A Statistical Overview of Fixed Wing Air Medical Transportation Operations in the United States (2019-2020).

Air medical transportation (AMT) services provide the transportation of patients, medical teams, and organs for the US health care system. Interfacility transfers account for 54% of air medical transports, and delivering specialty care and organs accounts for 13% of air medical transports. Interfacility transfer, specialty care, and organ delivery are predominantly conducted using fixed wing aircraft. The AMT fixed wing fleet has grown 2.2% per year over the last decade along with a 3.6% per year expansion in the number of AMT base airports with fixed wing operations. This article aims to characterize the operations of fixed wing AMT in the United States for the period of 2019 to 2020. This information can be used for aircraft design, airport and air traffic control infrastructure assessment and funding, and AMT industry sector analysis and strategic planning. Data from 12 databases were combined to identify AMT flights and generate operational statistics including the number of vehicles; ownership; flight distances; flight frequency; geographic distribution; and the types of airports, air traffic control, and navigation systems used.

3D magnetic resonance fingerprinting with quadratic RF phase.

PURPOSE: To implement 3D magnetic resonance fingerprinting (MRF) with quadratic RF phase (qRF-MRF) for simultaneous quantification of T1 , T2 , ΔB0 , and T2∗ . METHODS: 3D MRF data with effective undersampling factor of 3 in the slice direction were acquired with quadratic RF phase patterns for T1 , T2 , and T2∗ sensitivity. Quadratic RF phase encodes the off-resonance by modulating the on-resonance frequency linearly in time. Transition to 3D brings practical limitations for reconstruction and dictionary matching because of increased data and dictionary sizes. Randomized singular value decomposition (rSVD)-based compression in time and reduction in dictionary size with a quadratic interpolation method are combined to be able to process prohibitively large data sets in feasible reconstruction and matching times. RESULTS: Accuracy of 3D qRF-MRF maps in various resolutions and orientations are compared to 3D fast imaging with steady-state precession (FISP) for T1 and T2 contrast and to 2D qRF-MRF for T2∗ contrast and ΔB0 . The precision of 3D qRF-MRF was 1.5-2 times higher than routine clinical scans. 3D qRF-MRF ΔB0 maps were further processed to highlight the susceptibility contrast. CONCLUSION: Natively co-registered 3D whole brain T1 , T2 , T2∗ , ΔB0 , and QSM maps can be acquired in as short as 5 min with 3D qRF-MRF.

Quantification of creatine kinase reaction rate in mouse hindlimb using phosphorus-31 magnetic resonance spectroscopic fingerprinting.

The goal of this study was to evaluate the accuracy, reproducibility, and efficiency of a 31 P magnetic resonance spectroscopic fingerprinting (31 P-MRSF) method for fast quantification of the forward rate constant of creatine kinase (CK) in mouse hindlimb. The 31 P-MRSF method acquired spectroscopic fingerprints using interleaved acquisition of phosphocreatine (PCr) and γATP with ramped flip angles and a saturation scheme sensitive to chemical exchange between PCr and γATP. Parameter estimation was performed by matching the acquired fingerprints to a dictionary of simulated fingerprints generated from the Bloch-McConnell model. The accuracy of 31 P-MRSF measurements was compared with the magnetization transfer (MT-MRS) method in mouse hindlimb at 9.4 T (n = 8). The reproducibility of 31 P-MRSF was also assessed by repeated measurements. Estimation of the CK rate constant using 31 P-MRSF (0.39 ± 0.03 s-1 ) showed a strong agreement with that using MT-MRS measurements (0.40 ± 0.05 s-1 ). Variations less than 10% were achieved with 2 min acquisition of 31 P-MRSF data. Application of the 31 P-MRSF method to mice subjected to an electrical stimulation protocol detected an increase in CK rate constant in response to stimulation-induced muscle contraction. These results demonstrated the potential of the 31 P-MRSF framework for rapid, accurate, and reproducible quantification of the chemical exchange rate of CK in vivo.

Biological Therapy Interruption and Re-Treatment in Chronic Plaque Psoriasis.

