Monitoring of the conservation state of the internal wall surfaces of Room with Golden Vault in the Domus Aurea

This project describes the monitoring campaign, performed in situ with the collaboration of Konica Minolta Sensing Europe, in order to verify the actual conservation state of the internal wall surfaces of the Room with Golden Vault in the Domus Aurea in Rome. Particularly, the main aim of this work was to evaluate the problems caused by aggressive environmental conditions (combination of low air temperature and high relative humidity). During this survey, characterized by the integrated use of two and three-dimensional techniques, the environmental conditions were carefully monitored. Reference sample regions of the vault were acquired by means of the 3D laser scanner Konica Minolta Vivid 9i (optical triangulation-based) that allows capturing morphological details of the stucco decorations with a good resolution. Moreover, each detailed scan was supplied with related high resolution images taken by a digital reflex camera Olympus E-510 rigidly connected to the scanner. In Cultural Heritage monitoring applications it is important to integrate the data acquired with different instruments and techniques. Therefore, by this methodological approach, it has been possible to integrate both two and three dimensional data by the projection of the acquired images on the corresponding digital model. In order to complete the cognitive framework of the vault, systematic measures of spectrophotometry by means of the portable spectrophotometer Minolta 2600d were also carried out. The digital data, collected and elaborated by this monitoring campaign, allowed to create a database of morphological information, high resolution digital images, colorimetric values and reflectance curves that may be used in the future as reference data to periodically monitor the conservation state of the surfaces

S. aureus and IgE-mediated diseases: pilot or copilot? A narrative review

Introduction: S. aureus is a major opportunistic pathogen that has been implicated in the pathogenesis of several chronic inflammatory diseases including bronchial asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), chronic spontaneous urticaria (CSU), and atopic dermatitis. S. aureus can induce the production of both polyclonal and specific IgE that can elicit an inflammatory cascade. Areas covered: The link between the sensitization to S. aureus enterotoxins and the severity of several chronic inflammatory diseases is reviewed in detail, as well as its therapeutic implications. Expert opinion: An anti-IgE strategy to inhibit S. aureus enterotoxins would be a valid approach to treat several endotypes of severe asthma, CRSwNP and CSU in which IgE against S. aureus enterotoxins should represent, not only a marker of severity of the diseases but also a target of a treatment

Practice Recommendations for Diagnosis and Treatment of the Most Common Forms of Secondary Hypertension

The vast majority of hypertensive patients are never sought for a cause of their high blood pressure, i.e. for a \u2018secondary\u2019 form of arterial hypertension. This under detection explains why only a tiny percentage of hypertensive patients are ultimately diagnosed with a secondary form of arterial hypertension. The prevalence of these forms is, therefore, markedly underestimated, although, they can involve as many as one-third of the cases among referred patients and up to half of those with difficult to treat hypertension. The early detection of a secondary form is crucial, because if diagnosed in a timely manner, these forms can be cured at long-term, and even when cure cannot be achieved, their diagnosis provides a better control of high blood pressure, and allows prevention of hypertension-mediated organ damage, and related cardiovascular complications. Enormous progress has been made in the understanding, diagnostic\ua0work-up, and management of secondary hypertension in the last decades. The\ua0aim of this minireview is, therefore, to provide updated concise information on the screening, diagnosis, and management of the most common forms, including primary aldosteronism, renovascular hypertension, pheochromocytoma and paraganglioma, Cushing\u2019s syndrome, and obstructive sleep apnea

Role of perfusion CT in the evaluation of metastatic nodal tumor response after radiochemotherapy in head and neck cancer: preliminary findings

OBJECTIVE: To assess changes of CT perfusion parameters (ΔPCTp) of cervical lymph node metastases from head and neck cancer (HNC) before and after radiochemotherapy (RT-CT) and their association with nodal tumor persistence. PATIENTS AND METHODS: Eligibility criteria included HNC (Stage III-IV) candidates for RT-CT. Patients underwent perfusion CT (PCT) at baseline 3 weeks and 3 months after RT-CT. Blood volume (BV), blood flow (BF), mean transit time (MTT) and permeability surface (PS) were calculated. PET/CT examination was also performed at baseline and 3 months after treatment for metabolic assessment. RESULTS: Between July 2012 and May 2016, 27 patients were evaluated. Overall, only 3 patients (11%) experienced tumor persistence in the largest metastatic lymph node. A significant reduction of all PCTp values (p<0.0001), except MTT (from 6.3 to 5.7 s; p=0.089), was observed at 3 weeks post-RT-CT compared to baseline. All PCTp values including MTT were significantly lower at 3-month follow-up compared to baseline (p<0.05). Moreover, a statistical significant association was observed between nodal tumor persistence and high BF values (p=0.045) at 3 months after treatment that did not occur for the other parameters. CONCLUSIONS: Our preliminary findings show that all PCTp except MTT are significantly reduced after RT-CT. High BF values at 3 months post-RTCT are predictive of nodal tumor persistence

