Modelling a new approach for radio-ablation after resection of breast ductal carcinoma in-situ based on the BAT-90 medical device

The majority of local recurrences, after conservative surgery of breast cancer, occurs in the same anatomical area where the tumour was originally located. For the treatment of ductal carcinoma in situ (DCIS), a new medical device, named BAT-90, (BetaGlue Technologies SpA) has been proposed. BAT-90 is based on the administration of 90Y β-emitting microspheres, embedded in a bio-compatible matrix. In this work, the Geant4 simulation toolkit is used to simulate BAT-90 as a homogenous cylindrical 90Y layer placed in the middle of a bulk material. The activity needed to deliver a 20 Gy isodose at a given distance z from the BAT-90 layer is calculated for different device thicknesses, tumour bed sizes and for water and adipose bulk materials. A radiobiological analysis has been performed using both the Poisson and logistic Tumour Control Probability (TCP) models. A range of radiobiological parameters (α and β), target sizes, and densities of tumour cells were considered. Increasing α values, TCP increases too, while, for a fixed α value, TCP decreases as a function of clonogenic cell density. The models predict very solid results in case of limited tumour burden while the activity/dose ratio could be further optimized in case of larger tumour beds.

The combined action of lead and physical load in a subchorionic experiment on rats

Introduction. Exposure to lead associated with working conditions (especially in mining and metallurgical production) is usually combined with muscular work. However, the influence of this combination on the pathological process development has not been thoroughly studied. Materials and methods. During six weeks, white outbred male rats received intraperitoneal lead acetate at a dose of 11 mg / kg, corresponding to 1/20 LD50, three times a week and/or five times a week physical exercises (forced running for 10 minutes at a speed of 25 m/min). Results. As can be seen from the results, lead caused statistically significant shifts in 33.5% of the organism’s status indices, pointing to the onset of a moderate subchronic intoxication. Content of coproporphyrin in urine and percentage of reticulocytes in the peripheral blood increased, the average content of haemoglobin in the erythrocyte decreased. Under physical activity the harmful effect of lead enhanced in 23.7% of indices and weakened in 28.9% of indices. We did not find changes in 47.4% of indices. Conclusion. Lead intoxication changes ambiguously under the influence of physical exercises. The type of combined effect of lead toxicity and physical activities depends on the outcome by which this type is assessed, on this outcome’s level and the dose ratio.

Inter Molecular Level Interaction Studies of Combination Drug Crizotinib And Temozolomide in Glioblastoma Multiforme Targets: An In-silico Approach

Combination drug treatments are frequently used in many diseases, including cancers and AIDS. The main aims of these treatments are to reduce toxicity, decrease or delay drug resistance, and improve drug efficacy by inhibiting the activity of a specific target or groups of targets in a cell. The net effect of combination drug efficacy is mainly quantified and interpreted by various terminologies like synergy, additive, agonism, and antagonism based on drugs dose ratio. In single or combination drug treatment, drug action occurs on cells due to the intermolecular level interaction of drugs with protein/DNA/RNA/Enzyme. This type of inter molecular level interaction can be detected with the help of docking software. The current study aims to identify the inter-molecular level interaction of combination drug Crizotinib and Temozolomide with C-MET, C-ROS1, and ALK targets in Glioblastoma Multiforme(GBM). To identify this, we performed forward and reverse docking of drugs with these proteins, and the results were evaluated by drug properties and the complex energy. From the analysis study, we recognized that first, Crizotinib and then, after Temozolomide bounded docked complexes showed the least complex energy in all the docked complex structures, and the better complexes were identified from the result by MD simulation.

Converging Proton Minibeams with Magnetic Fields for Optimized Radiation Therapy: A Proof of Concept

Proton MiniBeam Radiation Therapy (pMBRT) is a novel strategy that combines the benefits of minibeam radiation therapy with the more precise ballistics of protons to further optimize the dose distribution and reduce radiation side effects. The aim of this study is to investigate possible strategies to couple pMBRT with dipole magnetic fields to generate a converging minibeam pattern and increase the center-to-center distance between minibeams. Magnetic field optimization was performed so as to obtain the same transverse dose profile at the Bragg peak position as in a reference configuration with no magnetic field. Monte Carlo simulations reproducing realistic pencil beam scanning settings were used to compute the dose in a water phantom. We analyzed different minibeam generation techniques, such as the use of a static multislit collimator or a dynamic aperture, and different magnetic field positions, i.e., before or within the water phantom. The best results were obtained using a dynamic aperture coupled with a magnetic field within the water phantom. For a center-to-center distance increase from 4 mm to 6 mm, we obtained an increase of peak-to-valley dose ratio and decrease of valley dose above 50%. The results indicate that magnetic fields can be effectively used to improve the spatial modulation at shallow depth for enhanced healthy tissue sparing.