While biological treatments for chronic plaque psoriasis should be administered continuously to maximize and maintain efficacy, interruptions in therapy may be necessary for a number of reasons. We reviewed the evidence from clinical trials on efficacy, safety and immunogenicity in clinical trials for approved biologic agents for chronic plaque psoriasis. A systematic search of three major medical databases was performed and a total of 35 articles were included into the analysis, including 13 controlled trials. Trials assessing continuous therapy against dosing as-needed therapy (including infliximab, etanercept and secukinumab) have demonstrated superior efficacy for continuous regimes. However, randomized withdrawal trials for etanercept, adalimumab, ixekizumab, brodalumab, guselkumab, risankizumab and tildrakizumab, showed no significant impact on skin clearance rates in patients who are interrupted once and then re-treated. With the possible exception of infliximab, temporary interruption in biologic therapy appears to be safe and most agents will regain efficacy after re-introduction. J Drugs Dermatol. 2021;20(10):1063-1071. doi:10.36849/JDD.5716.

SARS-CoV-2 (COVID-19) vaccination in dermatology patients on immunomodulatory and biologic agents: Recommendations from the Australasian Medical Dermatology Group.

As the phase III COVID-19 vaccine trials excluded patients on immunosuppressive treatments, or patients with significant autoimmunity, the Australasian Medical Dermatology Group make the following preliminary recommendations around COVID-19 vaccination in dermatology patients on immunomodulatory and/or biologic agents. Vaccination against COVID-19 is strongly encouraged for all patients on immunomodulatory drugs and/or biologic agents. There are currently insufficient data to recommend one COVID-19 vaccine or vaccine type (mRNA, recombinant, inactivated virus) over another. No specific additional risk in patients on immunomodulatory or biologic therapies has so far been identified. Data on vaccine efficacy in patients on immunomodulatory or biologic therapies are missing, so standard vaccination protocols are recommended until otherwise advised.

COVID-19 and the use of immunomodulatory and biologic agents for severe cutaneous disease: An Australian/New Zealand consensus statement.

Patients on immunomodulators, including biologic agents and new small molecular inhibitors, for cutaneous disease, represent a potentially vulnerable population during the COVID-19 pandemic. There is currently insufficient evidence to determine whether patients on systemic immunomodulators are at increased risk of developing COVID-19 disease or more likely to have severe disease. As such, clinicians need to assess the benefit-to-risk ratio on a case-by-case basis. In patients with suspected or confirmed COVID-19 disease, all immunomodulators used for skin diseases should be immediately withheld, with the possible exception of systemic corticosteroid therapy, which needs to be weaned. In patients who develop symptoms or signs of an upper respiratory tract infection, but COVID-19 is not yet confirmed, consider dose reduction or temporarily cessation for 1-2 weeks. In otherwise well patients, immunomodulators and biologics should be continued. In all patients, and their immediate close contacts, the importance of preventative measures to minimise human-to-human transmission cannot be overemphasised.

Magnetic resonance fingerprinting with quadratic RF phase for measurement of T2* simultaneously with δf , T1 , and T2.

PURPOSE: This study explores the possibility of using a gradient moment balanced sequence with a quadratically varied RF excitation phase in the magnetic resonance fingerprinting (MRF) framework to quantify T2* in addition to δf , T1 , and T2 tissue properties. METHODS: The proposed quadratic RF phase-based MRF method (qRF-MRF) combined a varied RF excitation phase with the existing balanced SSFP (bSSFP)-based MRF method to generate signals that were uniquely sensitive to δf , T1 , T2 , as well as the distribution width of intravoxel frequency dispersion, Γ . A dictionary, generated through Bloch simulation, containing possible signal evolutions within the physiological range of δf , T1 , T2 , and Γ , was used to perform parameter estimation. The estimated T2 and Γ were subsequently used to estimate T2* . The proposed method was evaluated in phantom experiments and healthy volunteers (N = 5). RESULTS: The T1 and T2 values from the phantom by qRF-MRF demonstrated good agreement with values obtained by traditional gold standard methods (r2 = 0.995 and 0.997, respectively; concordance correlation coefficient = 0.978 and 0.995, respectively). The T2* values from the phantom demonstrated good agreement with values obtained through the multi-echo gradient-echo method (r2 = 0.972, concordance correlation coefficient = 0.983). In vivo qRF-MRF-measured T1 , T2 , and T2* values were compared with measurements by existing methods and literature values. CONCLUSION: The proposed qRF-MRF method demonstrated the potential for simultaneous quantification of δf , T1 , T2 , and T2* tissue properties.

Late-onset malalignment of the great toenails.

Great toenail malalignment is characterised by lateral deviation of the longitudinal axis of the nail plate with respect to the hallux, and is usually post-traumatic, iatrogenic or due to congenital malalignment of the great toenails. We present cases of great toenail malalignment with onset in adolescence or young adulthood without preceding nail surgery or acute trauma. We postulate that this may represent a late-onset presentation of congenital malalignment of the great toenails.

