Self-Diagnostic and Self-Compensation Methods for Resistive Displacement Sensors Tailored for In-Field Implementation.

This paper presents a suitably general model for resistive displacement sensors where the model parameters depend on the current sensor conditions, thereby capturing wearout and failure, and proposes a novel fault detection method that can be seamlessly applied during sensor operation, providing self-diagnostic capabilities. On the basis of the estimation of model parameters, an innovative self-compensation method is derived to increase the accuracy of sensors subject to progressive wearout. The proposed model and methods have been validated by both numerical simulations and experimental tests on two real resistive displacement sensors, placed in undamaged and faulty conditions, respectively. The fault detection method has shown an accuracy of 97.2%. The position estimation error is < ±0.2% of the full-scale span for the undamaged sensor, while the self-compensation method successfully reduces the position estimation error from ±15% to approximately ±2% of the full-scale span for the faulty sensor.

Objective Evaluation of Active Interactions between the Operator and Display Screen Equipment Using an Innovative Acquisition System.

The occupational risk of operators using display screen equipment (DSE) is usually evaluated according to the extent of time spent in active operator-DSE interactions. Risk assessment is based on activity data collected through questionnaires. We evaluated an original and innovative system that can objectively assess active operator-DSE interactions by collecting electrical impulses generated by the activation of mouse, keyboard and a camera that collects attentive eye-screen fixation. The main aim of this study was to evaluate the system's performance on an employee sample involved in the task of active reading and copying at a DSE workstation connected to the system. In the context of mandatory health surveillance at work, we enrolled 38 DSE operators with normal neuropsychological and eye assessments who were required to complete two predefined reading and writing tasks. The obtained results show that the system is able to collect activity data derived from operator-DSE interactions through screen fixation, keyboard tapping and mouse handling. In the copying task, the session duration as recorded by the system was highly related to the screen fixation time. In the copying task, mouse and keyboard activities were more strongly related to session duration than screen fixation. For the copying task, it was also possible to obtain individual profiles of operator-DSE interactions while performing the same standardized tasks. Collected data can allow an objective evaluation of active time spent by DSE operators at their workstations, thus allowing a more accurate occupational health risk assessment and management. Prospective analysis of individual operator-DSE interaction profiles can favor the setup of targeted preventive and organizational interventions from an of even wider worker wellbeing perspective.

Flexible Passive Sensor Patch with Contactless Readout for Measurement of Human Body Temperature.

A passive flexible patch for human skin temperature measurement based on contact sensing and contactless interrogation is presented. The patch acts as an RLC resonant circuit embedding an inductive copper coil for magnetic coupling, a ceramic capacitor as the temperature-sensing element and an additional series inductor. The temperature affects the capacitance of the sensor and consequently the resonant frequency of the RLC circuit. Thanks to the additional inductor, the dependency of the resonant frequency from the bending of the patch has been reduced. Considering a curvature radius of the patch of up to 73 mm, the maximum relative variation in the resonant frequency has been reduced from 812 ppm to 7.5 ppm. The sensor has been contactlessly interrogated by a time-gated technique through an external readout coil electromagnetically coupled to the patch coil. The proposed system has been experimentally tested within the range of 32-46 °C, giving a sensitivity of -619.8 Hz/°C and a resolution of 0.06 °C.

Precocious puberty under stressful conditions: new understanding and insights from the lessons learnt from international adoptions and the COVID-19 pandemic.

Neuro-biological variations in the timing of sexual maturation within a species are part of an evolved strategy that depend on internal and external environmental conditions. An increased incidence of central precocious puberty (CPP) has been described in both adopted and "covid-19 pandemic" children. Until recently, it was hypothesised that the triggers for CPP in internationally adopted children were likely to be better nutrition, greater environmental stability, and improved psychological wellbeing. However, following data collected during and after the coronavirus (COVID-19) global pandemic, other possibilities must be considered. In a society with high levels of child wellbeing, the threat to life presented by an unknown and potentially serious disease and the stressful environment created by lockdowns and other public health measures could trigger earlier pubertal maturation as an evolutionary response to favour early reproduction. The main driver for increased rates of precocious and rapidly progressive puberty during the pandemic could have been the environment of "fear and stress" in schools and households. In many children, CPP may have been triggered by the psychological effects of living without normal social contact, using PPE, being near adults concerned about financial and other issues and the fear of getting ill. The features and time of progression of CPP in children during the pandemic are similar to those observed in adopted children. This review considers the mechanisms regulating puberty with a focus on neurobiological and evolutionary mechanisms, and analyses precocious puberty both during the pandemic and in internationally adopted children searching for common yet unconsidered factors in an attempt to identify the factors which may have acted as triggers. In particular, we focus on stress as a potential factor in the early activation of the hypothalamic-pituitary-gonadal axis and its correlation with rapid sexual maturation.

