended to use a CM other than the responsible one, taking into account cross-reactivity patterns; in the case of patients with histories of severe reactions, the presence of an anesthesiologist is also recommended and a premedication is suggested.

Background: Hip fracture (HF) is a burdening health problem in older people. The orthogeriatric approach has been shown to favour functional recovery and reduce mortality, but its implementation in clinical practice cannot rely upon shared management protocols and greatly varies among different healthcare systems. Here, we present the rationale and design of the Italian consensus document on the management of HF in older people. Methods: A panel of multidisciplinary experts from ten Italian scientific societies involved in the care of HF and including geriatricians, orthopaedics, anaesthesiologists, physiatrists and general practitioners, will join to establish the content validity of a list of statements. A Delphi consensus methodology will be applied to obtain the opinions of the panel and to provide the final recommendations. Objectives: The document will include indications on the following relevant topics: (1) optimal care path of older subjects with HF; (2) management of comorbidities and pre-operative alteration of physiological parameters; (3) management of selected categories of patients at expected increased risk of adverse outcomes; (4) continuity of care out of hospital; (5) screening and correction of risk factors for HF in older subjects; (6) information and divulgation of shared management strategies. The objective of the consensus will be to inform clinicians, patients, researchers, and health policy makers about the best management strategies for HF in older people and their inherent limitations, thus facilitating communication between stakeholders and promoting the most cost/effective models of care.

Pediatric adrenocortical tumors are rare and heterogeneous endocrine malignancies. Objectives To report clinical, biochemical, and histological features, staging, and therapeutic interventions in a cohort of 28 patients treated at a single tertiary center. Methods A retrospective review of medical records of children with PACT (diagnosed before Results Mean age at diagnosis was 4.6 years (range, 0.3–17.3 years) and median follow-up was 4.17 years (range, 0–12 years). Female to male ratio was 2.5:1. Signs and symptoms that prompted medical intervention were hormonal overproduction (57%), abdominal complaints (36%), and hypertensive encephalopathy (7%). In patients with clinically virilizing tumors (n=16) mean height standard deviation score (SDS) and bone age advance were significantly higher while body mass index (BMI) SDS was significantly lower than in those with clinical Cushing’s (n=10) (p Conclusions Height SDS and BMI SDS seem to mirror hormonal secretion in pediatric adrenocortical tumors. Higher DHEAS levels were found in patients with more advanced disease. Further large-scale studies are needed to validate a possible role for DHEAS as a biochemical marker of tumor stage and to draw robust conclusions on the use of adjuvant chemotherapy.

Lichen sclerosus (LS) is a disabling chronic inflammatory disease of skin and genital mucous membrane causing itch, pain, dysuria and restriction of micturition, and significant sexual dysfunction and dyspareunia both in women and men. If left untreated, LS is associated with a high degree of sclerosis and scarring, as well as with an elevated risk of cancer in the genital area. Although a central role of autoimmunity is suggested, the pathogenesis of LS is still not clearly understood and the disease remains difficult to treat. The goals of treatment of LS are to alleviate symptoms and discomfort, prevent anatomical changes and prevent malignant transformation. This guideline has been developed by an Italian group of experts. It summarizes evidence-based and expert- based recommendations. The highest level of evidence favors the use of topical high potency corticosteroids; second- and third-line treatments include topical calcineurin inhibitors and topical retinoids, respectively. Surgical treatment has become the treatment of choice in male genital LS with persistent phimosis not responsive to medical treatment. The aim of this paper is to offer evidence-based and easily applicable recommendations for the management of LS.

Background: Health outcomes of older subjects with hip fracture (HF) may be negatively influenced by multiple comorbidities and frailty. An integrated multidisciplinary approach (i.e. the orthogeriatric model) is, therefore, highly recommended, but its implementation in clinical practice suffers from the lack of shared management protocols and poor awareness of the problem. The present consensus document has been implemented to address these issues. Aim: To develop evidence-based recommendations for the orthogeriatric co-management of older subjects with HF. Methods: A 20-member Expert Task Force of geriatricians, orthopaedics, anaesthesiologists, physiatrists, physiotherapists and general practitioners was established to develop evidence-based recommendations for the pre-, peri-, intra- and postoperative care of older in-patients (≥ 65 years) with HF. A modified Delphi approach was used to achieve consensus, and the U.S. Preventive Services Task Force system was used to rate the strength of recommendations and the quality of evidence. Results: A total of 120 recommendations were proposed, covering 32 clinical topics and concerning preoperative evaluation (11 topics), perioperative (8 topics) and intraoperative (3 topics) management, and postoperative care (10 topics). Conclusion: These recommendations should ease and promote the multidisciplinary management of older subjects with HF by integrating the expertise of different specialists. By providing a convenient list of topics of interest, they might assist in identifying unmet needs and research priorities.

Background Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID‐19) pandemic. Methods A national registry, named DA‐COVID‐19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID‐19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID‐19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician‐ and patient‐reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. Results A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS‐CoV‐2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS‐CoV‐2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID‐related death occurred. Conclusions Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab‐treated patients., Among 1831 studied AD patients, 86.1% were treated with dupilumab. Patients continuing therapy experienced a marked reduction of disease severity during pandemic. The causes of treatment interruption included: fear of increased susceptibility to SARS‐CoV‐2 infection (24.8%), occurrence of comorbidities (5.9%), age above 60 years (5.2%), SARS‐CoV‐2 infection (2.8%), close contact with SARS‐CoV‐2‐positive subject (2.4%), other reasons, for example, inability to maintain drug supply, non‐medical/unspecified causes (58.7%).

