Detector for monitoring potential bleeding during electron intraoperative radiotherapy

Purpose: The aim of this work is to develop a bleeding detector integrated into the acrylic circular applicators for specific mobile linacs. Thus, a bleeding detector has been developed based on a capacitive sensor to be used with plastic applicators, as in the case of LIAC HWL from Sordina IORT Technologies SpA. According to the clinical impact, we have selected 0.5 cm as the minimum depth of fluid that should be detected. Methods: An experiment was developed using water-simulating blood. Two setups were considered: non-beveled applicators with 7 cm and 10 cm diameter. Measurements were done for applicators 0° and 45° tilted, both with respect to the horizontal surface, in order to mimic the worst clinical scenario according to the irradiation gantry and applicator bevel angle. The behavior of the detector under irradiation was analyzed and the impact of the stray radiation on the detector was also evaluated. Results: The detector was able to distinguish the presence of liquid at a minimum height of 0.5 cm. A linear behavior was obtained for both setups. We have also verified that the LIAC HWL radiation does not affect the measurements nor does the detector interfere with the stray radiation. The bleeding detector is a quasi-digital capacitive sensor with low-cost, high linearity, and easy to install. Conclusions: With this detector it is possible to perform a continuous monitoring of the liquid measurements even during the irradiation phase. Thus, it can operate not only as a pre-treatment detector but also as a continuous one

Improving bleeding detector features for electron intraoperative radiotherapy

Purpose: The aim of this work is to improve the potential bleeding detection during intraoperative radiotherapy with linac polymethyl methacrylate applicators (PMMA), based on one previously developed. The improvements carried out have been focused on: i) minimizing the impact of the detector on the visual through the plastic applicators and ii) avoiding the asymmetry in the detection capability when the applicator is tilted. Methods: Simulations have been made to select the geometry that provides a reduced visual impact on the applicator as well as allowing an independent response with the tilting angle of the applicator. A low-noise circuit for signal conditioning has been developed. Measurements have been made on three setups: 10 cm, 7 cm and 4 cm applicator diameters, 0° and 45° tilted. Results: The detector has a visibility through the applicator greater than 50%. Due to the geometry, optimal detection is ensured regardless of its orientation when the applicator is tilted. It is possible to detect the presence of fluid well below the typical perturbing fluid depth established by the clinic (1-1.5 cm). Conclusions: The detector can distinguish the presence of around 0.5 cm of fluid depth while showing a high visual field through the PMMA applicators and providing a measure that does not depend on the detector orientation when the applicator is tilted. The prototype is ready for its industrialization by embedding it into the applicator for clinical use. The detector would have a significant impact on both the quality assurance and the outcome of the treatment

Embedded bleeding detector into a PMMA applicator for electron intraoperative radiotherapy

Purpose: The aim of this work is to present a ready to industrialize low-cost and easy-to-install bleeding detector for use in intraoperative electron radiation therapy (IOERT). The detector works in stand-alone mode and is embedded into a translucent polymethylmethacrylate (PMMA) applicator avoiding any contact with the patient, which represent a novelty compared to previous designs. The use of this detector will prevent dose misadministration during irradiation in the event of accumulation of fluids in the applicator. Methods: The detector is based on capacitive sensor and wireless power-supply electronics. Both sensor and electronics have been embedded in the applicator, so that any contact with the patient would be avoided. Since access to the tumor can be done through different trajectories, the detector has been calibrated for different tilting angles. Results: The result of the calibration provides us with a fit curve that allows the interpolation of the results at any angle. Comparison of estimated fluid height vs real height gives an error of 1 mm for tilting angles less than 10º and 2 mm for tilting angles greater than 15º. This accuracy is better than the one required by clinic. Conclusions: The performance of the bleeding detector was evaluated in situ. No interference was observed between the detector and the beam. In addition, a user-friendly mobile application has been developed to help the surgical team making decisions before and during irradiation. The measurement provided by the mobile application was stable during the irradiation process

In vivo verification of treatment source dwell times in brachytherapy of postoperative endometrial carcinoma: a feasibility study

