Publications by authors named "Vittorio Ferrari"

65 Publications

Analysis of the Timing of Puberty in a Recent Cohort of Italian Girls: Evidence for Earlier Onset Compared to Previous Studies.

J Pediatr Adolesc Gynecol 2021 Jun 21. Epub 2021 Jun 21.

Department of Health Sciences, University of Florence, Anna Meyer Children's University Hospital, Florence, Italy.

Background: Throughout the 20 century, in developed countries there has been a secular trend toward earlier menarche. Over the past 2 decades, however, there has been an apparent stabilization in the average age of menarche age in most Western countries.

Objectives: The objective of this study was to analyze the mean age of menarche in a cohort of Italian girls, to analyze the mean age of breast button appearance (B2), and to correlate the B2 developmental stage and age at menarche with the most important clinical and auxological parameters.

Materials And Methods: We retrospectively evaluated the data of 1458 Italian girls born between 1995 and 2003. We collected the main auxological and clinical parameters, including age at B2, age at menarche, height, weight, and body mass index (BMI) at B2 and menarche and, when possible, adult/near adult height.

Results: The mean age of B2 was 10.16 ± 1.00 years, significantly earlier than previously reported for Italian girls (P < .05); the mean age of menarche was 12.07 ± 0.99 years, also significantly earlier than previously reported (P < .0001). Age at B2 and menarche inversely correlated with BMI standard deviation score (SDS) (P < .0001). The mean adult/near adult height of the girls in the study cohort was not statistically different from previously reported data for Italian women.

Conclusions: Our results suggest a new trend for an earlier appearance of thelarche and menarche in Italian girls. Our data confirm a significant relationship between BMI and age of B2 and menarche. The girls' final height seems to be in line with average height for the Italian female population.
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http://dx.doi.org/10.1016/j.jpag.2021.06.007DOI Listing
June 2021

High-Pressure Synthesis and Gas-Sensing Tests of 1-D Polymer/Aluminophosphate Nanocomposites.

ACS Appl Mater Interfaces 2021 Jun 3;13(23):27237-27244. Epub 2021 Jun 3.

ICGM, CNRS, Université de Montpellier, ENSCM, Montpellier 34095, France.

Recently, filling zeolites with gaseous hydrocarbons at high pressures in diamond anvil cells has been carried out to synthesize novel polymer-guest/zeolite-host nanocomposites with potential, intriguing applications, although the small amount of materials, 10 cm, severely limited true technological exploitation. Here, liquid phenylacetylene, a much more practical reactant, was polymerized in the 12 Å channels of the aluminophosphate Virginia Polytechnic Institute-Five (VFI) at about 0.8 GPa and 140 °C, with large volumes in the order of 0.6 cm. The resulting polymer/VFI composite was investigated by synchrotron X-ray diffraction and optical and H, C, and Al nuclear magnetic resonance spectroscopy. The materials, consisting of disordered π-conjugated polyphenylacetylene chains in the pores of VFI, were deposited on quartz crystal microbalances and tested as gas sensors. We obtained promising sensing performances to water and butanol vapors, attributed to the finely tuned nanostructure of the composites. High-pressure synthesis is used here to obtain an otherwise unattainable true technological material.
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http://dx.doi.org/10.1021/acsami.1c00625DOI Listing
June 2021

Case Report: Exceptional Response to Second Line Temozolomide Therapy in a Patient With Metastatic Adrenocortical Carcinoma.

Front Endocrinol (Lausanne) 2021 22;12:674039. Epub 2021 Apr 22.

Medical Oncology Unit, Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.

Background: In a recently published retrospective case series, Temozolomide was found active as second line approach in advanced ACC patients. The disease control rate obtained, however, was short-lived. We report here an ACC patient with extensive metastatic disease who obtained a remarkable long lasting response with this alkylating agent.

Case Presentation: a 22-year-old female patient with ACC presented at our Medical Oncology Department in poor general condition due the presence of extensive metastatic pulmonary involvement. The disease had progressed to etoposide, doxorubicin and cisplatin plus mitotane therapy. Second line temozolomide therapy was prescribed leading to a progressive improvement of patient general conditions. The disease restaging after 12 cycles revealed a complete response of lung lesions and the patient was free from progression for 14+ months.

Conclusion: Temozolomide therapy could be exceptionally efficacious in the management of ACC patients. The molecular mechanisms of sensitivity and resistance to this drug should be carefully studied, in order to select the patients destined to obtain a significant clinical benefit to the drug.
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http://dx.doi.org/10.3389/fendo.2021.674039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101262PMC
April 2021

Trabectedin for Patients with Advanced Soft Tissue Sarcoma: A Non-Interventional, Retrospective, Multicenter Study of the Italian Sarcoma Group.

Cancers (Basel) 2021 Mar 2;13(5). Epub 2021 Mar 2.

Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, 1 Via Pupilli, 40136 Bologna, Italy.

