Radial Basis Function for Breast Lesion Detection from MammoWave Clinical Data

Recently, a novel microwave apparatus for breast lesion detection (MammoWave), uniquely able to function in air with 2 antennas rotating in the azimuth plane and operating within the band 1-9 GHz has been developed. Machine learning (ML) has been implemented to understand information from the frequency spectrum collected through MammoWave in response to the stimulus, segregating breasts with and without lesions. The study comprises 61 breasts (from 35 patients), each one with the correspondent output of the radiologist's conclusion (i.e., gold standard) obtained from echography and/or mammography and/or MRI, plus pathology or 1-year clinical follow-up when required. The MammoWave examinations are performed, recording the frequency spectrum, where the magnitudes show substantial discrepancy and reveals dissimilar behaviours when reflected from tissues with/without lesions. Principal component analysis is implemented to extract the unique quantitative response from the frequency response for automated breast lesion identification, engaging the support vector machine (SVM) with a radial basis function kernel. In-vivo feasibility validation (now ended) of MammoWave was approved in 2015 by the Ethical Committee of Umbria, Italy (N. 6845/15/AV/DM of 14 October 2015, N. 10352/17/NCAV of 16 March 2017, N 13203/18/NCAV of 17 April 2018). Here, we used a set of 35 patients. According to the radiologists conclusions, 25 breasts without lesions and 36 breasts with lesions underwent a MammoWave examination. The proposed SVM model achieved the accuracy, sensitivity, and specificity of 91%, 84.40%, and 97.20%. The proposed ML augmented MammoWave can identify breast lesions with high accuracy

Tumori dell’intestino tenue: nostra esperienza in urgenza

I tumori dell’intestino tenue sono neoplasie relativamente rare. Sintomi di natura aspecifica ed esami diagnostici di basse sensibilità e validità sono complessivamente responsabili di una diagnosi ritardata e, in caso di malignità, di malattia spesso avanzata e per lo più incurabile con l’intervento. Uno studio retrospettivo è stato effettuato in 42 casi con presentazione clinica di acuzie, dal 1972 al 2001; l’età media dei pazienti è stata di 52 anni (range 14-79 anni); c’è stata una lieve prevalenza del sesso femminile (57.1% vs 42.9%). La presentazione acuta più comune è stata l’occlusione (57.1%), seguita da sanguinamento gastrointestinale (23.8%), perforazione (14.3%) e occlusione/perforazione (4.8%). I tumori benigni si sono presentati nel 38.1% (16 casi), l’adenoma rappresenta il tipo più comune; le forme maligne sono state il 61.9% (26 casi), l’adenocarcinoma e i linfomi rappresentano l’istotipo più comune. La chirurgia radicale è stata possibile solo nel 57% delle forme maligne (24 pazienti): la morbidità è stata del 4.8% (2 casi: 1 deiscenza anastomotica e 1 ascesso subfrenico); la mortalità è stata del 14.3%. Dal nostro studio retrospettivo possiamo affermare che la sopravvivenza per le lesioni maligne è strettamente dipendente dalla precocità della diagnosi TNM e dalla possibilità di una procedura chirurgica radicale, prima che la lesione diventi non resecabile, come è accaduto nel 42% dei nostri casi. Un indice di sospetto estremamente elevato nella valutazione di sintomi, spesso aspecifici, integrato con studi diagnostici specifici, potrebbe rappresentare l’approccio più appropriato. La prognosi per le forme benigne è invece eccellente in tutti i casi

Effects of the load size on the maximum local SAR at 7T

In this study we investigated the effects of the load size on the maximum local SAR at 7T. Specifically, we resorted to: i) 3D full wave numerical electromagnetic simulations for analyzing a surface loop loaded with anatomic human calves models; ii) 2D analytical approach for analyzing a volume resonator loaded with homogeneous cylindrical phantoms having average tissue dielectric properties. In both cases we noticed that the maximum local SAR decreases with decreasing load size: this holds true if the RF magnetic fields (B1+) for the different load sizes are scaled so to achieve the same slice average value of 1ìT

Breast lesion detection through MammoWave device: microwave images’ parameters

MammoWave is a microwave imaging device for breast lesions detection, which operates using two (azimuthally rotating) antennas without any matching liquid. Images, subsequently obtained by resorting to Huygens Principle, are intensity maps, representing the homogeneity of tissues’ dielectric properties. In the paper: “Breast lesion detection through MammoWave device: empirical detection capability assessment of microwave images’ parameters”, we propose to generate, for each breast, a set of conductivity weighted microwave images by using different values of conductivity in the Huygens Principle imaging algorithm. Next, microwave images’ parameters, i.e. features, are introduced to quantify the non-homogenous behaviour of the image. This data set contains such features. We empirically verify on 103 breasts that a selection of these features may allow distinction between breasts with no radiological finding (NF ) and breasts with radiological findings (WF), i.e. with lesions which may be benign or malign. Statistical significance was set at p <0.05. We obtained single features Area Under the receiver operating characteristic Curves (AUCs) spanning from 0.65 to 0.69. In addition, an empirical rule-of-thumb allowing breast assessment is introduced using a binary score S operating on an appropriate combination of features. Performances of such rule-of-thumb are evaluated empirically, obtaining a sensitivity of 74%, which increases to 84% when considering dense breasts only

Granulocytes-Rich Thrombi in Cerebral Large Vessel Occlusion Are Associated with Increased Stiffness and Poorer Revascularization Outcomes