Background The susceptibility of patients with chronic plaque psoriasis and the risks or benefits related to the use of biological therapies for COVID-19 are unknown. Few data about prevalence, clinical course and outcomes of COVID-19 among psoriatic patients were reported. The aims of this study were 1) to assess the prevalence and severity of COVID-19 in psoriatic patients treated with biologic agents during the first phase of the emergency (22 February to 22 April 2020) in Italy, and 2) to report the clinical outcomes of patients who have been exposed to individuals with confirmed SARS-CoV-2 infection. Methods Patients with moderate-to-severe chronic plaque psoriasis, aged ≥18 years and undergoing treatment with biologic agents as of 22 February 2020, were eligible to be included in PSO-BIO-COVID study. Demographic and clinical characteristics of patients using any biologic for psoriasis treatment between 22 February and 22 April 2020 were registered. For all confirmed or suspected cases of COVID-19, data about concomitant disease, ongoing therapies, and comorbidities were also reported. Results A total of 12,807 psoriatic patients were included in the PSO-BIO-COVID study. In this cohort twenty-six patients (0.2%) had a swab confirmation of SARS-CoV-2 infection. Eleven patients required hospitalization and two died. 125 of 12807 patients (1.0%) with exposure to a patient with COVID-19 under quarantine or active health surveillance, were reported. Conclusion The incidence of COVID-19 observed in our cohort of psoriatic patients (0.2%) is similar to that seen in the general population (0.31%) in Italy. However, the course of the disease was mild in most patients. Biological therapies may likely lessen "cytokine storm" of COVID-19, which sometimes lead to multiple organ failure, ARDS, and death.

Aims Risk stratification in patients with advanced chronic heart failure (HF) is an unmet need. Circulating microRNA (miRNA) levels have been proposed as diagnostic and prognostic biomarkers in several diseases including HF. The aims of the present study were to characterize HF‐specific miRNA expression profiles and to identify miRNAs with prognostic value in HF patients. Methods and results We performed a global miRNome analysis using next‐generation sequencing in the plasma of 30 advanced chronic HF patients and of matched healthy controls. A small subset of miRNAs was validated by real‐time PCR (P

Introduction: Perception of illness varies among individuals and psoriasis of the same severity can be perceived in different ways by patients, making it essential to evaluate quality of life (QoL) since it can provide information on the impact of the disease on the patient's overall well-being. The use of patient-reported outcomes in clinical trials provides the ability to integrate objective clinical assessment with the patient's perception of their own state of health. Areas covered: The introduction of anti-IL17 agents in clinical practice has given patients the possibility to achieve a PASI90 response (almost clear skin) or even higher (complete clear skin) in the majority of patients. There is accumulating evidence in support of PASI90 response as the new standard goal for therapy based on its greater correlation with health-related QoL. The present review summarizes current knowledge of the effects of secukinumab on the QoL of patients with psoriasis using patient-reported outcome measures. Expert Opinion: Secukinumab, the first approved drug of this new class, has fully reached a new therapeutic paradigm not only in terms of clinical efficacy, but also in terms of patient satisfaction and self-rated health.

Objective: Our pharmacogenomic study evaluated the influence of the presence/absence of genetic variants of psoriasis-risk loci on the clinical response to secukinumab. Differences in the single-nucleotide polymorphism (SNP) pattern characterizing HLA-Cw6+ or HLA-Cw6- patient subpopulations, showing high or low responses to secukinumab, were also analyzed. Methods: 417 SNPs were analyzed by Next-Generation Sequencing technology, in a cohort of 62 psoriatic patients and undergone secukinumab treatment. Univariate regression analysis was employed to examine the association between SNP and clinical response to secukinumab. Multivariate analysis was also performed to assess multivariate differences in SNP pattern of HLA-Cw6+ or HLA-Cw6- patients showing high or low responses to secukinumab. Results: Eight SNPs in HLA-C and upstream region (rs13207315, rs6900444, rs12189871, rs12191877, rs4406273, and rs10484554), including HLA-Cw6 classical allele (rs1131118), and three in MICB-DT (rs9267325), DDX58 (rs34085293) and TYK2 (rs2304255) genes, associating with excellent response to secukinumab were identified. Importantly, rs34085293 or rs2304255 SNP status defined a subgroup of super-responder patients. We also found that HLA-Cw6+ and HLA-Cw6- patients carried out specific patterns of SNPs associating with different responses to secukinumab. Conclusion: Assessment of HLA-Cw6, together with other allelic variants of genes, could be helpful to define patients which better benefit from anti-IL-17 therapy. Abbreviations: PASI: Psoriasis Area and Severity Index; SNP: Single-Nucleotide Polymorphism Rs: Reference SNP; PASI75: 75% reduction in Psoriasis Area and Severity Index; PASI90: 90% reduction in Psoriasis Area and Severity Index; PASI100: 100% reduction in Psoriasis Area and Severity Index; NGS: Next-Generation Sequencing; OR: Odds Ratio; CAP: Canonical Analysis of Principal coordinates; BMI: Body Mass Index; LD: Linkage Disequilibrium.

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, caused by a combination of genetic and environmental factors. In recent years, a role in MS pathogenesis was assigned to the gut microbiota. However, different signatures of gut dysbiosis have been shown to depend on environmental factors, like diet and lifestyle. In this study, we compared the gut microbiome in MS patients and their household healthy relatives sharing lifestyle and environmental factors. Faecal metagenomic DNA was extracted and the V3–V4 regions of the conserved bacterial 16S ribosomal RNA gene were amplified and sequenced. While overall bacterial communities were similar, specific families differed between healthy and MS subjects. We observed an increase in Ruminococcaceae, Christensenellaceae, Desulfovibrionaceae, Clostridiales, and Family XIII in MS patients, while Bacteroidaceae, Tannerellaceae, Veillonellaceae, and Burkholderiaceae were more abundant in healthy controls. In addition, principle coordinate analysis showed that the gut microbiome of all MS patients formed a cluster being less diverse than the household relatives and that gut microbiota of MS patients with EDSS 4.5–7 formed a distinct cluster in respect to their controls. Overall, our study is consistent with the hypothesis that MS patients have gut microbial dysbiosis and evidenced the importance of environmental factors in shaping the gut microbiome.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is creating an unprecedented global public health emergency with the continuous growth of infected individuals worldwide. Italy was one of the first European country to face the first wave of infection outside mainland China. The first case of COVID-19 was confirmed in Lombardy on February 20th , 2020, and subsequently, a rapid increase in the number of detected cases was observed, spreading through Italy and the rest of Europe.3 As of April 22nd , confirmed COVID-19 cases in Italy were 183,957.

