Do patients' and referral centers' characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register.

BACKGROUND: Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. METHODS: This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000-2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing-remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers' characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. RESULTS: In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. DISCUSSION: Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers' characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.

Work-Related Stress Questionnaire: confirmatory factor analysis for construct validation by the PHRASI study.

OBJECTIVE: The purpose of this study is to validate the 13-item version of the Work-Related Stress Questionnaire (WRSQ) on a representative sample of Italian public health residents. MATERIALS AND METHODS: The WRSQ was administered as part of the Public Health Residents' Anonymous Survey in Italy (PHRASI) from 14 June to 26 July 2022. Collinearity between each questionnaire item was assessed with Kendall's τ statistic. The latent factors identified associating similar items based on the authors' observations were workplace, job demand, support and unpleasant workplace. Goodness-of-fit was assessed with confirmatory factor analysis calculating: Comparative Fit Index (CFI), Tucker-Lewis Index (TLI), Root Mean Square Error of Approximation (RMSEA), Standardized Root-Mean-Residual (SRMR). Cronbach's alpha (α) and Omega McDonald (ω) were calculated to evaluate the reliability of the questionnaire. R 4.2.2 was used to perform the analyses. RESULTS: 379 Public Health residents (58% women) responded to the questionnaire. No significant collinearity was found between the items (τ range -0.31 to 0.49). Confirmatory Factor Analysis showed CFI = 0.975, TLI = 0.967, RMSEA = 0.041 and SRMR = 0.051. Internal consistency of the WRSQ Total Score was α = 0.80 and ω = 0.85. CONCLUSIONS: Although validated in a sectorial subpopulation of healthcare workers, the WRSQ proved to be an excellent tool for assessing work-related stress. Unpleasant workplace latent factors showed lower factor loading and internal consistency than others. This could be due to the fact that topics investigated with unpleasant workplace items (e.g., abuse and discrimination) are experienced on a less regular basis than the ones assessed through the other items.

Analytical characterization of laser-generated copper nanoparticles for antibacterial composite food packaging.

A new type of nanomaterial has been developed as antibacterial additive for food packaging applications. This nanocomposite is composed of copper nanoparticles embedded in polylactic acid, combining the antibacterial properties of copper nanoparticles with the biodegradability of the polymer matrix. Metal nanoparticles have been synthesised by means of laser ablation, a rising and easy route to prepare nanostructures without any capping agent in a liquid environment. As prepared, nanoparticle suspensions have been easily mixed to a polymer solution. The resulting hybrid solutions have been deposited by drop casting, thus obtaining self-standing antibacterial packages. All samples have been characterized by UV-Vis spectroscopy, X-ray photoelectron spectroscopy and electro-thermal atomic absorption spectroscopy. Ion release data have been matched with bioactivity tests performed by Japanese Industrial Standard (JIS) method (JIS Z 2801:2000) against Pseudomonas spp., a very common Gram-negative microbial group able to proliferate in processed food.

Study of breast implant rupture: MRI versus surgical findings.

PURPOSE: This study evaluated the role of breast magnetic resonance (MR) imaging in the selective study breast implant integrity. MATERIALS AND METHODS: We retrospectively analysed the signs of breast implant rupture observed at breast MR examinations of 157 implants and determined the sensitivity and specificity of the technique in diagnosing implant rupture by comparing MR data with findings at surgical explantation. RESULTS: The linguine and the salad-oil signs were statistically the most significant signs for diagnosing intracapsular rupture; the presence of siliconomas/seromas outside the capsule and/or in the axillary lymph nodes calls for immediate explantation. CONCLUSIONS: In agreement with previous reports, we found a close correlation between imaging signs and findings at explantation. Breast MR imaging can be considered the gold standard in the study of breast implants.

Vacuum-assisted biopsy diagnosis of atypical ductal hyperplasia and patient management.

