Outcome of brain metastases from adrenocortical carcinoma: a pooled analysis.

PURPOSE: Brain metastases rarely complicate the natural history of patients with adrenocortical carcinoma (ACC). No information is available regarding the life expectancy and efficacy of treatments in ACC patients with brain involvement. METHODS: A pooled analysis was performed by searching on PubMed and using the keywords: "brain metastases in adrenocortical carcinoma", and "leptomeningeal metastases in adrenocortical carcinoma". Four patients diagnosed at Spedali Civili Hospital in Brescia were added to the analysis. Data concerning demographic, disease characteristics, adopted treatments and patient prognosis were collected. RESULTS: A total of 27 patients (18 adults and 9 children) were included in this study, 22 of them had an adequate follow-up. Brain metastases occurred late in the natural history of adult patients but not in that of children. Surgery plus/minus radiation therapy was the treatment of choice. Adult patients with brain metastases had a poor prognosis with a median progression-free survival (PFS) and overall survival (OS) of 2 and 7 months, respectively. Median PFS and OS were not attained in children. CONCLUSION: Brain metastases in ACC patients are rare and are associated with poor prognosis, particularly in adults. Surgery plus/minus radiotherapy is the only therapeutic approach that can offer patients a chance to obtain durable local disease control.

Cardiovascular and metabolic comorbidities in patients with thyroid nodules: the impact of incidental diagnosis.

PURPOSE: The prevalence of thyroid nodules (TN) in the general population has increased as screening procedures are implemented and an association with metabolic and cardiovascular disorders has been reported. The aim of this study was to investigate the reason leading to the diagnosis of TN and to compare the clinical characteristics of patients diagnosed incidentally with those of patients diagnosed for thyroid-related reasons. METHODS: We designed a retrospective cross-sectional study including consecutive patients with TN from two high-volume hospital-based centers for thyroid diseases (Pavia and Messina) in Italy. Data regarding reason leading to TN diagnosis, age, sex, BMI, presence of cardio-metabolic comorbidities were collected. RESULTS: Among the 623 enrolled subjects, the US diagnosis of TN was prompted by thyroid-related reasons in 421 (67.6%, TD group) and incidental in 202 (32.4%, ID group) with a similar distribution in the two centers (p = 0.960). The ID group patients were more frequently males (38.6% vs 22.1%, p < 0.001) and significantly older (58.9 ± 13.7 vs 50.6 ± 15.5 years, p < 0.001) than the TD group ones, and had a higher rate of cardiovascular comorbidities (73.8% vs 47.5%, p < 0.001), despite having a similar BMI (27.9 ± 5.2 vs 27.8 ± 13.5, p = 0.893). CONCLUSIONS: Stratification of patients with TN according to the diagnostic procedure leading to diagnosis allows a better epidemiological characterization of this inhomogeneous and large population.

Denosumab improves trabecular bone score in relationship with decrease in fracture risk of women exposed to aromatase inhibitors.

PURPOSE: Trabecular bone score (TBS) is a gray-level textural metric that has shown to correlate with risk of fractures in several forms of osteoporosis. The value of TBS in predicting fractures and the effects of bone-active drugs on TBS in aromatase inhibitors (AIs)-induced osteoporosis are still largely unknown. The primary objective of this retrospective study was to assess the effects of denosumab and bisphosphonates (BPs) on TBS and vertebral fractures (VFs) in women exposed to AIs. METHODS: 241 consecutive women (median age 58 years) with early breast cancer undergoing treatment with AIs were evaluated for TBS, bone mineral density (BMD) and morphometric VFs at baseline and after 18-24 months of follow-up. During the study period, 139 women (57.7%) received denosumab 60 mg every 6 months, 53 (22.0%) BPs, whereas 49 women (20.3%) were not treated with bone-active drugs. RESULTS: Denosumab significantly increased TBS values (from 1.270 to 1.323; P < 0.001) accompanied by a significant decrease in risk of VFs (odds ratio 0.282; P = 0.021). During treatment with BPs, TBS did not significantly change (P = 0.849) and incidence of VFs was not significantly different from women untreated with bone-active drugs (P = 0.427). In the whole population, women with incident VFs showed higher decrease in TBS vs. non-fractured women (P = 0.003), without significant differences in changes of BMD at any skeletal site. CONCLUSIONS: TBS variation predicts fracture risk in AIs treated women. Denosumab is effective to induce early increase of TBS and reduction in risk of VFs.