Introduction: There is very limited kn3e safety of COVID-19 vaccines in patients with psoriasis who are being treated with biological agents. We present our experience in 369 patients with moderate-to-severe psoriasis undergoing therapy with anti-IL agents who were vaccinated against SARS-CoV-2.Areas covered: None of the 369 patients referred to any serious adverse event related to vaccination against COVID-19, while about one-third reported mild adverse events similar to those seen in the general population that were resolved within 48 hours. No patient discontinued biological therapy to receive a COVID-19 vaccine.Expert opinion: Our observations provide evidence that COVID-19 vaccines can be considered safe in patients with moderate-to-severe psoriasis who are receiving anti-IL therapy.

Introduction The aim of this study was to present two outbreaks of bovine abortion due to Leptospira infection in cattle herds located in the northern part of Sicily (Italy). The animals were positive for Leptospira interrogans serogroup Sejroe serovar Hardjo in a microscopic agglutination test (MAT). Material and Methods A total of 23 Charolaise cows (farm A) and 75 Limousine bulls and Cinisara and Modicana cows (farm B) were enrolled in this study. The blood samples were collected from all subjects at the following time points: before a cycle of intramuscular treatment with oxytetracycline dihydrate (T0), after 5–6 weeks from the treatment (T1), and every 10 weeks until seronegativisation (T2 in Farm A and T3 in Farm B). A serological test (MAT) was used for the diagnosis of leptospirosis. Results Two samples from farm A (2/23) and 29 samples from farm B (29/75) were positive to Leptospira interrogans, serogroup Sejroe, serovar Hardjo in the MAT. Leptospira spp. DNA was detected by real-time PCR in the urine sample of one positive cow on farm A, and in placenta and brain samples belonging to one aborted foetus on farm B. Conclusion It is important to use serological and molecular diagnostic techniques complementarily to identify infected individuals.

Introduction: Microbial translocation (MT) markers are indicators of HIV-related immune activation, but reference values are mostly derived from European or North American populations and could be substantially different in populations living in developing countries. Here we evaluate possible differences in MT markers levels in HIV+ pregnant women of different geographical provenance. Methodology: This study is nested within an observational study of pregnant women with HIV in Italy. Women were dichotomized on the basis of provenance in two groups of European (n = 14) and African (n = 26) origin. Soluble CD14, lipopolysaccharide-binding protein (LBP) and intestinal-fatty acid binding protein (I-FABP) were measured in plasma samples collected between the first and second trimester of pregnancy. Results: Demographic and viroimmunological characteristics were similar between groups, although European women were more commonly smokers and HCV-coinfected. Irrespective of origin, LBP plasma levels were positively correlated with I-FABP (r = 0.467, p = 0.004) and sCD14 levels (r = 0.312 p = 0.060). Significantly higher levels of sCD14 (1885 vs. 1208 ng/mL, p = 0.005) LBP (28.5 vs. 25.3 µg/mL, p = 0.050) and I-FABP (573.4 vs. 358.2 pg/mL, p = 0.002) were observed in European compared with African women. A multivariable linear regression analysis, adjusted for smoking and HCV coinfection confirmed the association between sCD14 levels and women provenance (p = 0.03). Conclusions: Our observations indicate significant differences in soluble markers among women of different provenance. In the design and analysis of studies evaluating MT markers, population-specific reference values should be considered.

Background: Real-life data often highlight the side effects of certain drugs not previously reported in randomized controlled trials (RCTs).Objective: To describe cutaneous inflammatory eruptions i...

Background Functional neurological disorders (FNDs) are neurological symptoms that cannot be explained by an underlying neurological lesion or other medical illness and that do not have clear neuropathological correlates. Psychogenic non-epileptic seizures (PNES) are a common and highly disabling form of FND, characterized by paroxysmal episodes of involuntary movements and altered consciousness that can appear clinically similar to epileptic seizures. PNES are unique among FNDs in that they are diagnosed by video electroencephalographic (VEEG), a well-established biomarker for the disorder. The course of illness and response to treatment of PNES remain controversial. This study aims to describe the epidemiology of PNES in the Department of Veterans Affairs Healthcare System (VA), evaluate outcomes of veterans offered different treatments, and compare models of care for PNES. Methods This electronic health record (EHR) cohort study utilizes an informatics search tool and a natural language processing algorithm to identify cases of PNES nationally. We will use VA inpatient, outpatient, pharmacy, and chart abstraction data across all 170 medical centers to identify cases in fiscal years 2002-2018. Outcome measurements such as seizure frequency, emergency room visits, hospital admissions, suicide-related behavior, and the utilization of psychotherapy prior to and after PNES diagnosis will be used to assess the effectiveness of models of care. Discussion This study will describe the risk factors and course of treatment of a large cohort of people with PNES. Since PNES are cared for by a variety of different modalities, treatment orientations, and models of care, effectiveness outcomes such as seizure outcomes and utilization of emergency visits for seizures will be assessed. Outcome measurements such as seizure frequency, emergency room visits, hospital admissions, suicide-related behavior, and psychotherapy prior to and after PNES diagnosis will be used to assess the effectiveness of models of care.

BackgroundData sparsity is a major limitation to estimating national and global dementia burden. Surveys with full diagnostic evaluations of dementia prevalence are prohibitively resource-intensive in many settings. However, validation samples from nationally representative surveys allow for the development of algorithms for the prediction of dementia prevalence nationally.MethodsUsing cognitive testing data and data on functional limitations from Wave A (2001–2003) of the ADAMS study (n = 744) and the 2000 wave of the HRS study (n = 6358) we estimated a two-dimensional item response theory model to calculate cognition and function scores for all individuals over 70. Based on diagnostic information from the formal clinical adjudication in ADAMS, we fit a logistic regression model for the classification of dementia status using cognition and function scores and applied this algorithm to the full HRS sample to calculate dementia prevalence by age and sex.ResultsOur algorithm had a cross-validated predictive accuracy of 88% (86–90), and an area under the curve of 0.97 (0.97–0.98) in ADAMS. Prevalence was higher in females than males and increased over age, with a prevalence of 4% (3–4) in individuals 70–79, 11% (9–12) in individuals 80–89 years old, and 28% (22–35) in those 90 and older.ConclusionsOur model had similar or better accuracy as compared to previously reviewed algorithms for the prediction of dementia prevalence in HRS, while utilizing more flexible methods. These methods could be more easily generalized and utilized to estimate dementia prevalence in other national surveys.