Upper and lower airway inflammation in severe asthmatics: a guide for a precision biologic treatment

Background and aims: Severe asthma may require the prescription of one of the biologic drugs currently available, using surrogate markers of airway inflammation (serum IgE levels and allergic sensitization for anti-IgE, or blood eosinophils for anti-IL5/IL5R). Our objective: to assess upper and lower airway inflammation in severe asthmatics divided according to the eligibility criteria for one of the target biologic treatments. Methods: We selected 91 severe asthmatics, uncontrolled despite high-dose ICS-LABA, and followed for &gt;6 months with optimization of asthma treatment. Patients underwent clinical, functional and biological assessment, including induced sputum and nasal cytology. They were then clustered according to the eligibility criteria for omalizumab or mepolizumab/benralizumab. Results: Four clusters were selected: A (eligible for omalizumab, n = 23), AB (both omalizumab and mepolizumab, n = 26), B (mepolizumab, n = 22) and C (non-eligible for both omalizumab and mepolizumab, n = 20). There was no difference among clusters for asthma control (Asthma Control Test and Asthma Control Questionnaire 7), pre-bronchodilator forced expiratory volume in 1 s, serum IgE and fractional exhaled nitric oxide levels. Sputum eosinophils were numerically higher in clusters AB and B, in agreement with the higher levels of blood eosinophils. Allergic rhinitis was more frequent in clusters A and AB, while chronic rhinosinusitis with nasal polyps prevalence increased progressively from A to C. Eosinophils in nasal cytology were higher in clusters AB, B and C. Conclusion: Eosinophilic upper and lower airway inflammation is present in the large majority of severe asthmatics, independently from the prescription criteria for the currently available biologics, and might suggest the use of anti-IL5/IL5R or anti IL4/13 also in patients without blood eosinophilia. The reviews of this paper are available via the supplemental material section

Clinical Evidence of Type 2 Inflammation in Non-allergic Rhinitis with Eosinophilia Syndrome: a Systematic Review

Purpose of Review: Non-allergic rhinitis (NAR) includes different subtypes, among which NAR with eosinophilia syndrome (NARES) is the most important because of severity of symptoms and the high risk of comorbidities. Its pathophysiology is still object of debate, but a crucial role of chronic eosinophilic inflammation has been recognized. The aim of this review is to critically analyze the current evidence regarding the hypothesis that NARES may be considered a type 2 inflammatory disorder. Recent Findings: The definition and diagnostic criteria for NARES are not universally shared and adopted, thus generating difficulties in reproducing the results. At present, there is extreme heterogeneity in sampling methods and disagreement in the cut-off of local eosinophilic count to determine a diagnosis of NARES. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standard was applied to identify English-language experimental and clinical articles regarding NARES. The search was performed in April 2021. Twenty-six articles were included. Summary: Our data suggest a particular heterogeneity regarding sampling and specific cut-offs adopted for diagnosis of NARES and consensus should be reached. We suggest that eosinophil count should be reported as an absolute value for at least 10 observed rich fields in order to increase the level of standardization. Consensus among authors on this topic should be reached with particular attention to the cut-off for diagnosis. In the future, this limitation may be overcome by the identification of repeatable biomarkers to refine diagnosis and prognosis of NARES. Furthermore, our data strongly suggest that NARES have numerous similarities with clinical features of the most common type 2 diseases such as eosinophilic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP): late onset, association with type 2 comorbidities, selective eosinophilic tissue infiltration, remarkable response to oral and intranasal corticosteroids, and progression in a type 2 CRSwNP

Mepolizumab Improves Outcomes of Chronic Rhinosinusitis with Nasal Polyps in Severe Asthmatic Patients: A Multicentric Real-Life Study

