Compartmentalized role of xCT in supporting pancreatic tumor growth, inflammation and mood disturbance in mice.

xCT (Slc7a11), the specific subunit of the cystine/glutamate antiporter system xc-, is present in the brain and on immune cells, where it is known to modulate behavior and inflammatory responses. In a variety of cancers -including pancreatic ductal adenocarcinoma (PDAC)-, xCT is upregulated by tumor cells to support their growth and spread. Therefore, we studied the impact of xCT deletion in pancreatic tumor cells (Panc02) and/or the host (xCT-/- mice) on tumor burden, inflammation, cachexia and mood disturbances. Deletion of xCT in the tumor strongly reduced tumor growth. Targeting xCT in the host and not the tumor resulted only in a partial reduction of tumor burden, while it did attenuate tumor-related systemic inflammation and prevented an increase in immunosuppressive regulatory T cells. The latter effect could be replicated by specific xCT deletion in immune cells. xCT deletion in the host or the tumor differentially modulated neuroinflammation. When mice were grafted with xCT-deleted tumor cells, hypothalamic inflammation was reduced and, accordingly, food intake improved. Tumor bearing xCT-/- mice showed a trend of reduced hippocampal neuroinflammation with less anxiety- and depressive-like behavior. Taken together, targeting xCT may have beneficial effects on pancreatic cancer-related comorbidities, beyond reducing tumor burden. The search for novel and specific xCT inhibitors is warranted as they may represent a holistic therapy in pancreatic cancer.

Children born after assisted reproduction more commonly carry a mitochondrial genotype associating with low birthweight.

Children conceived through assisted reproductive technologies (ART) have an elevated risk of lower birthweight, yet the underlying cause remains unclear. Our study explores mitochondrial DNA (mtDNA) variants as contributors to birthweight differences by impacting mitochondrial function during prenatal development. We deep-sequenced the mtDNA of 451 ART and spontaneously conceived (SC) individuals, 157 mother-child pairs and 113 individual oocytes from either natural menstrual cycles or after ovarian stimulation (OS) and find that ART individuals carried a different mtDNA genotype than SC individuals, with more de novo non-synonymous variants. These variants, along with rRNA variants, correlate with lower birthweight percentiles, independent of conception mode. Their higher occurrence in ART individuals stems from de novo mutagenesis associated with maternal aging and OS-induced oocyte cohort size. Future research will establish the long-term health consequences of these changes and how these findings will impact the clinical practice and patient counselling in the future.

Introduction of ultra-hypofractionation in breast cancer: Implications for costs and resource use.

PURPOSE: A shift towards (ultra-)hypofractionated breast irradiation can have important implications for the practice of contemporary radiation oncology. This paper presents a systematic analysis of the impact of different fractionation schedules on multiple key performance indicators, namely resource use, costs, work times, throughput and waiting times. MATERIALS AND METHODS: Time-driven activity-based costing (TD-ABC) is applied to calculate the costs and resources consumed where the perspective of the radiotherapy department in adopted. Three fractionation regimens are considered: ultra-hypofractionation (5 x 5.2 Gy, UHF), moderate hypofractionation (15 x 2.67 Gy, HF) and conventional fractionation (25 x 2 Gy, CF). Subsequently, a discrete event simulation (DES) model of the radiotherapy care pathway is developed and scenarios are compared in which the following factors are varied: distribution of fractionation regimens, patient volume and operating hours. RESULTS: The application of (U)HF can permit radiotherapy departments to reduce the use of scarce resources, realise work time and cost savings, increase throughput and reduce waiting times. The financial advantages of (U)HF are, however, reduced in cases of excess capacity and cost savings may therefore be limited in the short-term. Moreover, although an extension of operating hours has favourable effects on throughput and waiting times, it may also reduce cost differences between fractionation schedules by increasing the capacity of resources. CONCLUSION: By providing an in-depth analysis of the consequences associated with a shift towards (U)HF in breast cancer, the present study demonstrates how a DES model based on TD-ABC costing can assist radiotherapy professionals in making data-driven decisions.

