Giant congenital fibroblastic connective tissue nevus associated with vascular anomalies.

We described an unusual combination of fibroblastic connective nevus (FCTN) already present at birth with underlying vascular anomalies. Overall, the lesion appeared as a large purplish-brown mass in the groin region up to the third of the right thigh, with partial spontaneous regression during the first three months of life. The FCTN observed exhibited several unusual characteristics: it was congenital, large in size, and located in the lower limbs. Finally, it represented the first case described in which an FCTN arose in association with vascular anomalies.

Venous malformations in children: comparison between magnetic resonance imaging and histopathological findings.

BACKGROUND: Among low-flow vascular malformations, venous malformations are relatively frequent. The pathological patterns vary in severity and are generally characterized by dilated vessels and low-flow blood that over time can organize into phleboliths. Sometimes small capillary and/or lymphatic vessels may be associated, micro- and/or macro-shunts may form alone or in different combinations, and finally adipose tissue may be interposed between the malformed vessels. Magnetic resonance imaging (MRI) is a crucial examination for confirming venous malformations because it can accurately identify different features of the lesions. OBJECTIVE: The aim of our study was to compare MRI and histopathological findings of venous malformations in children to assess the possibilities and limitations of MRI. MATERIALS AND METHODS: In a retrospective study, two observers independently evaluated the contrast-enhanced MRI of 26 children with venous malformations. Several radiological parameters were considered and compared with histopathological findings. The agreement between the interobserver radiological evaluation and between histopathological and radiological diagnosis was verified using Cohen's kappa. RESULTS: MRI interobserver agreement was excellent for micro-shunts and good for the remaining findings. The radiological-pathological agreement was perfect for the presence/absence of phleboliths and of macro-shunts and almost perfect for the presence of intralesional adipose tissue, lymphatic component, and micro-shunts. CONCLUSION: MRI in venous malformations can detect the presence of phleboliths, adipose tissue, and lymphatic components with excellent accuracy and good to excellent interobserver agreement. Furthermore, MR angiography can detect micro-shunts in simple and combined venous malformations with substantial agreement with histopathological findings.

Lacosamide in monotherapy in BTRE (brain tumor-related epilepsy): results from an Italian multicenter retrospective study.

PURPOSE: Lacosamide (LCM) is a third-generation anti-seizure medication (ASM) approved for focal onset epilepsy in patients aged ≥ 4.378 Previous studies have reported an efficacy of LCM as add-on treatment in brain tumor-related epilepsy (BTRE). To date, there are no studies in the literature focusing on lacosamide used in monotherapy to treat BTRE. In our retrospective study we investigated efficacy and tolerability of LCM in monotherapy in a multicenter national cohort of primary brain tumor patients. METHODS: We collected from 12 Italian Centers 132 patients with primary brain tumors who were treated with LCM in monotherapy. For each patient we evaluated seizure freedom at 3 and 6 months (primary endpoints), side effects and drop-out rate (secondary endpoints). RESULTS: Overall, LCM led to seizure freedom in 64.4% of patients at 3 months and 55% at 6 months. Patients who used two or more ASMs before LCM had a worse seizure control than patients in monotherapy with LCM as first choice. In 14 patients, we observed seizure control despite tumor progression on magnetic resonance (MRI). Multivariate analysis showed that gross-total resection at diagnosis was significantly associated with higher seizure freedom rate at 6 months. Side effects were mainly mild (grade 1-2 according to CTCAE classification) and drop-out rate was low (1.5%). Main side effects were dizziness and somnolence. CONCLUSIONS: This is the first study showing a good efficacy and tolerability of LCM when used in monotherapy in BTRE. Further prospective studies are needed to confirm these preliminary data, investigating also quality of life and neurocognitive functions.

Use of Dupilumab in 543 Adult Patients With Moderate-to-Severe Atopic Dermatitis: A Multicenter, Retrospective Study.

