Aerosol Release, Distribution and Prevention during Aerosol Therapy: A Simulated Model for Infection Control.

Background: Aerosol therapy is used to deliver medical therapeutics directly to the airways to treat respiratory illnesses. A potential side-effect of this form of treatment is the release of fugitive aerosols into the environment and the exposure of caregivers, other patients, and bystanders to potential viral infections. The aim of this work was to use both flow visualisation and aerosol particle characterisation techniques to study the dispersion, concentrations and size distributions of fugitive aerosols emitted during aerosol therapy delivered via a standard mouthpiece.Methods: Aerosol therapy was delivered via a nebuliser, aerosol holding chamber and mouthpiece to a spontaneously breathing adult patient model that could mimic the release of patient-derived bioaerosol. A combination of laser and Schlieren imaging were used to non-invasively visualise the release and dispersion of fugitive aerosol particles. Time varying aerosol particle number concentrations and size distributions were measured with optical particle sizers at clinically relevant positions. Results: The addition of a capture filter to the expiratory port of the mouthpiece significantly reduced the release and spread of fugitive aerosols. Capture filters were effective in curtailing the release of fugitive aerosols of respirable size, ≤ 5 µm in diameter (P ≤ 0.05). Conclusions: The findings suggest that, where possible, capture filters should be added to the expiratory ports of all aerosol therapy devices to prevent airborne transmission of respiratory illnesses and create safer conditions for healthcare workers and patients.

Navigation of Frameless Fixation for Gammaknife Radiosurgery Using Fixed Augmented Reality

Augmented reality (AR) offers a new medical treatment approach. We aimed to evaluate frameless fixation navigation using a 3D-printed patient model with fixed-AR technology for gammaknife radiosurgery. Fixed-AR navigation was developed using the inside-out method with visual inertial odometry algorithms, and the flexible Quick Response (QR) marker was created for object-feature recognition. Virtual 3D-patient models for AR-rendering were created via 3D-scanning utilizing TrueDepth and cone-beam computed tomography (CBCT) to generate a new GammaKnife IconTM model. A 3D-printed patient model included fiducial markers, and virtual 3D-patient models were used to validate registration accuracy. Registration accuracy between initial frameless fixation and re-fixation navigated fixed-AR was validated through visualization. The quantitative method was validated through set-up errors, fiducial marker coordinates, and high-definition motion management (HDMM) values. 3D-printed models and virtual models were correctly overlapped under frameless fixation. Virtual models from both 3D-scanning and CBCT were enough to tolerate the navigated frameless re-fixation. Although the CBCT virtual model consistently delivered more accurate results, 3D-scanning was sufficient. Frameless re-fixation accuracy navigated in virtual models had mean set-up errors within 1 mm and 1.5° in all axes. Mean fiducial marker differences from coordinates in virtual models were within 2.5 mm in all axes, and mean 3D errors were within 3 mm. Mean HDMM difference values in virtual models were within 1.5 mm of initial HDMM values. The variability from navigation fixed-AR is enough to consider repositioning frameless fixation without CBCT scanning for treating patients fractionated with large multiple metastases lesions (>3 cm) who have difficulty enduring long beam-on time. This system could be applied to novel radiosurgery navigation for frameless fixation with reduced preparation time.

Computational Assessment of Hemodynamic Significance in Patients with Intramural Anomalous Aortic Origin of the Coronary Artery Using Virtually Derived Fractional Flow Reserve and Downstream Microvascular Resistance

Anomalous aortic origin of a coronary artery (AAOCA) is the second most common cause of sudden cardiac death in young athletes. One of the hypothesized mechanisms of ischemia in these patients is the lateral compression of the anomalous artery with an intramural or interarterial course. The presence of a narrowing in the anomalous artery will cause physiologic changes in downstream resistance that should be included for computational assessment of possible clinical ramifications. In the current study, we created different compression levels, i.e., proximal narrowing, in the intramural course of a representative patient model and calculated virtual fractional flow reserve (vFFR). Models also included the effect of the distal hyperemic microvascular resistance (HMR) on vFFR. Our results were in agreement with similar FFR studies indicating that FFR was increased with increasing HMR, and that different compression levels could have similar FFR depending on the HMR. For example, vFFR at HSR:1.0-1.3 and HMR: 2.30 mmHg/cm/s is 0.68 and close to vFFR at HSR:0.6-0.7 and HMR: 1.6 mmHg/cm/s, which is 0.7. The current findings suggest that functional assessment of anomalous coronary arteries through FFR should consider the vascular resistance distal to the narrowing in addition to the impact of a proximal narrowing and provides computational approaches for implementation of these important considerations.

