Multi-institutional application of Failure Mode and Effects Analysis (FMEA) to CyberKnife Stereotactic Body Radiation Therapy (SBRT)

Background A multidisciplinary and multi-institutional working group applied the Failure Mode and Effects Analysis (FMEA) approach to assess the risks for patients undergoing Stereotactic Body Radiation Therapy (SBRT) treatments for lesions located in spine and liver in two CyberKnife\uae Centres. Methods The various sub-processes characterizing the SBRT treatment were identified to generate the process trees of both the treatment planning and delivery phases. This analysis drove to the identification and subsequent scoring of the potential failure modes, together with their causes and effects, using the risk probability number (RPN) scoring system. Novel solutions aimed to increase patient safety were accordingly considered. Results The process-tree characterising the SBRT treatment planning stage was composed with a total of 48 sub-processes. Similarly, 42 sub-processes were identified in the stage of delivery to liver tumours and 30 in the stage of delivery to spine lesions. All the sub-processes were judged to be potentially prone to one or more failure modes. Nineteen failures (i.e. 5 in treatment planning stage, 5 in the delivery to liver lesions and 9 in the delivery to spine lesions) were considered of high concern in view of the high RPN and/or severity index value. Conclusions The analysis of the potential failures, their causes and effects allowed to improve the safety strategies already adopted in the clinical practice with additional measures for optimizing quality management workflow and increasing patient safety

The pandemic brain: Neuroinflammation in non-infected individuals during the COVID-19 pandemic

While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected remains underexplored. However, a global increase in the prevalence of fatigue, brain fog, depression and other “sickness behavior”-like symptoms implicates a possible dysregulation in neuroimmune mechanisms even among those never infected by the virus. We compared fifty-seven ‘Pre-Pandemic’ and fifteen ‘Pandemic’ datasets from individuals originally enrolled as control subjects for various completed, or ongoing, research studies available in our records, with a confirmed negative test for SARS-CoV-2 antibodies. We used a combination of multimodal molecular brain imaging (simultaneous positron emission tomography / magnetic resonance spectroscopy), behavioral measurements, imaging transcriptomics and serum testing to uncover links between pandemic-related stressors and neuroinflammation. Healthy individuals examined after the enforcement of 2020 lockdown/stay-at-home measures demonstrated elevated brain levels of two independent neuroinflammatory markers (the 18 kDa translocator protein, TSPO, and myoinositol) compared to pre-lockdown subjects. The serum levels of two inflammatory markers (interleukin-16 and monocyte chemoattractant protein-1) were also elevated, although these effects did not reach statistical significance after correcting for multiple comparisons. Subjects endorsing higher symptom burden showed higher TSPO signal in the hippocampus (mood alteration, mental fatigue), intraparietal sulcus and precuneus (physical fatigue), compared to those reporting little/no symptoms. Post-lockdown TSPO signal changes were spatially aligned with the constitutive expression of several genes involved in immune/neuroimmune functions. This work implicates neuroimmune activation as a possible mechanism underlying the non-virally-mediated symptoms experienced by many during the COVID-19 pandemic. Future studies will be needed to corroborate and further interpret these preliminary findings

Stable tracer investigations in humans for assessing the biokenetics of ruthenium and zirconium radionuclides.

The interest in the biokinetics of ruthenium and zirconium in humans is justified by the potential radiological risk represented by their radionuclides. Only a few data related to the biokinetics of ruthenium and zirconium in humans are available and, accordingly, the biokinetic models currently recommended by the ICRP for these elements are mainly based on data from animal experiments. The use of stable isotopes as tracers, coupled with a proper analytical technique (nuclear activation analysis with protons) for their determination in biological samples, represents an ethically acceptable methodology for biokinetic investigations, being free from any radiation risk for the volunteer subjects. In this work, the results obtained in eight biokinetic investigations for ruthenium, conducted on a total of three healthy volunteers, and six for zirconium, performed on a total of three subjects, are presented and compared to the predictions of the ICRP models

Honeycomb arrays of carbon nanotubes in alumina templates for field emission based devices and electron sources

anodicaluminiumoxide(AAO)templatehavebeeninvestigated.A50-mm-thickAAOtemplatewas fabricatedbyelectrochemicaltechniques.ThenanotubesweresynthesizedinaCVDquartzhotwall furnaceusingC2H2/N2 mixturesasfeedinggas. I–V measurementshavebeenperformedonsamplesafter the nanotubesgrowth(typeIsamples)andafterapartialAl2O3 removal(typeIIsamples)inorderto obtainsegmentsofnanotubesprotrudingfromthenanopores.Theeffectsoftheconditioningprocess and adsorbatesreleasehavebeeninvestigated.Theemissioncurveshavebeenanalysedinthe frameworkoftheFowler–Nordheimmodel.Forthe b factor enhancement,adifferentdependenceon time hasbeenevidencedfortwotypesofinvestigatedsamplesandhasbeententativelycorrelatedwith materialsmodificationsoccurringundertheHVpolarisation(incaseoftypeIsamples)andwiththe damageinducedbychemicaletching(incaseoftypeIIsamples).Thevaluesofemittedcurrentdensity (up to40mA/cm2) andtheemissionpropertiesindicatethattheproposedpreparationmethodologyis suitablefortherealizationofrobustandefficientCNT-basedfieldemissiondevicesandelectronsources

Sorafenib Dose Escalation Is Not Uniformly Associated With Blood Pressure Elevations in Normotensive Patients With Advanced Malignancies

Hypertension with vascular endothelial growth factor (VEGF) receptor inhibitors is associated with superior treatment outcomes for advanced cancer patients. To determine whether increased doses of sorafenib cause incremental increases in blood pressure (BP) we measured 12-hour ambulatory BP in 41 normotensive advanced solid tumor patients in a randomized dose escalation study. After 7 days’ sorafenib (400mg BID) mean diastolic BP (DBP) increased in both study groups. After dose escalation, group A (400mg TID) had marginally significant further increase in 12-hour mean DBP (p=0.053) but group B (600mg BID) did not achieve statistically significant increases (p=0.25). Within groups, individuals varied in BP response to sorafenib dose escalation, but these differences did not correlate with changes in steady state plasma sorafenib concentrations. These findings in normotensive patients suggest BP is a complex pharmacodynamic biomarker of VEGF inhibition. Patients have intrinsic differences in sensitivity to the BP elevating effects of sorafenib

DNA methylation of shelf, shore and open sea CpG positions distinguish high microsatellite instability from low or stable microsatellite status colon cancer stem cells

Aim: To investigate the genome-wide methylation of genetically characterized colorectal cancer stem cell (CR-CSC) lines. Materials & methods: Eight CR-CSC lines were isolated from primary colorectal cancer (CRC) tissues, cultured and characterized for aneuploidy, mutational status of CRC-related genes and microsatellite instability (MSI). Genome-wide DNA methylation was assessed by MethylationEPIC microarray. Results: We describe a distinctive methylation pattern that is maintained following in vivo passages in immune-compromised mice. We identified an epigenetic CR-CSC signature associated with MSI. We noticed that the preponderance of the differentially methylated positions do not reside at CpG islands, but spread to shelf and open sea regions. Conclusion: Given that CRCs with MSI-high status have a lower metastatic potential, the identification of a MSI-related methylation signature could provide new insights and possible targets into metastatic CRC