Changes in body composition in early breast cancer patients treated with aromatase inhibitors.

PURPOSE: The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs). METHODS: This is a prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors. RESULTS: A significant increase in fat body mass (mean + 7.2%, 95% confidence interval [CI]: 5.5;8.9%) and a reduction in lean body mass (mean -3.1%, 95% CI -3.9; -2.4) were documented in this population. The changes in fat and lean body mass varied considerably according to different body districts ranging between + 3.2% to + 10.9% and from-1.3% to -3.9%, respectively. CONCLUSION: Aromatase inhibitor adjuvant therapy in early breast cancer is associated with changes in body composition, with a wide variability among different body districts, leading to a risk of sarcopenic obesity. Supervised physical exercise that focuses on single body parts that may display detrimental variations may be beneficial for AIs treated patients.

Phase II study of cabazitaxel as second-third line treatment in patients with metastatic adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. No efficacious treatment options are currently available for patients with advanced metastatic disease with disease progression to standard etoposide, doxorubicin, cisplatin and mitotane (EDP-M) therapy. We assessed the activity and tolerability of cabazitaxel as a second/third-line approach in metastatic ACC. PATIENTS AND METHODS: Patients included in this single-center, phase II study (ClinicalTrials.gov identifier NCT03257891) had disease progression to a cisplatin-containing regimen (such as EDP) plus mitotane, plus/minus a further chemotherapy line. Cabazitaxel was administered intravenously at 25 mg/m2 on day 1 of a 21-day cycle, for a maximum of six cycles. The primary endpoint was a disease control rate after 4 months. RESULTS: From March 2018 to September 2019, 25 eligible patients were enrolled. A disease control rate after 4 months was obtained in six patients (24%). No patients attained a disease response according to RECIST 1.1, 9 patients (36%) had stable disease and 16 patients (64%) progressive disease. Median progression-free survival and overall survival were 1.5 months (range 0.3-7 months) and 6 months (range 1-22.2 months), respectively. Cabazitaxel therapy was well tolerated and only three (12%) patients developed grade 3 toxicity which were nausea in one patient (4%) and anemia in two patients (8%). CONCLUSIONS: Cabazitaxel has a manageable toxicity profile but is poorly active as second/third-line treatment in advanced ACC patients. These results do not support further evaluation of cabazitaxel in this setting.

S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study.

OBJECTIVE: Adrenocortical carcinoma (ACC) has an aggressive but variable clinical course. Prognostic stratification based on the European Network for the Study of Adrenal Tumours stage and Ki67 index is limited. We aimed to demonstrate the prognostic role of a points-based score (S-GRAS) in a large cohort of patients with ACC. DESIGN: This is a multicentre, retrospective study on ACC patients who underwent adrenalectomy. METHODS: The S-GRAS score was calculated as a sum of the following points: tumour stage (1-2 = 0; 3 = 1; 4 = 2), grade (Ki67 index 0-9% = 0; 10-19% = 1; ≥20% = 2 points), resection status (R0 = 0; RX = 1; R1 = 2; R2 = 3), age (<50 years = 0; ≥50 years = 1), symptoms (no = 0; yes = 1), and categorised, generating four groups (0-1, 2-3, 4-5, and 6-9). Endpoints were progression-free survival (PFS) and disease-specific survival (DSS). The discriminative performance of S-GRAS and its components was tested by Harrell's Concordance index (C-index) and Royston-Sauerbrei's R2D statistic. RESULTS: We included 942 ACC patients. The S-GRAS score showed superior prognostic performance for both PFS and DSS, with best discrimination obtained using the individual scores (0-9) (C-index = 0.73, R2D = 0.30, and C-index = 0.79, R2D = 0.45, respectively, all P < 0.01vs each component). The superiority of S-GRAS score remained when comparing patients treated or not with adjuvant mitotane (n = 481 vs 314). In particular, the risk of recurrence was significantly reduced as a result of adjuvant mitotane only in patients with S-GRAS 4-5. CONCLUSION: The prognostic performance of S-GRAS is superior to tumour stage and Ki67 in operated ACC patients, independently from adjuvant mitotane. S-GRAS score provides a new important guide for personalised management of ACC (i.e. radiological surveillance and adjuvant treatment).