The Analysis of the Intraoperative Complications During the Transitional Period from In-patient Cataract Surgery to Ambulatory Day Surgery

Purpose: To report the incidence of posterior capsular rupture (PCR) of phacoemulsification and the contributing factors during the transitional period from in-patient model to ambulatory day surgery model. Method: The medical records and intraoperative complication reports were systemically reviewed during the period of August 2015 to October 2020. The PCR rate was analyzed according to the following factors: type of surgery (day surgery vs. in-patient surgery), gender, age, surgery performed in the month containing long holiday (Chinese New Year and National day), surgery performed in the first month of the residents’ rotation, increase of surgical volume comparing to the previous month, stage of the day surgery transition and whether it was before or after the implementation of safety recommendation based on clinical audit results in January 2018. The univariable logistic regression model was initially performed.Results: Within the study period, 29 493 cases of phacoemulsification surgery were enrolled in the study, 14 451 of them were performed as day surgery while 15 042 of them were inpatient surgery. The overall incidence of PCR was 1.17% (346 cases) among the 29 493 planned phacoemulsification surgery. The increase incidence of PCR was associated with older age and male gender. The incidence of PCR decreased significantly after the implementation of safety recommendations. Conclusion: The ambulatory day surgery for cataract patients could provide safe, efficient, and quality services. During the transitional period from in-patient to day surgery, careful planning and organization with dynamic clinical audit surveillance can further reduce the incidence of intraoperative complications, especially intraoperative PCR.

Development of an inside-out augmented reality technique for neurosurgical navigation

OBJECTIVE With the advancement of 3D modeling techniques and visualization devices, augmented reality (AR)–based navigation (AR navigation) is being developed actively. The authors developed a pilot model of their newly developed inside-out tracking AR navigation system. METHODS The inside-out AR navigation technique was developed based on the visual inertial odometry (VIO) algorithm. The Quick Response (QR) marker was created and used for the image feature–detection algorithm. Inside-out AR navigation works through the steps of visualization device recognition, marker recognition, AR implementation, and registration within the running environment. A virtual 3D patient model for AR rendering and a 3D-printed patient model for validating registration accuracy were created. Inside-out tracking was used for the registration. The registration accuracy was validated by using intuitive, visualization, and quantitative methods for identifying coordinates by matching errors. Fine-tuning and opacity-adjustment functions were developed. RESULTS ARKit-based inside-out AR navigation was developed. The fiducial marker of the AR model and those of the 3D-printed patient model were correctly overlapped at all locations without errors. The tumor and anatomical structures of AR navigation and the tumors and structures placed in the intracranial space of the 3D-printed patient model precisely overlapped. The registration accuracy was quantified using coordinates, and the average moving errors of the x-axis and y-axis were 0.52 ± 0.35 and 0.05 ± 0.16 mm, respectively. The gradients from the x-axis and y-axis were 0.35° and 1.02°, respectively. Application of the fine-tuning and opacity-adjustment functions was proven by the videos. CONCLUSIONS The authors developed a novel inside-out tracking–based AR navigation system and validated its registration accuracy. This technical system could be applied in the novel navigation system for patient-specific neurosurgery.