BACKGROUND: Dupilumab has proven to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, real-world experience with dupilumab in a broader population is limited. METHODS: The study population comprised adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at 10 Italian teaching hospitals. We analyzed physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index [DLQI]), and serological markers (IgE and eosinophil count) after 16 weeks. RESULTS: We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median (IQR) change from baseline to 16 weeks of treatment in the EASI score was -87.5 (22.0) (P<.001). The EASI-50, EASI-75, and EASI-90 response rates were 98.1%, 81.5%, and 50.8% after 16 weeks. At 16 weeks, 93.0% of the patients had achieved a 4-point or higher improvement in DLQI from baseline. During treatment with dupilumab, 12.2% of the patients developed conjunctivitis, and total IgE decreased significantly (P<.001). Interestingly, in the multivariate logistic regression model, the risk of developing dupilumab-related conjunctivitis was associated with early onset of AD (OR, 2.25; 95%CI, 1.07-4.70; P=.03) and presence of eosinophilia (OR, 1.91; 95%CI, 1.05-3.39; P=.03). CONCLUSION: This is the broadest real-life study in AD patients treated with dupilumab to date. We observed more significant improvements induced by dupilumab in adult patients with moderate-to-severe AD than those reported in clinical trials.

Moderate-to-severe atopic dermatitis in adolescents treated with dupilumab: A multicentre Italian real-world experience.

BACKGROUND: Moderate-to-severe atopic dermatitis (AD) in the adolescence is a high burden disease, and its treatment can be very challenging due to paucity of approved systemic drugs for this age and their side-effects. Dupilumab was recently approved for treatment of adolescent AD. OBJECTIVES: A multicentre, prospective, real-world study on the effectiveness and safety of dupilumab in adolescents (aged from ≥12 to <18 years) with moderate-to-severe AD was conducted. The main AD clinical phenotypes were also examined. METHODS: Data of adolescents with moderate-to-severe AD treated with dupilumab at label dosage for 16 weeks were collected. Treatment outcome was assessed by EASI, NRS itch, NRS sleep loss and CDLQI scores at baseline and after 16 weeks of treatment. The clinical scores were also evaluated according to clinical phenotypes. RESULTS: One hundred and thirty-nine adolescents were enrolled in the study. Flexural eczema and head and neck eczema were the most frequent clinical phenotypes, followed by hand eczema and portrait-like dermatitis. Coexistence of more than 1 phenotype was documented in 126/139 (88.5%) adolescents. Three patients (2.1%) contracted asymptomatic SARS-CoV-2 infection and 1 of the discontinued dupilumab treatment before the target treatment period. A significant improvement in EASI, NRS itch, NRS sleep loss and CDLQI was observed after 16 weeks of treatment with dupilumab. This outcome was better than that observed in clinical trials. Dupilumab resulted effective in all AD phenotypes, especially in diffuse eczema. Twenty-eight (20.1%) patients reported adverse events, conjunctivitis and flushing being the most frequent. None of patients discontinued dupilumab due to adverse event. CONCLUSIONS: Dupilumab in adolescent AD showed excellent effectiveness at week 16 with consistent improvement of all clinical scores. Moreover, dupilumab showed a good safety profile also in this COVID-19 pandemic era.

Long-term effects of bronchopulmonary dysplasia on lung function: a pilot study in preschool children's cohort.