The DS-14 questionnaire: psychometric characteristics and utility in patients with obstructive sleep apnea.

Little is known about type D personality in patients with obstructive sleep apnea (OSA). The DS-14 questionnaire is the standard tool to assess this personality type, but it has not been properly validated in patients with OSA, nor has it been correlated with clinical features in these patients. PURPOSE: To determine the internal consistency and test-retest reliability of the DS-14 questionnaire, as well as the prevalence of type D personality in the overall OSA sample and subgroups. We assessed the influence of type D on perceived symptoms and its congruence with self-reported measures of personality, depression, fatigue, anxiety, quality of life, and quality of sleep. METHODS: Patients with OSA completed the DS-14 questionnaire, Big Five Inventory-2 questionnaire, Hospital Anxiety and Depression Scale, SF-36 Health Survey Questionnaire, Epworth Sleepiness Scale and Stanford Sleepiness Scale, Pittsburgh Sleep Quality Index and Insomnia Severity Index, Fatigue Assessment Scale, and Checklist Individual Strength. After 1 month, the DS-14 questionnaire was repeated. RESULTS: The overall prevalence of type D personality was 32%. Internal consistency (negative affectivity: α = 0.880, social inhibition: α = 0.851) and diagnostic test-retest reliability (kappa value = 0.664) of the DS-14 questionnaire were high. Significantly more symptoms of anxiety, depression, poor sleep quality, fatigue, and a worse health perception were found in OSA with type D. Neither OSA severity nor REM predominance altered these observations. CONCLUSION: The DS-14 questionnaire showed excellent psychometric properties in patients with OSA. The prevalence of type D personality in patients with OSA was higher than in the general population. The presence of type D personality was associated with higher symptom burden.

Nanobody-mediated SPECT/CT imaging reveals the spatiotemporal expression of programmed death-ligand 1 in response to a CD8+ T cell and iNKT cell activating mRNA vaccine.

Rationale: Although promising responses are obtained in patients treated with immune checkpoint inhibitors targeting programmed death ligand 1 (PD-L1) and its receptor programmed death-1 (PD-1), only a fraction of patients benefits from this immunotherapy. Cancer vaccination may be an effective approach to improve the response to immune checkpoint inhibitors anti-PD-L1/PD-1 therapy. However, there is a lack of research on the dynamics of PD-L1 expression in response to cancer vaccination. Methods: We performed non-invasive whole-body imaging to visualize PD-L1 expression at different timepoints after vaccination of melanoma-bearing mice. Mice bearing ovalbumin (OVA) expressing B16 tumors were i.v. injected with the Galsome mRNA vaccine: OVA encoding mRNA lipoplexes co-encapsulating a low or a high dose of the atypical adjuvant α-galactosylceramide (αGC) to activate invariant natural killer T (iNKT) cells. Serial non-invasive whole-body immune imaging was performed using a technetium-99m (99mTc)-labeled anti-PD-L1 nanobody, single-photon emission computerized tomography (SPECT) and X-ray computed tomography (CT) images were quantified. Additionally, cellular expression of PD-L1 was evaluated with flow cytometry. Results: SPECT/CT-imaging showed a rapid and systemic upregulation of PD-L1 after vaccination. PD-L1 expression could not be correlated to the αGC-dose, although we observed a dose-dependent iNKT cell activation. Dynamics of PD-L1 expression were organ-dependent and most pronounced in lungs and liver, organs to which the vaccine was distributed. PD-L1 expression in lungs increased immediately after vaccination and gradually decreased over time, whereas in liver, vaccination-induced PD-L1 upregulation was short-lived. Flow cytometric analysis of these organs further showed myeloid cells as well as non-immune cells with elevated PD-L1 expression in response to vaccination. SPECT/CT imaging of the tumor demonstrated that the expression of PD-L1 remained stable over time and was overall not affected by vaccination although flow cytometric analysis at the cellular level demonstrated changes in PD-L1 expression in various immune cell populations following vaccination. Conclusion: Repeated non-invasive whole-body imaging using 99mTc-labeled anti-PD-L1 nanobodies allows to document the dynamic nature of PD-L1 expression upon vaccination. Galsome vaccination rapidly induced systemic upregulation of PD-L1 expression with the most pronounced upregulation in lungs and liver while flow cytometry analysis showed upregulation of PD-L1 in the tumor microenvironment. This study shows that imaging using nanobodies may be useful for monitoring vaccine-mediated PD-L1 modulation in patients and could provide a rationale for combination therapy. To the best of our knowledge, this is the first report that visualizes PD-L1 expression upon cancer vaccination.

