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IntroductionEpithelioid hemangioendothelioma (EHE) is an ultra-rare sarcoma, marked by distinctive molecular and pathological features and with a variable clinical behavior. Its natural history is still partially understood, reliable prognostic and predictive factors are lacking and many questions are still open on the optimal management. In the context of EURACAN, a prospective registry specifically dedicated to EHE was developed and launched with the aim of providing, through high-quality prospective data collection, a better understanding of this disease.Study designRegistry-based cohort study including only new cases of patients with a pathological and molecularly confirmed diagnosis of EHE.ObjectivesTo improve the understanding of EHE natural history, validate and identify new prognostic and predictive factors, clarify the activity and efficacy of currently available treatment options, describe treatment pattern.MethodsSettings and participantsIt is an hospital-based registry established in centers with expertise in EHE including adult patients with a new pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023. The characteristics of each patient in the facility who meets the above-mentioned inclusion criteria will be collected prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for routine patient follow-up. VariablesFull details on patients and disease features, treatment and outcome will be collected, according to common clinical practice guidelines developed and shared with all the contributing centers. In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will also be collected. Statistical methodsThe data analyses will include descriptive statistics and analytical analyses. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause-specific mortality will be used to determine independent predictors of overall survival, recurrence and progression.ResultsThe registry has been joined by 21 sarcoma reference centers across EU and UK, covering 10 countries. Patients' recruitment started in December 2023. The estimated completion date is December 2033 upon agreement on the achievement of all the registry objectives. The already established collaboration and participation of EHE patient's associations involved in the project will help in promoting the registry and fostering accrual.

Basal cell carcinoma (BCC) is a skin cancer with low local aggressiveness and a low tendency to metastasize. Basosquamous Carcinoma (BSC) represents an aggressive histological subtype of BCC with intermediate features between Squamous Cell Carcinoma (SCC) and BCC. Cemiplimab is currently approved as first-line therapy in SCC and second-line therapy in BCC patients who have progressed on or are intolerant of a Hedgehog pathway Inhibitor (HHI). Our study describes the case of a 59-year-old man with BSC who was successfully treated with 5 cycles of Cemiplimab as first-line therapy and Sonidegib as second-line therapy. Currently, the efficacy of Cemiplimab against BSC and other histopathological subtypes of BCC has not been fully elucidated, as has the role of sequential or combination therapy with Cemiplimab and HHI in the management of BSC. The aim of this case report is to highlight the need to outline the use of checkpoint inhibitors in BCCs and focus attention on the synergistic role of Cemiplimab and HHIs in such a controversial entity as BSC.

The correlation between health and diet has always been a subject of interest in the field of dermatology and medicine in general. However, studies in the literature are still scarce, and need further investigation in the field of inflammatory skin diseases. In this paper, we report a case of a patient with atopic dermatitis whose complete recovery occurred only after combining dupilumab therapy with a Mediterranean diet regimen.

The aim of this contribution is to present numerical comparisons of model-order reduction methods for geometrically nonlinear structures in the general framework of finite element (FE) procedures. Three different methods are compared: the implicit condensation and expansion (ICE), the quadratic manifold computed from modal derivatives (MD), and the direct normal form (DNF) procedure, the latter expressing the reduced dynamics in an invariant-based span of the phase space. The methods are first presented in order to underline their common points and differences, highlighting in particular that ICE and MD use reduction subspaces that are not invariant. A simple analytical example is then used in order to analyze how the different treatments of quadratic nonlinearities by the three methods can affect the predictions. Finally, three beam examples are used to emphasize the ability of the methods to handle curvature (on a curved beam), 1:1 internal resonance (on a clamped-clamped beam with two polarizations), and inertia nonlinearity (on a cantilever beam).

Basal cell carcinoma (BCC) is a skin cancer with low local aggressiveness and a low tendency to metastasize. Basosquamous Carcinoma (BSC) represents an aggressive histological subtype of BCC with intermediate features between Squamous Cell Carcinoma (SCC) and BCC. Cemiplimab is currently approved as first-line therapy in SCC and second-line therapy in BCC patients who have progressed on or are intolerant of a Hedgehog pathway Inhibitor (HHI). Our study describes the case of a 59-year-old man with BSC who was successfully treated with 5 cycles of Cemiplimab as first-line therapy and Sonidegib as second-line therapy. Currently, the efficacy of Cemiplimab against BSC and other histopathological subtypes of BCC has not been fully elucidated, as has the role of sequential or combination therapy with Cemiplimab and HHI in the management of BSC. The aim of this case report is to highlight the need to outline the use of checkpoint inhibitors in BCCs and focus attention on the synergistic role of Cemiplimab and HHIs in such a controversial entity as BSC. [ABSTRACT FROM AUTHOR]