The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft tissue sarcoma, pretreated with ≥1 anthracycline-based treatment, and treated with trabectedin every three weeks. Primary endpoint was to describe real-life use of trabectedin across Italy. Secondary endpoints included objective response rate (ORR) and safety. Overall, 512 patients from 20 Italian centers were evaluated. Leiomyosarcoma (37.7%)/liposarcoma (30.3%) were the most prevalent histological types (abbreviated as L-sarcoma). Patients received a median of four trabectedin cycles (range: 1-40), mostly as a second-line treatment (~60% of patients). The ORR was 13.7% superior ( < 0.0001) in patients with L-sarcoma compared with patients with non-L-sarcoma (16.6% vs. 9.0%). Median progression-free survival (PFS) was 5.1 months, whereas median overall survival (OS) was 21.6 months. Significantly better PFS and OS were observed in patients with L-sarcoma, those with objective responses and/or disease stabilization, treated in an early line and treated with reduced dose. Bone marrow toxicity (61.4%) and transaminase increases (21.9%) were the most common grade 3/4 adverse events. The results of this real-life study suggest that trabectedin is an active treatment, which is mostly given as a second-line treatment to patients with a good performance status and high-grade, metastatic L-sarcoma (clinical trial information: NCT02793050).
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http://dx.doi.org/10.3390/cancers13051053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958606PMC
March 2021

Clinical Prognostic Factors in Patients With Metastatic Adrenocortical Carcinoma Treated With Second Line Gemcitabine Plus Capecitabine Chemotherapy.

Front Endocrinol (Lausanne) 2021 24;12:624102. Epub 2021 Feb 24.

Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia at ASST Spedali Civili, Brescia, Italy.

Gemcitabine plus Capecitabine (Gem/Cape) is a frequently adopted second line chemotherapy for metastatic adrenocortical carcinoma (ACC), but only a minority of patients is destined to obtain a clinical benefit. The identification of baseline predictive factors of efficacy is relevant. We retrospectively analyzed clinical data from 50 consecutive patients with metastatic progressing ACC treated between 2011 and 2019. Patients received intravenous Gemcitabine and oral Capecitabine on a metronomic schedule. Previous mitotane therapy was maintained. Clinical benefit (partial response + stable disease) at 4 months was 30%, median progression-free survival (PFS) and disease-specific survival (DSS) from Gem/Cape start were 3 and 8 months, respectively. Among clinical variables evaluated before the start of Gem/Cape, presence of ECOG performance status ≥1 [HR 6.93 95% confidence interval (CI) 0.03-0.54, p.004] and neutrophil-to-lymphocyte ratio (NLR) ≥5 [HR 3.88, 95% (CI) 0.81-0.90, p.003] were independent indicators of poor PFS at multivariate analysis. Conversely, surgery of primary tumor, the presence of lung or lymph-node metastases, blood mitotane level, anemia, and the Advanced Lung cancer Inflammation index (ALI) failed to be independently associated. This study confirms that the Gem/Cape schedule is modestly active in heavily pretreated ACC patients (28% received at least two previous chemotherapy lines). NLR and performance status (PS) are easily available clinical parameters that are helpful to identify patients not likely to derive significant advantage from Gem/Cape chemotherapy.
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http://dx.doi.org/10.3389/fendo.2021.624102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943871PMC
February 2021

Maintenance everolimus beyond progression in pancreatic NET to control insulinoma syndrome.

Endocrine 2021 01 13;71(1):258. Epub 2021 Jan 13.

Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Medical Oncology, University of Brescia at ASST Spedali Civili, Brescia, Italy.

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http://dx.doi.org/10.1007/s12020-020-02604-xDOI Listing
January 2021

Frequency and outcome of SARS-CoV-2 infection in patients with adrenocortical carcinoma followed at a reference center in Italy.

Endocrine 2021 04 5;72(1):20-23. Epub 2021 Jan 5.

Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia. ASST Spedali Civili, Brescia, Italy.

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http://dx.doi.org/10.1007/s12020-020-02569-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782048PMC
April 2021

Bronchoesophageal Fistula.

N Engl J Med 2020 Dec;383(25):e137

ASST Spedali Civili di Brescia, Brescia, Italy

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http://dx.doi.org/10.1056/NEJMicm2018535DOI Listing
December 2020

Is androgen deprivation therapy protective against SARS-CoV-2 infection and related complications in prostate cancer patients?

Minerva Urol Nefrol 2020 12 5;72(6):778-779. Epub 2020 Oct 5.

Unit of Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, ASST Spedali Civili of Brescia, University of Brescia, Brescia, Italy.

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http://dx.doi.org/10.23736/S0393-2249.20.04021-7DOI Listing
December 2020

The Spread of SARS-CoV-2 Infection Among the Medical Oncology Staff of ASST Spedali Civili of Brescia: Efficacy of Preventive Measures.

Front Oncol 2020 18;10:1574. Epub 2020 Aug 18.

Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia at ASST Spedali Civili, Brescia, Italy.