Neuromuscular end-point predictive capability of published rocuronium pharmacokinetic/pharmacodynamic models: An observational trial.

BACKGROUND: Objective neuromuscular monitoring remains the single most reliable method to ensure optimal perioperative neuromuscular management. Nevertheless, the prediction of clinical neuromuscular endpoints by means of Pharmacokinetic (PK) and Pharmacodynamic (PD) modelling has the potential to complement monitoring and improve perioperative neuromuscular management.s STUDY OBJECTIVE: The present study aims to assess the performance of published Rocuronium PK/PD models in predicting intraoperative Train-of-four (TOF) ratios when benchmarked against electromyographic TOF measurements. DESIGN: Observational trial. SETTING: Tertiary Belgian hospital, from August 2020 up to September 2021. PATIENTS AND INTERVENTIONS: Seventy-four patients undergoing general anaesthesia for elective surgery requiring the administration of rocuronium and subject to continuous EMG neuromuscular monitoring were included. PK/PD-simulated TOF ratios were plotted and synchronised with their measured electromyographic counterparts and their differences analysed by means of Predictive Error derivatives (Varvel criteria). MAIN RESULTS: Published rocuronium PK/PD models overestimated clinically registered TOF ratios. The models of Wierda, Szenohradszky, Cooper, Alvarez-Gomez and McCoy showed significant predictive consistency between themselves, displaying Median Absolute Performance Errors between 38% and 41%, and intra-individual differences (Wobble) between 14 and 15%. The Kleijn model outperformed the former with a lower Median Absolute Performance Error (16%, 95%CI [0.01; 57]) and Wobble (11%, 95%CI [0.01; 34]). All models displayed considerably wide 95% confidence intervals for all performance metrics, suggesting a significantly variable performance. CONCLUSIONS: Simulated TOF ratios based on published PK/PD models do not accurately predict real intraoperative TOF ratio dynamics. TRIAL REGISTRATION: NCT04518761 (clinicaltrials.gov), registered on 19 August 2020.

Neurofilament light chain: A possible fluid biomarker in the intrahippocampal kainic acid mouse model for chronic epilepsy?

OBJECTIVE: In the management of epilepsy, there is an ongoing quest to discover new biomarkers to improve the diagnostic process, the monitoring of disease progression, and the evaluation of treatment responsiveness. In this regard, biochemical traceability in biofluids is notably absent in contrast to other diseases. In the present preclinical study, we investigated the potential of neurofilament light chain (NfL) as a possible diagnostic and response fluid biomarker for epilepsy. METHODS: We gained insights into NfL levels during the various phases of the intrahippocampal kainic acid mouse model of temporal lobe epilepsy-namely, the status epilepticus (SE) and the chronic phase with spontaneous seizures. To this end, NfL levels were determined directly in the cerebral interstitial fluid (ISF) with cerebral open flow microperfusion as sampling technique, as well as in cerebrospinal fluid (CSF) and plasma. Lastly, we assessed whether NfL levels diminished upon curtailing SE with diazepam and ketamine. RESULTS: NfL levels are higher during SE in both cerebral ISF and plasma in kainic acid-treated mice compared to sham-injected mice. Additionally, ISF and plasma NfL levels are lower in mice treated with diazepam and ketamine to stop SE compared with the vehicle-treated mice. In the chronic phase with spontaneous seizures, higher NfL levels could only be detected in ISF and CSF samples, and not in plasma. No correlations could be found between NfL levels and seizure burden, nor with immunohistological markers for neurodegeneration/inflammation. SIGNIFICANCE: Our findings demonstrate the translational potential of NfL as a blood-based fluid biomarker for SE. This is less evident for chronic epilepsy, as in this case higher NfL levels could only be detected in ISF and CSF, and not in plasma, acknowledging the invasive nature of CSF sampling in chronic epilepsy follow-up.