The correlation between health and diet has always been a subject of interest in the field of dermatology and medicine in general. However, studies in the literature are still scarce, and need further investigation in the field of inflammatory skin diseases. In this paper, we report a case of a patient with atopic dermatitis whose complete recovery occurred only after combining dupilumab therapy with a Mediterranean diet regimen. [ABSTRACT FROM AUTHOR]

The ubiquitous diffusion of Power Electronic Converters (PECs) in many fields of application including traction and energy conversion suggests the possibility of new and better integration of advanced power conversion and Information and Communication Technology (ICT) services. This work investigates the possible advancements in the use of optical communication links made of plastic optical fibers for control of PECs. The optical communication link connects the switching control to the converter control, following the line of separation between the expertise of power electronic and control engineers. Control wise, a PEC is a black box compatible with any off-board controller, now immune from the Electromagnetic Interference (EMI) produced by the power switches. The redundant optical link is ready for the high switching and sampling frequencies, made possible by relying on SiC power semiconductor devices (100+ kHz). Distributed control of multiple PEC units and advanced telemetry for diagnostics and prognostics are targeted. A proof-of-concept demonstrator is presented and tested. Moreover, the possible evolution towards a power electronic cloud with remote management and orchestration is described.

Background: The Link between allergic rhinitis and asthma is well known. Bronchial hyperreactivity (BHR) may be present in rhinitics. The present study is aimed at evaluating a large group of subjects suffering from allergic rhinitis alone to investigate the presence of spirometric impairment and BHR both during and outside the pollen season. Methods: 360 rhinitics (subdivided in 3 groups: seasonal, SAR, perennial, PAR, and polysensitized, PolysR) were investigated by spirometry and methacholine challenge. Results: There was a significant seasonal difference concerning the number of rhinitics with impaired FEV1 (p

Abstract Background We previously demonstrated in a group of patients with perennial allergic rhinitis alone impairment of spirometric parameters and high percentage of subjects with bronchial hyperreactivity (BHR). The present study aimed at evaluating a group of polysensitized subjects suffering from allergic rhinitis alone to investigate the presence of spirometric impairment and BHR during the pollen season. Methods One hundred rhinitics sensitized both to pollen and perennial allergens were evaluated during the pollen season. Spirometry and methacholine bronchial challenge were performed. Results Six rhinitics showed impaired values of FEV1 without referred symptoms of asthma. FEF 25–75 values were impaired in 28 rhinitics. Sixty-six patients showed positive methacholine bronchial challenge. FEF 25–75 values were impaired only in BHR positive patients (p < 0.001). A significant difference was observed both for FEV1 (p < 0.05) and FEF 25–75 (p < 0.001) considering BHR severity. Conclusions This study evidences that an impairment of spirometric parameters may be observed in polysensitized patients with allergic rhinitis alone during the pollen season. A high percentage of these patients had BHR. A close relationship between upper and lower airways is confirmed.

We present three members of an Italian family affected by tubular aggregate myopathy ( TAM) and congenital miosis harboring a novel missense mutation in ORAI1. All patients had a mild, late onset TAM revealed by asymptomatic creatine kinase ( CK) elevation and congenital miosis consistent with a Stormorken-like Syndrome, in the absence of thrombocytopathy. Muscle biopsies showed classical histological findings but ultrastructural analysis revealed atypical tubular aggregates ( TAs). The whole body muscle magnetic resonance imaging ( MRI) showed a similar pattern of muscle involvement that correlated with clinical severity. The lower limbs were more severely affected than the scapular girdle, and thighs were more affected than legs. Molecular analysis revealed a novel c. 290C>G (p. S97C) mutation in ORAI1 in all affected patients. Functional assays in both human embryonic kidney (HEK) cells and myotubes showed an increased rate of Ca2+ entry due to a constitutive activation of the CRAC channel, consistent with a 'gain-of-function' mutation. In conclusion, we describe an Italian family harboring a novel heterozygous c. 290C>G (p. S97C) mutation in ORAI1 causing a mild- and late-onset TAM and congenital miosis via constitutive activation of the CRAC channel. Our findings extend the clinical and genetic spectrum of the ORAI1-related TAM. [ABSTRACT FROM AUTHOR]