STrategically Acquired Gradient Echo (STAGE) imaging, part III: Technical advances and clinical applications of a rapid multi-contrast multi-parametric brain imaging method.

One major thrust in radiology today is image standardization with a focus on rapidly acquired quantitative multi-contrast information. This is critical for multi-center trials, for the collection of big data and for the use of artificial intelligence in evaluating the data. Strategically acquired gradient echo (STAGE) imaging is one such method that can provide 8 qualitative and 7 quantitative pieces of information in 5 min or less at 3 T. STAGE provides qualitative images in the form of proton density weighted images, T1 weighted images, T2* weighted images and simulated double inversion recovery (DIR) images. STAGE also provides quantitative data in the form of proton spin density, T1, T2* and susceptibility maps as well as segmentation of white matter, gray matter and cerebrospinal fluid. STAGE uses vendors' product gradient echo sequences. It can be applied from 0.35 T to 7 T across all manufacturers producing similar results in contrast and quantification of the data. In this paper, we discuss the strengths and weaknesses of STAGE, demonstrate its contrast-to-noise (CNR) behavior relative to a large clinical data set and introduce a few new image contrasts derived from STAGE, including DIR images and a new concept referred to as true susceptibility weighted imaging (tSWI) linked to fluid attenuated inversion recovery (FLAIR) or tSWI-FLAIR for the evaluation of multiple sclerosis lesions. The robustness of STAGE T1 mapping was tested using the NIST/NIH phantom, while the reproducibility was tested by scanning a given individual ten times in one session and the same subject scanned once a week over a 12-week period. Assessment of the CNR for the enhanced T1W image (T1WE) showed a significantly better contrast between gray matter and white matter than conventional T1W images in both patients with Parkinson's disease and healthy controls. We also present some clinical cases using STAGE imaging in patients with stroke, metastasis, multiple sclerosis and a fetus with ventriculomegaly. Overall, STAGE is a comprehensive protocol that provides the clinician with numerous qualitative and quantitative images.

Five-Year Longitudinal Study of Neck Vessel Cross-Sectional Area in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Alterations of neck vessel cross-sectional area in multiple sclerosis have been reported. Our aim was to investigate the evolution of the neck vessel cross-sectional area in patients with MS and healthy controls during 5 years. MATERIALS AND METHODS: Sixty-nine patients with MS (44 relapsing-remitting MS, 25 progressive MS) and 22 age- and sex-matched healthy controls were examined twice, 5 years apart, on a 3T MR imaging scanner using 2D neck MR angiography. Cross-sectional areas were computed for the common carotid/internal carotid arteries, vertebral arteries, and internal jugular veins for all slices between the C3 and C7 cervical levels. Longitudinal cross-sectional area differences at each cervical level and the whole-vessel course were tested within study groups and between patients with MS with and without cardiovascular disease using mixed-model analysis and the related-samples Wilcoxon singed rank test. The Benjamini-Hochberg procedure was performed to correct for multiple comparisons. RESULTS: No significant cross-sectional area differences were seen between patients with MS and healthy controls at baseline or at follow-up. During the follow-up, significant cross-sectional area decrease was found in patients with MS for the common carotid artery-ICAs (C4: P = .048; C7: P = .005; whole vessel: P = .012), for vertebral arteries (C3: P = .028; C4: P = .028; C7: P = .028; whole vessel: P = .012), and for the internal jugular veins (C3: P = .014; C4: P = .008; C5: P = .010; C6: P = .010; C7: P = .008; whole vessel: P = .002). Patients with MS without cardiovascular disease had significantly greater change than patients with MS with cardiovascular disease for internal jugular veins at all levels. CONCLUSIONS: For 5 years, patients with MS showed significant cross-sectional area decrease of all major neck vessels, regardless of the disease course and cardiovascular status.

