The role of contrast-enhanced mammography in the preoperative evaluation of invasive lobular carcinoma of the breast.

AIM: To assess the performance of contrast-enhanced mammography (CEM) in the preoperative staging of invasive lobular carcinoma (ILC) of the breast. MATERIALS AND METHODS: The present study was a multicentre, multivendor, multinational retrospective study of women with a histological diagnosis of ILC who had undergone CEM from December 2013 to December 2021. Index lesion size and multifocality were recorded for two-dimensional (2D) mammography, CEM, and when available magnetic resonance imaging (MRI). Comparison with histological data was undertaken for women treated by primary surgical excision. Pearson correlation coefficients and Bland-Altman's analysis of agreement were used to assess differences with a significance level of 0.05. RESULTS: One hundred and fifteen ILC lesions were included, 46 (40%) presented symptomatically and 69 were screening detected. CEM demonstrated superior sensitivity when compared to standard mammography. The correlation between the histological size measured on the surgical excision specimen size was greater than with standard mammography (r=0.626 and 0.295 respectively, p=0.001), with 19% of lobular carcinomas not visible without a contrast agent. The sensitivity of CEM for multifocal disease was greater than standard mammography (70% and 20% respectively, p<0.0001). CEM overestimated tumour size by an average of 1.5 times, with the size difference increasing for larger tumour. When MRI was performed (n=22), tumour size was also overestimated by an average of 1.3 times. The degree of size overestimation was similar for both techniques, with the tumour size on CEM being on average 0.5 cm larger than MRI. CONCLUSION: CEM is a useful tool for the local staging of lobular carcinomas and could be an alternative to breast MRI.

Core needle biopsy for the assessment of unilateral male breast lesions.

The importance of preoperative histological diagnosis in the assessment of breast lesions in women is widely established, but in men with breast lesions histological diagnosis is obtained in a limited number of cases. The aim of this study was to report our single-center experience in a large series of 131 CNB performed for suspicious male breast lesions. Our data confirmed that CNB is an effective method in distinguishing between benign and neoplastic lesions in the male breast, thus validating the few published data. CNB should be a routine part of the unilateral male breast swelling diagnostic assessment, being precious tool for the clinicians for surgery planning or avoidance.

Impact of molecular subtypes classification concordance between preoperative core needle biopsy and surgical specimen on early breast cancer management: Single-institution experience and review of published literature.

BACKGROUND: Core needle biopsy (CNB) plays a crucial role as diagnostic tool for breast cancer (BC). The characterization of biomarkers status before surgical treatment is crucial when primary systemic therapy is a therapeutic option. The aim of this analysis was to report concordance between preoperative CNB and surgical specimen (SS) in evaluating biomarkers and molecular subtypes. METHODS: Data have been collected from a cohort of 101 patients affected by early BC treated at Careggi Florence University Hospital, between January 2014 and March 2015. The conformity between molecular subtype classification was tested using kappa (κ) test. RESULTS: Mean age was 57.5 years (range 29-86). There was concordance between the estrogen receptor (ER) assessment on CNB and SS in 95 cases (94.1%). Concordance of the progesterone receptor (PgR) assessment was observed in 89 cases (88.1%). Concordance for detecting immunohistochemistry-assessed BC molecular subtypes was 87.1% (κ = 0.78). Concerning Ki-67 evaluation, we report a concordance rate of 88.1% (κ = 0.68). The evaluation of luminal A plus luminal B/HER negative subgroup showed a κ-value of 0.65. CONCLUSIONS: CNB showed good accuracy in evaluating hormonal receptors status, HER2, and BC molecular subtypes. Evaluation of Ki67 status was less accurate than other biomarkers; therefore, we recommend that it should be detected both on CNB and SS samples, especially in hormonal positive HER2 negative tumors, in order to avoid a misclassification of tumor subtypes that could lead to an omission of potential effective systemic therapy.

Safety and efficacy of a device to narrow the coronary sinus for the treatment of refractory angina: A single-centre real-world experience.