Validity and reliability of Eforto®, a system to (self-)monitor grip strength and muscle fatigability in older persons.

INTRODUCTION: We developed Eforto®, an innovative system for (self-)monitoring of grip strength (GS) and muscle fatigability (Fatigue Resistance (FR = time until GS decreased to 50% of maximum during sustained contraction) and grip work (GW = area under the strength-time curve)). The Eforto® system consists of a rubber bulb that is wirelessly connected to a smartphone-based application, and a telemonitoring platform. The aim was to evaluate the validity and reliability of Eforto® to measure muscle fatigability. METHODS: Community-dwelling older persons (n = 61), geriatric inpatients (n = 26) and hip fracture patients (n = 25) were evaluated for GS and muscle fatigability. In community dwellers fatigability was tested twice in the clinic (once with Eforto®, once with Martin Vigorimeter (MV), standard analog handgrip system) and for six consecutive days as a self-assessment at home with Eforto®. In hospitalized participants, fatigability was tested twice using Eforto®, once by a researcher and once by a health professional. RESULTS: Criterion validity was supported by good to excellent correlations between Eforto® and MV for GS (r = 0.95) and muscle fatigability (FR r = 0.81 and GW r = 0.73), and no significant differences in measurements between both systems. Inter-rater and intra-rater reliability for GW were moderate to excellent (intra-class correlation: 0.59-0.94). The standard error of measurement for GW was small for geriatric inpatients and hip fracture patients (224.5 and 386.5 kPa*s) and higher for community-dwellers (661.5 kPa*s). DISCUSSION/CONCLUSION: We established the criterion validity and reliability of Eforto® in older community-dwelling persons and hospitalized patients, supporting the implementation of Eforto® for (self-)monitoring of muscle fatigability.

Qualitative plasma viral load determination as a tool for screening of viral reservoir size in PWH.

OBJECTIVES: Suppression of viral replication in patients on antiretroviral therapy (ART) is determined by plasma viral load (pVL) measurement. Whenever pVL reaches values below the limit of quantification, the qualitative parameter 'target detected' or 'target not detected' is available but often not reported to the clinician. We investigated whether qualitative pVL measurements can be used to estimate the viral reservoir size. DESIGN: The study recruited 114 people with HIV (PWH) who are stable on ART between 2016 and 2018. The percentage of pVL measurements qualitatively reported as 'target detected' (PTD) within a 2-year period was calculated. METHODS: t-DNA and US-RNA were used to estimate viral reservoir size and were quantified on peripheral blood mononuclear cells (PBMCs) using droplet digital PCR. RESULTS: A median of 6.5 pVL measurements over a 2-year period was evaluated for each participant to calculate PTD. A positive correlation was found between t-DNA and PTD (r = 0.24; P = 0.011) but not between US-RNA and PTD (r = 0.1; P = 0.3). A significantly lower PTD was observed in PWH with a small viral reservoir, as estimated by t-DNA less than 66 copies/106 PBMCs and US-RNA less than 10 copies/106 PBMCs, compared with PWH with a larger viral reservoir (P = 0.001). We also show that t-DNA is detectable whenever PTD is higher than 56% and that ART regimen does not affect PTD. CONCLUSION: Our study shows that PTD provides an efficient parameter to preselect participants with a small viral reservoir based on already available pVL data for future HIV cure trials.

Optimization of Performance by Combining Most Sensitive and Specific Models in Data Science Results in Majority Voting Ensemble.