Optimization of an Impact-Based Frequency Up-Converted Piezoelectric Vibration Energy Harvester for Wearable Devices.

This work presents a novel development of the impact-based mechanism for piezoelectric vibration energy harvesters. More precisely, the effect of an impacting mass on a cantilever piezoelectric transducer is studied both in terms of the tip mass value attached to the cantilever and impact position to find an optimal condition for power extraction. At first, the study is carried out by means of parametric analyses at varying tip mass and impact position on a unimorph MEMS cantilever, and a suitable physical interpretation of the associated electromechanical response is given. The effect of multiple impacts is also considered. From the analysis, it emerges that the most effective configuration, in terms of power output, is an impact at the cantilever tip without a tip mass. By changing the value of the tip mass, a sub-optimal impact position along the beam axis can also be identified. Moreover, the effect of a tip mass is deleterious on the power performance, contrary to the well-known case of a resonant energy harvester. A mesoscale prototype with a bimorph transducer is fabricated and tested to validate the computational models. The comparison shows a good agreement between numerical models and the experiments. The proposed approach is promising in the field of consumer electronics, such as wearable devices, in which the impact-based device moves at the frequencies of human movement and is much lower than those of microsystems.

Vid2CAD: CAD Model Alignment Using Multi-View Constraints From Videos.

We address the task of aligning CAD models to a video sequence of a complex scene containing multiple objects. Our method can process arbitrary videos and fully automatically recover the 9 DoF pose for each object appearing in it, thus aligning them in a common 3D coordinate frame. The core idea of our method is to integrate neural network predictions from individual frames with a temporally global, multi-view constraint optimization formulation. This integration process resolves the scale and depth ambiguities in the per-frame predictions, and generally improves the estimate of all pose parameters. By leveraging multi-view constraints, our method also resolves occlusions and handles objects that are out of view in individual frames, thus reconstructing all objects into a single globally consistent CAD representation of the scene. In comparison to the state-of-the-art single-frame method Mask2CAD that we build on, we achieve substantial improvements on the Scan2CAD dataset (from 11.6% to 30.7% class average accuracy).

Transcription regulators and ultra-rare and other rare translocation-related sarcomas treated with trabectedin: A proof of principle from a post-hoc analysis.

Background: Among sarcomas, which are rare cancers with an incidence of <6 per 100.000/year cases, ultra-rare sarcomas have an incidence of approximately ≤1/1,000,000/year cases and altogether account for ~20% of all soft tissue sarcomas (STS) and bone sarcomas. The Italian Sarcoma Group has recently performed a non-interventional, retrospective TrObs study with data from 512 anthracycline-pretreated patients with advanced multiple STS histologies and treated with trabectedin (Palmerini, Cancers 2021; ClinicalTrials.gov Identifier: NCT02793050). Methods: A post-hoc analysis of case series to evaluate the efficacy and safety of trabectedin on patients with ultra-rare and other rare translocation-related sarcomas included in TrObs study was performed. Main outcomes comprised investigator-assessed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Results: Thirty-six patients (18 women) with ultra-rare and other rare sarcoma and a median age of 53.0 years (range: 22-81) were included. Most patients had solitary fibrous tumor (SFT; n=11) followed by epithelioid sarcoma (n=5), malignant peripheral nerve sheath tumor (MPNST; n=4), extraskeletal myxoid chondrosarcoma (EMC; n=3), desmoplastic small round cell tumor (DSRCT; n=3), and alveolar soft part sarcoma (ASPS), rhabdomyosarcoma and clear cell sarcoma (n=2 each). Thirty-five patients had metastatic disease and 23 patients received trabectedin as a second-line treatment. Among 35 patients evaluable for response, two patients with SFT and ASPS had a partial response and one patient with DSRCT obtained a complete response, reaching an ORR of 8.6% (95% CI: 2.8-23.4%). Among patients with an ORR, 6-months PFS was 100% in patients with ASPS, 45.7% in patients with SFT and 33.3% in those with DSRCT. Two patients with epithelioid sarcoma and myoepithelioma had disease stabilization lasting >24 months. Nine patients had at least one grade 3/4 adverse event, mostly being bone marrow toxicity (n=6). Conclusions: Trabectedin has some anti-tumor activity in some ultra-rare and other rare sarcomas, particularly translocation-related sarcomas, with the well-known manageable safety profile.