OBJECTIVE: The coronary sinus Reducer is a recently introduced device to treat patients with severe angina symptoms refractory to optimal medical therapy and not amenable for conventional revascularisation. We aimed to assess the safety and efficacy of the Reducer in a real-world cohort of patients with refractory angina. METHODS: This is a single-centre retrospective registry. Patients with severe angina symptoms, objective evidence of myocardial ischaemia using any adequate non-invasive modality and without options for conventional revascularisation were regarded eligible for Reducer implantation. RESULTS: Twenty-three patients (74 % male, mean age 70 ±â€¯8 years, 91.3 % previous bypass surgery, 82.6 % previous percutaneous intervention, 47.8 % previous myocardial infarction, 52.2 % diabetes mellitus) underwent Reducer implantation. The safety endpoint (successful implantation of the first device without device-related adverse events) was met in all patients. After a median follow-up of 9 (8-14) months the efficacy (any reduction in Canadian Cardiovascular Society (CCS) class and revascularisation-free survival) was reached in 17 patients (74 %): 8 patients (34.8 %) improved by 1 CCS class, 7 (30.4 %) by 2 CCS classes and 2 (8.7 %) by 3 CCS classes. One patient died 4 months after implantation because of progressive heart failure (not associated with Reducer implantation). CONCLUSION: In this single-centre real-world experience, Reducer implantation was safe and demonstrated excellent clinical efficacy in the treatment of refractory angina at mid-term follow-up.

Integration of electromagnetic induction sensor data in soil sampling scheme optimization using simulated annealing.

Soil survey is generally time-consuming, labor-intensive, and costly. Optimization of sampling scheme allows one to reduce the number of sampling points without decreasing or even increasing the accuracy of investigated attribute. Maps of bulk soil electrical conductivity (EC a ) recorded with electromagnetic induction (EMI) sensors could be effectively used to direct soil sampling design for assessing spatial variability of soil moisture. A protocol, using a field-scale bulk EC a survey, has been applied in an agricultural field in Apulia region (southeastern Italy). Spatial simulated annealing was used as a method to optimize spatial soil sampling scheme taking into account sampling constraints, field boundaries, and preliminary observations. Three optimization criteria were used. the first criterion (minimization of mean of the shortest distances, MMSD) optimizes the spreading of the point observations over the entire field by minimizing the expectation of the distance between an arbitrarily chosen point and its nearest observation; the second criterion (minimization of weighted mean of the shortest distances, MWMSD) is a weighted version of the MMSD, which uses the digital gradient of the grid EC a data as weighting function; and the third criterion (mean of average ordinary kriging variance, MAOKV) minimizes mean kriging estimation variance of the target variable. The last criterion utilizes the variogram model of soil water content estimated in a previous trial. The procedures, or a combination of them, were tested and compared in a real case. Simulated annealing was implemented by the software MSANOS able to define or redesign any sampling scheme by increasing or decreasing the original sampling locations. The output consists of the computed sampling scheme, the convergence time, and the cooling law, which can be an invaluable support to the process of sampling design. The proposed approach has found the optimal solution in a reasonable computation time. The use of bulk EC a gradient as an exhaustive variable, known at any node of an interpolation grid, has allowed the optimization of the sampling scheme, distinguishing among areas with different priority levels.

The immunohistochemical peptidergic expression of leptin is associated with recurrence of malignancy in laryngeal squamous cell carcinoma.

Leptin is a peptide that plays a key role in the control of satiety, energy expenditure, food intake and various reproductive processes. In the last years, the expression of leptin had been found in malignant cells of various origins. The aim of this study is to evaluate leptin expression in human laryngeal squamous cell carcinoma (SCC) and to investigate its possible role in predicting prognosis. Leptin expression was determined by immunohistochemistry in pathological and healthy tissue specimens from 24 patients with laryngeal SCC. Specimens were stained with an anti-leptin antibody. All measurements were performed using a computer-based image analysis system and scale of staining intensity was determined. All tumoural specimens showed significant immunoreactivity for leptin compared to healthy tissues (p ≤ 0.05), but showed different immunoreactivity that was related to clinicopathological features. High leptin expression was not significantly related with TNM, histological grading (HG) or advanced (III and IV) clinical stage (p > 0.05). Recurrence of malignancy was found to be significantly related with high expression of leptin by Spearman's rank correlation test (r = 0.59; p = 0.002), Fisher's test (p = 0.017) and Kaplan- Meier product-limit estimate (Log-rank test, p ≤ 0.05). In particular, multivariate logistic regression analysis showed that recurrences were significantly related with nodal involvement, HG and leptin expression (p ≤ 0.05). These preliminary results suggest that leptin may be a valuable parameter for predicting prognosis in laryngeal SCC.