Patients with cancer are at a higher risk of developing serious disease-related complications in case of contracting SARS-CoV-2. Oncology units should implement all possible preventive measures to reduce the risk of viral transmission by healthcare professionals (HCPs) to patients. We conducted a surveillance for SARS-CoV-2 infection among the staff members of the Medical Oncology Unit of ASST Spedali Civili in Brescia, one of the Italian areas most affected by the SARS-CoV-2 pandemic. The aim of this study was to demonstrate whether the recommended preventive measures, promptly implemented by the unit, have been effective in reducing the spread of the virus among the HCPs. Between February 24 and May 19, 2020, SARS-CoV-2 infection was detected in 10 out of 76 healthy HCPs (13%). Six of them developed a symptomatic disease, leading to home quarantine, and four remained asymptomatic. The infection was revealed when a serology test was performed on all staff members of the unit. In seven HCPs, in which it was possible to trace the person-to-person infection, the contagion occurred as a result of unprotected contacts or partially protected with surgical masks. In particular, four asymptomatic HCPs did not stop working, but a widespread outbreak in the unit was avoided. Adherence to the recommended preventive strategies, in particular, wearing of surgical masks by both the HCPs and the patients, is effective in reducing and preventing the viral spread.
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http://dx.doi.org/10.3389/fonc.2020.01574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462005PMC
August 2020

Technique and Circuit for Contactless Readout of Piezoelectric MEMS Resonator Sensors.

Sensors (Basel) 2020 Jun 19;20(12). Epub 2020 Jun 19.

Department of Information Engineering, University of Brescia, via Branze 38, I25123 Brescia, Italy.

A technique and electronic circuit for contactless electromagnetic interrogation of piezoelectric micro-electromechanical system (MEMS) resonator sensors are proposed. The adopted resonator is an aluminum-nitride (AlN) thin-film piezoelectric-on-silicon (TPoS) disk vibrating in radial contour mode at about 6.3 MHz. The MEMS resonator is operated in one-port configuration and it is connected to a spiral coil, forming the sensor unit. A proximate electronic interrogation unit is electromagnetically coupled through a readout coil to the sensor unit. The proposed technique exploits interleaved excitation and detection phases of the MEMS resonator. A tailored electronic circuit manages the periodic switching between the excitation phase, where it generates the excitation signal driving the readout coil, and the detection phase, where it senses the transient decaying response of the resonator by measuring through a high-impedance amplifier the voltage induced back across the readout coil. This approach advantageously ensures that the readout frequency of the MEMS resonator is first order independent of the interrogation distance between the readout and sensor coils. The reported experimental results show successful contactless readout of the MEMS resonator independently from the interrogation distance over a range of 12 mm, and the application as a resonant sensor for ambient temperature and as a resonant acoustic-load sensor to detect and track the deposition and evaporation processes of water microdroplets on the MEMS resonator surface.
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http://dx.doi.org/10.3390/s20123483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349374PMC
June 2020

Should everolimus be stopped after radiological progression in metastatic insulinoma? A "cons" point of view.

Endocrine 2020 09 2;69(3):481-484. Epub 2020 Jun 2.

Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Medical Oncology, University of Brescia at ASST Spedali Civili, Brescia, Italy.

Insulinoma is a rare pancreatic neuroendocrine tumor (pNET) potentially associated with severe hypoglycaemic crisis. The great majority of these tumors are benign. In patients with metastatic malignant insulinoma, systemic therapies aim to control both the syndrome and tumor growth. Everolimus is a drug approved for the management of advanced pNETs that can achieve both these goals. According to international guidelines and regulatory authorities, everolimus in patients with pNET should be continued until the demonstration of disease progression with standard radiologic imaging techniques. The drug is neither recommended nor authorized beyond progression. This could not be the case of advanced insulinoma patients since the antineoplastic and the glycaemic effects of everolimus seem to follow independent mechanisms. The authors present here their point of view in favor of continuing everolimus beyond progression in symptomatic insulinoma patients on the basis of a robust rationale and describing a case.
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http://dx.doi.org/10.1007/s12020-020-02368-4DOI Listing
September 2020

Use of a natural multicomponent mouthwash plus oral hygiene vs oral hygiene alone to prevent everolimus-induced stomatitis: the STOP multicenter, randomized trial.

Tumori 2020 May 3:300891620915786. Epub 2020 May 3.

Genitourinary Unit, IRCCS National Cancer Institute, Milan, Italy.

Background: Stomatitis is highly prevalent in patients with cancer treated with the mammalian target of rapamycin inhibitor everolimus; it usually has an early onset and may compromise treatment dose intensity and patients' quality of life. Within the randomized controlled Stomatitis Prevention trial (STOP, ISRCTN14568888), we investigated the possibility of using a commercial natural multicomponent mouthwash (Orasol Plus) to prevent the development of stomatitis of any grade in patients with advanced renal cell carcinoma (RCC) treated with everolimus.

Methods: Overall, 62 patients were randomized to receive either Orasol Plus in addition to oral hygiene or oral hygiene alone (31 patients per treatment arm).

Results: In the whole study population, 28 episodes of stomatitis were observed (41.9%); in only 2 patients, stomatitis occurred more than once (2 episodes). As expected, the episodes of stomatitis occurred early in the course of treatment with everolimus. Treatment with Orasol Plus prevented the onset of everolimus-induced stomatitis: only 8 episodes of stomatitis were observed in the treated group with Orasol Plus in addition to oral hygiene vs 20 episodes in the group treated with oral hygiene only ( = 0021). Also, a reduction in the average duration of mucositis in patients treated with Orasol Plus compared to patients treated with oral hygiene only was observed (8 days vs 11.2 days, = 0.0416).

Conclusion: This study showed that the use of a natural multicomponent mouthwash coupled with regular oral hygiene was able to reduce the severity and duration of everolimus-induced stomatitis in patients with RCC.