Objective: The objective of this study was to assess the effectiveness and safety of dupilumab in treating elderly patients with atopic dermatitis from baseline to 52 weeks. Methods: A retrospective observational real-life study was conducted in a group of elderly patients with severe atopic dermatitis treated with dupilumab for 52 weeks. Inclusion criteria were: age ≥ 65 years; diagnosis of atopic dermatitis made by an expert dermatologist; Eczema Area and Severity Index ≥ 24; and a contraindication, side effects, or failure to respond to cyclosporine. The primary outcome was the mean percentage reduction in the Eczema Area and Severity Index score from baseline to week 52. Secondary measures includedthe mean percentage reduction in the Pruritus and Sleep Numerical Rating Scales and the Dermatology Life Quality Index, and the types and rates of adverse events from baseline to week 52. Results: One hundred and five patients were eligible for the study. Flexural dermatitis was the most frequent clinical phenotype (63.8%). The coexistence of more than one clinical phenotype was found in 70/105 (66.6%) patients. We observed a reduction in all disease severity scores from baseline to week 52 (p < 0.001). Adverse events were recorded in 30/105 (28.6%) patients, with conjunctivitis and injection-site reaction the most frequent. Conclusions: In this study, dupilumab is an effective and safe treatment for the long-term management of atopic dermatitis in patients aged over 65 years.

Purpose: To evaluate associations between CD4/CD8 ratio and pregnancy outcomes in women with HIV. Methods: We evaluated, in a national study of pregnant women with HIV receiving antiretroviral treatment (ART), values of CD4/CD8 ratio at entry in pregnancy, changes between first and third trimester, and possible associations with preterm delivery, low birthweight, and HIV-RNA < 50 copies/ml at third trimester in univariate and multivariate analyses. Results: Among 934 women, 536 (57.4%) were already on ART at conception. CD4/CD8 ratio (baseline value 0.570) increased significantly between the first and third trimesters, particularly in women who started ART in pregnancy (+ 0.163, vs. + 0.036 in women already on treatment). The rate of CD4/CD8 ratio normalization, defined by achieving a ratio ≥ 1 at the third trimester, was 13.2%. In multivariable analyses, women who entered pregnancy with a CD4/CD8 ratio < 0.3, compared to women with ratio ≥ 1, were almost four-times less likely to have third-trimester HIV-RNA < 50 copies/ml (AOR 0.258, 95%CI 0.111–0.601), and more than twice as likely to have preterm delivery (AOR 2.379, 95%CI 1.082–5.232). For preterm delivery, also a baseline CD4/CD8 ratio between 0.3 and 0.45 was significantly associated with an increased risk (AOR: 3.415, 95%CI 1.690–6.900). Conclusion: We described for the first time independent associations of low CD4/CD8 ratio with preterm delivery and HIV-RNA suppression.

Aim of this study is to report a laboratory investigation performed following the isolation of Brucella ovis, causing ovine epididymitis, in a traditional sheep farm in Sicily (South Italy). This disease represents a newly emerging risk for Italian livestock and is listed among diseases of EU priority (EU Reg 2016/429). Blood samples from 56 rams and 143 ewes were analyzed by both Enzyme-Linked Immunosorbent Assay (ELISA) and Complement Fixation Test (CFT). Genital swabs from all rams and 15 lactating ewes were collected to perform real-time PCR. Eighteen serologically positive rams were slaughtered and postmortem-inspected. Samples of testicle, epididymis, lymph nodes, and urine were also collected in order to perform microbiological, molecular, and histopathological analysis. Twelve slaughtered rams showed anatomo-pathological lesions. Real-time PCR for B. ovis BOV_A0504 gene was positive for 13 testicles and epididymis and 11 urine while B. ovis was isolated from epididymis and testicles of 7 slaughtered rams. This is the first exhaustive laboratory report of a microbiological, molecular, and serological pattern of the disease in sheep in Italy. Despite the impact on health and animal welfare, the epidemiology of B. ovis infection is still unknown, particularly in our country where the disease is considered endemic.

ObjectiveThe increased rate of suicide associated with epilepsy has been described, but no studies have reported the rates of suicide and suicide-related behavior (SRB) associated with psychogenic nonepileptic seizures (PNESs).MethodsThis retrospective cohort study analyzed data from October 2002 to October 2017 within Veterans Health Administration services. Of 801,734 veterans, 0.09% had PNES, 1.37% had epilepsy, and 98.5% had no documented seizures. Veterans coded for completed suicide, suicide attempts, and suicidal ideation were identified from electronic health records. The primary measure was the suicide-specific standardized mortality ratio (SMR) based on the number of suicide deaths and CDC national suicide mortality database. A Poisson regression was used to calculate the relative risk (RR) of suicide across groups.ResultsA total of 1,870 veterans (mean age [SD] 33.76 [7.81] years) completed suicide. Veterans with PNES (RR = 1.75, 95% confidence interval [CI] 0.84–4.24) and veterans with epilepsy (RR = 2.19, 95% CI 2.10–2.28) had a higher risk of suicide compared with the general veteran population. Veterans with PNES or epilepsy had a higher risk of suicide and SRB if they had comorbid alcohol abuse, illicit drug abuse, major depression, posttraumatic stress disorder, and use of psychotropic medications. Conversely, those who were married or attained higher education were at a decreased risk. The SMR for completed suicide for PNES, epilepsy, and the comparison group was 2.65 (95% CI 1.95–5.52), 2.04 (95% CI 1.60–2.55), and 0.70 (95% CI 0.67–0.74), respectively.ConclusionsVeterans with seizures (both psychogenic and epileptic) are at a greater risk of death by suicide and SRB than the comparison group. These findings suggest that although the pathophysiology of PNES and epilepsy is different, the negative impact of seizures is evident in the psychosocial outcomes in both groups.