Effect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach

Background: Tacrolimus (Tac) is characterized by large between- and within-patient (IPV) variability in pharmacokinetics and exposure. Aim: This study aimed to assess and validate the effect of Tac IPV and trough concentration-to-dose ratio (C0/D) over 6–12 months on reduced estimated glomerular filtration rate (eGFR) values in the late period after kidney transplantation (Tx), applying Monte Carlo (MC) simulation. Methods: The previously published linear regression was the basis for MC simulation, performed to determine how variations in significant predictors affect the distribution of eGFR from 13 to 36 months post-transplantation. The input C0/D values were derived from CYP3A5 genotype subgroups. Results: Patients characterized by high Tac IPV and low mean C0/D over 6–12 months could have been at greater risk of lower eGFR values in a three-year period following Tx compared to the other patient groups. This effect was more pronounced in patients with a lower eGFR at the 6th month and a history of acute rejection. The proven contribution of CYP3A5 expresser genotype to low C0/D values may suggest its indirect effect on long-term graft function. Conclusion: The findings indicate that simultaneous assessment of Tac IPV, C0/D, and CYP3A5 genotype may identify patients at risk of deterioration of graft function in the long-term post-transplantation period.

Abstract 9160: Epinephrine-Dominant versus Non-Epinephrine Dominant Resuscitation for In-Hospital Cardiac Arrest

Introduction: Vasopressors are used during CPR to increase arterial resistance and aortic diastolic pressure, improving coronary perfusion and likelihood of ROSC. In comparison to epinephrine, vasopressin remains effective in an acidemic environment, has favorable cerebral perfusion, and does not directly increase myocardial oxygen demand. Studies comparing epinephrine and vasopressin report variable ROSC, survival, and neurological outcome. Most studies used few vasopressin doses and it is unclear whether greater vasopressin use leads to clinical benefit. Hypothesis: We hypothesized that a non-epinephrine dominant CPR approach with vasopressin would lead to greater ROSC than an epinephrine-dominant approach. Methods: This was a retrospective, single-center study conducted at an 800-bed academic medical center. All first cardiac arrests among adult inpatients between Jan 2018 and Mar 2021 were screened, and those with at least 2 vasopressor doses used were included. Patients who received epinephrine-dominant resuscitation (epinephrine-to-vasopressin dose ratio >2 or CPR using only epinephrine) were compared to patients who received a non-epinephrine dominant approach (epinephrine-to-vasopressin dose ratio ≤2). The incidence of ROSC was analyzed using a Chi-squared test where p <0.05 was considered significant. Secondary outcomes included survival to discharge with favorable neurologic outcome, survival to discharge, and Cerebral Performance Category scores. Results: Of 663 in-hospital cardiac arrests screened, 264 were included. Two hundred twenty-eight (86%) presented with PEA/asystole as the initial rhythm, and the most common etiologies were circulatory (41%) and respiratory (26%). The epinephrine-dominant arm achieved ROSC in 89 (66%) patients compared to 87 (67%) patients in the non-epinephrine dominant arm (RR 0.99, 95% CI 0.84-1.18, p=0.93). Survival to discharge was higher in the epinephrine-dominant arm (25% vs 15%, p=0.04). Conclusion: There was no difference in ROSC between epinephrine-dominant and non-epinephrine dominant resuscitation for adult in-hospital cardiac arrest. Future studies should examine the impact of non-epinephrine dominant CPR on long term neurologic outcomes.

Tumor-to-normal tissue (T/N) dosimetry ratios role in assessment of 90Y selective internal radiation therapy (SIRT)