Trial Registration Number: ISRCTN14568888.
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http://dx.doi.org/10.1177/0300891620915786DOI Listing
May 2020

Hyperthermic Intraperitoneal Chemotherapy for Primary or Recurrent Adrenocortical Carcinoma. A Single Center Study.

Cancers (Basel) 2020 Apr 14;12(4). Epub 2020 Apr 14.

Surgical Clinic, Department of Clinical and Experimental Sciences, University of Brescia at ASST Spedali Civili di Brescia, 25123 Brescia, Italy.

Background: This study explores the impact of Hypertermic Intra PEritoneal Chemotherapy (HIPEC) on adrenocortical carcinoma (ACC) management through a safety analysis completed by a preliminary evaluation of survival performances.

Methods: Retrospective chart review of 27 patients submitted to surgical treatment completed by HIPEC for primary (SP, 13 patients) or recurrent (SR, 14 patients, 17 treatments) ACC. Safety was evaluated by means of procedural morbidity and mortality. Survival performances included multiple end points: local/peritoneal disease-free survival (l/pDFS), overall progression-free survival (OPFS), and overall survival (OS).

Results: In the SP group, mortality was nil and morbidity was 46% (major 23%). At a median follow-up of 25 months, the median value for all the different survival measures had not been reached. Mortality was also nil in the SR group. However, morbidity was 77% (major 18%). Median l/pDFS and OPFS were 12 ± 4 and 8 ± 2 months, respectively. At a median follow-up of 30 months, median OS had not been reached.

Conclusion: Surgery and HIPEC is an invasive procedure. Its employment in the surgery for primary setting deserves attention as it may affect oncologic outcomes positively. Its value in the management of recurrences seems less appreciable, albeit it may find its place in the multimodal management of a rare disease for which multiple therapeutic options do not yet exist.
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http://dx.doi.org/10.3390/cancers12040969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226100PMC
April 2020

Efficacy of the EDP-M Scheme Plus Adjunctive Surgery in the Management of Patients with Advanced Adrenocortical Carcinoma: The Brescia Experience.

Cancers (Basel) 2020 Apr 10;12(4). Epub 2020 Apr 10.

Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia at ASST Spedali Civili, 25123 Brescia, Italy.

Etoposide, doxorubicin and cisplatin plus oral mitotane (EDP-M) comprise the reference regimen in the management of patients with adrenocortical carcinoma (ACC). In this paper, we described the outcome of 58 patients with advanced/metastatic ACC consecutively treated with EDP-M in a reference center for this rare disease in Italy. In this series, EDP-M obtained a partial response in 50% of patients; median progression free survival (PFS) and overall survival were 10.1 months (95% Confidence Interval [CI 95%] 8.1-12.8) and 18.7 months (95% CI: 14.6-22.8), respectively. EDP-M was not interrupted in five patients showing disease progression after two cycles without the appearance of new lesions and mitotane levels below the therapeutic range. In two of them, the disease remained stable at further imaging evaluations and the other three obtained a partial response. Twenty-six responding patients underwent surgery of residual disease and 13 of them became disease free. Surgery identified a pathological complete response (pCR) in four patients (7%) and Ki67 expression in post-chemotherapy tumor specimens, inferior to 15% (median value), was associated with better PFS and survival. In the present study, the EDP-M regimen is confirmed to have a limited efficacy. Early disease progression does not mean treatment inefficacy. Surgery of residual disease in partially responding patients allows for the detection of pCR in few of them and this condition is predictive of long-term survival. Ki67 expression of post-chemotherapy residual disease could be an additional prognostic factor that deserves to be studied further.
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http://dx.doi.org/10.3390/cancers12040941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226395PMC
April 2020

Activity and safety of temozolomide in advanced adrenocortical carcinoma patients.

Eur J Endocrinol 2019 Dec;181(6):681-689

Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili, Brescia, Italy.

Objective: Temozolomide has shown a significant anti-proliferative activity on adrenocortical cancer (ACC) cells in vitro.

Design: On the basis of these results the drug was prescribed as second/third line in advanced metastatic ACC patients in four referral centers in Italy.

Methods: We retrospectively collected anagraphic, clinical and pathological data of patients with advanced ACC with disease progression to standard chemotherapy plus mitotane who were treated with temozolomide at the dose of 200 mg/m2/die given for 5 consecutive days every 28 days. The primary endpoint was the disease control rate, defined as objective response or disease stabilization after 3 months. Secondary endpoints were overall survival (OS), progression-free survival (PFS) and drug safety.

Results: Twenty-eight patients have been included in the study. Ten patients (35.8%, 95% CI: 17.8-53.8) obtained a disease control from temozolomide treatment. In particular, 1 patient had a complete response, 5 patients a partial response and 4 patients stable disease. Median PFS was 3.5 months and median OS was 7.2 months. Disease response was more frequently observed in patients with methylation of O6-methylguanine-DNA methyltransferase (MGMT) gene. Temozolomide therapy was well tolerated and most toxicities were limited to grade G1-2 according to WHO criteria.