PURPOSE: This study sought to evaluate the accuracy of vacuum-assisted biopsy (VAB) in the diagnosis of atypical ductal hyperplasia (ADH) by determining the rate of VAB underestimation compared with definitive histology. In addition, an attempt was made to identify parameters that could help determine the most appropriate patient management. MATERIALS AND METHODS: We retrospectively reviewed 1,776 VAB procedures performed between November 1999 and January 2008 for suspicious subclinical breast lesions visible only at mammography. A total of 177 patients with a VAB diagnosis of pure ADH were studied. Patients with a diagnosis of ADH associated with other lesions (lobular intraepithelial neoplasia, papilloma), atypical lobular hyperplasia, lobular carcinoma in situ and any lesions with a microhistological diagnosis other than ADH were excluded. Mammographic appearance of lesions was as follows: 152 mostly clustered microcalcifications (86%); five opacities with microcalcifications (3%); 12 single opacities (3%); and eight parenchymal distortions (4%), of which five were without and three were with microcalcifications. In cases underestimated by VAB, we evaluated the extent of ADH within ducts and lobules. Based on results, patients were subdivided into two groups: ≤2 ADH foci; >2 ADH foci. Patients were subdivided into two groups: one was referred for surgery and the other for follow-up care. The decision to either perform or not perform surgery was based on combined analysis of the following parameters: patient age; risk factors in the patient's history; mammographic extent of microcalcifications; complete excision of microcalcifications at VAB; and final Breast Imaging Reporting and Data System (BI-RADS) assessment. RESULTS: In the first group (n=98), comparison of microhistology with final histology revealed that 19 cases of ADH had been underestimated by VAB. In the second group (n=79), six cases of ADH showed progression of the mammographic abnormality, which was subsequently confirmed by surgical biopsy. CONCLUSIONS: The most relevant parameters affecting the decision to proceed to surgical excision were lesion diameter >7 mm on mammography, >2 ADH foci, incomplete removal of the calcifications and a family and/or personal history of breast cancer. Although there are no definite mammographic predictors of malignancy, a radiological assessment of suspicious lesion in the presence of an additional equivocal parameter always warrants surgical management.

Breast carcinoma in elderly women. Our experience.

PURPOSE: To analyze the biological features of breast cancer in women aged more than 70 years and to evaluate the utility of complete breast examination in elderly patients. PATIENTS AND METHODS: In the period between January 2000 and March 2009, 147.189 women aged more than 39 years underwent breast examination. In 1.527 diagnosis of breast carcinoma was made. Patients affected by breast carcinoma were subdivided into two groups basing on age (< 70 and ≥ 70 years). The two groups were compared for tumor size on imaging studies, histology, pT stage, grading and the presence of estrogen and progesterone receptors. RESULTS: In comparison with younger women, breast carcinoma in elderly presented as invasive ductal form in most of cases (p 0.004), T1 and T2 stages (p 0.0001), G1 grade (p 0.0001) and positive for the presence of estrogen and progesterone receptors (p <0.0001). CONCLUSIONS: Basing on the incidence rate and the biological features of breast cancer in elderly women without co-morbility, breast cancer prevention in women is considered useful until the age of 74 years.

Femtosecond and picosecond laser drilling of metals at high repetition rates and average powers.

The influence of pulse duration on the laser drilling of metals at repetition rates of up to 1 MHz and average powers of up to 70 W has been experimentally investigated using an ytterbium-doped-fiber chirped-pulse amplification system with pulses from 800 fs to 19 ps. At a few hundred kilohertz particle shielding causes an increase in the number of pulses for breakthrough, depending on the pulse energy and duration. At higher repetition rates, the heat accumulation effect overbalances particle shielding, but significant melt ejection affects the hole quality. Using femtosecond pulses, heat accumulation starts at higher repetition rates, and the ablation efficiency is higher compared with picosecond pulses.

High speed laser drilling of metals using a high repetition rate, high average power ultrafast fiber CPA system.

We present an experimental study on the drilling of metal targets with ultrashort laser pulses at high repetition rates (from 50 kHz up to 975 kHz) and high average powers (up to 68 Watts), using an ytterbium-doped fiber CPA system. The number of pulses to drill through steel and copper sheets with thicknesses up to 1 mm have been measured as a function of the repetition rate and the pulse energy. Two distinctive effects, influencing the drilling efficiency at high repetition rates, have been experimentally found and studied: particle shielding and heat accumulation. While the shielding of subsequent pulses due to the ejected particles leads to a reduced ablation efficiency, this effect is counteracted by heat accumulation. The experimental data are in good qualitative agreement with simulations of the heat accumulation effect and previous studies on the particle emission. However, for materials with a high thermal conductivity as copper, both effects are negligible for the investigated processing parameters. Therefore, the full power of the fiber CPA system can be exploited, which allows to trepan high-quality holes in 0.5mm-thick copper samples with breakthrough times as low as 75 ms.