Ensemble modeling is an increasingly popular data science technique that combines the knowledge of multiple base learners to enhance predictive performance. In this paper, the idea was to increase predictive performance by holding out three algorithms when testing multiple classifiers: (a) the best overall performing algorithm (based on the harmonic mean of sensitivity and specificity (HMSS) of that algorithm); (b) the most sensitive model; and (c) the most specific model. This approach boils down to majority voting between the predictions of these three base learners. In this exemplary study, a case of identifying a prolonged QT interval after administering a drug-drug interaction with increased risk of QT prolongation (QT-DDI) is presented. Performance measures included accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Overall performance was measured by calculating the HMSS. Results show an increase in all performance measure characteristics compared to the original best performing algorithm, except for specificity where performance remained stable. The presented approach is fairly simple and shows potential to increase predictive performance, even without adjusting the default cut-offs to differentiate between high and low risk cases. Future research should look at a way of combining all tested algorithms, instead of using only three. Similarly, this approach should be tested on a multiclass prediction problem.

The Effect of a Pain Educational Video Upon Child Pain-Related Memory and the Moderating Role of Parental Pain- and Non-Pain-Attending Verbalizations: An Experimental Lab-Based Study.

OBJECTIVES: Early memories of pain contribute to fear and may underlie the maintenance and development of chronic pain into adulthood. Accordingly, understanding determinants that may impact children's pain memory development is key. This study examined (a) the effect of a brief engaging pain educational video in healthy children before undergoing an experimental pain task upon children's recalled pain intensity and pain-related fear and (b) the moderating role of parental pain- and non-pain-attending verbalizations before and after the pain task. METHODS: Seventy-seven children (8-15 years old) participated in an experimental heat pain task, including actual heat pain stimuli delivered through a thermode on their forearm. Children were randomized to the experimental group (i.e., watching a pain educational video) or the control group (i.e., no video). Children's recalled pain intensity and pain-related fear were elicited 2 weeks later. RESULTS: Findings showed that recalled pain intensity (but not recalled pain-related fear) of children who watched the pain educational video was significantly lower compared to the control group (p = .028). Further, parental pain-attending verbalizations before the pain task moderated the impact of the video upon children's recalled pain intensity (p = .038). Specifically, children in the control group, but not the experimental group, whose parents used less pain-attending verbalizations recalled higher pain intensity, whereas children whose parents used more pain-attending verbalizations recalled lower pain intensity. CONCLUSIONS: As children's pain memories have important implications for pain assessment, treatment, and health across the lifespan, these findings might have important implications for the prevention of development or maintenance of maladaptive pain-related outcomes.

Group sequential designs for in vivo studies: Minimizing animal numbers and handling uncertainty in power analysis.

Interim analysis is the practice of performing a statistical analysis when the data have only been partially collected, for example, to save resources or to handle the uncertainty of the true effect size. Most statistical designs featuring interim analysis have been developed either in a general statistical setting or for application in clinical trials. As a result, most of them make assumptions and have conditions that in a preclinical setting are usually not met. In this paper, we present necessary changes to the most common forms of interim analysis enhanced for animal experiments, specifically for the t-test and the one-way ANOVA. Finally, we present software that allows freeware use to serve the research community to facilitate the design of experiments featuring interim analyses. The app can be found at icds.be/gsdesigner. It is in the public domain and its code can be found on github.com/ICDS-vubUZ/gsd-designer. In this GitHub folder, one can also find a tutorial for the app.

Lifespan extension with preservation of hippocampal function in aged system xc--deficient male mice.

The cystine/glutamate antiporter system xc- has been identified as the major source of extracellular glutamate in several brain regions as well as a modulator of neuroinflammation, and genetic deletion of its specific subunit xCT (xCT-/-) is protective in mouse models for age-related neurological disorders. However, the previously observed oxidative shift in the plasma cystine/cysteine ratio of adult xCT-/- mice led to the hypothesis that system xc- deletion would negatively affect life- and healthspan. Still, till now the role of system xc- in physiological aging remains unexplored. We therefore studied the effect of xCT deletion on the aging process of mice, with a particular focus on the immune system, hippocampal function, and cognitive aging. We observed that male xCT-/- mice have an extended lifespan, despite an even more increased plasma cystine/cysteine ratio in aged compared to adult mice. This oxidative shift does not negatively impact the general health status of the mice. On the contrary, the age-related priming of the innate immune system, that manifested as increased LPS-induced cytokine levels and hypothermia in xCT+/+ mice, was attenuated in xCT-/- mice. While this was associated with only a very moderate shift towards a more anti-inflammatory state of the aged hippocampus, we observed changes in the hippocampal metabolome that were associated with a preserved hippocampal function and the retention of hippocampus-dependent memory in male aged xCT-/- mice. Targeting system xc- is thus not only a promising strategy to prevent cognitive decline, but also to promote healthy aging.