Conclusion: Temozolomide was found active in the management of advanced ACC patients. The disease control rate obtained, however, was short-lived and the prognosis of treated patients was poor.
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http://dx.doi.org/10.1530/EJE-19-0570DOI Listing
December 2019

Middle Phalangectomy for the Correction of Toe Clinodactyly With Longitudinal Epiphyseal Bracket in Young Children.

J Foot Ankle Surg 2019 Sep;58(5):1002-1005

Professor, Department of Pediatric Orthopaedic Surgery, Amiens University Hospital and Jules Verne University of Picardy, Amiens, France. Electronic address:

Toe clinodactyly is often owed to the presence of a longitudinal epiphyseal bracket. We developed middle phalangectomy as a simple surgical solution for correction of toe clinodactyly because of longitudinal epiphyseal bracket in childhood. Ten children (ages 1-5 years) were operated on by the same surgeon between October 2007 and May 2012 (n = 15 feet). The same surgical technique was used in all the cases. A clinical evaluation included the appearance of the foot, the parents' level of satisfaction, and the presence or absence of bothersome symptoms (such as pain and discomfort when wearing footwear). A radiological evaluation under weight-bearing conditions enabled us to 1) rate the achievement of a natural-looking toe parabola and 2) detect the recurrence of clinodactyly (defined as an angle of >40° between 2 adjacent phalanges). The mean follow-up period was 5.4 (range 3.3 to 8.1) years. Nine sets of parents (90%) were satisfied with the results of the procedure. None had difficulties wearing boots, and only 1 child (10%) had residual pain during sports activities. Clinodactyly recurred in 3 feet in 3 patients (20% of feet, 30% of patients). Two (20%) of the latter patients underwent repeat surgery and achieved a lasting, satisfactory outcome. Middle phalangectomy is an appropriate procedure for the treatment of toe clinodactyly because of longitudinal epiphyseal bracket in young children. However, the patients' long-term outcomes (notably once bone growth has ended) must be assessed.
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http://dx.doi.org/10.1053/j.jfas.2018.12.030DOI Listing
September 2019

Eight-week interval in flushing and locking port-a-cath in cancer patients: A single-institution experience and systematic review.

Eur J Cancer Care (Engl) 2019 Mar 10;28(2):e12978. Epub 2018 Dec 10.

Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Medical Oncology, University of Brescia at ASST Spedali Civili, Brescia, Italy.

Port-a-cath (PAC) system is one of the most frequently employed venous accesses for administration of chemotherapy and supportive care. To prevent late complications, the latest guidelines recommend flushing/locking procedures every four weeks. In this retrospective study, we evaluate the frequencies of late complications with a eight-week flushing/locking procedure compared to the standard one. This study retrospectively compares the frequency of complications occurred using standard versus delayed flushing schedules. We performed a systematic review of the published studies about PAC complications associated with longer flushing intervals. Three hundred and ninety fully available patients were enrolled. One hundred and six patients had their PAC flushed/locked every month, 347 patients performed the flushing/locking procedures every eight weeks, 63 patients switched from the four to the eight-week schedule. No difference was seen in the number of occlusions, infections and mechanical dysfunctions between the two patient groups. The systematic literature review confirmed, in a total of 1,347 patients, the absence of an increased proportion of complications with delayed schedules. PAC flushing and locking every eight weeks are feasible and safe. This delayed schedule may improve patients' quality of life and decrease both nursing workload and costs for the national health system.
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http://dx.doi.org/10.1111/ecc.12978DOI Listing
March 2019

Interrogation Techniques and Interface Circuits for Coil-Coupled Passive Sensors.

Micromachines (Basel) 2018 Sep 9;9(9). Epub 2018 Sep 9.

Department of Information Engineering, University of Brescia, Via Branze, 38-25123 Brescia, Italy.

Coil-coupled passive sensors can be interrogated without contact, exploiting the magnetic coupling between two coils forming a telemetric proximity link. A primary coil connected to the interface circuit forms the readout unit, while a passive sensor connected to a secondary coil forms the sensor unit. This work is focused on the interrogation of sensor units based on resonance, denoted as resonant sensor units, in which the readout signals are the resonant frequency and, possibly, the quality factor. Specifically, capacitive and electromechanical piezoelectric resonator sensor units are considered. Two interrogation techniques, namely a frequency-domain technique and a time-domain technique, have been analyzed, that are theoretically independent of the coupling between the coils which, in turn, ensure that the sensor readings are not affected by the interrogation distance. However, it is shown that the unavoidable parasitic capacitance in parallel to the readout coil introduces, for both techniques, an undesired dependence of the readings on the interrogation distance. This effect is especially marked for capacitance sensor units. A compensation circuit is innovatively proposed to counteract the effects of the parasitic input capacitance, and advantageously obtain distance-independent readings in real operating conditions. Experimental tests on a coil-coupled capacitance sensor with resonance at 5.45 MHz have shown a deviation within 1.5 kHz, i.e., 300 ppm, for interrogation distances of up to 18 mm. For the same distance range, with a coil-coupled quartz crystal resonator with a mechanical resonant frequency of 4.432 MHz, variations of less than 1.8 Hz, i.e., 0.5 ppm, have been obtained.
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http://dx.doi.org/10.3390/mi9090449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187290PMC
September 2018

Hepatoprotective effect of N-acetylcysteine in trabectedin-induced liver toxicity in patients with advanced soft tissue sarcoma.