Borrelia burgdorferi is a bacterial pathogen transmitted by Ixodes ticks and is responsible for Lyme disease in both humans and dogs. The aim of this work was to evaluate B. burgdorferi diffusion among stray dogs in Palermo (Sicily, Italy) by serological methods in order to study the risk factors associated with the infection. Serum and blood samples of 316 dogs were collected from a shelter in Palermo, and were analyzed for the presence of antibodies against B. burgdorferi by indirect immunofluorescence assay (IFA), and of the ospA gene by real-time PCR, respectively. Seventeen sera (5.4%) were positive for the antibodies via IFA and one blood (0.3%) for ospA via real time PCR. On the basis of serological results, the evaluation of the potential risk factors (sex, age, breed and coat color) was carried out. The multivariate analysis indicated that male sex is a factor significantly associated with B. burgdorferi seropositivity. This study confirms that male dogs have a higher risk of developing the disease than females, and represents the first investigation on the spread of B. burgdorferi among stray dogs in Sicily.

Background: Treatment of moderate-to-severe atopic dermatitis (AD) in the elderly may be challenging, due to side-effects of traditional anti-inflammatory drugs and to comorbidities often found in this age group. Furthermore, efficacy and safety of innovative drugs such as dupilumab are not yet well known. Objectives: A multicentre retrospective, observational, real-life study on the efficacy and safety of dupilumab was conducted in a group of patients aged ≥65years and affected by severe AD. Their main clinical features were also examined. Methods: Data of elderly patients with severe (EASI ≥24) AD treated with dupilumab at label dosage for 16weeks were retrospectively collected. Treatment outcome was assessed by comparing objective (EASI) and subjective (P-NRS, S-NRS and DLQI) scores at baseline and after 16weeks of treatment. Results: Two hundred and seventy-six patients were enrolled in the study. They represented 11.37% of all patients with severe AD. Flexural eczema was the most frequent clinical phenotype, followed by prurigo nodularis. The coexistence of more than one phenotype was found in 63/276 (22.82%) subjects. Data on the 16-week treatment with dupilumab were available for 253 (91.67%) patients. Efficacy of dupilumab was demonstrated by a significant reduction of all the scores. No statistically significant difference regarding efficacy was found in elderly patients when compared to the group of our AD patients aged 18–64years, treated with dupilumab over the same period. Furthermore, only 18 (6.52%) patients discontinued the drug due to inefficacy. Sixty-one (22.51%) patients reported adverse events, conjunctivitis and flushing being the most frequent. One (0.36%) patient only discontinued dupilumab due to an adverse event. Conclusions: Therapy with dupilumab led to a significant improvement of AD over a 16-week treatment period, with a good safety profile. Therefore, dupilumab could be considered as an efficacious and safe treatment for AD also in the elderly.

Alopecia Areata (AA) is an organ-specific autoimmune disorder that targets anagen phase hair follicles. The course is unpredictable and current available treatments have variable efficacy. Nowadays, there is relatively little evidence on treatment of AA from well-designed clinical trials. Moreover, none of the treatments or devices commonly used to treat AA are specifically approved by the Food and Drug Administration (FDA). The Italian Study Group for Cutaneous Annexial Disease of the Italian Society of dermatology (SIDeMaST) proposes these Italian guidelines for diagnosis and treatment of Alopecia Areata deeming useful for the daily management of the disease. This article summarizes evidence-based treatment associated with expert-based recommendations.

Background Autism spectrum disorders (ASDs) and schizophrenia spectrum disorders (SSDs), although conceptualized as separate entities, may share some clinical and neurobiological features. ASD symptoms may have a relevant role in determining a more severe clinical presentation of schizophrenic disorder but their relationships with cognitive aspects and functional outcomes of the disease remain to be addressed in large samples of individuals. Aims To investigate the clinical, cognitive, and functional correlates of ASD symptoms in a large sample of people diagnosed with schizophrenia. Methods The severity of ASD symptoms was measured with the PANSS Autism Severity Scale (PAUSS) in 921 individuals recruited for the Italian Network for Research on Psychoses multicenter study. Based on the PAUSS scores, three groups of subjects were compared on a wide array of cognitive and functional measures. Results Subjects with more severe ASD symptoms showed a poorer performance in the processing speed (p = 0.010), attention (p = 0.011), verbal memory (p = 0.035), and social cognition (p = 0.001) domains, and an overall lower global cognitive composite score (p = 0.010). Subjects with more severe ASD symptoms also showed poorer functional capacity (p = 0.004), real-world interpersonal relationships (p p Conclusions These findings strengthen the notion that ASD symptoms may have a relevant impact on different aspects of the disease, crucial to the life of people with schizophrenia. Prominent ASD symptoms may characterize a specific subpopulation of individuals with SSD.

The infection caused by novel beta-coronavirus (SARS-CoV-2) was officially declared a pandemic by the World Health Organization in March 2020. However, in the last 20 years, this has not been the only viral infection to cause respiratory tract infections leading to hundreds of thousands of deaths worldwide, referring in particular to severe acute respiratory syndrome (SARS), influenza H1N1 and Middle East respiratory syndrome (MERS). Although in this pandemic period SARS-CoV-2 infection should be the first diagnosis to exclude, many other viruses can cause pulmonary manifestations and have to be recognized. Through the description of the main radiological patterns, radiologists can suggest the diagnosis of viral pneumonia, also combining information from clinical and laboratory data.

Background Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparative data in pregnant women are limited. We assessed the safety and activity profile of these two drugs in pregnancy using data from a national observational study. Methods Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measures and main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatal gestational age-adjusted birthweight Z-score). Results Final analysis included 500 pregnancies with either atazanavir (n = 409) or darunavir (n = 91) exposure. No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA, haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the two groups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides (median 235.5 versus 179 mg/dL; P = 0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03 versus 3.27; P = 0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54 versus 0.32 mg/dL; P

Background: Limited information is available from real-life studies evaluating the long-term efficacy and drug retention of ustekinumab.Research design and methods: Data from 378 patients with moderate-severe psoriasis were retrospectively analyzed. Over 8 years, disease severity and treatment response were evaluated using the PASI score. Predictors of PASI response were evaluated by logistic regression. Ustekinumab retention rate was calculated by the Kaplan-Meier method.Results: Over the 8 years, >80% of patients achieved a PASI score of