Assessment of Internal Jugular Vein Size in Healthy Subjects with Magnetic Resonance and Semiautomatic Processing.

Background and Objectives. The hypothesized link between extracranial venous abnormalities and some neurological disorders awoke interest in the investigation of the internal jugular veins (IJVs). However, different IJV cross-sectional area (CSA) values are currently reported in literature. In this study, we introduced a semiautomatic method to measure and normalize the CSA and the degree of circularity (Circ) of IJVs along their whole length. Methods. Thirty-six healthy subjects (31.22 ± 9.29 years) were recruited and the 2D time-of-flight magnetic resonance venography was acquired with a 1.5 T Siemens scanner. The IJV were segmented on an axial slice, the contours were propagated in 3D. Then, IJV CSA and Circ were computed between the first and the seventh cervical levels (C1-C7) and normalized among subjects. Inter- and intrarater repeatability were assessed. Results. IJV CSA and Circ were significantly different among cervical levels (p < 0.001). A trend for side difference was observed for CSA (larger right IJV, p = 0.06), but not for Circ (p = 0.5). Excellent inter- and intrarater repeatability was obtained for all the measures. Conclusion. This study proposed a reliable semiautomatic method able to measure the IJV area and shape along C1-C7, and suitable for defining the normality thresholds for future clinical studies.

Individual Thresholding of Voxel-based Functional Connectivity Maps. Estimation of Random Errors by Means of Surrogate Time Series.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Neural Signals and Images". BACKGROUND: Voxel-based functional connectivity analysis is a common method for resting state fMRI data. However, correlations between the seed and other brain voxels are corrupted by random estimate errors yielding false connections within the functional connectivity map (FCmap). These errors must be taken into account for a correct interpretation of single-subject results. OBJECTIVES: We estimated the statistical range of random errors and propose two methods for an individual setting of correlation threshold for FCmaps. METHODS: We assessed the amount of random errors by means of surrogate time series and described its distribution within the brain. On the basis of these results, the FCmaps of the posterior cingulate cortex (PCC) from 15 healthy subjects were thresholded with two innovative methods: the first one consisted in the computation of a unique (global) threshold value to be applied to all brain voxels, while the second method is to set a different (local) threshold of each voxel of the FCmap. RESULTS: The distribution of random errors within the brain was observed to be homogeneous and, after thresholding with both methods, the default mode network areas were well identifiable. The two methods yielded similar results, however the application of a global threshold to all brain voxels requires a reduced computational load. The inter-subject variability of the global threshold was observed to be very low and not correlated with age. Global threshold values are also almost independent from the number of surrogates used for their computation, so the analyses can be optimized using a reduced number of surrogate time series. CONCLUSIONS: We demonstrated the efficacy of FCmaps thresholding based on random error estimation. This method can be used for a reliable single-subject analysis and could also be applied in clinical setting, to compute individual measures of disease progression or quantitative response to pharmacological or rehabilitation treatments.

In vitro antibacterial activity of some aliphatic aldehydes from Olea europaea L.

In the present paper we report the 'in vitro' activity of eight aliphatic long-chain aldehydes from olive flavor (hexanal, nonanal, (E)-2-hexenal, (E)-2-eptenal, (E)-2-octenal, (E)-2-nonenal, (E)-2-decenal and (E,E)-2,4-decadienal) against a number of standard and freshly isolated bacterial strains that may be causal agents of human intestinal and respiratory tract infections. The saturated aldehydes characterized in the present study do not exhibit significant antibacterial activity, while the alpha,beta-unsaturated aldehydes have a broad antimicrobial spectrum and show similar activity against Gram-positive and Gram-negative microorganisms. The effectiveness of the aldehydes under investigation seems to depend not only on the presence of the alpha,beta-double bond, but also on the chain length from the enal group and on the microorganism tested.

Fertility in thalassemia: the Greek experience.