Support Care Cancer 2018 Aug 15;26(8):2929-2935. Epub 2018 Mar 15.

Dipartimento di Specialità Medico-Chirurgiche, Scienze Radiologiche e Sanità Pubblica, Oncologia Medica, Università degli Studi di Brescia, ASST Spedali Civili, Brescia, Italy.

Purpose: Trabectedin is one of the few active agents in soft tissue sarcoma (STS) but hepatotoxicity is frequent and represents a dose-limiting factor. Protective strategies aiming at counteracting this important side effect have a crucial clinical impact. Due to its antioxidant properties, N-acetylcysteine (NAC) has a recognized hepatoprotective effect and this provides the rationale for testing NAC in the management of trabectedin-induced hepatotoxicity.

Methods: Patients with recurrent or metastatic soft tissue sarcoma, consecutively observed at our institution, who were considered eligible to trabectedin, received concomitant NAC if they had impaired hepatic or renal function at baseline or developed hepatotoxicity during treatment. The study aim was to retrospectively explore trabectedin administration in terms of number of cycles, mean dose, and dose intensity (DI) in patients who received NAC as compared with those who did not. Secondary end points were progression-free survival (PFS) and overall survival (OS).

Results: A total number of 18 patients were enrolled in this study. Nine received NAC and nine did not. The median number of administered trabectedin cycles, mean trabectedin dose/cycles, and median DI was comparable in the two groups (p = 0.450, p = 0.534, and p = 0.450, respectively). The PFS and OS curves overlapped.

Conclusion: This explorative study suggests that NAC can have a hepatoprotective activity in patients receiving trabectedin allowing to maintain an adequate dose intensity and continuative administration in patients with impaired liver and renal function or developing treatment-induced hepatotoxicity. A prospective randomized trial is warranted.
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http://dx.doi.org/10.1007/s00520-018-4129-xDOI Listing
August 2018

Adding metyrapone to chemotherapy plus mitotane for Cushing's syndrome due to advanced adrenocortical carcinoma.

Endocrine 2018 07 10;61(1):169-172. Epub 2017 Oct 10.

Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy.

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http://dx.doi.org/10.1007/s12020-017-1428-9DOI Listing
July 2018

Autonomous Sensors Powered by Energy Harvesting from von Karman Vortices in Airflow.

Sensors (Basel) 2017 Sep 13;17(9). Epub 2017 Sep 13.

Department of Information Engineering, University of Brescia, Via Branze 38, 25123 Brescia, Italy.

In this paper an energy harvesting system based on a piezoelectric converter to extract energy from airflow and use it to power battery-less sensors is presented. The converter is embedded as a part of a flexure beam that is put into vibrations by von Karman vortices detached from a bluff body placed upstream. The vortex street has been investigated by Computational Fluid Dynamics (CFD) simulations, aiming at assessing the vortex shedding frequency as a function of the flow velocity. From the simulation results the preferred positioning of the beam behind the bluff body has been derived. In the experimental characterization the electrical output from the converter has been measured for different flow velocities and beam orientations. Highest conversion effectiveness is obtained by an optimal orientation of the beam, to exploit the maximum forcing, and for flow velocities where the repetition frequency of the vortices allows to excite the beam resonant frequency at its first flexural mode. The possibility to power battery-less sensors and make them autonomous has been shown by developing an energy management and signal conditioning electronic circuit plus two sensors for measuring temperature and flow velocity and transmitting their values over a RF signal. A harvested power of about 650 μW with retransmission intervals below 2 min have been obtained for the optimal flow velocity of 4 m/s.
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http://dx.doi.org/10.3390/s17092100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5621374PMC
September 2017

Outcome of patients with lung adenocarcinoma with transformation to small-cell lung cancer following tyrosine kinase inhibitors treatment: A systematic review and pooled analysis.

Cancer Treat Rev 2017 Sep 31;59:117-122. Epub 2017 Jul 31.

University of Brescia, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Medical Oncology and Department of Molecular and Translational Medicine Section of Pathology, at Spedali Civili Hospital, Brescia, Italy. Electronic address:

Background: Lung adenocarcinoma can transform to small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. This phenomenon has repeatedly been described in several case reports and small patient series. The characteristics and treatment outcomes of this population, however, have not been comprehensively reported.

Methods: We performed a systematic review of the published literature to obtain explorative information on the clinical and pathological features and prognosis of the reported cases.

Results: Twenty-five eligible publications were identified, contributing to 39 patients. The median time from initial diagnosis of lung adenocarcinoma to the transformation to SCLC (ttSCLC) was 19months (range 1-61months). The median survival after SCLC diagnosis was 6months. Female gender was significantly associated with longer ttSCLC at the multivariable analysis. Smoking status seemed to be associated with worse prognosis after the diagnosis of SCLC.

Conclusion: In this series of published cases, the transformation to a SCLC phenotype after an initial diagnosis of lung adenocarcinoma following TKI therapy appeared to be a late phenomenon. The prognosis after SCLC diagnosis is poor and current treatment strategies derived from primary SCLC seem to be largely inefficacious. New therapies are needed in the management of transformed SCLC.
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http://dx.doi.org/10.1016/j.ctrv.2017.07.007DOI Listing
September 2017

Amiloride Is Effective in the Management of Abiraterone-Induced Mineralocorticoid Excess Syndrome without Interfering with Its Antineoplastic Activity.