INTRODUCTION: Although the long term negative effects of bronchopulmonary dysplasia (BPD) are well known, follow-up studies of preterm infants with BPD into childhood are lacking. METHODS: Forty-two preschool children (age range 3-6 years) who were born before 32 weeks of gestational age and affected by BPD were enrolled. Pre-, peri-, and post-natal data were collected. During the follow up appointment complete physical examination and lung function (impulse oscillometry (IOS)) were recorded. The European Community Respiratory Health Survey (ECRHS) questionnaire was administered to all enrolled subjects. RESULTS: Thirty patients were included in the final analysis. The BPD group did not differ in comparison to the non-BPD group in terms of lung function (p > 0.05). By comparing all subjects enrolled, We detected extremely low-birth-weight (ELBW) infants with height-, weight-, and gender-related reference values and a significant trend of increasing resistance values (R5Hz, R5-20 Hz) and respiratory impedance (Z5Hz) (p < 0.05). No significant difference in bronchial reversibility test was observed among BPD non-BPD groups (p < 0.05). The frequency of gastroesophageal reflux disease was significantly higher in patients with BPD when compared to non-BPD group (p < 0.05). Significant differences in gestational age, oxygen supplementation (days), mechanical ventilation therapy (days), and sepsis between BPD and non-BPD groups were also observed (p < 0.05). There were no significant differences in the prevalence of family and personal history of atopy and/or allergic diseases, tobacco exposure, respiratory symptoms, respiratory syncytial virus bronchiolitis, exercise induced dyspnea, treatment with ß-2 bronchodilators and inhaled corticosteroids among the groups (p > 0.05). CONCLUSIONS: The respiratory function in preschool children born with ELBW is characterized by an increase in impedance and resistance of small airways. No statistically significant differences were found between ELBW children with BPD and without BPD. With regards to the smallest gestational age, the longer duration of O2 therapy during hospitalization, and sepsis significantly resulted in a worse respiratory function.

Dupilumab therapy of atopic dermatitis of the elderly: a multicentre, real-life study.

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 ≥65 years 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 16 weeks were retrospectively collected. Treatment outcome was assessed by comparing objective (EASI) and subjective (P-NRS, S-NRS and DLQI) scores at baseline and after 16 weeks 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 18-64 years, 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.

Efficacy and safety of dupilumab in atopic dermatitis in elderly patients: a retrospective study.

Atopic dermatitis (AD) is a common inflammatory skin disease with high prevalence in both children (15-30%) and adults (2-10%), but limited data are available for older people. Elderly patients form a challenging group, as multiple comorbidities, associated polypharmacy and failures with previous treatments are common. We performed a retrospective observational study on elderly (≥ 65 years) patients treated with dupilumab, monoclonal antibody to the shared alpha subunit of the interleukin-4 and -13 receptor approved for the treatment of moderate-to-severe AD in adults.

Sex- and gender-associated clinical and psychosocial characteristics of patients with psoriasis.

BACKGROUND: Sex and gender may affect disease prevalence, adverse effects and response to therapy. AIM: To analyse sex and gender differences in outpatients with psoriasis. METHODS: A cross-sectional study was conducted at IDI-IRCCS, Rome, over a 3-year period. In total, 3023 patients with psoriasis were enrolled. Anthropometric and demographic characteristics were recorded, and a dermatologist evaluated the clinical severity of disease. Quality of life (QoL) questionnaires were collected. Univariate and multivariate analyses were performed to examine factors associated with sex. RESULTS: We found sex- and gender-associated differences in clinical characteristics, disease severity, psychological distress and quality of life. Male sex was associated with body mass index, smoking, alcohol consumption, Psoriasis Area Severity Index ≥ 10 and age at onset ≥ 20 years. Female sex was associated with family history of diabetes, joint involvement, clinical type other than diffuse plaque psoriasis, higher psychological distress and a greater effect on QoL. CONCLUSION: Our study identified sex and gender differences of potential clinical relevance in psoriasis.

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

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

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

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

Acquired haemophilia in cancer: A systematic and critical literature review.

