Periodontal condition in growing subjects with Marfan Syndrome: a case-control study

Background Marfan’s syndrome (MFS) is a systemic disorder of connective tissue caused by mutations in the extracellular matrix protein fibrillin-1. Orofacial characteristics may be useful in identification of the syndrome. Severe periodontitis is sometimes observed in MFS patients, but no in-depth information has been reported in Italian groups of growing subjects with MFS. The aim of this study was to analyze the periodontal condition on a group of growing subjects affected by MFS, in comparison with a typically developed control group. Methods A group of 16 subjects with diagnosed MFS were recruited from the Centre for Rare Diseases for Marfan Syndrome and Related Disorders of Tor Vergata University Hospital. The Marfan Group (MG) was compared with a Control Group (CG) composed by 20 nonsyndromic subjects. The periodontal clinical parameters like Marginal Gingival Thickness (GT), Plaque Index (PI), Bleeding On Probing (BOP) and Modified Periodontal Screening and Recording (PSR) were assessed. Results The mean value of PI in MG was 59%, instead in CG it reached 21%. Analysis showed a significant difference between MG and CG also for the BOP. In MG the mean value of BOP attained 36% and in CG it reached 16%. A statistical significant difference of distribution of PSR index between the two groups was found for all sextant examined. Discussion Patients with Marfan syndrome reveal a higher presence of plaque and consequently a generalized inflammation in the oral cavity when compared with a control group

Inverted Scanning Microwave Microscope for In Vitro Imaging and Characterization of Biological Cells

This paper presents for the first time an innovative instrument called an inverted scanning microwave microscope (iSMM), which is capable of noninvasive and label-free imaging and characterization of intracellular structures of a live cell on the nanometer scale. In particular, the iSMM is sensitive to not only surface structures, but also ectromagnetic properties up to one micrometer below the surface. Conveniently, the iSMM can be constructed through straightforward conversion of any scanning probe microscope, such as the atomic force microscope or the scanning tunneling microscope, with a simple metal probe to outperform traditional SMM in terms of ruggedness, and width, sensitivity and dynamic range. By contrast, the application of the traditional SMM to date has been limited to mainly surface physics and semiconductor technology, because the traditional SMM requires a fragile and expensive probe and is incompatible with saline solution or live biological cells.Comment: 5 pages, 4 figures, published in Applied Physics Letter

Level II Oncoplastic Surgery as an Alternative Option to Mastectomy with Immediate Breast Reconstruction in the Neoadjuvant Setting: A Multidisciplinary Single Center Experience

: Oncoplastic surgery level II techniques (OPSII) are used in patients with operable breast cancer. There is no evidence regarding their safety and efficacy after neoadjuvant chemotherapy (NAC). The aim of this study was to compare the oncological and aesthetic outcomes of this technique compared with those observed in mastectomy with immediate breast reconstruction (MIBR), in post-NAC patients undergoing surgery between January 2016 and March 2021. Local disease-free survival (L-DFS), regional disease-free survival (R-DFS), distant disease-free survival (D-DFS), and overall survival (OS) were compared; the aesthetic results and quality of life (QoL) were evaluated using BREAST-Q. A total of 297 patients were included, 87 of whom underwent OPSII and 210 of whom underwent MIBR. After a median follow-up of 39.5 months, local recurrence had occurred in 3 patients in the OPSII group (3.4%), and in 13 patients in the MIBR group (6.1%) (p = 0.408). The three-year L-DFS rates were 95.1% for OPSII and 96.2% for MIBR (p = 0.286). The three-year R-DFS rates were 100% and 96.4%, respectively (p = 0.559). The three-year D-DFS rate were 90.7% and 89.7% (p = 0.849). The three-year OS rates were 95.7% and 95% (p = 0.394). BREAST-Q highlighted significant advantages in physical well-being for OPSII. No difference was shown for satisfaction with breasts (p = 0.656) or psychosocial well-being (p = 0.444). OPSII is safe and effective after NAC. It allows oncological and aesthetic outcomes with a high QoL, and is a safe alternative for locally advanced tumors which are partial responders to NAC

A Hydrogenated amorphous silicon detector for Space Weather Applications

The characteristics of a hydrogenated amorphous silicon (a-Si:H) detector are presented here for monitoring in space solar flares and the evolution of large energetic proton events up to hundreds of MeV. The a-Si:H presents an excellent radiation hardness and finds application in harsh radiation environments for medical purposes, for particle beam characterization and in space weather science and applications. The critical flux detection threshold for solar X rays, soft gamma rays, electrons and protons is discussed in detail.Comment: 32 pages, 13 figures, submitted to Experimental Astronom

BRCA Mutation Status in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Pivotal Role for Treatment Decision-Making