Introduction: Aquaporins (AQPs) are a family of transmembrane proteins involved in the maintenance of osmotic gradients. AQP4 is abundant in skeletal muscle, where it seems to be associated with glycolytic metabolism. We investigated the pattern of expression of AQP4 in normal human myofibers relative to the main forms of myosin heavy chain (MHC).Methods: Six normal human muscle biopsies were analyzed by double immunofluorescence for co-expression of AQP4 and slow or fast MHC.Results: A high percentage (64-99%) of MHC-fast positive fibers showed immunoreaction for AQP4. Immunoreactivity for AQP4 was also present in MHC-slow positive fibers, but with a higher variability (5-72%) among biopsies.Discussion: The expression pattern of AQP4 in human myofibers is highly variable among different patients and cannot be predicted for single fibers depending on MHC type expression. Other factors, possibly related to muscle activity, may modulate AQP4 expression. Muscle Nerve 57: 856-859, 2018. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Depression may increase the risk of developing Alzheimer's disease (AD). Recent studies have shown modifications in blood beta-amyloid (A[beta]) levels in depressed patients. This literature review examines the potential relationship between A[beta]-mediated neurotoxicity and pathophysiology of mood disorders. DESIGN: We conducted a review of the literature focusing on recent studies reporting alterations of plasma and serum A[beta] peptides levels in patients suffering from mood disorders. RESULTS: Different data suggest that patients with mood disorders are at great risk of developing cognitive impairment and dementia. In particular, low plasma levels of A[beta]42 peptide and a high A[beta]40/A[beta]42 ratio have been found in depressed patients. In addition, changes in A[beta] protein levels in patients with mood disorders have been associated with the severity of cognitive impairment and correlated positively with the number of episodes and severity of illness course. CONCLUSIONS: Given the intriguing association between change in plasma level of A[beta], depression and cognitive impairment, future work should focus on the relationship between A[beta] peripheral level(s), biomarkers of neurodegeneration and development of dementia in patients affected by mood disorders. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective Depression may increase the risk of developing Alzheimer's disease (AD). Recent studies have shown modifications in blood beta-amyloid (Aβ) levels in depressed patients. This literature review examines the potential relationship between Aβ-mediated neurotoxicity and pathophysiology of mood disorders. Design We conducted a review of the literature focusing on recent studies reporting alterations of plasma and serum Aβ peptides levels in patients suffering from mood disorders. Results Different data suggest that patients with mood disorders are at great risk of developing cognitive impairment and dementia. In particular, low plasma levels of Aβ42 peptide and a high Aβ40/Aβ42 ratio have been found in depressed patients. In addition, changes in Aβ protein levels in patients with mood disorders have been associated with the severity of cognitive impairment and correlated positively with the number of episodes and severity of illness course. Conclusions Given the intriguing association between change in plasma level of Aβ, depression and cognitive impairment, future work should focus on the relationship between Aβ peripheral level(s), biomarkers of neurodegeneration and development of dementia in patients affected by mood disorders. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims: Alterations of plasma amyloid-β (Aβ) peptides have been related to a high risk for cognitive impairment and dementia. The present study aimed to measure plasma Aβ peptides (Aβ40, Aβ42) and the Aβ40/Aβ42 ratio in a sample of drug-resistant bipolar depressed patients, as well as to explore the possible correlation between biological parameters and clinical changes along an electroconvulsive therapy (ECT) course. Methods: Aβ40 and Aβ42 were measured by means of an ELISA assay in 25 drug-resistant bipolar depressed patients before (T0) and 1 week after (T1) the end of ECT. The patients were clinically evaluated by means of the Hamilton Rating Scale for Depression, 21-item (HRSD-21), the Mini-Mental State Examination, and the Clinical Global Impressions-Severity of Illness Scale. Results: Plasma Aβ levels and the Aβ40/Aβ42 ratio were similar at T0 and T1. The Aβ40/Aβ42 ratio correlated positively with the HRSD total score at both T0 and T1. At T0, a negative correlation was found between the Aβ40/Aβ42 ratio and the improvement of depressive and cognitive symptoms. Moreover, remitters (n = 9; HRSD ≤10) showed a significantly lower Aβ40/Aβ42 ratio at T0 than nonremitters. Conclusion: The present data suggest that a low Aβ40/Aβ42 ratio might characterize a subgroup of depressed patients who respond to ECT, while higher values of this parameter seem to be typical of more severe cases of patients with cognitive impairment. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that the brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of mood disorders and that its peripheral levels represent a reliable mirror of its concentration in the brain. The aim of the present study was to measure BDNF plasma levels in patients affected by major depression and to explore the possible relationship between the biological parameter and characteristics of the illness. Method: BDNF plasma levels were evaluated in 30 inpatients suffering from major depression, according to DSM-IV criteria, by means of a commonly employed ELISA method. The clinical characteristics were assessed by the Hamilton Rating Scale for Depression (HRSD) and the Clinical Global Impression Scale. Results: BDNF plasma levels were significantly lower in the patients with the severest illness compared with the others, and the same was true for patients with dissociative symptoms, severe sleep disturbance and recurrent depression. A significant and negative correlation was observed between the biological parameter and the retardation factor score of the HRSD. Conclusion: These findings suggest that low BDNF levels are related to both recurrence and severity of depression, as well as to symptoms typical of dysfunctions of the hypothalamic-pituitary-adrenal axis. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A close link exists between allergic rhinitis and asthma. Small airway disease (SAD), defined by a reduction in forced expiratory flow at 25–75% of the pulmonary volume (FEF25–75) and normal spirometry (normal forced expiratory volume at 1 second [FEV1], forced vital capacity [FVC], and FEV1/FVC ratio), may be a marker for early allergic or inflammatory involvement of the small airways in subjects with allergic diseases and no asthma. The aim of this study was to determine if there is a relationship between SAD, the outcome variable, and several allergic predictors in patients without asthma but with allergic rhinitis. A cross-sectional study was performed. Two hundred eleven midshipmen attending the third and fifth course of the Navy Academy of Livorno were screened. Fifty-eight midshipmen showed slight spirometric anomalies. Thus, they were referred to the Navy Hospital of La Spezia for standardized tests: skin-prick test, nasal cytology, spirometry, and methacholine bronchial challenge. A reduced FEF25–75 was arbitrarily defined as <80% of predicted. All 58 subjects had a normal FEV1, FVC, and FEV1/FVC ratio. Twenty subjects had a reduced FEF25–75, consistent with the definition of SAD. A mean value of FEF25–75 of 70.3 (SD, 8.5) was measured in patients with a reduced FEF, and it was 108.0 (SD, 14.3) in patients with preserved FEF25–75. All the candidate allergic predictors appeared to be strongly associated with a reduced FEF25–75. The proportion of subjects with reduced FEF25–75 appeared to increase with increasing severity of the allergic predictors, and, correspondingly, the mean value of FEF25–75 appeared to decrease. This study provides evidence that there is a relationship between SAD and allergic parameters such as nasal symptoms and eosinophils. [ABSTRACT FROM AUTHOR]