A Personalized Therapeutics Approach Using an In Silico Drosophila Patient Model Reveals Optimal Chemo- and Targeted Therapy Combinations for Colorectal Cancer

In silico models of biomolecular regulation in cancer, annotated with patient-specific gene expression data, can aid in the development of novel personalized cancer therapeutic strategies. Drosophila melanogaster is a well-established animal model that is increasingly being employed to evaluate such preclinical personalized cancer therapies. Here, we report five Boolean network models of biomolecular regulation in cells lining the Drosophila midgut epithelium and annotate them with colorectal cancer patient-specific mutation data to develop an in silico Drosophila Patient Model (DPM). We employed cell-type-specific RNA-seq gene expression data from the FlyGut-seq database to annotate and then validate these networks. Next, we developed three literature-based colorectal cancer case studies to evaluate cell fate outcomes from the model. Results obtained from analyses of the proposed DPM help: (i) elucidate cell fate evolution in colorectal tumorigenesis, (ii) validate cytotoxicity of nine FDA-approved CRC drugs, and (iii) devise optimal personalized treatment combinations. The personalized network models helped identify synergistic combinations of paclitaxel-regorafenib, paclitaxel-bortezomib, docetaxel-bortezomib, and paclitaxel-imatinib for treating different colorectal cancer patients. Follow-on therapeutic screening of six colorectal cancer patients from cBioPortal using this drug combination demonstrated a 100% increase in apoptosis and a 100% decrease in proliferation. In conclusion, this work outlines a novel roadmap for decoding colorectal tumorigenesis along with the development of personalized combinatorial therapeutics for preclinical translational studies.

Modelling intensive care unit capacity under different epidemiological scenarios of the COVID-19 pandemic in three Western European countries

Background The coronavirus disease 2019 (COVID-19) pandemic has placed enormous strain on intensive care units (ICUs) in Europe. Ensuring access to care, irrespective of COVID-19 status, in winter 2020–2021 is essential. Methods An integrated model of hospital capacity planning and epidemiological projections of COVID-19 patients is used to estimate the demand for and resultant spare capacity of ICU beds, staff and ventilators under different epidemic scenarios in France, Germany and Italy across the 2020–2021 winter period. The effect of implementing lockdowns triggered by different numbers of COVID-19 patients in ICUs under varying levels of effectiveness is examined, using a ‘dual-demand’ (COVID-19 and non-COVID-19) patient model. Results Without sufficient mitigation, we estimate that COVID-19 ICU patient numbers will exceed those seen in the first peak, resulting in substantial capacity deficits, with beds being consistently found to be the most constrained resource. Reactive lockdowns could lead to large improvements in ICU capacity during the winter season, with pressure being most effectively alleviated when lockdown is triggered early and sustained under a higher level of suppression. The success of such interventions also depends on baseline bed numbers and average non-COVID-19 patient occupancy. Conclusion Reductions in capacity deficits under different scenarios must be weighed against the feasibility and drawbacks of further lockdowns. Careful, continuous decision-making by national policymakers will be required across the winter period 2020–2021.

Optimization of the Clinical Setting Using Numerical Simulations of the Electromagnetic Field in an Obese Patient Model for Deep Regional Hyperthermia of an 8 MHz Radiofrequency Capacitively Coupled Device in the Pelvis

Background: The purpose of this study was to evaluate the effectiveness of the clinical setting for deep regional hyperthermia of an 8 MHz radiofrequency (RF) capacitively coupled device in the pelvis by using numerical simulations of the electromagnetic field. Methods: A three-dimensional patient model of cervical cancer of the uterus in an obese patient was reconstructed with computed tomography data. The specific absorption rate (SAR) and temperature distributions among the various heating settings were evaluated using numerical simulations. Results: The averaged SAR value of the deep target tumor was similar between with or without overlay boluses (OBs), and that of the subcutaneous fat (SF) at the edges of cooling boluses with OBs was lower than that of the SF without OBs. The use of OBs reduced the overheating of the SF. The 0.5% salt solution in the OB produced the least overheated areas outside the deep target tumor compared with the other concentrations. The insertion of the intergluteal cleft (IGC) bolus could improve the temperature concentration of the deep target tumor. Conclusions: The use of OBs and the salt solution concentration in the OB were important to optimize the temperature distribution. IGC bolus might contribute to temperature optimization. Further studies with individualized numerical simulations in each patient are expected.