Simple Summary In this retrospective observational study, we evaluated data from patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NACT) in order to better define the impact of germline BRCA1/2 (gBRCA1/2) mutation status on outcomes in this patient population. Our results show that patients with BRCA1/2 mutation had a higher pathologic complete response (pCR) rate than non-mutated patients; nevertheless, the benefit was confirmed only in the subset of patients who received a platinum-based NACT. Furthermore, pCR was associated with improved Event Free Survival (EFS) and Overall Survival (OS), regardless of BRCA1/2 mutation status and type of NACT received. Long-term follow-up analyses are needed to further define the impact of gBRCA mutation status in patients with early-TNBC. Triple-negative breast cancer (TNBC) is characterized by earlier recurrence and shorter survival compared with other types of breast cancer. Moreover, approximately 15 to 25% of all TNBC patients harbor germline BRCA (gBRCA) 1/2 mutations, which confer a more aggressive phenotype. However, TNBC seems to be particularly sensitive to chemotherapy, the so-called 'triple negative paradox'. Therefore, Neoadjuvant chemotherapy (NACT) is currently considered the preferred approach for early-stage TNBC. BRCA status has also been studied as a predictive biomarker of response to platinum compounds. Although several randomized trials investigated the addition of carboplatin to standard NACT in early-stage TNBC, the role of BRCA status remains unclear. In this retrospective analysis, we evaluated data from 136 consecutive patients with Stage I-III TNBC who received standard NACT with or without the addition of carboplatin, in order to define clinical features and outcomes in BRCA 1/2 mutation carriers and non-carrier controls. Between January 2013 and February 2021, 67 (51.3%) out of 136 patients received a standard anthracyclines/taxane regimen and 69 (50.7%) patients received a platinum-containing chemotherapy regimen. Deleterious germline BRCA1 or BRCA2 mutations were identified in 39 (28.7%) patients. Overall, patients with deleterious gBRCA1/2 mutation have significantly higher pCR rate than non-carrier patients (23 [59%] of 39 vs. 33 [34%] of 97; p = 0.008). The benefit of harboring a gBRCA mutation was confirmed only in the subset of patients who received a platinum-based NACT (17 [65.4%] of 26 vs. 13 [30.2%] of 43; p = 0.005) while no differences were found in the platinum-free subgroup. Patients who achieved pCR after NACT had significantly better EFS (OR 4.5; 95% CI 1.9-10.7; p = 0.001) and OS (OR 3.3; 95% CI 1.3-8.9; p = 0.01) than patients who did not, regardless of BRCA1/2 mutation status and type of NACT received. Our results based on real-world evidence show that TNBC patients with the gBRCA1/2 mutation who received platinum-based NACT have a higher pCR rate than non-carrier patients, supporting the use of this chemotherapy regimen in this patient population. Long-term follow-up analyses are needed to further define the role of gBRCA mutation status on clinical outcomes in patients with early-TNBC

Impact on survival of primary tumor resection in patients with metastatic breast cancer: preliminary results of a retrospective analisys

Background: Treatment of de novo metastatic breast cancer is usually centered around systemic therapy, with local therapy (surgery and radiation therapy) largely reserved for palliation in patients with significant symptoms from primary tumour. The efficacy of locoregional treatment like surgery and/or radiotherapy is still controversial and the debate about surgical resection of primary tumor (PT) in de novo metastatic breast cancer (MBC) patients persists. Methods: All patients with de novo MBC undergone surgical treatment between January 2015 and January 2020 at the Multidisciplinary Breast Center of the Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome were included in this study. The primary endpoint was overall survival (OS) after PT resection, the secondary endpoint was progression free survival (PFS). The survival analyses were done using Kaplan-Meier method. Patients and tumour characteristics were analyzed in an exploratory modality in order to identify prognostic factor. Results: 45 patients received resection of the primary breast cancer (26 mastectomy and 19 breast conserving surgery). Median age of diagnosis was 53 years old (range 25-75 years old). Median follow-up was 25.67 months. The median OS was not reached with 75% of patients alive over 2 years from PT resection. The median PFS was not reached with 64% of patients alive over 2 years from PT resection. For both PFS and OS only the triple negative (TN) immunophenotype appears to be a prognostically unfavorable factor in multivariate analysis. Conclusions: In view of the low number of disease progression events and deaths, although our results are preliminary, surgical treatment of primary breast cancer in metastatic setting seems to be an option after systemic therapies in luminal and HER2 positive breast cancer. Randomized prospective trials in for each immunophenotype are necessary order to confirm this evidence

Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

Background: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths

Modelling and Experimental Characterization of new Microwave Microscopy Techniques for Quantitative Measurements