AIM: There is a paucity of data on the clinical presentation and management of cancer patients with acquired haemophilia (AH), we here report a systematic literature review on acquired haemophilia in the context of cancer. METHODS: Treatment outcomes of AH were defined as complete response (CR), partial response (PR) or no response (NR), based on inhibitor eradication, coagulation factor VIII levels and bleeding control. Reported deaths were either related to cancer or bleeding. RESULTS: Overall, 105 cases were collected and analyzed according to classification of cancer and efficacy of treatments for inhibitor and malignancy. The mean age was 68 years for both males (range 37-86 years) and females (range 43-89 years), 39 patients were female subjects and 66 were males. A solid cancer was diagnosed in 60 subjects, while 45 patients suffered a haematological malignancy. Solid cancers affected mainly males; however, the incidence of solid tumours vs haematological malignancies was not statistically significant (P = .09). Not all patients were treated for their underlying cancer, bleeding and/or inhibitor, in two cases outcome is unavailable. CR was reported in 62.1% (64/103) cases, PR in 9.7% (10/103) cases, NR with or without death was reported in 28.1% (29/103) cases. CONCLUSION: CR was best achieved when successful and complete elimination of autoantibodies occurred contemporaneously with the successful treatment of the underlying malignancy. In some cases, recurrent autoantibodies were harbingers of relapsed cancer. Type of cancer, inhibitor titer, treatments administered for bleeding control and inhibitor eradication did not significantly affect clinical outcome of analyzed cases.

Residual vein obstruction in patients diagnosed with acute isolated distal deep vein thrombosis associated with active cancer.

After acute proximal deep vein thrombosis (DVT) the thrombotic mass decreases, especially during the first months of anticoagulation. The persistence of residual vein obstruction (RVO) may predict future recurrence in patients with cancer-associated DVT. We aimed to evaluate the proportion of patients with RVO after an episode of cancer associated isolated distal DVT (IDDVT), to identify variables associated with RVO, and to provide initial evidence of its association with recurrent VTE. We performed a post-hoc analysis of a multicenter cohort study of patients with isolated cancer-associated acute IDDVT. We included patients who underwent a control ultrasonography at the end of the anticoagulant treatment between day 30 and day 365 after index IDDVT, given that no recurrent VTE had already occurred on anticoagulant treatment. A total of 153 patients had ultrasonographic follow-up after a median of 92 days from index IDDVT: 45.8% had RVO and 54.2% exhibited complete recanalization. Female sex, Body Mass Index > 30 Kg/m2 and involvement of axial calf veins showed the strongest association with RVO. The risk of recurrence was twofold higher in patients with (versus without) RVO. RVO persisted in approximately half of patients with an episode of cancer-associated IDDVT at anticoagulant discontinuation. Patients with RVO appeared to be at a higher risk for recurrent events.

THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: a pilot prospective study.

Lower urinary tract dysfunctions (LUTDs) are commonly reported in multiple sclerosis (MS) patients and are mainly related to neurogenic overactive bladder (OAB). The aim of this observational study was to assess the effect of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray on resistant OAB by means of clinical and instrumental tools. Twenty-one MS patients were screened, and 15 cases have been evaluated. They underwent a specific clinical assessment (overactive bladder symptom score, OABSS) and a urodynamic assessment evaluating the maximal cystometric capacity (CCmax), bladder compliance (Qmax), maximum detrusor pressure (Pdet max), detrusor pressure at the first desire (Pdet first), bladder volume at the first desire (BVFD), leakage volume (LV), and post-void residual volume (PVR), before and after 4 weeks of THC/CBD administration. A complete neurological evaluation, including the assessment of their spasticity using the Modified Ashworth Scale (MAS) and the spasticity 0-10 numerical rating scale (NRS), was performed at the same times. Mobility was evaluated through the 25-ft walking-time test (T25-WT). The THC/CBD treatment successfully reduced the OAB symptoms (p = 0.001). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016), while BVFD and CCmax were increased although the difference was not statistically significant. THC/CBD oromucosal spray has shown to be effective in improving overactive bladder symptoms in MS patients demonstrating a favorable impact on detrusor overactivity.

The effect of smartphone addiction on hand joints in psoriatic patients: an ultrasound-based study.