Background: In brachytherapy, there are still many manual procedures that can cause adverse events which can be detected with in vivo dosimetry systems. Plastic scintillator dosimeters (PSD) have interesting properties to achieve this objective such as real-time reading, linearity, repeatability, and small size to fit inside brachytherapy catheters. The purpose of this study was to evaluate the performance of a PSD in postoperative endometrial brachytherapy in terms of source dwell time accuracy. Methods: Measurements were carried out in a PMMA phantom to characterise the PSD. Patient measurements in 121 dwell positions were analysed to obtain the differences between planned and measured dwell times. Results: The repeatability test showed a relative standard deviation below 1% for the measured dwell times. The relative standard deviation of the PSD sensitivity with accumulated absorbed dose was lower than 1.2%. The equipment operated linearly in total counts with respect to absorbed dose and also in count rate versus absorbed dose rate. The mean (standard deviation) of the absolute differences between planned and measured dwell times in patient treatments was 0.0 (0.2) seconds. Conclusions: The PSD system is useful as a quality assurance tool for brachytherapy treatments

Extracellular histones trigger oxidative stress-dependent induction of the NF-kB/CAM pathway via TLR4 in endothelial cells.

Extracellular histones have been reported to aggravate different pathophysiological processes by increasing vascular permeability, coagulopathy, and inflammation. In the present study, we elucidate how extracellular histones (10-100 mu g/mL) concentration dependently increase cytosolic reactive oxygen species (ROS) production using human umbilical vein endothelial cells (HUVECs). Furthermore, we identify cyclooxygenase (COX) and NADPH oxidase (NOX) activity as sources of ROS production in extracellular histone-treated HUVEC. This COX/NOX-mediated ROS production is also involved in enhanced NF-kB activity and cell adhesion molecules (VCAM1 and ICAM1) expression in histone-treated HUVEC. Finally, by using different toll-like receptor (TLR) antagonists, we demonstrate the role of TLR4 in CAMs overexpression triggered by extracellular histones in endothelial cells. In conclusion, our data suggest that through TLR4 signaling, extracellular histones increase endothelial cell activation, a mechanism involving increased COX- and NOX-mediated ROS. These findings increase our understanding on how extracellular histones enhance systemic inflammatory responses in diseases in which histone release occurs as part of the pathological processes

High exposure to tacrolimus is associated to spontaneous remission of recurrent membranous nephropathy after kidney transplantation

Introduction We aimed to characterize the incidence and clinical presentation of membranous nephropathy (MN) after kidney transplantation (KT), and to assess allograft outcomes according to proteinuria rates and immunosuppression management. Methods Multicenter retrospective cohort study including patients from six Spanish centers who received a KT between 1991-2019. Demographic, clinical, and histological data were collected from recipients with biopsy-proven MN as primary kidney disease (n = 71) or MN diagnosed de novo after KT (n = 4). Results Up to 25.4% of patients with biopsy-proven MN as primary kidney disease recurred after a median time of 18.1 months posttransplant, without a clear impact on graft survival. Proteinuria at 3-months post-KT was a predictor for MN recurrence (rMN, HR 4.28; P = 0.008). Patients who lost their grafts had higher proteinuria during follow-up [1.0 (0.5-2.5) vs 0.3 (0.1-0.5) g/24 h], but only eGFR after recurrence treatment predicted poorer graft survival (eGFR < 30 ml/min: RR = 6.8). We did not observe an association between maintenance immunosuppression and recurrence diagnosis. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence (trough concentration/dose ratio: 2.86 vs 1.18; P = 0.028). Up to 94.4% of KT recipients received one or several treatments after recurrence onset: 22.2% rituximab, 38.9% increased corticosteroid dose, and 66.7% ACEi/ARBs. Only 21 patients had proper antiPLA2R immunological monitoring. Conclusions One-fourth of patients with biopsy-proven MN as primary kidney disease recurred after KT, without a clear impact on graft survival. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence.12 página

Safety, Fear and Neuromuscular Responses after a Resisted Knee Extension Performed to Failure in Patients with Severe Haemophilia