Inside the Noonan "universe": Literature review on growth, GH/IGF axis and rhGH treatment: Facts and concerns.

Noonan syndrome (NS) is a disorder characterized by a typical facial gestalt, congenital heart defects, variable cognitive deficits, skeletal defects, and short stature. NS is caused by germline pathogenic variants in genes coding proteins with a role in the RAS/mitogen-activated protein kinase signaling pathway, and it is typically associated with substantial genetic and clinical complexity and variability. Short stature is a cardinal feature in NS, with evidence indicating that growth hormone (GH) deficiency, partial GH insensitivity, and altered response to insulin-like growth factor I (IGF-1) are contributing events for growth failure in these patients. Decreased IGF-I, together with low/normal responses to GH pharmacological provocation tests, indicating a variable presence of GH deficiency/resistance, in particular in subjects with pathogenic PTPN11 variants, are frequently reported. Nonetheless, short- and long-term studies have demonstrated a consistent and significant increase in height velocity (HV) in NS children and adolescents treated with recombinant human GH (rhGH). While the overall experience with rhGH treatment in NS patients with short stature is reassuring, it is difficult to systematically compare published data due to heterogeneous protocols, potential enrolment bias, the small size of cohorts in many studies, different cohort selection criteria and varying durations of therapy. Furthermore, in most studies, the genetic information is lacking. NS is associated with a higher risk of benign and malignant proliferative disorders and hypertrophic cardiomyopathy, and rhGH treatment may further increase risk in these patients, especially as dosages vary widely. Herein we provide an updated review of aspects related to growth, altered function of the GH/IGF axis and cell response to GH/IGF stimulation, rhGH treatment and its possible adverse events. Given the clinical variability and genetic heterogeneity of NS, treatment with rhGH should be personalized and a conservative approach with judicious surveillance is recommended. Depending on the genotype, an individualized follow-up and close monitoring during rhGH treatments, also focusing on screening for neoplasms, should be considered.

Piezoelectric Energy Harvesting from Low-Frequency Vibrations Based on Magnetic Plucking and Indirect Impacts.

This work proposes a mono-axial piezoelectric energy harvester based on the innovative combination of magnetic plucking and indirect impacts, e.g., impacts happening on the package of the harvester. The harvester exploits a permanent magnet placed on a non-magnetic mass, free to move within a predefined bounded region located in front of a piezoelectric bimorph cantilever equipped with a magnet as the tip mass. When the harvester is subjected to a low-frequency external acceleration, the moving mass induces an abrupt deflection and release of the cantilever by means of magnetic coupling, followed by impacts of the same mass against the harvester package. The combined effect of magnetic plucking and indirect impacts induces a frequency up-conversion. A prototype has been designed, fabricated, fastened to the wrist of a person by means of a wristband, and experimentally tested for different motion levels. By setting the magnets in a repulsive configuration, after 50 s of consecutive impacts induced by shaking, an energy of 253.41 µJ has been stored: this value is seven times higher compared to the case of harvester subjected to indirect impacts only, i.e., without magnetic coupling. This confirms that the combination of magnetic plucking and indirect impacts triggers the effective scavenging of electrical energy even from low-frequency non-periodical mechanical movements, such as human motion, while preserving the reliability of piezoelectric components.

Auxological and Endocrinological Features in Children and Adolescents with Cystic Fibrosis.

Cystic fibrosis (CF) is a multisystem autosomal recessive disease caused by mutations that lead to deficient or dysfunctional CF transmembrane conductance regulator (CFTR) proteins. Patients typically present malnutrition resulting from the malabsorption of fundamental nutrients and recurring lung infections, with a progressive worsening of the respiratory function. For these reasons, the clinical management of CF requires a multidisciplinary team. From an endocrinological point of view, patients often present major complications, such as diabetes, bone disease, thyroid disorders, delayed growth and puberty, hypogonadism and infertility, which negatively affect their quality of life and, in some cases, significantly reduce life expectancy. These complications can arise as a direct result of CFTR dysfunction and/or as a consequence of a deterioration in the function of the organs affected. The objective of this review is to analyze all the possible endocrinological complications that can occur in patients with CF by evaluating the most recent papers in the literature.

Supportive therapies in patients with advanced adrenocortical carcinoma submitted to standard EDP-M regimen.