Acute stroke; Flow cytometry; Mechanical thrombectomyIctus agut; Citometria de flux; Trombectomia mecànicaIctus agudo; Citometría de flujo; Trombectomía mecánicaWe aim to identify a profile of intracranial thrombus resistant to recanalization by mechanical thrombectomy (MT) in acute stroke treatment. The first extracted clot of each MT was analyzed by flow cytometry obtaining the composition of the main leukocyte populations: granulocytes, monocytes, and lymphocytes. Demographics, reperfusion treatment, and grade of recanalization were registered. MT failure (MTF) was defined as final thrombolysis in cerebral infarction score IIa or lower and/or need of permanent intracranial stenting as a rescue therapy. To explore the relationship between stiffness of intracranial clots and cellular composition, unconfined compression tests were performed in other cohorts of cases. Thrombi obtained in 225 patients were analyzed. MTF were observed in 30 cases (13%). MTF was associated with atherosclerosis etiology (33.3% vs. 15.9%; p = 0.021) and higher number of passes (3 vs. 2; p < 0.001). Clot analysis of MTF showed higher percentage of granulocytes [82.46 vs. 68.90% p < 0.001] and lower percentage of monocytes [9.18% vs.17.34%, p < 0.001] in comparison to successful MT cases. The proportion of clot granulocytes (aOR 1.07; 95% CI 1.01–1.14) remained an independent marker of MTF. Among thirty-eight clots mechanically tested, there was a positive correlation between granulocyte proportion and thrombi stiffness (Pearson’s r = 0.35, p = 0.032), with a median clot stiffness of 30.2 (IQR, 18.9–42.7) kPa. Granulocytes-rich thrombi are harder to capture by mechanical thrombectomy due to increased stiffness, so a proportion of intracranial granulocytes might be useful to guide personalized endovascular procedures in acute stroke treatment.Open Access Funding provided by Universitat Autonoma de Barcelona. This work was supported by “Project 355/C/2017, Fundació La Marató de TV3 in Strokes and Traumatic Spinal Cord and Brain Injury, 2017 Call of Projects.

Granulocytes-Rich Thrombi in Cerebral Large Vessel Occlusion Are Associated with Increased Stiffness and Poorer Revascularization Outcomes

Altres ajuts: acords transformatius de la UABWe aim to identify a profile of intracranial thrombus resistant to recanalization by mechanical thrombectomy (MT) in acute stroke treatment. The first extracted clot of each MT was analyzed by flow cytometry obtaining the composition of the main leukocyte populations: granulocytes, monocytes, and lymphocytes. Demographics, reperfusion treatment, and grade of recanalization were registered. MT failure (MTF) was defined as final thrombolysis in cerebral infarction score IIa or lower and/or need of permanent intracranial stenting as a rescue therapy. To explore the relationship between stiffness of intracranial clots and cellular composition, unconfined compression tests were performed in other cohorts of cases. Thrombi obtained in 225 patients were analyzed. MTF were observed in 30 cases (13%). MTF was associated with atherosclerosis etiology (33.3% vs. 15.9%; p = 0.021) and higher number of passes (3 vs. 2; p < 0.001). Clot analysis of MTF showed higher percentage of granulocytes [82.46 vs. 68.90% p < 0.001] and lower percentage of monocytes [9.18% vs.17.34%, p < 0.001] in comparison to successful MT cases. The proportion of clot granulocytes (aOR 1.07; 95% CI 1.01-1.14) remained an independent marker of MTF. Among thirty-eight clots mechanically tested, there was a positive correlation between granulocyte proportion and thrombi stiffness (Pearson's r = 0.35, p = 0.032), with a median clot stiffness of 30.2 (IQR, 18.9-42.7) kPa. Granulocytes-rich thrombi are harder to capture by mechanical thrombectomy due to increased stiffness, so a proportion of intracranial granulocytes might be useful to guide personalized endovascular procedures in acute stroke treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s13311-023-01385-1

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

Assessing the pathogenicity of BRCA1/2 variants of unknown significance: Relevance and challenges for breast cancer precision medicine

IntroductionBreast cancer (BC) is the leading cause of cancer-related death in women worldwide. Pathogenic variants in BRCA1 and BRCA2 genes account for approximately 50% of all hereditary BC, with 60-80% of patients characterized by Triple Negative Breast Cancer (TNBC) at an early stage phenotype. The identification of a pathogenic BRCA1/2 variant has important and expanding roles in risk-reducing surgeries, treatment planning, and familial surveillance. Otherwise, finding unclassified Variants of Unknown Significance (VUS) limits the clinical utility of the molecular test, leading to an “imprecise medicine”.MethodsWe reported the explanatory example of the BRCA1 c.5057A&gt;C, p.(His1686Pro) VUS identified in a patient with TNBC. We integrated data from family history and clinic-pathological evaluations, genetic analyses, and bioinformatics in silico investigations to evaluate the VUS classification.ResultsOur evaluation posed evidences for the pathogenicity significance of the investigated VUS: 1) association of the BRCA1 variant to cancer-affected members of the family; 2) absence of another high-risk mutation; 3) multiple indirect evidences derived from gene and protein structural analysis.DiscussionIn line with the ongoing efforts to uncertain variants classification, we speculated about the relevance of an in-depth assessment of pathogenicity of BRCA1/2 VUS for a personalized management of patients with BC. We underlined that the efficient integration of clinical data with the widest number of supporting molecular evidences should be adopted for the proper management of patients, with the final aim of effectively guide the best prognostic and therapeutic paths