Oral antidiabetic therapy in a large Italian sample: drug supply and compliance for different therapeutic regimens.

OBJECTIVES: To define the main features of patients treated with oral antidiabetics, evaluating monotherapy (MT), loose-dose combination therapy (LDCT) and fixed-dose combination therapy (FDCT); to describe medication adherence to the different therapies; and to evaluate the differences in compliance with the prescribed therapy regimen among prevalent and incident patient cohorts. STUDY DESIGN: This study was a retrospective cohort analysis based on the ARNO database, a national record that tracks reimbursable prescription claims submitted from selected pharmacies to the Italian national health system. In total, 169,375 subjects, from an overall population of 4,040,624 were included in this study. The patients represented 12 different local health units. Each patient had at least one oral antidiabetic prescription claim (A10B ATC code). METHODS: Patients were divided into four groups according to their treatment regimen during the recruitment period (1 January 2008-31 December 2008): MT, FDCT, LDCT and switching therapy. A timespan of 5 years was considered, from 4 years before to 1 year after the index date (i.e. date of the prescription selected in the recruitment period). A medication possession ratio (MPR) with a cut-off value of 80% was used to measure medication adherence. Descriptive statistics and multiple logistic regression were used to define the objectives, while P < 0.05 was considered to indicate significance. RESULTS: The median age of patients (n = 169,375, prevalence 4.2%) was 70 years [interquartile range (IQR) 17], and 49.1% were females. Considering the entire sample, the median MPRs for the treatment regimens were: MT, 0.73 (IQR 0.53; 43.9% compliant); FDCT, 1 (IQR 0.29, 68,5% compliant); and LDCT, 0.89 (IQR 0.33, 60.3% compliant). FDCT and LDCT were significantly correlated with MPR. Compliance was 48.9% in the prevalent patient cohort (i.e. patients prescribed oral antidiabetic therapy in both prerecruitment and recruitment periods); median MPRs for the treatment regimens were: MT, 0.73 (IQR 0.52); FDCT, 1 (IQR 0.28); and LDCT, 0.90 (IQR 0.32). Compliance was 43.0% in the incident patient cohort (i.e. patients who were first prescribed oral antidiabetic therapy in the recruitment period); median MPRs for the treatment regimens were: MT, 0.70 (IQR, 0.58); FDCT, 1 (IQR 0.34); and LDCT, 0.64 (IQR 0.39). CONCLUSIONS: Compliance was better for FDCT than the other therapeutic regimens in the study population. The same trend was observed in both the prevalent and incident patient cohorts. As type 2 diabetes is a chronic lifelong pathology, and multiple agents are often required to achieve glycaemic control, the preference for FDCT in the population, when clinically applicable, could be an effective strategy for functional administration of clinical outcome and sources. Evaluation of specific population fractions (age, sex, compliance, etc.) and specific agents or drug combinations could also be relevant in order to reach the healthcare objectives.

The molecular landscape of ASPM mutations in primary microcephaly.

BACKGROUND: Autosomal recessive primary microcephaly (MCPH) is a model disease to study human neurogenesis. In affected individuals the brain grows at a reduced rate during fetal life resulting in a small but structurally normal brain and mental retardation. The condition is genetically heterogeneous with mutations in ASPM being most commonly reported. METHODS AND RESULTS: We have examined this further by studying three cohorts of microcephalic children to extend both the phenotype and the mutation spectrum. Firstly, in 99 consecutively ascertained consanguineous families with a strict diagnosis of MCPH, 41 (41%) were homozygous at the MCPH5 locus and all but two families had mutations. Thus, 39% of consanguineous MCPH families had homozygous ASPM mutations. Secondly, in 27 non-consanguineous, predominantly Caucasian families with a strict diagnosis of MCPH, 11 (40%) had ASPM mutations. Thirdly, in 45 families with a less restricted phenotype including microcephaly and mental retardation, but regardless of other neurological features, only 3 (7%) had an ASPM mutation. This report contains 27 novel mutations and almost doubles the number of MCPH associated ASPM mutations known to 57. All but one of the mutations lead to the use of a premature termination codon, 23 were nonsense mutations, 28 deletions or insertions, 5 splicing, and 1 was a translocation. Seventeen of the 57 mutations were recurrent. There were no definitive missense mutations found nor was there any mutation/phenotype correlation. ASPM mutations were found in all ethnic groups studied. CONCLUSION: This study confirms that mutations in ASPM are the most common cause of MCPH, that ASPM mutations are restricted to individuals with an MCPH phenotype, and that ASPM testing in primary microcephaly is clinically useful.