Background: low–moderate intensity strength training to failure increases strength and muscle hypertrophy in healthy people. However, no study assessed the safety and neuromuscular response of training to failure in people with severe haemophilia (PWH). The purpose of the study was to analyse neuromuscular responses, fear of movement, and possible adverse effects in PWH, after knee extensions to failure. Methods: twelve severe PWH in prophylactic treatment performed knee extensions until failure at an intensity of five on the Borg CR10 scale. Normalised values of amplitude (nRMS) and neuromuscular fatigue were determined using surface electromyography for the rectus femoris, vastus medialis, and vastus lateralis. After the exercise, participants were asked about their perceived change in fear of movement, and to report any possible adverse effects. Results: Patients reported no adverse effects or increased fear. The nRMS was maximal for all the muscles before failure, the median frequency decreased, and wavelet index increased during the repetitions. The vastus lateralis demonstrated a higher maximum nRMS threshold and earlier fatigue, albeit with a lower and more progressive overall fatigue. Conclusions: severe PWH with adequate prophylactic treatment can perform knee extensions to task failure using a moderate intensity, without increasing fear of movement, or adverse effects

EMG, Rate of Perceived Exertion, Pain, Tolerability and Possible Adverse Effects of a Knee Extensor Exercise with Progressive Elastic Resistance in Patients with Severe Haemophilia

In people with haemophilia (PWH), elastic band training is considered an optimal option, even though the literature is scarce. The aim was to evaluate normalized electromyographic amplitude (nEMG), rate of perceived exertion (RPE), pain, tolerability, and possible adverse effects during the knee extension exercise using multiple elastic resistance intensities in PWH. During a single session, 14 severe PWH undergoing prophylactic treatment performed knee extensions without resistance and with different intensity levels of elastic resistance. nEMG was measured for the knee extensors and participants rated their RPE, tolerability and pain intensity after each condition. Patients had to report the possible adverse effects after the session. In most of the cases, an nEMG increase is only evidenced after increasing the resistance by two to three levels. Significant associations were found between RPE and the nEMG (&rho; = 0.61), as well as between the elastic resistance level and nEMG (&rho; = 0.69) and RPE (&rho; = 0.71). All conditions were generally tolerated, without increased pain, and no adverse effects were reported. A wide variety of elastic resistance intensities during the knee extension are safe, tolerated, and do not increase knee pain in the majority of severe PWH undergoing prophylactic treatment

Epidemiology of invasive pneumococcal disease in older people in Spain (2007-2009): implications for future vaccination strategies

Background: Recently, the 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for adults. We analyzed the epidemiology of invasive pneumococcal disease (IPD) in older adults in Spain before PCV13 introduction. Methodology/Principal Findings: IPD episodes, defined as clinical findings together with an invasive pneumococcal isolate, were prospectively collected from patients aged over 65 years in three hospitals in Spain from 2007 to 2009. A total of 335 IPD episodes were collected. Pneumonia was the main clinical syndrome, while chronic obstructive pulmonary disease, diabetes mellitus and cancer were the main underlying diseases. Pneumococcal isolates were serotyped and the molecular typing was performed by PFGE/MLST. PCV13 serotypes accounted for 59.3% of isolates, the most prevalent being serotypes 19A (15.1%), 3 (9.6%), 7F (7.5%), 14 (6.9%) and 1 (5.4%). The most frequent non-PCV13 serotypes were serotypes 16F (4.5%), 22F (3.6%), 24F (3.3%) and 6C (2.1%). The most common genotypes were CC230 (8.5%, serotypes 19A and 24F), CC156 (8.2%, serotypes 9V and 14), ST191 (7.9%, serotype 7F), CC260 (6.6%, serotype 3), ST306 (5.2%, serotype 1), CC30 (4.6%, serotype 16F) and ST433 (3.6%, serotype 22F). Comparing the 335 IPD isolates to 174 invasive pneumococci collected at the same hospitals in 1999-2000, PCV7 serotypes decreased (45.4% vs 18.4%,p,0.001), non-PCV7 serotypes included in PCV13 increased (26.4% vs 41.0%,p = 0.001) and two non-PCV13 serotypes increased (serotype 6C 0% vs 2.1%, p = 0.05; serotype 24F 0.6% vs 3.3%, p = 0.04,). Conclusion: In our older adult population two serotypes (19A and 3) included in PCV13 accounted for about a quarter of IPD episodes in people $65 years. Non-PCV13 emerging serotypes should be carefully monitored in future surveillance studies