Summary: Background: Allergic rhinitis and its impact on asthma (ARIA) document underlines the link between upper and lower airways. Patients suffering from allergic rhinitis frequently (up to 80%) show bronchial hyperreactivity (BHR). Objectives: This study aimed at evaluating a group of subjects suffering from persistent allergic rhinitis, with BHR but with nasal symptoms only, to investigate the type and intensity of nasal symptoms, nasal and bronchial airflow, and BHR grade during the pollen season. Methods: One hundred and twenty one polysensitized rhinitics were investigated. Total symptom score (TSS) was assessed in all patients. Rhinomanometry, spirometry and methacholine bronchial challenge were performed in all patients. Results: 65 (53.7%) patients had impaired FEF 25–75 values. TSS correlated with nasal airflow () and BHR grade (). Nasal airflow correlated with FEF 25–75 values () and BHR (). FEF 25–75 values correlated with FEV1 levels (), BHR grade (), and nasal obstruction symptom (). Severe BHR correlated with FEV1 () and FEF 25–75 () values, nasal airflow () and nasal symptoms (). Conclusions: This study evidences that early bronchial impairment is frequently detectable in patients with persistent allergic rhinitis and BHR. Moreover, nasal function is strictly related with bronchial calibre and BHR grade. Therefore, careful evaluation of lower airways should be investigated in all rhinitics as suggested by the ARIA document. [Copyright &y& Elsevier]