The real prognostic impact of MitraClip in patients with significant functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction remains to be elucidated. Two randomized controlled trials (RCTs) with conflicting results have been recently published. We conducted a comprehensive meta-analysis of all RCTs and adjusted observational studies to evaluate the clinical impact of percutaneous mitral valve repair when compared with optimal medical therapy (OMT) alone, in patients with symptomatic FMR and LV dysfunction. Death from any cause and heart failure rehospitalizations at the longest available follow-up were the primary endpoints. Cardiac death, one year and short-term death were the secondary ones. 2255 patients (1207 for MitraClip and 1048 for OMT-only) from 8 studies (2 RCTs and 6 observational studies) were included. At a median (mid-term) follow-up of 438 days (IQR 360-625) MitraClip was associated with a significant reduction of all-cause death (odds Ratio [OR] 0.55, 95%CI 0.41-0.73, p 0.001; [ORadj] 0.66, 95%CI 0.49-0.90, p = 0.009) and rehospitalization (OR 0.49, 95%CI 0.24-1.00, p = 0.05 and ORadj 0.63, 95%CI 0.43-0.94, p = 0.02). At one year, adjusted analysis demonstrated a trend favoring the experimental cohort (ORadj 0.73, 95%CI 0.53-1.02, p = 0.07). Meta-regression suggested that benefit of MitraClip on mid-term survival persists even after accounting for the prevalence of implanted CRT, burden of comorbidities, NYHA class, cardiomyopathy etiology and LV function and dimensions. In conclusion, MitraClip for FMR in patients with LV dysfunction is associated with a considerable reduction of death and HF hospitalization at mid-term follow-up. Further ongoing RCTs are needed to strengthen present results.

The skin is a peripheral lymphoid organ, being the first immunological defense against infections as the initial interface between the organism and the external background. The maintenance of the skin immune homeostasis depends on a finely equilibrium of well-regulated relations between different cells and exogenous pathogens. Inflammatory skin diseases are directly linked to the dysregulation of this equilibrium. The present review discusses the role of the immune system, of T cells, in the etiopathogenesis of psoriasis, illustrating a potential rationale for innovative therapeutic intervention.

Pseudoaneurysm (PSA) or false aneurysm is a vascular lesion resulting from a focal and incomplete rupture of the arterial wall (intimate and/or elastic lamina), that allows blood to escape into the arterial wall; this small contained break causes a contained collection of blood and the creation of a “new” less resistant vessel wall, consisting of adventitia and perivascular tissues. Intrasplenic pseudoaneurysms are rare and more frequently recognize traumatic origin, sometimes are also unexpected lesions due to non-recent trauma. In contrast, non-traumatic intrasplenic pseudoaneurysms are rare complications usually due to splenic infarction, infiltration by malignant systemic disorders, infectious process, chronic pancreatitis, and arteritis. Both traumatic and non-traumatic PSA are potentially life threatening, known to cause spontaneous rupture of the spleen with massive hemoperitoneum. Contrast-enhanced CT is the gold standard technique to detect splenic PSA; however, it is important to know how to recognize it also with other imaging methods such as with ultrasound (US) and contrast-enhanced ultrasound (CEUS). US and CEUS can be often the first-line diagnostic techniques and allow to detect these lesions; they are also very useful in the follow-up. Our case report can be a reminder of the utility of the US and CEUS in detecting splenic pseudoaneurysms, which are potentially a life-threatening complication; we also recall the semiotics of these lesions with baseline ultrasound (US), color Doppler US and contrast-enhanced ultrasound (CEUS). Then, we highlight the role of contrast-enhanced CT in confirming the diagnosis and we report about the diagnostic and therapeutic value of angiography. We have to think about the possibility of a pseudoaneurysm even in the absence of a recent trauma, associated with other conditions such as a lymphoproliferative disease.

Introduction: Psoriasis is a relatively common condition, with a lot of discordance in studies about the peak of onset. In a large German study, an almost linear prevalence increase was reported during childhood, ranging from 0.12% at 1 year to 1-2% at 18 years. According to recent studies, plaque psoriasis is the most common variant in childhood disease. Areas covered: This article focuses on topical, systemic and biologic therapies used in childhood psoriasis. The authors performed a full literature PubMed research, while incorporating case reports and experience. Topical agents are considered the first step, but they always have little efficacy in the extensive form of the disease. In this case, systemic and particularly biological therapy must be evaluated. The most studied treatment in the pediatric population is etanercept, but adalimumab and ustekinumab are also approved in pediatric and adolescent populations. Expert opinion: Larger studies are needed to further investigate the use of new compounds in childhood psoriasis. Recent evidence suggests that practitioners should consider interceding in the early immunologic psoriatic process to halt this march and stunt immunological scar development. An early investment would provide lasting effects and serious impact in long-term disease modification.

Diuretic resistance is a common issue in patients with acute decompensation of advanced chronic heart failure (ACHF). The aim of this trial was to compare boluses and continuous infusion of furosemide in a selected population of patients with ACHF and high risk for diuretic resistance. In this single-centre, double-blind, double-dummy, randomized trial, we enrolled 80 patients admitted for acute decompensation of ACHF (NYHA IV, EF ≤ 30%) with criteria of high risk for diuretic resistance (SBP ≤ 110 mmHg, wet score ≥ 12/18, and sodium ≤ 135 mMol/L). Patients were assigned in a 1:1 ratio to receive furosemide by bolus every 12 h or by continuous infusion. Diuretic treatment and dummy treatment were prepared by a nurse unassigned to patients’ care. The study treatment was continued for up to 72 h. Coprimary endpoints were total urinary output and freedom from congestion at 72 h. 80 patients were enrolled with 40 patients in each treatment arm. Mean daily furosemide was 216 mg in continuous-infusion arm and 195 mg in the bolus intermittent arm. Freedom from congestion (defined as jugular venous pressure of

The IL-17/IL-23 axis is now understood to influence psoriasis, and the development of novel IL-17 inhibitor medications marks a sea change in the treatment of psoriasis. Brodalumab is a recombinant, fully human immunoglobulin IgG2 monoclonal antibody specifically targeted against IL-17RA. This article discusses the mechanism of action and the efficacy and safety profile of brodalumab presented in the literature. Brodalumab, the latest approved anti-IL-17-class medication, is the only one that exerts its effects on IL-17C as well as on IL-17A and IL-17F, blocking the shared IL-17 receptor A. In this sense, considering the recent evidence, brodalumab could have beneficial effects not only on psoriasis, but also on atopic dermatitis. It could also serve as a therapeutic alternative in patients who develop paradoxical eczematous reactions or atopic-like dermatitis during treatment with other anti-IL-17A (secukinumab, ixekizumab).