Pharmacology 2017 11;100(5-6):261-268. Epub 2017 Aug 11.

Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.

Background: The administration of abiraterone acetate (abiraterone) leads to an adrenocorticotropic hormone (ACTH)-driven increase in mineralocorticoid hormones, requiring glucocorticoid supplementation that may stimulate the growth of prostate cancer (PCa). Amiloride is a drug that selectively reduces the aldosterone-sensitive Na+/K+ exchange and could be effective in the management of mineralocorticoid excess syndrome (MCES).

Methods: The efficacy of amiloride + hydrochlorothiazide (HCT) in the clinical management of abiraterone-induced MCES was assessed in 5 consecutive patients with castration-resistant PCa (CRPC). Then, using the in vitro experimental model of PCa cell lines, the possible effects of drugs usually used in the clinical management of CRPC patients on PCa cell viability were investigated.

Results: Amiloride/HCT led to a complete disappearance of all clinical and biochemical signs of abiraterone-induced MCES in the 5 treated patients. The in vitro study showed that abiraterone treatment significantly decreased cell viability of both androgen receptor (AR)-expressing VCaP (vertebral-cancer of the prostate) and LNCaP (lymph node carcinoma of the prostate) cells, with no effect on AR-negative PC-3 cells. Prednisolone, spironolactone, and eplerenone increased LNCaP cell viability, while amiloride reduced it. The non-steroid aldosterone antagonist PF-03882845 did not modify PCa cell viability.

Conclusions: The combination of amiloride/HCT was effective in the management of abiraterone-induced MCES. Amiloride did not negatively interfere with the abiraterone inhibition of PCa cell viability in vitro.
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http://dx.doi.org/10.1159/000477547DOI Listing
July 2018

Learning Semantic Part-Based Models from Google Images.

IEEE Trans Pattern Anal Mach Intell 2018 06 7;40(6):1502-1509. Epub 2017 Jul 7.

We propose a technique to train semantic part-based models of object classes from Google Images. Our models encompass the appearance of parts and their spatial arrangement on the object, specific to each viewpoint. We learn these rich models by collecting training instances for both parts and objects, and automatically connecting the two levels. Our framework works incrementally, by learning from easy examples first, and then gradually adapting to harder ones. A key benefit of this approach is that it requires no manual part location annotations. We evaluate our models on the challenging PASCAL-Part dataset [1] and show how their performance increases at every step of the learning, with the final models more than doubling the performance of directly training from images retrieved by querying for part names (from 12.9 to 27.2 AP). Moreover, we show that our part models can help object detection performance by enriching the R-CNN detector with parts.
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http://dx.doi.org/10.1109/TPAMI.2017.2724029DOI Listing
June 2018

Analysis and Validation of Contactless Time-Gated Interrogation Technique for Quartz Resonator Sensors.

Sensors (Basel) 2017 Jun 2;17(6). Epub 2017 Jun 2.

Department of Information Engineering, University of Brescia, Via Branze 38, Brescia 25123, Italy.

A technique for contactless electromagnetic interrogation of AT-cut quartz piezoelectric resonator sensors is proposed based on a primary coil electromagnetically air-coupled to a secondary coil connected to the electrodes of the resonator. The interrogation technique periodically switches between interleaved excitation and detection phases. During the excitation phase, the resonator is set into vibration by a driving voltage applied to the primary coil, whereas in the detection phase, the excitation signal is turned off and the transient decaying response of the resonator is sensed without contact by measuring the voltage induced back across the primary coil. This approach ensures that the readout frequency of the sensor signal is to a first order approximation independent of the interrogation distance between the primary and secondary coils. A detailed theoretical analysis of the interrogation principle based on a lumped-element equivalent circuit is presented. The analysis has been experimentally validated on a 4.432 MHz AT-cut quartz crystal resonator, demonstrating the accurate readout of the series resonant frequency and quality factor over an interrogation distance of up to 2 cm. As an application, the technique has been applied to the measurement of liquid microdroplets deposited on a 4.8 MHz AT-cut quartz crystal. More generally, the proposed technique can be exploited for the measurement of any physical or chemical quantities affecting the resonant response of quartz resonator sensors.
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http://dx.doi.org/10.3390/s17061264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492439PMC
June 2017

Visually Grounded Meaning Representations.

IEEE Trans Pattern Anal Mach Intell 2017 11 2;39(11):2284-2297. Epub 2016 Dec 2.

In this paper we address the problem of grounding distributional representations of lexical meaning. We introduce a new model which uses stacked autoencoders to learn higher-level representations from textual and visual input. The visual modality is encoded via vectors of attributes obtained automatically from images. We create a new large-scale taxonomy of 600 visual attributes representing more than 500 concepts and 700 K images. We use this dataset to train attribute classifiers and integrate their predictions with text-based distributional models of word meaning. We evaluate our model on its ability to simulate word similarity judgments and concept categorization. On both tasks, our model yields a better fit to behavioral data compared to baselines and related models which either rely on a single modality or do not make use of attribute-based input.
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http://dx.doi.org/10.1109/TPAMI.2016.2635138DOI Listing
November 2017

Behavior Discovery and Alignment of Articulated Object Classes from Unstructured Video.