Objective: The upcoming introduction of mepolizumab represents a promising treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). The present study aimed to evaluate the effectiveness of mepolizumab on sinonasal outcomes of comorbid CRSwNP and severe asthma in a real-life setting. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test (SNOT)-22 score, Nasal Polyp (NP) score, and blood eosinophil count during a 12-month treatment with mepolizumab. Secondary endpoints were to quantify mepolizumab's effects on the mentioned parameters, identify clinical variables influencing the degree of response to treatment, and portray responder and nonresponder patients. Methods: A multicentric retrospective no-profit observational study on severe asthmatic patients, treated with mepolizumab, and comorbid CRSwNP was conducted. All patients were followed for at least 12 months. SNOT-22 score, NP score, and blood eosinophil count (and other CRS-specific variables) were collected at baseline and after 12 months. Results: Forty-three patients were included. A statistically significant reduction was observed for SNOT-22 score (mean t0 SNOT-22 54.8 +/- 25.9; mean t12 SNOT-22 31.5 +/- 21.3, p &lt; 0.0001), NP score (median t0 NPS 3 (IQR 3); median t12 NPS 2 (IQR 4), p &lt; 0.0001), and blood eosinophil count (mean t0 blood eosinophils 804.7 +/- 461.5 cell/mu L; mean t12 blood eosinophils 107.5 +/- 104.6 cell/mu L, p &lt; 0.0001) after 12 months of treatment. Twenty patients (47%) gained improvement both in clinical and endoscopic outcome. Mepolizumab responder patients presented a t0 SNOT-22 significantly higher than nonresponders (p = 0.0011). Conclusions: Mepolizumab improved CRSwNP outcomes in a population of severe asthmatic patients. No clinical feature emerged to outline the profile of a "typical" responder patient, except for baseline SNOT-22 score, which seemed to affect the response to treatment. Further studies would be necessary to supplement these preliminary evaluations

Endothelin-1 (ET-1) modulates epithelial-mesenchymal transition (EMT), which contributes to kidney tubulo-interstitial fibrosis in angiotensin II-dependent hypertension

The origin of myofibroblasts remains uncertain, but studies suggest that the epithelial cells may acquire a fibroblast-like phenotype via epithelial-mesenchymal transition (EMT). Objective of the study was to investigate whether EMT may contribute to the development of kidney fibrosis in a model of angiotensin II-dependent hypertension and to identify the role of ET-1 via ETA/ETB receptors. Transgenic rats TGRen2 (n=35) received for 4 weeks one of the following treatments a) irbesartan, b) bosentan, non selective ETA /ETB receptor antagonist, c) BMS-182874, selective ETA,antagonist, d) BMS+irbesartan, e) placebo. EMT was assessed by investigating coexpression of a marker of epithelial cell (E-cadherin) and one of myofibroblast (S100A4 or alfa-SMA) with double immunofluorescence. Specific immunoreactivity was measured using QWinStandard Leica ImageTMsoftware. A reduction in blood pressure was found only with irbesartan, whereas both bosentan and irbesartan significantly lowered tubulo-interstitial fibrosis. Coexpression of E-cadherin and S100A4, or E-cadherin and alfa-SMA, markedly decreased in the tubular cells of TGRen2 treated with irbesartan or bosentan. Alfa-SMA expression decreased after irbesartan, bosentan and BMS+irbesartan, but not after BMS. S100A4 expression was reduced after irbesartan, bosentan and BMS+irbesartan. E-cadherin increased only after irbesartan. Coexpression of the markers of myofibroblasts and kidney epithelial cells, by demonstrating the development of EMT during the onset of kidney hypertension-induced damage, suggests a crucial role of EMT in the pathogenesis of Ang II-mediated fibrosis. The reduction of myofibroblast markers not only after irbesartan, but also after blockade of ETA/ETB receptors, suggests an involvement of ET-1 in the development of Ang II-mediated EMT

Endothelin-1 (ET-1) modulates epithelial-mesenchymal transition (EMT), which contributes to kidney tubulo-interstitial fibrosis in angiotensin II-dependent hypertension

The origin of myofibroblasts remains uncertain, but studies suggest that the epithelial cells may acquire a fibroblast-like phenotype via epithelial-mesenchymal transition (EMT). Objective of the study was to investigate whether EMT may contribute to the development of kidney fibrosis in a model of angiotensin II-dependent hypertension and to identify the role of ET-1 via ETA/ETB receptors. Transgenic rats TGRen2 (n=35) received for 4 weeks one of the following treatments a) irbesartan, b) bosentan, non selective ETA /ETB receptor antagonist, c) BMS-182874, selective ETA,antagonist, d) BMS+irbesartan, e) placebo. EMT was assessed by investigating coexpression of a marker of epithelial cell (E-cadherin) and one of myofibroblast (S100A4 or alfa-SMA) with double immunofluorescence. Specific immunoreactivity was measured using QWinStandard Leica ImageTMsoftware. A reduction in blood pressure was found only with irbesartan, whereas both bosentan and irbesartan significantly lowered tubulo-interstitial fibrosis. Coexpression of E-cadherin and S100A4, or E-cadherin and alfa-SMA, markedly decreased in the tubular cells of TGRen2 treated with irbesartan or bosentan. Alfa-SMA expression decreased after irbesartan, bosentan and BMS+irbesartan, but not after BMS. S100A4 expression was reduced after irbesartan, bosentan and BMS+irbesartan. E-cadherin increased only after irbesartan. Coexpression of the markers of myofibroblasts and kidney epithelial cells, by demonstrating the development of EMT during the onset of kidney hypertension-induced damage, suggests a crucial role of EMT in the pathogenesis of Ang II-mediated fibrosis. The reduction of myofibroblast markers not only after irbesartan, but also after blockade of ETA/ETB receptors, suggests an involvement of ET-1 in the development of Ang II-mediated EMT