Baseline ultrasound is the first-choice technique in traumatic hemodynamically stable children, and is essential in the early assessment of unstable patients to detect hemoperitoneum or other potentially fatal conditions. Despite the technological advancements in new ultrasound equipment and the experience of the operators, it is not always possible to rule out the presence of parenchymal traumatic lesions by means of baseline ultrasound nor to suspect them, especially in the absence of hemoperitoneum. For this reason, in the last decades, basic ultrasound has been associated with contrast-enhanced ultrasound (CEUS) to evaluate the stable little patient in cases such as low-energy blunt abdominal trauma. Because it relies on second-generation contrast agents, the CEUS technique allows for better detection of parenchymal injuries. CEUS has been demonstrated to be almost as sensitive as contrast-enhanced CT in the detection of traumatic injuries in patients affected by low-energy isolated abdominal trauma, with levels of sensitivity and specificity up to 95%. A very important point in favor of CEUS is its capacity to help distinguish the healthy patient, who can be discharged, from the one needing prolonged monitoring, operative management or hospitalization. Finally, we also have the ability to follow-up on low-grade traumatic lesions using CEUS, always keeping in mind patients’ clinical conditions and their hemodynamics.

Targeted therapies with MAPK inhibitors have proven to modulate the clinical manifestations of patients with Langerhans cell histiocytosis (LCH). We explored the presence of BRAFV600E mutation in our cohort of patients with LCH and cholestasis, sclerosing cholangitis, or liver fibrosis that presented resistance to chemotherapy. The BRAFV600E mutation was detected either in the diagnosis (skin and bone) or liver biopsy in our cohort of 13 patients. Thus, we observed a high incidence of BRAFV600E mutation in 100% either in diagnostic biopsy (skin and bone) or liver biopsy in patients with progressive liver disease, sequela, or liver transplant requirement.

ObjectiveTo describe the clinical, histopathological and molecular features of a novel inherited SRY allele (p.Met64Val; consensus box position 9) observed within an extensive pedigree: two 46, XY sisters with primary amenorrhea (16 and 14 years of age; probands P1 and P2), their normal father and brother, and an affected paternal XY grandaunt.Design, Setting, Participants and Outcome MeasurementsFollowing DNA sequencing to identify the SRY mutation, hormonal studies of the probands and histopathological examination of their gonads were performed. Functional consequences of p.Met64Val (and other mutations at this site) were also investigated.ResultsBreast development in P1 and P2 was Tanner II and IV, respectively. Müllerian structures and gonads resembling ovaries were found in each sister. Histopathology revealed gonadal dysgenesis, gonadablastoma and dysgerminoma. AMH/MIS, P450 SCC, and P450 aromatase were expressed in gonadoblastoma tissues. Genomic sequencing revealed no candidate mutations in other genes related to sexual differentiation. Variant p.Met64Val impaired Sox9 transcriptional activation associated with attenuated occupancy of the testis-specific enhancers Enh13 and TESCO. Biophysical studies indicated that the mutant HMG box retains specific DNA binding and DNA bending but with accelerated rate of protein-DNA dissociation.ConclusionThe partial biological activity of p.Met64Val SRY, maintained at the threshold of SRY function, rationalizes opposing paternal and proband phenotypes (the “the father-daughter paradox”). Steroidal biosynthesis by gonadoblastoma may delay genetic diagnosis and recognition of gonadal tumors. Quantitative assessment of inherited SRY alleles highlights the tenuous transcriptional threshold of developmental decision-making in the bipotential gonadal ridge.

Total knee arthroplasty (TKA) is a successful and safe surgical procedure for treating osteoarthritic knees, but despite the overall good results, some patients remain dissatisfied. The aim of this study is to evaluate the influence of patient-related and surgery-related variables in a consecutive group of patients that underwent TKA. Individuals (n = 648) who had TKA performed between 01 January 2013 and 31 December 2017 were enrolled in the study. Postoperative Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Injury and Osteoarthritis Outcome Score (KOOS) and Forgotten Joint score (FJS-12) were collected at a mean follow-up of 4.79 years. Patient satisfaction was assessed with a questionnaire. Determinants of satisfaction (age, sex, smoking, presence of diabetes or cardiovascular disease, pain in other joints, preoperative arthritic stage) and components of satisfaction (slope variation, mechanical axis variation, outlier final alignment, surgeon experience) were examined to identify which variables correlated with positive outcome. Correlations with septic and mechanicals failures were also evaluated. Thirteen percent of patients were unsatisfied, despite good results in KOOS, WOMAC and FJS-12 tests. Female gender, low Kellgren–Lawrence grade and the presence of back pain and pain in other joints were factors associated with poor clinical results. Poorer clinical results were also reported in younger patients. Infection rate was correlated with active smoking and mechanical failure with an outlier final alignment. Comorbidities, smoking habits and high expectations have a big influence on TKA results and on final satisfaction after surgery.

Secukinumab, a fully human monoclonal antibody, neutralizes interleukin-17A, a cornerstone cytokine driving the multiple manifestations of psoriasis. This post-hoc analysis of the SUPREME study was performed to determine the sustainability of response to secukinumab in terms of Psoriasis Area and Severity Index (PASI) 90 in patients with moderate-to-severe plaque psoriasis. Based on PASI 90 response at week 16, patients were stratified as PASI 90 responders (PASI90R, n = 337) or non-responders (PASI90NR, n = 72). At week 20, 94.2% (n = 295/313) achieved PASI 90/100 response in PASI90R, with response maintained through week 48 (89.6%, n = 189/211). An increased proportion of patients achieved PASI 90/100 response in PASI90NR (week 20: 29.9%, n = 20/67; week 48: 57.1%, n = 20/35). Overall, 64.4% patients achieved absolute PASI score = 0 at week 24 with response sustained to week 48 (66.9%). Secukinumab showed sustained and stable efficacy in maintaining PASI 90 response in patients with moderate-to-severe plaque psoriasis up to week 48.