Cytomegalovirus ulcers following radiotherapy for a Marjolin ulcer in a renal transplant recipient.

Cytomegalovirus (CMV) infection represents a major cause of morbidity and mortality in immunocompromised hosts. Skin ulceration is a rare manifestation of tissue-invasive disease, with the anogenital region being the most typical site of involvement. We present a case of CMV ulceration on the right leg occurring 16 years following renal transplantation and 1 year after adjuvant radiotherapy for a Marjolin ulcer at this site. We suggest radiotherapy may provide a mechanism for local reactivation of the virus in the skin of seropositive patients.

Regularly incremented phase encoding - MR fingerprinting (RIPE-MRF) for enhanced motion artifact suppression in preclinical cartesian MR fingerprinting.

PURPOSE: The regularly incremented phase encoding-magnetic resonance fingerprinting (RIPE-MRF) method is introduced to limit the sensitivity of preclinical MRF assessments to pulsatile and respiratory motion artifacts. METHODS: As compared to previously reported standard Cartesian-MRF methods (SC-MRF), the proposed RIPE-MRF method uses a modified Cartesian trajectory that varies the acquired phase-encoding line within each dynamic MRF dataset. Phantoms and mice were scanned without gating or triggering on a 7T preclinical MRI scanner using the RIPE-MRF and SC-MRF methods. In vitro phantom longitudinal relaxation time (T1 ) and transverse relaxation time (T2 ) measurements, as well as in vivo liver assessments of artifact-to-noise ratio (ANR) and MRF-based T1 and T2 mean and standard deviation, were compared between the two methods (n = 5). RESULTS: RIPE-MRF showed significant ANR reductions in regions of pulsatility (P < 0.005) and respiratory motion (P < 0.0005). RIPE-MRF also exhibited improved precision in T1 and T2 measurements in comparison to the SC-MRF method (P < 0.05). The RIPE-MRF and SC-MRF methods displayed similar mean T1 and T2 estimates (difference in mean values < 10%). CONCLUSION: These results show that the RIPE-MRF method can provide effective motion artifact suppression with minimal impact on T1 and T2 accuracy for in vivo small animal MRI studies. Magn Reson Med 79:2176-2182, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

High-resolution dynamic oxygen-17 MR imaging of mouse brain with golden-ratio-based radial sampling and k-space-weighted image reconstruction.

PURPOSE: The current study aimed to develop a three-dimensional (3D) dynamic oxygen-17 (17 O) MR imaging method with high temporal and spatial resolution to delineate the kinetics of 17 O water uptake and washout in the brains of mice with glioblastoma (GBM). METHODS: A 3D imaging method with a stack-of-stars golden-ratio-based radial sampling scheme was employed to acquire 17 O signal in vivo. A k-space-weighted image reconstruction method was used to improve the temporal resolution while preserving spatial resolution. Simulation studies were performed to validate the method. Using this method, the kinetics of 17 O water uptake and washout in the brains of mice with GBM were delineated after an intravenous bolus injection of 17 O water. RESULTS: The proposed 17 O imaging method achieved an effective temporal resolution of 7.56 s with a nominal voxel size of 5.625 µL in the mouse brain at 9.4 T. Reduced uptake and prolonged washout of 17 O water were observed in tumor tissue, suggesting compromised cerebral perfusion. CONCLUSION: This study demonstrated a promising dynamic 17 O imaging approach that can delineate 17 O water kinetics in vivo with high temporal and spatial resolution. It can also be used to image cerebral oxygen consumption rate in oxygen-17 inhalation studies. Magn Reson Med 79:256-263, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Fast magnetic resonance fingerprinting for dynamic contrast-enhanced studies in mice.

PURPOSE: The goal of this study was to develop a fast MR fingerprinting (MRF) method for simultaneous T1 and T2 mapping in DCE-MRI studies in mice. METHODS: The MRF sequences based on balanced SSFP and fast imaging with steady-state precession were implemented and evaluated on a 7T preclinical scanner. The readout used a zeroth-moment-compensated variable-density spiral trajectory that fully sampled the entire k-space and the inner 10 × 10 k-space with 48 and 4 interleaves, respectively. In vitro and in vivo studies of mouse brain were performed to evaluate the accuracy of MRF measurements with both fully sampled and undersampled data. The application of MRF to dynamic T1 and T2 mapping in DCE-MRI studies were demonstrated in a mouse model of heterotopic glioblastoma using gadolinium-based and dysprosium-based contrast agents. RESULTS: The T1 and T2 measurements in phantom showed strong agreement between the MRF and the conventional methods. The MRF with spiral encoding allowed up to 8-fold undersampling without loss of measurement accuracy. This enabled simultaneous T1 and T2 mapping with 2-minute temporal resolution in DCE-MRI studies. CONCLUSION: Magnetic resonance fingerprinting provides the opportunity for dynamic quantification of contrast agent distribution in preclinical tumor models on high-field MRI scanners.

