Metastatic adult-type non-rhabdomyosarcoma soft tissue sarcomas in children and adolescents: A cohort study from the European paediatric Soft tissue sarcoma Study Group

Background

Limited data exist on the clinical behavior of pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) with distant metastases at onset, and a clear standard of care has not yet been defined.

Methods

This cohort study reports on pediatric adult-type metastatic NRSTS enrolled in two concurrent prospective European studies, i.e., the randomized BERNIE study and the single-arm MTS 2008 study developed by the European paediatric Soft tissue sarcoma Study Group. Treatment programs were originally designed for patients with metastatic rhabdomyosarcoma, i.e., nine courses of multidrug chemotherapy (with or without bevacizumab in the BERNIE study), followed by 12 cycles of maintenance therapy, whereas radiotherapy and/or surgery (on primary tumor and/or metastases) were delayed until after seven courses of chemotherapy had been administered.

Results

The study included 61 patients <21 years old treated from July 2008 to December 2016. The lung was the site of metastases in 75% of the cases. All patients received multi-agent chemotherapy, 44% had local therapy to primary tumor, and 18% had treatment of metastases. Median time to progression/relapse was 6 months. A high rate of tumor progression was observed during the initial part of the chemotherapy program. With a median follow-up of 41.5 months (range, 2–111 months), 3-year event-free survival and overall survival were 15.4% (95% confidence interval [CI], 7.6–25.7) and 34.9% (95% CI, 22.7–47.5), respectively. There were no statistically significant differences in outcome depending on the type of treatment administered.

Conclusions

The study confirmed the overall poor outcome for patients with metastatic NRSTS, whose treatment remains a challenge.

Plain Language Summary

• Pediatric non-rhabdomyosarcoma soft tissue sarcomas form a heterogeneous group of rare tumors.
• Although recent international studies have defined the standard of care for patients with localized disease, limited data are available on the clinical behavior of patients with distant metastases.
• This study on 61 metastatic cases treated on two prospective European protocols confirms that the chances of survival of such patients are often dismal and a standard treatment is still lacking.

     

Risk behaviors among Italian healthcare students: a cross-sectional study for health promotion of future healthcare workers

Background:Risk behaviors are frequent among young adults and they are particularly relevant when considering healthcare students.Objectives:The study is aimed to examine the prevalence of smoking, binge drinking, physical inactivity, and excessive bodyweight in a population of healthcare students attending an Italian university.Methods:Healthcare students filled an anonymous multiple-choice questionnaire on the occasion of the occupational health visit that preceded their hospital internship. The questionnaire covered socio-demographic characteristics (including student’s working status and cohabitation) and risk behaviors. We evaluated the prevalence of risk behaviors and their association with socio-demographic characteristics.Results:The sample consisted of 494 students (65% women): 23.2% were smokers, 7.9% had excessive bodyweight, 35% did not practice any physical activity and 50% reported binge drinking at least once in the last 12 months. We found associations of male sex (30.5%) and being nursing students (29.9%) with smoking habit. The frequency of binge drinking was higher in men (38.4%), working students (53.9%), and among those who lived without family (50%). Physical inactivity was associated with female sex (44.2%) and living without family (57.1%). Finally, the co-presence of 2 risk behaviors or more was higher in men (36.8%), in nursing students (39.6%) and in working students (44.7%).Conclusions:Our findings regarding the prevalence of risk behaviors and their potential association with socio-demographic factors may be a clue to the definition of targeted strategies aimed at reducing of risk behaviors among healthcare students.Key words: risk behaviors, healthcare students, smoking, binge drinking, physical inactivity     

Healthcare utilization following spinal cord injury: Objective findings from a regional hospital registry

Objective: The purpose was to describe the prevalence and characteristics of healthcare utilization among individuals with spinal cord injury (SCI) from a Level I trauma center.

Design: Retrospective data analysis utilizing a local acute trauma registry for initial hospitalization and merged with the Dallas-Fort Worth Hospital Council registry to obtain subsequent health care utilization in the first post-injury year.