Background: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic. Methods: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. Results: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection, 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred. Conclusions: Most AD patients continued systemic treatments during COVID pandemicand lockdown period, without high impact on disease control, particularly dupilumab-treatedpatients.

Introduction: Some cases of psoriasis still unfortunately do not respond, do not respond adequately or lose response to biotechnological therapies available to help control psoriasis. The common so...

Background: Information is limited from real-life studies evaluating the efficacy and safety of brodalumab.Research design and methods: In this real-life study, we retrospectively examined a database of 90 patients with moderate-to-severe psoriasis treated with brodalumab (210 mg, s.c.) and followed for 1 year. Disease severity and treatment response were assessed by the Psoriasis Area and Severity Index (PASI) at baseline and after 4, 12, 24, 36, and 48 weeks. Predictors of a PASI response were evaluated by logistic regression.Results: After 48 weeks, 92.2% of patients (mean age 50.2 ± 15 years) treated with brodalumab achieved a PASI score of

Sanitary management and population control of feral pigs remains a major problem in public health, particularly in natural parks where hunting is prohibited and the extensive farming of livestock is common. Macracanthorhynchus hirudinaceus is a zoonotic parasite species with a worldwide distribution of which the natural definitive hosts are primarily pigs and wild boars (Sus scrofa). The present study describes the main anatomo-pathological and parasitological findings in the first case of M. hirudinaceus in feral pigs in the Madonie park in Sicily (Southern Italy). Overall, 52 acanthocephalans were collected from the small intestine of four infected feral pigs. The prevalence among the 36 examined animals was 11.1% with a mean Abundance (mA) and mean Intensity (mI) of 1.4 and 13, respectively. Pathological examination revealed grossly visible nodules on the external surface of the intestines, corresponding to the proboscis of M. hirudinaceus attached deeply into the intestinal wall. In these sites, severe inflammatory reactions in the tissue involved and the destruction of normal intestinal architecture, as well as necrosis and ulceration in the mucosa, submucosa, and part of the muscolaris mucosae were described. This is the first official report of this neglected zoonosis in Italy, in particular in a natural park where the extensive farming of domestic pigs is practiced. This could favor the spread of this parasite in domestic animals and the environment, increasing the accidental risk of infection in human residents of these areas.

Background No published studies have evaluated in pregnant women with HIV weight gain with different antiretroviral drug classes. Methods Data from a national cohort study were used. We compared absolute weight gain and occurrence of excessive weight gain in women with HIV who received during pregnancy integrase inhibitors (INSTI), protease inhibitors (PI), or non-nucleoside reverse transcriptase inhibitors (NNRTI). Excessive weight gain was defined according to the Institute of Medicine recommendations. Possible predictors of weight gain were assessed using univariate and multivariate analyses. Results Among 273 cases (PI: 191, NNRTI: 43, INSTI: 39), the mean weight increase was 11.3 kg, and 25.4% of the mothers had an excessive weight increase. No significant differences were found among the three treatment groups for absolute weight increase, occurrence of excessive weight gain, infant birthweight, and other pregnancy and laboratory outcomes. The comparisons of individual drugs, although based on a limited number of cases, suggested no major differences. A significant positive correlation was found between weight gain and CD4+ T-cell increase during pregnancy. In multivariate analyses, drug class and nucleoside backbone were not associated with absolute or excessive weight increase. Excessive weight increase was significantly associated with week of delivery (adjusted odds ratio: 1.74, 95% CI 1.15, 2.63), obesity (5.21, 95% CI 1.85, 14.64), overweight (7.95, 95% CI 3.26, 19.39), recent substance use (5.96, 95% CI 1.13, 31.40) and fasting 2nd trimester hyperglycaemia (3.94, 95% CI 1.14, 13.65). Conclusions No significant differences in absolute weight change or occurrence of excessive weight gain were found among women with HIV who received during pregnancy different classes of antiretroviral drugs.

Background & Aims Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarker-driven therapeutic strategy targeting DDR and replication stress in PC. Methods We interrogated the transcriptome, genome, proteome, and functional characteristics of 61 novel PC patient–derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient-derived xenografts and human PC organoids. Results Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, cosegregates with response to platinum (P < .001) and PARP inhibitor therapy (P < .001) in vitro and in vivo. We generated a novel signature of replication stress that predicts response to ATR (P < .018) and WEE1 inhibitor (P < .029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < .001) but was not associated with DDR deficiency. Conclusions Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR-proficient PC and after platinum therapy., Graphical abstract

Objective Cognitive frailty is a condition recently defined by operationalized criteria describing the simultaneous presence of physical frailty and mild cognitive impairment (MCI). Two subtypes for this clinical construct have been proposed: "potentially reversible" cognitive frailty (physical frailty plus MCI) and "reversible" cognitive frailty (physical frailty plus pre-MCI subjective cognitive decline). Here the prevalence of a potentially reversible cognitive frailty model was estimated. It was also evaluated if introducing a diagnosis of MCI in older subjects with physical frailty could have an additive role on the risk of dementia, disability, and all-cause mortality in comparison with frailty state or MCI condition alone, with analyses separately performed for inflammatory state. Methods In 2,373 individuals from the population-based Italian Longitudinal Study on Aging with a 3.5-year-follow-up, we operationally categorized older individuals without dementia into four groups: non-frail/non-MCI, non-frail/MCI, frail/non-MCI, and frail/MCI. Results The prevalence of potentially reversible cognitive frailty was 1%, increasing with age and more represented in women than in men, and all groups were associated with significant increased incident rate ratios of dementia, disability, and mortality. A significant difference in rates of disability has been found between the MCI and non-MCI groups (contrasts of adjusted predictions: 0.461; 95% confidence interval: 0.187–0.735) in frail individuals with high inflammatory states (fibrinogen >339 mg/dL). Conclusion In older individuals without dementia and with elevated inflammation, a potentially reversible cognitive frailty model could have a significant additional predictive effect on the risk of disability than the single conditions of frailty or MCI.