Towards localization of malignant sites of asymmetry across bilateral mammograms.

BACKGROUND AND OBJECTIVES: The analysis of patterns of asymmetry between the left and right mammograms of a patient can provide meaningful insights into the presence of an underlying tumor in its early stage. However, the identification of breast cancer by investigating bilateral asymmetry is difficult to perform due to the indistinct and borderline nature of the asymmetric signs as they appear on mammograms. METHODS: In this study, to increase the positive-predictive value of asymmetry in mammographic screening, a novel computerized approach for the automatic localization of malignant sites of asymmetry in mammograms is proposed. The sites of anatomical correspondence between the right and left regions of each radiographic projection were extracted by means of two bilateral masking procedures, inspired by radiologists' criteria in interpreting mammograms and based on the use of detected landmarking structures. Relative variations of spatial patterns of intensity values and of orientations of directional components within each site were quantified by combining multidirectional Gabor filters and indices of structural similarity. The localization of the sites of malignant asymmetry was performed by coupling two quadratic discriminant analysis classifiers, one for each masking procedure, that assigned the likelihood of malignancy to each site of correspondence. RESULTS: The performance of the proposed method was assessed on 94 mammographic images from two publicly available databases and containing at least one asymmetric site. Sensitivity, specificity and balanced accuracy levels of 0.83 (0.09), 0.75 (0.06), and 0.79 (0.04), respectively were obtained in the classification of malignant asymmetric sites vs benign/normal sites using cross-validation. In addition, a further blind test on a dataset of Full Field Digital Mammograms achieved levels of sensitivity, specificity, and balanced accuracy of 0.86, 0.65, and 0.75, respectively. CONCLUSIONS: The achieved performance indicates that the proposed system is effective in localizing sites of malignant asymmetry and it is expected to improve computer-aided diagnosis of breast cancer.

Enhanced biostability and cellular uptake of zinc oxide nanocrystals shielded with a phospholipid bilayer.

The widespread use of ZnO nanomaterials for biomedical applications, including therapeutic drug delivery or stimuli-responsive activation, as well as imaging, imposes a careful control over the colloidal stability and long-term behaviour of ZnO in biological media. Moreover, the effect of ZnO nanostructures on living cells, in particular cancer cells, is still under debate. This paper discusses the role of surface chemistry and charge of zinc oxide nanocrystals, of around 15 nm in size, which influence their behaviour in biological fluids and effect on cancer cells. In particular, we address this problem by modifying the surface of pristine ZnO nanocrystals (NCs), rich of hydroxyl groups, with positively charged amino-propyl chains or, more innovatively, by self-assembling a double-lipidic membrane, shielding the ZnO NCs. Our findings show that the prolonged immersion in simulated human plasma and in the cell culture medium leads to highly colloidally dispersed ZnO NCs only when coated by the lipidic bilayer. In contrast, the pristine and amine-functionalized NCs form huge aggregates after already one hour of immersion. Partial dissolution of these two samples into potentially cytotoxic Zn2+ cations takes place, together with the precipitation of phosphate and carbonate salts on the NCs' surface. When exposed to living HeLa cancer cells, higher amounts of lipid-shielded ZnO NCs are internalized with respect to the other samples, thus showing a reduced cytotoxicity, based on the same amount of internalized NCs. These results pave the way for the development of novel theranostic platforms based on ZnO NCs. The new formulation of ZnO shielded with a lipid-bilayer will prevent strong aggregation and premature degradation into toxic by-products, and promote a highly efficient cell uptake for further therapeutic or diagnostic functions.

Contact dermatitis in hospital patients.