BACKGROUND: Distal interphalangeal (DIP) arthritis is a frequent form of psoriatic arthritis being often linked to nail psoriasis. Modern society is characterized by overuse of smartphones. Indeed, literature has recently focalized on research into smartphone addiction and health-related problems. OBJECTIVES: As smartphone addiction is able to determine overuse and repeated movements of DIP joints and nails, the aim of this study was to evaluate the impact of smartphone use on hand joints of young psoriatic patients. METHODS: An observational study involving four different groups such as non-smartphone-addicted (SA) psoriatic patients, SA psoriatic patients, non-SA controls and SA controls was performed. Each subject underwent an ultrasound examination of both hands by three independent and blinded to group assignment radiologists. A specific score was used to evaluate the inflammatory state of the analysed joints. RESULTS: The total ultrasound score was statistically significantly higher in SA controls respect to non-SA controls (3.4 vs. 1.4; P < 0.05) as well as in SA psoriasis patients compared to non-SA psoriatic subjects (15.2 vs. 6.7; P < 0.01). Higher mean of ultrasound score was found for left hand in controls (both SA or not) and for right hand in psoriatic subjects (both SA or not), however without reaching statistical significance. CONCLUSIONS: Smartphone overuse was found to be linked with higher signs of inflammation of musculoskeletal structures of hands joints in both psoriasis and controls through ultrasound examination. Therefore, smartphone overuse may be a factor which facilitate or speed up the possible development of psoriatic arthritis.

The first joint ESGAR/ ESPR consensus statement on the technical performance of cross-sectional small bowel and colonic imaging.

OBJECTIVES: To develop guidelines describing a standardised approach to patient preparation and acquisition protocols for magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound (US) of the small bowel and colon, with an emphasis on imaging inflammatory bowel disease. METHODS: An expert consensus committee of 13 members from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) and European Society of Paediatric Radiology (ESPR) undertook a six-stage modified Delphi process, including a detailed literature review, to create a series of consensus statements concerning patient preparation, imaging hardware and image acquisition protocols. RESULTS: One hundred and fifty-seven statements were scored for agreement by the panel of which 129 statements (82 %) achieved immediate consensus with a further 19 (12 %) achieving consensus after appropriate modification. Nine (6 %) statements were rejected as consensus could not be reached. CONCLUSIONS: These expert consensus recommendations can be used to help guide cross-sectional radiological practice for imaging the small bowel and colon. KEY POINTS: • Cross-sectional imaging is increasingly used to evaluate the bowel • Image quality is paramount to achieving high diagnostic accuracy • Guidelines concerning patient preparation and image acquisition protocols are provided.

Interaction-based quantum metrology showing scaling beyond the Heisenberg limit.

Quantum metrology aims to use entanglement and other quantum resources to improve precision measurement. An interferometer using N independent particles to measure a parameter χ can achieve at best the standard quantum limit of sensitivity, δχ ∝ N(-1/2). However, using N entangled particles and exotic states, such an interferometer can in principle achieve the Heisenberg limit, δχ ∝ N(-1). Recent theoretical work has argued that interactions among particles may be a valuable resource for quantum metrology, allowing scaling beyond the Heisenberg limit. Specifically, a k-particle interaction will produce sensitivity δχ ∝ N(-k) with appropriate entangled states and δχ ∝ N(-(k-1/2)) even without entanglement. Here we demonstrate 'super-Heisenberg' scaling of δχ ∝ N(-3/2) in a nonlinear, non-destructive measurement of the magnetization of an atomic ensemble. We use fast optical nonlinearities to generate a pairwise photon-photon interaction (corresponding to k = 2) while preserving quantum-noise-limited performance. We observe super-Heisenberg scaling over two orders of magnitude in N, limited at large numbers by higher-order nonlinear effects, in good agreement with theory. For a measurement of limited duration, super-Heisenberg scaling allows the nonlinear measurement to overtake in sensitivity a comparable linear measurement with the same number of photons. In other situations, however, higher-order nonlinearities prevent this crossover from occurring, reflecting the subtle relationship between scaling and sensitivity in nonlinear systems. Our work shows that interparticle interactions can improve sensitivity in a quantum-limited measurement, and experimentally demonstrates a new resource for quantum metrology.