Miconazole as adjuvant therapy for oral lichen planus: a double-blind randomized controlled trial.

BACKGROUND: Topical steroids are the first choice for the treatment of oral lichen planus (OLP). Antifungal drugs are often employed together with them, to prevent secondary oral candidosis, although it has been suggested anecdotally that they can also be beneficial for OLP itself. OBJECTIVES: To compare the effect of clobetasol propionate with and without a topical antifungal drug (miconazole) on the symptoms and extension of OLP. METHODS: A randomized, parallel, double-blind trial was conducted at the Unit of Oral Medicine and Pathology of the University of Milan. Thirty-five outpatients with histologically proven OLP were randomly assigned to receive either clobetasol propionate and miconazole, or clobetasol propionate and placebo for 6 weeks. Primary outcomes included symptoms and extension of lesions; adverse effects were also recorded. RESULTS: All the patients who concluded the study (30 of 35) showed clinical and subjective improvement within 3 weeks. The addition of miconazole did not affect in a significant way the signs and symptoms of OLP. No cases of clinical candidosis were seen in the patients taking miconazole, while one-third (five of 15) of the placebo group were affected. CONCLUSIONS: Although effective in preventing iatrogenic candidosis, the addition of miconazole to topical steroid treatment does not improve the efficacy of the therapy.

1.5 Mb de novo 22q11.21 microduplication in a patient with cognitive deficits and dysmorphic facial features.

The 22q11.2 microduplication syndrome is caused by non-allelic homologous recombination mediated by misalignments of low copy repeats located in the region deleted in the DiGeorge syndrome (DGS)/velocardiofacial syndrome (VCFS). The variable phenotype of such condition, consisting in a combination of dysmorphic facial features, cognitive deficits, velopharyngeal insufficiency, congenital heart defects and immunologic derangement, is caused usually in 90% of cases by a 3 Mb deletion or in a minority of cases (7%) by a 1.5 Mb deletion. The most common reciprocal event of deletion is the 3 Mb duplication, reported more recently with a variable phenotype, ranging from multiple defects to normality. In this study, we report a 2.5-year-old girl with cognitive deficits and dysmorphic facial features such as superior placement of eyebrows, upslanting palpebral fissures, widely spaced eyes, broad nasal bridge and epicanthal folds. Fluorescent in situ hybridization for DGS/VCFS region on metaphase chromosomes did not show any apparent anomaly. Subsequent array comparative genomic hybridization study, confirmed by multiplex ligation-dependent probe assay and microsatellite analysis, disclosed a 1.5 Mb de novo 22q11.21 duplication concerning the same chromosomal region deleted in a minority of patients with DGS. These findings identify the minimal duplicated region leading to this emerging syndrome.

Protection of corneal endothelium from irrigation damage: a comparison of sodium hyaluronate and hydroxypropylmethylcellulose.

PURPOSE: To compare the endothelial protection of sodium hyaluronate and hydroxypropylmethylcellulose against endothelial damage induced by irrigation. METHODS: An in vitro assay with freshly excised porcine eyes was developed using the Janus green photometry technique. Irrigation and aspiration technique was standardised. Forty pairs of porcine eyes were used. One randomly chosen eye was filled with sodium hyaluronate (SH) and the other with hydroxypropylmethylcellulose (HPMC). Irrigation and aspiration was carried out with balanced salt solution for 5 min. Twenty additional pairs of porcine eyes served as controls. Student's t-test was used for statistical analysis. RESULTS: Both viscoelastic agents protected the endothelium as compared with controls. The endothelial protection, determined with the Janus green photometric technique, was significantly greater with HPMC than with SH. CONCLUSIONS: Viscoelastic agents are effective in protecting the endothelium from irrigation damage in porcine eyes in vitro. HPMC provided greater protection than SH in this particular model.

Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids.