Contact dermatitis in hospital patients resulting from diagnostic and therapeutic procedures presents various causes and clinical aspects. Antiseptics are the most frequent cause of contact dermatitis in patients undergoing surgery. Thimerosal may cause allergic sensitization mainly in patients previously exposed to contact with different sources of these mercurials, such as tinctures and preservatives in other products. Iodine-containing solutions and quaternary ammonium compounds rarely sensitize. They may cause irritation under certain circumstances, however. Adhesive tapes formulated on a rubber and colophony base are rarely found nowadays in medical adhesives; however, some tapes and skin closures have still been found to contain them. Acrylate-based adhesives sensitize less frequently. Cardiology patients may present contact dermatitis from several different sources. Electrode gels and pastes may cause allergic contact dermatitis mainly from preservatives. Modern electrocardiographic equipment does not require the use of these products, so many of these problems are now easy to avoid. Adhesive-coated pregelled foam disks for holding long-term chest contacts may cause irritant dermatitis. Transdermal drug delivery systems such as nitroglycerin disks may cause irritation attributable to the acrylic adhesives. Silicone-based adhesive disks are a good alternative in this case. Sensitization to nitroglycerin itself is rare. Dermatitis originated from implantation of pacemakers is attributable either to epoxy resin or to the metal used for the casing of the pacemaker. Changing to a different material solves the problem. In other instances, the etiology remains unclear. Dermatoses in patients with stomas constitute an important problem not only because of their frequency but also because of the multiplicity of pictures involved. Irritant dermatitis from intestinal efflux in ileostomy patients is the most frequent problem. Allergic dermatitis may originate from the ostomy device, cementing materials, or topical medicaments. Individuals receiving hemodialysis have been reported to develop widespread dermatitis, probably secondary to rubber or metal components leached out from the hemodialysis apparatus. Systemic exposure to these compounds, although not certainly proved, seems to be the explanation. Allergic dermatitis at the puncture site on arteriovenous shunts has been demonstrated to be produced by epoxy resin adhesives present in catheters. Identification of the allergen allows one to find a safe alternative for these patients who depend on this procedure to survive. Contact dermatitis in hospital patients requires a precise diagnosis. Extensive patch testing is sometimes needed for establishing the cause, which in turn provides a more accurate prognosis and a rational treatment.

Breast cancer diagnosis under the age of forty years.

The authors report on a multicentric consecutive series of 382 cases of primary breast cancer detected before the age of 40 years. Physical examination (PE) was always performed, whereas other diagnostic tests were performed in selected cases, namely mammography (M) in 334, fine needle aspiration cytology (CYT) in 188 and thermography (TH) in 123 cases. Single tests showed a high rate of false-negative/benign cases (PE, 0.23; M, 0.26; CYT, 0.37 and TH, 0.50), especially when the T1 subgroup was considered (PE, 0.34; M, 0.38; CYT, 0.42 and TH, 0.78). The poor results recorded for TH make its current diagnostic use highly questionable. The policy of extensive biopsy of all "dubious" benign lesions on PE allowed for the detection of 41 of 382 cancers and reduced the PE false-negative/benign rate to 0.12 for the total or 0.15 for T1 cancers, although about 80 unnecessary biopsies for each cancer detected were performed in this way. The association of PE to one or more tests resulted in even lower false-negative rates (0.06 for the total, 0.10 for T1 cancers). The authors criticize the aggressive policy of extensive biopsy recommendation based only on a dubious report on PE alone and stress the opportunity of the routine association of M and CYT to PE, since this combination seems to achieve a higher breast cancer detection rate even in this age group.

Estimation of the breast skin-line in mammograms using multidirectional Gabor filters.

Segmentation of the breast region is a fundamental step in any system for computerized analysis of mammograms. In this work, we propose a novel procedure for the estimation of the breast skin-line based upon multidirectional Gabor filtering. The method includes an adaptive values-of-interest (VOI) transformation, extraction of the skin-air ribbon by Otsu's thresholding method and the Euclidean distance transform, Gabor filtering with 18 real kernels, and a step for suppression of false edge points using the magnitude and phase responses of the filters. On a test set of 361 images from different acquisition modalities (screen-film and full-field digital mammograms), the average Hausdorff and polyline distances obtained were 2.85 mm and 0.84 mm, respectively, with reference to the ground-truth boundaries provided by an expert radiologist. When compared with the results obtained by other state-of-the-art methods on the same set of images and with respect to the same ground-truth boundaries, our method mostly outperformed the other approaches. The results demonstrate the effectiveness and robustness of the proposed algorithm.

Positive predictive value for malignancy on surgical excision of breast lesions of uncertain malignant potential (B3) diagnosed by stereotactic vacuum-assisted needle core biopsy (VANCB): a large multi-institutional study in Italy.