Objective: The purpose of our work is to assess the role of tumor-to-normal tissue (T/N) dosimetry ratios for predicting response in patients undergoing locoregional therapy to the liver with 90Y microspheres. Methods: 39 patients (seven femal:32 male, mean age 68.3 ± 7.6y), underwent PET/CT imaging after treatment with 90Y microspheres. For attenuation correction and localization of the 90Y microspheres, the low dose, non-diagnostic CT images from PET/CT were used. The acquisition took 15 min and the reconstruction matrix size was 200 × 200×75 mm and voxel size of 4.07 × 4.07×3.00 mm. For dosimetry calculations the local deposition method with known activity of 90Y was used. For each patient, regions-of-interest (ROIs) for tumor(s) and whole liver were manually created; the normal tissue ROI was created automatically. mRECIST criteria on MRI done at a month post treatment and subsequently every three months after90Y treatment, were used to assess response. Results: For 39 patients, the mean liver, tumor and normal tissue doses (mean ± SD) were, 55.17 ± 26.04 Gy, 911.87 ± 866.54 Gy and 47.79 ± 20.47 Gy respectively. Among these patients, 31 (79%) showed complete response (CR) and 8 (21%) showed progression of disease (PD). For patients with CR, the mean T/N dose ratio obtained was 24.91 (range 3.09–80.12) and for patients with PD, the mean T/N dose ratio was significantly lower, at 6.69 (range 0.36–14.75). Conclusion: Our data shows that patients with CR have a statistically higher T/N dose ratio than those with PD. Because, the number of PD cases was limited and partial volume effect was not considered, further investigation is warranted. Advances in knowledge: Tumor-to-normal tissue dosimetry ratios can be used for assessing response in patients undergoing locoregional therapy to the liver with 90Y microspheres.

Interactions Between Remimazolam and Propofol in Combination With Sufentanil for Anesthesia During Gastroscopy

Background This study was conducted to determine how remimazolam and propofol interact when given with sufentanil. Methods In this single-arm study, patients were assigned to one of five groups. The sample size was not determined in advance. When the median effective dose(ED50) and 95% confidence intervals were calculated, participants were stopped. The study included 159 patients who were scheduled for a gastrointestinal endoscopic examination and had an American Society of Anesthesiologists physical status of I/II. Patients were intravenously administered sufentanil (0.1 µg/kg), along with different doses of remimazolam and propofol depending on the group to which they were assigned. The endpoint for an effective response was the disappearance of the bilateral eyelash reflex. The up-and-down method was used to determine the ED50 within each treatment group. The ED50 deviations from the additive line were analyzed using isoradiometric analysis. The interaction coefficients were calculated by algebraic analysis. Interval estimation is used in statistical inference. Results In combination with sufentanil, the ED50 of remimazolam and propofol was determined to be 0.065 (0.057-0.074) mg/kg and 0.657 (0.590-0.724) mg/kg, respectively. After sufentanil administered, when 0.25, 0.5, and 0.75 ED50 remimazolam were given in combination with propofol, the interaction coefficients were 1.03,1.2and 1.08, respectively. Conclusions The dose of propofol with remimazolam may need to be reduced regardless of the additive or synergistic effect. There was a strong synergistic effect when the dose ratio of the two drugs was about 6:1 in mg/kg. Trial registration: The project was retrospectively registered on October 26, 2021 in Chinese clinical trial center with the registration number of ChiCTR2100052425.

Clinical implications of concentration of alveolar nitric oxide in asthmatic and non-asthmatic subacute cough

Background and objective: Asthma is one of the important causes of subacute cough. Concentration of alveolar nitric oxide (CANO) is a sensitive inflammatory indicator of peripheral airways, which has received much less attention than fraction of exhaled nitric oxide (FeNO50). The main objective of this study was to explore the correlation between CANO and clinical parameters in asthmatic and non-asthmatic subacute cough, which might promote understanding the clinical utility of CANO in these special patient population. Materials and methods: 155 patients with subacute cough were included consecutively, of which 25 were diagnosed as asthma. Data for demographic characteristics, FeNO50, CANO, baseline spirometry, bronchial provocation test (or bronchodilation test) and response dose ratio (RDR) was collected. Differences between asthmatic and non-asthmatic group were analyzed. Spearman’s correlation coefficient (rho) was used to evaluate the correlation between FeNO50, CANO and other clinical parameters. Results: In patients with subacute cough, baseline CANO values did not differ between asthmatic and non-asthmatic patients (4.4(1.3, 11.4) versus 4.0(2.1, 6.8) ppb, P>0.05). Besides, CANO exhibited stronger association with pulmonary function parameters when compared with FeNO50. For asthmatic subacute cough, CANO was inversely correlated with FEV1/FVC (rho=-0.69, P<0.01) and small airway parameters including MEF25 (rho=-0.47, P<0.05) and MMEF (rho=-0.45, P<0.05). For non-asthmatic subacute cough, CANO was inversely correlated with MEF25 (rho=-0.19, P<0.05) and RDR (rho=-0.21, P<0.05). Conclusion: In subacute cough, asthmatic and non-asthmatic patients had similar values of baseline CANO. In both asthmatic and non-asthmatic subacute cough, CANO exhibited stronger association with pulmonary function parameters when compared with FeNO50. A low CANO value in non-asthmatic subacute cough corresponded to a higher value of RDR, which implied stronger tendency towards airway responsiveness.