Effect of air temperature on human births, preterm births and births associated with maternal hypertension.

OBJECTIVE: We studied potential effects of outdoor air temperatures or barometric pressure on births, preterm births and births associated with maternal hypertension. METHODS: 12,269 births were retrospectively reviewed in Brussel and 25,880 in South Reunion Island. National Belgium and French weather reference centers provided outdoor air temperatures and barometric pressures from the nearest weather stations on the corresponding birthdays. Poisson regression models were used to assess if outdoor air temperatures or barometric pressure could be correlated, immediately and several days later, with the number of daily births, preterm births and births associated with hypertension. RESULTS: Outdoor air temperature was significantly correlated to the number of daily births in Brussels. For each additional degree Celsius, overall births increased by 0.4% during the same day. Four days later, overall births increased by 1.8%, preterm births by 2.6% and births associated with hypertension by 5.7%. Similar observations on numbers of daily births were reported in South Reunion Island, without reaching statistical significance (p = .08). CONCLUSION: As previously demonstrated in recent studies, increased air temperature leads progressively to higher rates of births and preterm births. An even stronger delayed effect of air temperature was observed on births associated with hypertension. This would be worth further investigating.

Estimating lung cancer and cardiovascular mortality in female breast cancer patients receiving radiotherapy.

By integrating data of the PLCO cancer screening trial, SCORE-risk charts and radiotherapy excess ratios, we were able to create risk charts estimating radiotherapy-induced lung cancer and cardiovascular mortality in female breast cancer patients. These risk models might be useful to individualize radiotherapy and optimize lung cancer and cardiovascular prevention and screening.

Predictors of dopamine agonist resistance in prolactinoma patients.

BACKGROUND: Surgical resection of prolactinomas resistant to dopamine agonists is frequently incomplete due to fibrotic changes of the tumour under pharmacological therapy. In order to identify a subgroup of patients who may benefit from early surgery, we thought to investigate possible predictive factors of pharmacological resistance of prolactinomas to dopamine agonists. METHODS: We retrospectively analyzed a database of a Belgian tertiary reference center for patients with pituitary tumours from 2014 to 2016. The groups of interest were patients with dopamine agonist responsive and resistant prolactinomas. The possible predictive factors, including MRI findings, endocrinological parameters, response of tumour and patient factors for dopamine agonist resistance were investigated. RESULTS: We included 69 patients of whom 52 were women (75,4%) and 17 were men (24,6%). Rate of dopamine agonist resistance was 15.9%. We identified four significant predictors of dopamine agonist resistance: male gender, a large tumour volume, prolonged time to prolactin normalization and presence of a cystic, hemorrhagic and/or necrotic component. In addition, symptoms due to mass effect, high baseline prolactin level and a high contrast capture on MRI are factors that can be taken into consideration. CONCLUSION: We identified predictive factors for pharmacological resistance and developed a scoring system for patient specific prediction of resistance to dopamine agonists. This scoring system may have impact on the timing and decision of surgery in prolactinoma patients after further prospective evaluation.

Improving the Diagnosis of Nonfunctional Overreaching and Overtraining Syndrome.