PURPOSE: The management of patients with advanced/metastatic adrenocortical carcinoma (ACC) is challenging, EDP-M (etoposide, doxorubicin, cisplatin combined with mitotane) is the standard regimen. However, it is quite toxic, so an adequate supportive therapy is crucial to reduce as much as possible the side effects and maintain the dose intensity of cytotoxic agents. METHODS: We describe the main side effects of the EDP-M scheme and the best way to manage them based on the experience of the Medical Oncology Unit of the Spedali Civili of Brescia. We also deal with the administration of EDP-M in specific frail patients, such as those with huge disease extent and poor performance status (PS) and those with mild renal insufficiency. RESULTS: In patients with hormone secreting ACC the rapid control of Cushing syndrome using adrenal steroidogenesis inhibitors such as metyrapone or osilodrostat is mandatory before starting EDP-M. Primary prophylaxis of neutropenia with Granulocyte-Colony Stimulating Factors is crucial and should be introduced at the first chemotherapy cycle. Possible mitotane induced hypoadrenalism should be always considered in case of persistent nausea and vomiting and asthenia in the interval between one cycle to another. In case of poor PS. A 24 h continuous infusion schedule of cisplatin could be an initial option in patients with poor PS as well as to reduce the risk of nefrotoxocity in patients with mild renal impairment. CONCLUSION: A careful and accurate supportive care is essential to mitigate EDP-M side effects as much as possible and avoid that, due to toxicity, patients have to reduce doses and or postpone cytotoxic treatment with a negative impact on efficacy of this chemotherapy regimen.

Retrospective longitudinal analysis of the effects of postnatal weight gain on the timing and tempo of puberty and menarche in a cohort of Italian girls.

OBJECTIVE: over the last few decades there has been a progressive decline in the average age of onset of pubertal development stages in both sexes. The increase in the prevalence of childhood obesity seems to play an important role in this phenomenon. DESIGN: we undertook a retrospective, longitudinal evaluation of the average age of thelarche and menarche to evaluate the relationship between BMI and weight change during the first years of life and the timing and tempo of puberty. METHODS: we evaluated data for 577 Italian girls born between 1995 and 2003. We collected the main auxological and clinical parameters, including age at B2 and at menarche, BMI SDS at B2 and menarche, gestational age and birth weight and Z-score change from birth weight (BW) to BMI at B2 and menarche. RESULTS: the mean age of B2 was 10.06 ± 1.03 years and the mean age of menarche was 12.08 ± 1.02 years. Age at B2 and menarche were inversely correlated with BMI SDS (p < 0.0001). Both age at menarche and at thelarche have an inverse relationship with the Z-score change from birth weight and BMI at menarche and thelarche respectively (p < 0.0001). CONCLUSIONS: our data confirm a significant relationship between BMI and age of B2 and menarche. We observed a clear relationship among weight change during the first years of life, age at thelarche and menarche and the duration of puberty, demonstrating the importance of weight and weight gain in determining the timing and tempo of pubertal changes and growth.

Wearable Ball-Impact Piezoelectric Multi-Converters for Low-Frequency Energy Harvesting from Human Motion.

Multi-converter piezoelectric harvesters based on mono-axial and bi-axial configurations are proposed. The harvesters exploit two and four piezoelectric converters (PCs) and adopt an impinging spherical steel ball to harvest electrical energy from human motion. When the harvester undergoes a shake, a tilt, or a combination of the two, the ball hits one PC, inducing an impact-based frequency-up conversion. Prototypes of the harvesters have been designed, fabricated, fastened to the wrist of a person by means of a wristband and watchband, and experimentally tested for different motion levels. The PCs of the harvesters have been fed to passive diode-based voltage-doubler rectifiers connected in parallel to a storage capacitor, Cs = 220 nF. By employing the mono-axial harvester, after 8.5 s of consecutive impacts induced by rotations of the wrist, a voltage vcs(t) of 40.2 V across the capacitor was obtained, which corresponded to a stored energy of 178 µJ. By employing the bi-axial harvester, the peak instantaneous power provided by the PCs to an optimal resistive load was 1.58 mW, with an average power of 9.65 µW over 0.7 s. The proposed harvesters are suitable to scavenge electrical energy from low-frequency nonperiodical mechanical movements, such as human motion.

Piezoelectric MEMS Acoustic Transducer with Electrically-Tunable Resonant Frequency.