31 P magnetic resonance fingerprinting for rapid quantification of creatine kinase reaction rate in vivo.

The purpose of this work was to develop a 31 P spectroscopic magnetic resonance fingerprinting (MRF) method for fast quantification of the chemical exchange rate between phosphocreatine (PCr) and adenosine triphosphate (ATP) via creatine kinase (CK). A 31 P MRF sequence (CK-MRF) was developed to quantify the forward rate constant of ATP synthesis via CK ( kfCK), the T1 relaxation time of PCr ( T1PCr), and the PCr-to-ATP concentration ratio ( MRPCr). The CK-MRF sequence used a balanced steady-state free precession (bSSFP)-type excitation with ramped flip angles and a unique saturation scheme sensitive to the exchange between PCr and γATP. Parameter estimation was accomplished by matching the acquired signals to a dictionary generated using the Bloch-McConnell equation. Simulation studies were performed to examine the susceptibility of the CK-MRF method to several potential error sources. The accuracy of nonlocalized CK-MRF measurements before and after an ischemia-reperfusion (IR) protocol was compared with the magnetization transfer (MT-MRS) method in rat hindlimb at 9.4 T (n = 14). The reproducibility of CK-MRF was also assessed by comparing CK-MRF measurements with both MT-MRS (n = 17) and four angle saturation transfer (FAST) (n = 7). Simulation results showed that CK-MRF quantification of kfCK was robust, with less than 5% error in the presence of model inaccuracies including dictionary resolution, metabolite T2 values, inorganic phosphate metabolism, and B1 miscalibration. Estimation of kfCK by CK-MRF (0.38 ± 0.02 s-1 at baseline and 0.42 ± 0.03 s-1 post-IR) showed strong agreement with MT-MRS (0.39 ± 0.03 s-1 at baseline and 0.44 ± 0.04 s-1 post-IR). kfCK estimation was also similar between CK-MRF and FAST (0.38 ± 0.02 s-1 for CK-MRF and 0.38 ± 0.11 s-1 for FAST). The coefficient of variation from 20 s CK-MRF quantification of kfCK was 42% of that by 150 s MT-MRS acquisition and was 12% of that by 20 s FAST acquisition. This study demonstrates the potential of a 31 P spectroscopic MRF framework for rapid, accurate and reproducible quantification of chemical exchange rate of CK in vivo.

Optical and Magnetic Resonance Imaging Using Fluorous Colloidal Nanoparticles.

Improved imaging of cancerous tissue has the potential to aid prognosis and improve patient outcome through longitudinal imaging of treatment response and disease progression. While nuclear imaging has made headway in cancer imaging, fluorinated tracers that enable magnetic resonance imaging (19F MRI) hold promise, particularly for repeated imaging sessions because nonionizing radiation is used. Fluorine MRI detects molecular signatures by imaging a fluorinated tracer and takes advantage of the spatial and anatomical resolution afforded by MRI. This manuscript describes a fluorous polymeric nanoparticle that is capable of 19F MR imaging and fluorescent tracking for in vitro and in vivo monitoring of immune cells and cancerous tissue. The fluorous particle is derived from low-molecular-weight amphiphilic copolymers that self-assemble into micelles with a hydrodynamic diameter of 260 nm. The polymer is MR-active at concentrations as low as 2.1 mM in phantom imaging studies. The fluorinated particle demonstrated rapid uptake into immune cells for potential cell-tracking or delineation of the tumor microenvironment and showed negligible toxicity. Systemic administration indicates significant uptake into two tumor types, triple-negative breast cancer and ovarian cancer, with little accumulation in off-target tissue. These results indicate a robust platform imaging agent capable of immune cell tracking and systemic disease monitoring with exceptional uptake of the nanoparticle in multiple cancer models.

Rapid T2 mapping of mouse heart using the carr-purcell-meiboom-gill sequence and compressed sensing reconstruction.