INTRODUCTION: This study aimed to simplify and optimize the distinction between nonfunctional overreaching (NFO) and overtraining syndrome (OTS) by developing a multivariate approach (discriminant analysis [DA]) including hormonal and psychological changes measured during the Training Optimization (TOP) test. METHODS: Sensitivity of previously defined cutoff values for hypothalamic-pituitary-adrenal axis hormonal changes were recalculated on a larger database (n = 100). Discriminant analysis including hormonal and psychological variables measured during the TOP test was used to discriminate between NFO and OTS and predict the diagnosis of new cases. RESULTS: Adrenocorticotrophic hormone (ACTH) and prolactin (PRL) responses to the second exercise test were most sensitive to NFO and OTS. Cutoff values for ACTH and PRL response to the second test (NFO > cutoff value (200%) > OTS), showed a sensitivity of 67% for ACTH and 93% for PRL in case of OTS and 74% for both ACTH and PRL in case of NFO. A DA including hormonal and psychological changes measured during the TOP test, resulted in the accurate diagnosis of NFO and OTS with 98% sensitivity. The ACTH and PRL responses to the first and second exercise tests and feeling of fatigue were the most discriminating variables. CONCLUSIONS: The ACTH and PRL responses during the TOP test are the most sensitive markers to discriminate between NFO and OTS. Discriminant analysis including hormonal and psychological responses during the TOP test, can be used to optimize the diagnosis of NFO and OTS.

The METABANK score: A clinical tool to predict survival after stereotactic radiotherapy for oligometastatic disease.

BACKGROUND AND PURPOSE: Stereotactic radiotherapy (SRT, SBRT) is widely used in oligometastatic cancer, but the heterogeneity of the population complicates estimation of the prognosis. We investigated the role of different clinical and inflammatory parameters. MATERIALS AND METHODS: We included all patients treated with SRT for 1-5 oligometastases between 2003 and 2017 in our center. Patients were randomized between a model training set (2/3) and a separate validation set (1/3). A Cox regression model was built, validated and risk points were attributed to the resulting parameters. RESULTS: 403 patients received SRT for 760 metastases. Treated sites were mainly lung, liver, nodal areas, and brain. Most common primaries were colorectal and lung cancer. Median follow-up for living patients reached 42 months and median overall survival (MS) was 26.6 months (95% CI 23.8-29.3). Five independent adverse factors were discriminated: male sex, synchronous timing of oligometastases, brain metastasis, non-adenocarcinoma histology, KPS <80. A risk score is formed by summation of the points of each factor (M:4, T:2, B:7, N:7, K:8). Four risk groups were defined: (1) 0-2 points: MS 41.2 months (95% CI 30.2-52.3); (2) 3-8 points: 29.3 months (24.6-34.0); (3) 9-13 points: 17.4 months (10.1-24.7), and (4) 14-28 points: 7.9 months (5.5-10.3). CONCLUSION: We propose a prognostic score applicable in a variety of primary tumors and disease locations, including presence of brain metastases. The nomogram and risk groups can be used to stratify patients in new trials and to support individualized care for oligometastatic patients. An online calculator will become available at predictcancer.org.

Non-parametric frequency response function tissue modeling in bipolar electrosurgery.

High-frequency radio energy is applied to tissue therapeutically in a number of different medical applications. The ability to model the effects of RF energy on the collagen, elastin, and liquid content of the target tissue would allow for the refinement of the control of the energy in order to improve outcomes and reduce negative side-effects. In this paper, we study the time-varying impedance spectra of the circuit. It is expected that the collagen/elastin ratio does not change over time such that the time-varying impedance is a function of the liquid content. We apply a non-parametric model in which we characterize the measured impedance spectra by its frequency response function. The measurements indicate that the changing impedance as a function of time exhibit a polynomial shift which we characterize by a polynomial regression. Finally, we quantify the uncertainty to obtain prediction intervals for the estimated polynomial describing the time variation of the impedance spectra.

Glucose detection in human sweat using an electronic nose.

In the last years attempts to develop a non-invasive glucose system based on the glucose levels in sweat have been studied. In this paper, 32 metal oxide semiconductor (MOS) sensors operating at different temperatures have been used to develop a multisensor olfactory system that allows to study the glucose levels in sweat. In order to develop repeatable experiments, artificial sweat at different glucose concentrations were developed in the laboratory. The obtained results suggest high viability of the approach. Although, the sensitivity of the sensors system needs to be improved.