Int J Comput Vis 2017 10;121(2):303-325. Epub 2016 Aug 10.

1IPAB, School of Informatics, University of Edinburgh, Crichton Street 10, Edinburgh, EH8 9AB UK.

We propose an automatic system for organizing the content of a collection of unstructured videos of an articulated object class (e.g., tiger, horse). By exploiting the recurring motion patterns of the class across videos, our system: (1) identifies its characteristic behaviors, and (2) recovers pixel-to-pixel alignments across different instances. Our system can be useful for organizing video collections for indexing and retrieval. Moreover, it can be a platform for learning the appearance or behaviors of object classes from Internet video. Traditional supervised techniques cannot exploit this wealth of data directly, as they require a large amount of time-consuming manual annotations. The behavior discovery stage generates temporal video intervals, each automatically trimmed to one instance of the discovered behavior, clustered by type. It relies on our novel motion representation for articulated motion based on the displacement of ordered pairs of trajectories. The alignment stage aligns hundreds of instances of the class to a great accuracy despite considerable appearance variations (e.g., an adult tiger and a cub). It uses a flexible thin plate spline deformation model that can vary through time. We carefully evaluate each step of our system on a new, fully annotated dataset. On behavior discovery, we outperform the state-of-the-art improved dense trajectory feature descriptor. On spatial alignment, we outperform the popular SIFT Flow algorithm.
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http://dx.doi.org/10.1007/s11263-016-0939-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154839PMC
August 2016

Primary Ewing's sarcoma of the sinonasal tract in adults: A challenging disease.

Head Neck 2017 03 29;39(3):E45-E50. Epub 2016 Nov 29.

Unit of Otorhinolaryngology - Head and Neck Surgery, Department of Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.

Background: Sinonasal localization of Ewing's sarcoma in adults is an exceedingly rare event.

Methods: The clinical records of 5 patients with primary sinonasal Ewing's sarcoma treated from 1992 to 2012 were retrospectively analyzed. All pathologic slides were reviewed by 2 experienced pathologists. All patients underwent multimodality treatments.

Results: Median age was 36 years (range, 25-52 years). At referral, 2 patients had the original diagnosis changed by review of the histologic slides. Tumors were classified as T4aN0M0 (4 patients) and T2N0M0 (1 patient). Median follow-up was 110 months (range, 70-139 months). Only 1 patient, who started treatment elsewhere based on an incorrect histologic diagnosis, experienced multiple recurrences and eventually died of widespread metastasis.

Conclusion: Correct pathologic diagnosis can have a crucial impact on treatment planning and outcome. Multimodality therapy is the key for long-term successful results. Because of the rarity of the tumor, referral to highly experienced care centers is strongly recommended. © 2016 Wiley Periodicals, Inc. Head Neck 39: E45-E50, 2017.
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http://dx.doi.org/10.1002/hed.24649DOI Listing
March 2017

Comparison of the Tolerability Profile of Controlled-Release Oral Morphine and Oxycodone for Cancer Pain Treatment. An Open-Label Randomized Controlled Trial.

J Pain Symptom Manage 2016 12 11;52(6):783-794.e6. Epub 2016 Oct 11.

Palliative Care, Pain Therapy and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; European Palliative Care Research Centre (PRC), Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Context: Oxycodone and morphine are recommended as first-choice opioids for moderate/severe cancer pain, but evidence about their relative tolerability has significant methodological limitations.

Objectives: This study was mainly aimed at comparing the risk of developing adverse events (AEs) with controlled-release oral morphine vs. oxycodone; secondary aims were comparing their analgesic efficacy and testing heterogeneity in tolerability across different age and renal function subgroups.

Methods: An open-label multicenter RCT (EudraCT number: 2006-003151-21) was carried out in patients with moderate/severe cancer pain. At baseline, 7 and 14 days, patients scored on 0-10 rating scales (0-10 numerical rating scale) the intensity of pain and of a list of common opioid side effects. The primary end point was the percentage of patients reporting an AE (a worsening ≥ 2 points on any of the listed side effects); tolerability by subgroups and average follow-up pain intensity were compared through regression models.

Results: One hundred eighty-seven patients were enrolled (47% of originally planned). Intention to treat (ITT) analysis (N = 185, morphine 94, oxycodone 91) did not show any difference in the risk of developing AEs (risk difference -0.6%, 95% CI -11.0% to 9.9%) nor in analgesia (0-10 numerical rating scale pain intensity difference -0.28, 95% CI -0.83 to 0.27). No evidence of heterogeneity of tolerability across age and renal function patient subgroups emerged.

Conclusion: This trial failed to show any difference in tolerability and analgesic efficacy of morphine and oxycodone as first-line treatment for moderate/severe cancer pain but results interpretation is difficult due to lack of power, potential bias from open-label design, and concerns about assay sensitivity. These data, however, can significantly contribute to future meta-analyses comparing WHO Step-III opioids and are relevant in designing future randomized studies.
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http://dx.doi.org/10.1016/j.jpainsymman.2016.05.030DOI Listing
December 2016
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