Percutaneous core biopsy (CB) has been introduced to increase the ability of accurately diagnosing breast malignancies without the need of resorting to surgery. Compared to conventional automated 14 gauge needle core biopsy (NCB), vacuum-assisted needle core biopsy (VANCB) allows obtaining larger specimens and has recognized advantages particularly when the radiological pattern is represented by microcalcifications. Regardless of technical improvements, a small percentage of percutaneous CBs performed to detect breast lesions are still classified, according to European and UK guidelines, in the borderline B3 category, including a group of heterogeneous lesions with uncertain malignant potential. We aimed to assess the prevalence and positive predictive values (PPV) on surgical excision (SE) of B3 category (overall and by sub-categories) in a large series of non-palpable breast lesions assessed through VANCB, also comparison with published data on CB. Overall, 26,165 consecutive stereotactic VANCB were identified in 22 Italian centres: 3107 (11.9%) were classified as B3, of which 1644 (54.2%) proceeded to SE to establish a definitive histological diagnosis of breast pathology. Due to a high proportion of microcalcifications as main radiological pattern, the overall PPV was 21.2% (range 10.6%-27.3% for different B3 subtypes), somewhat lower than the average value (24.5%) from published studies (range 9.9%-35.1%). Our study, to date the largest series of B3 with definitive histological assessment on SE, suggests that B3 lesions should be referred for SE even if VANCB is more accurate than NCB in the diagnostic process of non-palpable, sonographically invisible breast lesions.

Occupational acne.

Occupational acne is probably one of the most frequent causes of work-related skin disease, second only to contact dermatitis. This article outlines the different forms of occupational acne: oil acne, coal-tar acne, and chloracne. Oil acne and coal-tar acne, though less common than in the past, still pose some problems in certain industries. Chloracne continues to be the most significant problem.

[Digital stereotactic breast microbiopsy with the mammotome: study of 122 cases]. / Microbiopsia mammaria stereotassica digitale con mammotome. Studio di 122 casi.

PURPOSE: To evaluate the diagnostic value of vacuum-assisted biopsy (VB) with digital stereotactic Mammotome on dubious mammary lesions clinically and sonographically negative as an alternative to surgical biopsy diagnosis. MATERIAL AND METHODS: From November 1999 to November 2000, 122 biopsies were performed using a vacuum suction aspiration device with digital stereotactic-guided Mammotome (Fischer prone table) on 116 patients between the age of 34 and 74 years (median 51 yrs). Sampling was performed with an 11 gauge probe. All patients were previously subjected to mammography in which dubious lesions were evidenced without clinical and sonogram confirmation. All lesions that were obviously benign or malignant were excluded. Mammography demonstrated isolated microcalcifications, small opacities and parenchymal distortions. Microcalcifications were then subdivided into lobular, rad-shaped, granular, mixed and pulverulent, according to Tabar's classification. The median diameter of lesions was 13 mm (range 3-50). The median number of Mammotome biopsy samples was 10.8 (range 3-19). All samples were radiographed and magnified. In 76 patients, the Mammotome biopies were incisional (only a part of the lesion was removed) and in 46 the biopsy was excisional (the entire lesion was removed). The biopsy site was marked with a non-magnetic metallic clip in 83 patients. Slight bleeding was noted during the procedure in two cases. Ultrasound visualization evidenced a hematoma at the biopsy site in one patient which was successfully resolved in one month with local therapy. No noticeable pain or patient intolerance to the procedure was observed. RESULTS: Histological probe sample examination was negative in 91 patients (74.6%) and positive in 31 patients (25.4%). The benign histologies included adenosis and epitheliosis (47 pts), sclerosing adenosis (7 pts), fibroadenoma (7 pts), fibrosis and fibrocystic mastopathy (30 pts). Of the 31 positive patients, 14 were infiltrating carcinomas (45%) and 17 ductal carcinomas in situ (DCIS) (55%). All positive cases underwent surgery. The post-surgical histological examination confirmed all diagnoses of infiltrating carcinoma while the diagnosis of DCIS was confirmed in 15 cases; infiltrating microfoci associated with DCIS were evidenced in two cases. CONCLUSIONS: VB with digital stereotactic Mammotome was shown to be a valid method for dubious mamographic lesions in which cytology often supplies an inadequate or false-negative responses. This method distinguishes between benign and malignant lesions rapidly without discomfort to the patient, thus reducing the number of diagnostic surgical biopsies. Moreover, in positive cases, it offers the advantage of avoiding extemporaneous intraoperative procedures and the possibility to perform biological tests on the tumor before surgery (estrogen and progesterone receptors, HER-2 neu, grading, Ki 67, p53 ), thus providing patient benefits and a distinct reduction of costs. However, this method is purely diagnostic and is not sufficient for therapeutical purposes.