PURPOSE: To develop and prove preliminary validation of a fast in vivo T2 mapping technique for mouse heart. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) experiments were performed on a 7T animal scanner. The standard Carr-Purcell-Meiboom-Gill (CPMG) sequence was modified to minimize the effect of stimulated echoes for accurate T2 quantification. The acquisition was further accelerated with the compressed sensing approach. The accuracy of the proposed method was first validated with both phantom experiments and numerical simulations. In vivo T2 measurement was performed on seven mice in a manganese-enhanced MRI study. RESULTS: In phantom studies, T2 values obtained with the modified CPMG sequence are in good agreement with the standard spin-echo method (P > 0.05). Numerical simulations further demonstrated that with the application of the compressed sensing approach, fast T2 quantification with a spatial resolution of 2.3 mm can be achieved at a high temporal resolution of 1 minute per slice. With the proposed technique, an average T2 value of 25 msec was observed for mouse heart at 7T and this number decreased significantly after manganese infusion (P < 0.001). CONCLUSION: A rapid T2 mapping technique was developed and assessed, which allows accurate T2 quantification of mouse heart at a temporal resolution of 1 minute per slice. J. Magn. Reson. Imaging 2016;44:375-382.

Pain Duration and Resolution following Surgery: An Inception Cohort Study.

OBJECTIVE: Preoperative determinants of pain duration following surgery are poorly understood. We identified preoperative predictors of prolonged pain after surgery in a mixed surgical cohort. METHODS: We conducted a prospective longitudinal study of patients undergoing mastectomy, lumpectomy, thoracotomy, total knee replacement, or total hip replacement. We measured preoperative psychological distress and substance use, and then measured pain and opioid use after surgery until patients reported the cessation of both opioid consumption and pain. The primary endpoint was time to opioid cessation, and those results have been previously reported. Here, we report preoperative determinants of time to pain resolution following surgery in Cox proportional hazards regression. RESULTS: Between January 2007 and April 2009, we enrolled 107 of 134 consecutively approached patients undergoing the aforementioned surgical procedures. In the final multivariate model, preoperative self-perceived risk of addiction predicted more prolonged pain. Unexpectedly, anxiety sensitivity predicted more rapid pain resolution after surgery. Each one-point increase (on a four point scale) of self-perceived risk of addiction was associated with a 38% (95% CI 3-61) reduction in the rate of pain resolution (P = 0.04). Furthermore, higher anxiety sensitivity was associated with an 89% (95% CI 23-190) increased rate of pain resolution (P = 0.004). CONCLUSIONS: Greater preoperative self-perceived risk of addiction, and lower anxiety sensitivity predicted a slower rate of pain resolution following surgery. Each of these factors was a better predictor of pain duration than preoperative depressive symptoms, post-traumatic stress disorder symptoms, past substance use, fear of pain, gender, age, preoperative pain, or preoperative opioid use.

Self-loathing aspects of depression reduce postoperative opioid cessation rate.

OBJECTIVE: We previously reported that increased preoperative Beck Depression Inventory II (BDI-II) scores were associated with a 47% (95% CI 24%-64%) reduction in the rate of opioid cessation following surgery. We aimed to identify the underlying factors of the BDI-II (affective/cognitive vs somatic) associated with a decreased rate of opioid cessation after surgery. METHODS: We conducted a secondary analysis of the data from a previously reported prospective, longitudinal, observational study of opioid use after five distinct surgical procedures (total hip replacement, total knee replacement, thoracotomy, mastectomy, and lumpectomy) in 107 patients. The primary endpoint was time to opioid cessation. After exploratory factor analysis of the BDI-II, mean summary scores were calculated for each identified factor. These scores were evaluated as predictors of time to opioid cessation using Cox proportional hazards regression. RESULTS: The exploratory factor analysis produced three factors (self-loathing symptoms, motivational symptoms, emotional symptoms). All three factors were significant predictors in univariate analysis. Of the three identified factors of the BDI-II, only preoperative self-loathing symptoms (past failure, guilty feelings, self-dislike, self-criticalness, suicidal thoughts, worthlessness) independently predicted a significant decrease in opioid cessation rate after surgery in the multivariate analysis (HR 0.86, 95% CI 0.75-0.99, P value 0.037). CONCLUSIONS: Our results identify a set of negative cognitions predicting prolonged time to postoperative opioid cessation. Somatic symptoms captured by the BDI-II were not primarily responsible for the association between preoperative BDI-II scores and postoperative prolonged opioid use.