To demonstrate the influence of n-3 PUFA supplementation on cytokine and eicosanoid production in peripheral blood mononuclear cells (PBMCs) of MS patients (MSP), we investigated the impact of a 6-month dietary supplementation with these fatty acids on the levels of interleukin-1 beta (IL-1 beta), IL-2, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the supernatants of stimulated PBMCs and serum soluble IL-2 receptors in a group of 20 relapsing-remitting (R-R) MSP and a group of 15 age-matched control individuals (CI). The production of PGE2 and LTB4 in the stimulated PBMCs was also assessed in patient and control groups supplemented with n-3 PUFAs. In both groups, n-3 PUFA supplementation led to a significant decrease in the levels of IL-1 beta and TNF-alpha, and this reduction was more pronounced in the 3rd and 6th month of supplementation. An analogous decrease was observed in the levels of IL-2 and IFN-gamma produced by stimulated PBMCs, and in the levels of serum soluble IL-2 receptors. n-3 PUFA supplementation also appeared to significantly affect prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production in PBMCs, both in MSP and the control group. The reduced production of these proinflammatory eicosanoids, and the decrease of some cytokines with an immunohenancing effect as a consequence of n-3 PUFA supplementation, could modulate some immune functions which have been demonstrated to be altered in MSP.

Physical properties of model viscoelastic materials.

Previous observations on polysaccharides used as viscoelastic agents in ophthalmic surgery suggest that the pseudoplasticity of solutions of hyaluronan (HA) and the low surface tension of hydroxypropylmethylcellulose (HPMC) solutions are physical properties that make these solutions useful clinically. Our laboratories are interested in correlating the physical properties of macromolecular solutions with the ability of these molecules to protect ocular structures during eye surgery. The purpose of this study is to compare the physical properties of model viscoelastics with the properties of HA and HPMC. The results of these studies suggest that polysaccharides that form extended structures in solution at low shear rates and that are characterized by large decreases in the axial ratio at high shear rates, exhibit pseudoplastic behavior. In this study pseudoplasticity is exhibited by polysaccharides with molecular weights in excess of 450 000, and is insensitive to the backbone chemistry for linear macromolecules. In addition, low surface tension is associated with charged macromolecules that have a high positive second virial coefficient.

Use of viscoelastic solutions in ophthalmology: a review of physical properties and long-term effects.

Solutions of flexible macromolecules are used in ophthalmic surgery for insertion of intraocular lens, during corneal transplantation, in cataract, corneal, glaucoma, trauma, and vitreo-retinal surgery. Polymeric materials used in formulating these solutions include hyaluronic acid, chondroitin sulfate, polyacrylamide, collagen, and mixtures of some of these materials. Although the physical properties of these materials have been studied extensively, the long-term effects resulting from transitory increases in intraocular pressure and loss of even a small number of corneal endothelial cells are still unknown. The purpose of this paper is to review the literature that is available on these topics.

In vivo observation of tear dynamics using fluorophotometry.

Fluorophotometry was used to evaluate the effect of the blinking process on tear spreading. In normal individuals, when the intensity of fluorescence was monitored over the central 1 mm of the cornea, forceful blinking was found to substantially increase tear film thickness. Weak blinking was found to decrease tear film thickness. When tear film fluorescence was monitored along different regions of the corneal vertical meridian, the tear film thickened superiorly while thinning inferiorly. It is postulated that the vertical spreading of meibomian oils is accompanied by the movement of a portion of the aqueous tear phase that thickens the superior tear film at the expense of thinning inferiorly.

Schirmer's test. A closer look.

In 50 normal subjects, results of kinetics studies of Schirmer's test demonstrated nonlinear wetting with an initial rapid phase of wetting followed by a progressive reduction in rate. This initial rapid phase of wetting indicated a reflex secretion of tears. In the majority of subjects, topical anesthesia with 0.5% proparacaine hydrochloride dampened the initial reflex secretion but could not completely suppress it. The data indicated that Schirmer's test with anesthesia was not capable of measuring a basic tear secretion independent of reflex components.

The dynamic film thickness of cushioning agents on contact lens materials.

Using an in vitro technique, a number of commercial as well as pure polymer solutions were evaluated for their ability to form thick aqueous layers on contact lens materials. It was demonstrated that the thickness of adhered pure polymer films was strictly viscosity dependent and did not depend upon the solution's wetting properties (ie, contact angle and surface tension) nor the surface upon which the solution was deposited (eg, glass, a hydrophilic surface versus Plexiglass, a relatively hydrophobic surface). The clinical implications of this study are that the desired solution properties of tear substitutes may be quite different from those of wetting and "cushioning" solutions.