Pregnancy in beta-thalassemic patients has become a not unusual event, especially in the last 10 years. The course and outcome of 19 pregnancies in 16 thalassemic women, followed in our unit, 12 with thalassemia major and 4 with thalassemia intermedia, were studied. Genetic counselling was provided and counselling regarding the planning or the continuation of the pregnancy was based mainly on cardiac performance at rest. Cardiac, endocrine and liver function were evaluated at baseline, monitored throughout pregnancy and reevaluated after delivery. Desferrioxamine treatment was discontinued as early as possible. During pregnancy the Hb level was maintained at about 10 g/dl in all women by transfusion. The course of pregnancy was essentially uneventful and elective Cesarean section was performed in all cases. The mean birth weight of the newborns was 3000 g. All babies were normal except for one with exomphalus. Pregnancy was well tolerated by the heart in all women and no endocrinological disorders were observed. In conclusion, pregnancies in beta-thalassemia can be safe for both mothers and their babies with careful selection and appropriate care.

[Bronchiolitis. Our clinical experience in the 4 years from 1981 to 1984]. / La bronchiolite. La nostra esperienza clinica nel quadriennio 1981-1984.

The clinical experience of 661 children with bronchiolitis is reported in four-years period to gain a better understanding of diagnosis and pathogenesis of bronchiolitis. Upper airways infections, expiratory dyspnea, clear sound by chest percussion, vesicular rales and whistling by chest auscultation, air trapping on the chest radiography were considered as essential data of diagnosis. It was found in 595 patients: expiratory dyspnea, air trapping, vesicular r. and whistling in 85% and whistling only in 15%; hypoxemia in 20% combined with hypercapnic acidosis in 10%; normoxemia in 80% combined with hypocapnia in 54%; hyperlactemia in 64% combined with an increment in the serum of CPK in 50% and of GPT in 30%; virus were cultured in 27%, adenovirus and RSV were identified in 90%. Instead it was found in 66 patients: air trapping but no difficult breath, with normal chest auscultation; crisis of cyanosis or paleness-cyanosis chilly sweat in 80% were motive of admission. The clinical and/or radiological features of "air trapping" were considered as essential symptoms and signs of bronchiolitis. The insufficient systemic perfusion was considered as a frequent occurrence and as cause for sudden respiratory and circulatory emergency.

[Education for health: the client as the subject of action]. / A educação para a saúde: o cliente como sujeito da ação.

The author make some considerations on the education for health based on the health-illness process view-point, where the significance of education is different in the traditional education and in the historical materalism context.

[Qualitative research: the systematization of the generating topics and group technics]. / A pesquisa qualitativa: sistematização de temas geradores e técnicas de grupo.

This study describes the systematization of generating themes into social representations, followed by group works with interventions that go through the stages of identification, domestication, relearning and performance redefinitions.

[Knowledge of the motives that lead a woman from Vargem Grande Paulista to undergo a Papanicolaou smear--I]. / Conhecimento dos motivos que levaram a mulher de Vargem Grande Paulista a realizar o Papanicolau--parte I.

In this first approach the authors discusses the state of the Program for Integral Assistance por Woman's Health in São Paulo and emphasize the deficit of information on social epidemiology of women's behaviors related to health practices. They focus on the preventive Pap smear and associate the motives that yeld women of Vargem Grande Paulista to have it made. They analyse this knowledge from criterian proposed by KULBOK for posteriory apply it in practice.

[Incentives that aid training in the nursing laboratory: the opinion of professors and students]. / Estímulos que favorecem o treinamento em laboratório de enfermagem: opinião de professores e alunos.

The authors developed a survey on a population of 5 professors and 48 students on the reasons, that can to stimulate or to disfavour the voluntary attendance of the students to practice the psychomotor ability in the nursing laboratory. The results showed positive and negative reasons expected by professors and students to evaluate nursing laboratory training.

[The specific characteristics of the physical exam performed by the nurse]. / Características específicas do exame físico realizado pelo enfermeiro.

The purpose of this work is focused on the physical examinations made by the nurse, identifying four basic assumption originated from the performance of this procedure. It also suggests indicative guidelines of specificity to the nursing physical examinations.

[The general principles of drug administration and nursing actions]. / Princípios gerais de administração de medicamentos e ações de enfermagem.

The authors analyse the responsibility of the nurse during the administration of drugs and solutions. Three aspects are approached: the ethic aspects of professional attitudes, scientific and iatrogenic.