The paper presents a technique to obtain an electrically-tunable matching between the series and parallel resonant frequencies of a piezoelectric MEMS acoustic transducer to increase the effectiveness of acoustic emission/detection in voltage-mode driving and sensing. The piezoelectric MEMS transducer has been fabricated using the PiezoMUMPs technology, and it operates in a plate flexural mode exploiting a 6 mm × 6 mm doped silicon diaphragm with an aluminum nitride (AlN) piezoelectric layer deposited on top. The piezoelectric layer can be actuated by means of electrodes placed at the edges of the diaphragm above the AlN film. By applying an adjustable bias voltage Vb between two properly-connected electrodes and the doped silicon, the d31 mode in the AlN film has been exploited to electrically induce a planar static compressive or tensile stress in the diaphragm, depending on the sign of Vb, thus shifting its resonant frequency. The working principle has been first validated through an eigenfrequency analysis with an electrically induced prestress by means of 3D finite element modelling in COMSOL Multiphysics®. The first flexural mode of the unstressed diaphragm results at around 5.1 kHz. Then, the piezoelectric MEMS transducer has been experimentally tested in both receiver and transmitter modes. Experimental results have shown that the resonance can be electrically tuned in the range Vb = ±8 V with estimated tuning sensitivities of 8.7 ± 0.5 Hz/V and 7.8 ± 0.9 Hz/V in transmitter and receiver modes, respectively. A matching of the series and parallel resonant frequencies has been experimentally demonstrated in voltage-mode driving and sensing by applying Vb = 0 in transmission and Vb = -1.9 V in receiving, respectively, thereby obtaining the optimal acoustic emission and detection effectiveness at the same operating frequency.

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

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.

Factors of Influence for Transfer Learning Across Diverse Appearance Domains and Task Types.

Transfer learning enables to re-use knowledge learned on a source task to help learning a target task. A simple form of transfer learning is common in current state-of-the-art computer vision models, i.e., pre-training a model for image classification on the ILSVRC dataset, and then fine-tune on any target task. However, previous systematic studies of transfer learning have been limited and the circumstances in which it is expected to work are not fully understood. In this paper we carry out an extensive experimental exploration of transfer learning across vastly different image domains (consumer photos, autonomous driving, aerial imagery, underwater, indoor scenes, synthetic, close-ups) and task types (semantic segmentation, object detection, depth estimation, keypoint detection). Importantly, these are all complex, structured output tasks types relevant to modern computer vision applications. In total we carry out over 2000 transfer learning experiments, including many where the source and target come from different image domains, task types, or both. We systematically analyze these experiments to understand the impact of image domain, task type, and dataset size on transfer learning performance. Our study leads to several insights and concrete recommendations: (1) for most tasks there exists a source which significantly outperforms ILSVRC'12 pre-training; (2) the image domain is the most important factor for achieving positive transfer; (3) the source dataset should include the image domain of the target dataset to achieve best results; (4) at the same time, we observe only small negative effects when the image domain of the source task is much broader than that of the target; (5) transfer across task types can be beneficial, but its success is heavily dependent on both the source and target task types.

Disseminated Kaposi sarcoma following COVID-19 in a 61-year-old Albanian immunocompetent man: a case report and review of the literature.

BACKGROUND: COVID-19 and its related anti-inflammatory treatment (steroids, immunomodulators) may induce the reactivation of latent bacterial, parasitic, and viral infections. According to our knowledge, no case of disseminated HHV-8-related Kaposi sarcoma (KS) after COVID-19 and its treatment has been described so far. Only one case of cutaneous KS concurrently with COVID-19 has been previously reported. CASE PRESENTATION: We describe a case of disseminated KS in a 61-year-old immunocompetent Albanian man after hospitalization for COVID-19. METHODS FOR LITERATURE RESEARCH: We used PubMed as biomedical database for the literature research. We selected keyword combinations including "Kaposi sarcoma," "HHV-8," "immunocompetent," "COVID-19," "SARS-CoV-2," and "steroids." No time or language limitation was set. Titles and abstracts of selected articles were systematically screened. Articles were included in the examination if they were published under free access through the digital library of the University of Brescia (Italy), and provided full text. Articles were excluded if the topic was beyond the aim of our study. Finally, we selected 15 articles. RESULTS: We describe a case of KS in COVID-19 patient and postulate that Interleukin-6 (IL-6) activity and steroid-induced immunodeficiency may play a major role in KS emergence. No published case of disseminated KS following COVID-19 in otherwise healthy individuals was found through the systematic literature review, despite the high incidence of COVID-19 in areas with medium-high prevalence of HHV-8 infection. This observation might be explained by the role of individual genetic susceptibility factors. CONCLUSIONS: SARS-CoV-2 infection and its treatment may lead to reactivation of several latent infections, including HHV-8 and its related clinical syndrome, Kaposi sarcoma.

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

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, 10-7 cm3, 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 cm3. The resulting polymer/VFI composite was investigated by synchrotron X-ray diffraction and optical and 1H, 13C, and 27Al 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.

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

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.

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

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 (p < 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).