Setting: Dallas, TX, USA.

Participants: Six hundred and sixty four patients were admitted with an acute traumatic SCI from January 2003 through June 2014 to a Level I trauma center. Fifty five patients that expired during initial hospitalization and 18 patients with unspecified SCI (defined by ICD-9 with no etiology or level of injury specified) were not included in the analysis, leaving a final sample of 591.

Outcome Measures: Data included demographic and clinical characteristics, charges, and healthcare utilization.

Results: Mean age was 46.1?years (±18.9?years), the majority of patients were male (74%), and Caucasian (58%). Of the 591 patients, 345 (58%) had additional inpatient or emergency healthcare utilization accounting for 769 additional visits (median of 3 visits per person). Of the 769 encounters, 534 (69%) were inpatient and 235 (31%) were emergency visits not resulting in an admission. The most prevalent ICD-9 codes listed were pressure ulcer, neurogenic bowel, neurogenic bladder, urinary tract infection, fluid electrolyte imbalance, hypertension, and tobacco use.

Conclusion: Individuals with SCI experience high levels of healthcare utilization which are costly and may be preventable. Increasing our understanding of the prevalence and causes for healthcare utilization after acute SCI is important to target preventive strategies.     

Use of a convolutional neural network and quantitative ultrasound for diagnosis of fatty liver

Quantitative ultrasound (QUS) was used to classify rabbits that were induced to have liver disease by placing them on a fatty diet for a defined duration and/or periodically injecting them with CCl₄. The ground truth of the liver state was based on lipid liver percents estimated via the Folch assay and hydroxyproline concentration to quantify fibrosis. Rabbits were scanned ultrasonically in vivo using a SonixOne scanner and an L9-4/38 linear array. Liver fat percentage was classified based on the ultrasonic backscattered radiofrequency (RF) signals from the livers using either QUS or a 1-D convolutional neural network (CNN). Use of QUS parameters with linear regression and canonical correlation analysis demonstrated that the QUS parameters could differentiate between livers with lipid levels above or below 5%. However, the QUS parameters were not sensitive to fibrosis. The CNN was implemented by analyzing raw RF ultrasound signals without using separate reference data. The CNN outputs the classification of liver as either above or below a threshold of 5% fat level in the liver. The CNN outperformed the classification utilizing the QUS parameters combined with a support vector machine in differentiating between low and high lipid liver levels (i.e., accuracies of 74% versus 59% on the testing data). Therefore, although the CNN did not provide a physical interpretation of the tissue properties (e.g., attenuation of the medium or scatterer properties) the CNN had much higher accuracy in predicting fatty liver state and did not require an external reference scan.     

Insights into the pathogenesis of ATP1A1‐related CMT disease using patient‐specific iPSCs

The development of patient‐specific induced pluripotent stem cells (iPSCs) offered interesting insights in modeling the pathogenesis of Charcot‐Marie‐Tooth (CMT) disease and thus we decided to explore the phenotypes of iPSCs derived from a single CMT patient carrying a mutant ATP1A1 allele (p.Pro600Ala). iPSCs clones generated from CMT and control fibroblasts, were induced to differentiate into neural precursors and then into post‐mitotic neurons. Control iPSCs differentiated into neuronal precursors and then into post‐mitotic neurons within 6‐8 days. On the contrary, the differentiation of CMT iPSCs was clearly defective. Electrophysiological properties confirmed that post‐mitotic neurons were less mature compared to the normal counterpart. The impairment of in vitro differentiation of CMT iPSCs only concerned with the neuronal pathway, because they were able to differentiate into mesendodermal cells and other ectodermal derivatives. ATP1A1 was undetectable in the few neuronal cells derived from CMT iPSCs. ATP1A1 gene mutation (p.Pro600Ala), responsible for a form of axonal CMT disease, is associated in vitro with a dramatic alteration of the differentiation of patient‐derived iPSCs into post‐mitotic neurons. Thus, the defect in neuronal cell development might lead in vivo to a decreased number of mature neurons in ATP1A1‐CMT disease.