Background: The pathogenesis of allergic rhinitis and its link with asthma are well known. Nevertheless, a complete cross-sectional evaluation of the usually available clinical, functional and immunological parameters has never been made. We assessed nasal symptoms and flow, cytology, cytokines, pulmonary function and methacholine positivity in a large number of patients with pure pollinosis. Methods: Young men presenting at a military hospital for routine follow-up were recruited for the study. They had to suffer from rhinitis alone (without asthma) for at least 2 years and had to have a positive skin prick test to pollens only. During the pollen season, they underwent symptom evaluation, measurement of nasal flow, nasal scraping and lavage (cell count and assay for IL-4, IL-5, IL-8 and IFNγ), pulmonary function tests and methacholine challenge. Results: Fifty subjects (23.7 ± 4.9 years old) were enrolled. All patients had high clinical scores (9.5 ± 1.6) and inflammatory cells (eosinophils: 10.5 ± 4 and neutrophils 21.3 ± 6) and low nasal flow (482 ± 111 ml/s). We found that the number of eosinophils in nasal scrapings highly correlated with all the above-mentioned parameters, including nasal flow, cytokines and spirometric values. A significant positive correlation was found between all inflammatory cells and all cytokines. IL-8, IL-4 and neutrophils displayed only a partial correlation with pulmonary parameters (FEV1, FVC and FEF25–75%), at variance wit IL-5 and eosinophils. Methacholine test positivity significantly correlated with the number of eosinophils in the nasal smear. Conclusion: Eosinophils in the nasal smear display the best correlation with all the clinical and immunological parameters in allergic rhinitis and also correlate well with methacholine response. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Nasal obstruction is a typical symptom of allergic rhinitis. Allergic rhinitis is characterized by a Th2-dependent inflammation. The aim of this study was to evaluate the possible relationships between allergic inflammation, including inflammatory cells and cytokine pattern, and nasal airflow in patients with nasal obstruction due to seasonal allergic rhinitis. Methods: Fifty patients (31 males and 19 females, mean age 31.9 ± 4.8 years) with seasonal allergic rhinitis were evaluated during the pollen season. All of them had moderate to severe nasal obstruction. Total symptom score, rhinomanometry, nasal lavage, and nasal scraping were assessed in all subjects. Inflammatory cells were counted by conventional staining; IL-4, IL-5, IL-8, and IFNγ were measured by immunoassay on fluids recovered from nasal lavage. Results: Significant positive relationships were demonstrated between eosinophil infiltration and IL-4 levels (p < 0.0001), eosinophils and IL-5 levels (p < 0.0001), and eosinophils and IL-8 levels (p < 0.0001). Significant negative relationships were demonstrated between eosinophil infiltration and IFNγ levels (p < 0.0001) and eosinophil infiltration and nasal airflow (p < 0.001). Conclusions: This study demonstrates the close connection between Th2 cytokines and eosinophil infiltration. In addition, there is clear evidence concerning the relationship between eosinophil infiltration and nasal airflow. These findings constitute first evidence of the relationship between nasal airflow impairment and Th2-related inflammation in seasonal allergic rhinitis. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: We previously demonstrated in a group of patients with perennial allergic rhinitis alone impairment of spirometric parameters and high percentage of subjects with bronchial hyperreactivity (BHR). The present study aimed at evaluating a group of polysensitized subjects suffering from allergic rhinitis alone to investigate the presence of spirometric impairment and BHR during the pollen season. Methods: One hundred rhinitics sensitized both to pollen and perennial allergens were evaluated during the pollen season. Spirometry and methacholine bronchial challenge were performed. Results: Six rhinitics showed impaired values of FEV1 without referred symptoms of asthma. FEF 25-75 values were impaired in 28 rhinitics. Sixty-six patients showed positive methacholine bronchial challenge. FEF 25-75 values were impaired only in BHR positive patients (p < 0.001). A significant difference was observed both for FEV1 (p < 0.05) and FEF 25-75 (p < 0.001) considering BHR severity. Conclusions: This study evidences that an impairment of spirometric parameters may be observed in polysensitized patients with allergic rhinitis alone during the pollen season. A high percentage of these patients had BHR. A close relationship between upper and lower airways is confirmed. [ABSTRACT FROM AUTHOR]

Background: Allergic disorders are characterized by a systemic involvement of the immune response. There is a clear link between allergic rhinitis and asthma. Bronchial hyperreactivity (BHR) may be present in rhinitics. Smaller airways may also be impaired in mild asthma. This study aimed at evaluating a group of subjects suffering from perennial allergic rhinitis alone to investigate the presence of BHR and spirometric impairment. Methods: One hundred rhinitics sensitized only to perennial allergens were evaluated. Spirometry and methacholine bronchial challenge were performed. Results: Five rhinitics showed reduced values of forced expiratory volume/1 s (FEV[sub 1] ) without symptoms of asthma. Forty-eight rhinitics had reduced forced expiratory flow at 25 and 75% of pulmonary volume (FEF[sub 25–75] ) values. Seventy-two patients showed a positive methacholine challenge. In this group, reduced values of FVC (p < 0.05), FEV[sub 1] (p < 0.05), and FEF[sub 25–75] (p < 0.01) were demonstrated in comparison with BHR-negative rhinitics. There was a relationship between the degree of BHR and FEV[sub 1] values (p < 0.05) and FEF[sub 25–75] values (p < 0.01). Conclusions: This study evidences that an impairment of spirometric parameters may be observed in patients with perennial allergic rhinitis alone. A high percentage of these patients have BHR. Thus, new management strategies should be employed in rhinitics. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]