Tecniche classiche di microscopia basate su interazioni in campo-lontano, come ad esempio il ben noto microscopio ottico tradizionale, hanno una risoluzione spaziale dell'ordine della lunghezza d'onda utilizzata. Perciò, se le dimensioni e le proprietà del campione variano in una scala di lunghezza minore della lunghezza d'onda, la risposta elettromagnetica del materiale è mediata su scale maggiori, e molti dettagli del campione vengono persi. Il Microscopio a Scansione a Microonde in Campo-vicino (NFSMM o semplicemente SMM) ha superato questo paradigma con il concetto di interazione di campo-vicino tra una sonda (sorgente) ed il campione. In questo caso la sonda eccita il campione con un segnale a microonde e genera un campo evanescente focalizzato in un'area estremamente piccola del materiale. Il microscopio misura le proprietà del campione catturando il segnale di risposta generato da questa interazione, con una risoluzione determinata principalmente dalla dimensione della punta piuttosto che dalla lunghezza d'onda. Inoltre, l'SMM non solo misura strutture superficiali, ma anche proprietà elettromagnetiche fino ad alcuni micrometri sotto la superficie del campione, grazie alla profondità di penetrazione delle microonde. Nonostante le interessanti possibilità ed applicazioni della tecnica, l'SMM presenta alcune limitazioni schematizzate di seguito: 1) banda e sensibilità limitata; 2) elevato numero di elementi parassiti; 3) ipersensibilità alla topografia del campione. Come conseguenza, molte proprietà elettromagnetiche del campione (oltre alla topografia) possono essere per la maggior parte invisibili nei dati acquisiti, poichè il contributo della topografia domina e nasconde questi effetti; 4) incompatibilità di utilizzo della tecnica in ambienti liquidi con perdite, come ad esempio all'interno di soluzioni saline. Questo rende l'utilizzo della tecnica estremamente complicata per applicazioni bio-compatibili, poichè il materiale biologico vivo è generalmente preservato all'interno di soluzioni fisiologiche per sopravvivere. Di conseguenza, l'SMM è ampiamente utilizzato nello studio dei materiali semiconduttori o superfici inorganiche, ma presenta molte difficoltà per l'analisi di materiali rugosi e morbidi, come ad esempio cellule biologiche vive. In questo contesto, il presente manoscritto illustra alcune soluzioni tecniche innovative, in particolare: 1) una nuova tecnica per la rimozione in tempo reale di effetti topografici indesiderati nelle immagini SMM. Il metodo ci ha permesso di rivelare proprietà elettromagnetiche dei materiali analizzati che erano inizialmente nascoste nei dati originali per via della ipersensibilità alla topografia del campione; 2) una nuova configurazione di microscopia chiamata microscopio a microonde invertito. Questo strumento presenta una banda migliorata e minor effetti parassiti rispetto a sistemi SMM convenzionali, permette l'analisi quantitativa delle proprietà elettromagnetiche dei campioni, ed è compatibile con l'ambiente fisiologico utilizzato per preservare materiale biologico vivo. In quest'ottica, il presente documento riporta i principali risultati sperimentali delle metodologie e degli strumenti sviluppati, illustra i loro aspetti teorici e descrive il range di applicazioni delle tecniche proposte, includendo una discussione sulle direzioni future della ricerca.The Near-field Scanning Microwave Microscopy (NFSMM or simply SMM) employs the near-field interaction between a probe (source) and a sample to image and characterize materials with atomic resolution. In these systems, the probe excites the sample with microwave frequencies and generates a near-field focused in an extremely small area of the material surface. The microscope measures the local properties of the sample by collecting the response signal originated from this interaction, and the probe dimension mainly determines the resolution, rather than the excitation wavelength. Moreover, the SMM senses not only surface structures, but also electromagnetic properties up to a few micrometres below the sample surface, due to the microwave penetration. Despite the intriguing features and possible applications of the technique, the SMM presents some limitations summarized below: - limited bandwidth and sensitivity; - high number of parasitic components; - hypersensitivity to sample topography; As a consequence, many electromagnetic properties of the sample (beyond the sample topography) can be mostly invisible in SMM data, because the topographic contribution dominates and masks these effects. - incompatibility with the lossy liquid environment, such as inside saline solutions. This makes the application of SMM in bio-compatible environments highly challenging because live biological material is generally stored inside physiological solutions to survive. As a consequence, SMM is mainly limited to studies of semiconductor materials or inorganic surfaces, and it presents many difficulties for the analysis of non-flat and soft samples such as a living biological cell. In this context, the present manuscript illustrates some innovative technical solutions, in particular - a new technique for the real-time removal of unwanted topographic effects in SMM images. This method enabled us to reveal electromagnetic features of the material, that were hidden in the original data due to the hypersensitivity to sample topography; - a new microscope configuration called inverted Scanning Microwave Microscope. This setup has higher bandwidth and reduced parasitic components with respect to existing conventional SMM systems, it enables the local quantitative characterization of sample properties, and it is compatible with the physiological environment used to preserve live biological material. With this in mind, the present dissertation reports the main experimental results of the developed instruments and methodologies, illustrates their theoretical aspects, and discusses the range of applications of the proposed techniques, including the future directions of the research