Non-surgical management of chronic rhinosinusitis with nasal polyps based on clinical-cytological grading: a precision medicine-based approach

La rinosinusite cronica con polipi nasali (CRSwNP) è una malattia cronica nasosinusale, a eziologia infiammatoria, con significativo impatto negativo sulla qualità di vita dei pazienti. La CRSwNP rappresenta ancora oggi una sfida terapeutica per lo specialista ORL, sia per la comprensione della sua eziopatogenesi, sia per il suo controllo clinico ed è questo è testimoniato dalla alta incidenza di recidiva dopo trattamento. Abbiamo voluto verificare lipotesi che un approccio terapeutico nuovo, standardizzato, e individualizzato sul grading clinico-citologico (clinical-cytological grading CCG) consentisse un miglior controllo dei sintomi della malattia, e di ridurre la necessità di ricorrere alla chirurgia. Abbiamo pertanto reclutato 204 pazienti affetti da CRSwNP, di cui 145 hanno regolarmente assunto la terapia rispettando il protocollo proposto, e 59 pazienti, invece, che non hanno assunto la terapia in modo sistematico e sono stati quindi inclusi come controlli. Dopo 5 anni di trattamento standardizzato, abbiamo notato che 15 pazienti su 145 (10,3%) del gruppo con terapia standardizzata avevano avuto un miglioramento dello staging endoscopico, 61 su 145 (42%) si erano mantenuti costanti, mentre 69/145 (47,5%) erano andati incontro a un peggioramento. Nel gruppo di controllo, invece, i pazienti peggiorati erano ben 49 su 59 (83%), con un peggioramento significativo in termini di grading endoscopico di almeno due classi (p < 0,05). I pazienti e i controlli sono stati successivamente stratificati sulla base del CCG in 3 sottogruppi: pazienti con CCG lieve, moderata e grave. Dopo tale suddivisione in classi, è stato possibile evidenziare che nel gruppo con CCG lieve (n = 27), il 92% dei pazienti manteneva negli anni un trend costante, in assenza di peggioramenti e senza necessità di ricorrere alla chirurgia nei 5 anni di osservazione, mentre nel gruppo di controllo, 1 paziente su 59 (1,6%; p = <0,05) ricorreva a chirurgia. Nel gruppo con CCG moderato (n = 83), invece, il 44% dei pazienti standardizzati non aveva avuto un peggioramento di grading endoscopico, con un 3,6% di pazienti che aveva avuto necessità di ricorrere alla chirurgia, contro il 13,6% del gruppo controllo (p < 0,05). Nel gruppo dei pazienti con CCG grave (n = 35), anche se nessun paziente riusciva a ottenere un miglioramento del grading endoscopico, il 40% dei pazienti veniva comunque giudicato controllato da un punto di vista clinico. Nel gruppo dei pazienti con CCG grave, ben il 5,7% dei pazienti necessitava di trattamento chirurgico, ma anche in questo caso, la percentuale dei pazienti operati era significativamente maggiore (p = 0,0000) nel gruppo di controllo (49%). Infine, lanalisi statistica effettuata ha dimostrato chiaramente che, da un punto di vista obiettivo, le dimensioni dei polipi nasali tendevano ad aumentare a una velocità maggiore nel gruppo controllo che nel gruppo standardizzato, con incrementi proporzionali nelle tre classi di CCG (lieve, moderato e grave). Lo studio attuale fornisce le basi per lo sviluppo e ladozione di un nuovo approccio per la gestione della CRSwNP sulla base di uno score clinico e citologico (CCG) che permetta di stimare con accuratezza la gravità della CRSwNP e di adattarne il trattamento. Tale approccio limita luso degli steroidi sistemici alle sole classi CCG di entità moderata-grave con dosi di steroidi inferiori rispetto a quanto precedentemente suggerito in letteratura. Il nostro protocollo può migliorare pertanto laderenza terapeutica dei pazienti, il tasso di controllo della malattia e può ridurre il ricorso alla chirurgia nel corso degli anni