Stability and reproducibility comparisons between deep inspiration breath-hold techniques for left-sided breast cancer patients: A prospective study.

PURPOSE: Deep inspiration breath-hold (DIBH) is crucial in reducing the lung and cardiac dose for treatment of left-sided breast cancer. We compared the stability and reproducibility of two DIBH techniques: Active Breathing Coordinator (ABC) and VisionRT (VRT). MATERIALS AND METHODS: We examined intra- and inter-fraction positional variation of the left lung. Eight left-sided breast cancer patients were monitored with electronic portal imaging during breath-hold (BH) at every fraction. For each patient, half of the fractions were treated using ABC and the other half with VRT, with an equal amount starting with either ABC or VRT. The lung in each portal image was delineated, and the variation of its area was evaluated. Intrafraction stability was evaluated as the mean coefficient of variation (CV) of the lung area for the supraclavicular (SCV) and left lateral (LLat) field over the course of treatment. Reproducibility was the CV for the first image of each fraction. Daily session time and total imaging monitor units (MU) used in patient positioning were recorded. RESULTS: The mean intrafraction stability across all patients for the LLat field was 1.3 ± 0.7% and 1.5 ± 0.9% for VRT and ABC, respectively. Similarly, this was 1.5 ± 0.7% and 1.6 ± 0.8% for VRT and ABC, respectively, for the SCV field. The mean interfraction reproducibility for the LLat field was 11.0 ± 3.4% and 14.9 ± 6.0% for VRT and ABC, respectively. Similarly, this was 13.0 ± 2.5% and 14.8 ± 9% for VRT and ABC, respectively, for the SCV. No difference was observed in the number of verification images required for either technique. CONCLUSIONS: The stability and reproducibility were found to be comparable between ABC and VRT. ABC can have larger interfractional variation with less feedback to the treating therapist compared to VRT as shown in the increase in geometric misses at the matchline.

Impact of Bariatric Surgery on Subtilisin/Kexin Type 9 (PCSK9) Gene Expression and Inflammation in the Adipose Tissue of Obese Diabetic Rats.

Bariatric surgery improves dyslipidaemia and reduces body weight, but it remains unclear how bariatric surgery modulates gene expression in fat cells to influence the proprotein convertase subtilisin/kexin type 9 (PCSK-9) and low-density lipoprotein receptor (LDLR) gene expression. The expression of the PCSK9/LDLR/tumor necrosis factor-alpha (TNFα) gene in adipose tissue was measured in two groups of Zucker Diabetic Sprague Dawley (ZDSD) rats after Roux-en-Y gastric bypass (RYGB) surgery or 'SHAM' operation. There was lower PCSK9 (p = 0.02) and higher LDLR gene expression (p = 0.02) in adipose tissue in rats after RYGB. Weight change did not correlate with PCSK9 gene expression (r = -0.5, p = 0.08) or TNFα gene expression (r = -0.4, p = 0.1). TNFα gene expression was positively correlated with PCSK9 gene expression (r = 0.7, p = 0.001) but not correlated with LDLR expression (r = -0.3, p = 0.3). Circulating triglyceride levels were lower in RYGB compared to the SHAM group (1.1 (0.8-1.4) vs. 1.5 (1.0-4.2), p = 0.038) mmol/L with no difference in cholesterol levels. LDLR gene expression was increased post-bariatric surgery with the potential to reduce the number of circulating LDL particles. PCSK9 gene expression and TNFα gene expression were positively correlated after RYGB in ZDSD rats, suggesting that the modulation of pro-inflammatory pathways in adipose tissue after RYGB may partly relate to PCSK9 and LDLR gene expression.

Dictionary learning compressed sensing reconstruction: pilot validation of accelerated echo planar J-resolved spectroscopic imaging in prostate cancer.

OBJECTIVES: This study aimed at developing dictionary learning (DL) based compressed sensing (CS) reconstruction for randomly undersampled five-dimensional (5D) MR Spectroscopic Imaging (3D spatial + 2D spectral) data acquired in prostate cancer patients and healthy controls, and test its feasibility at 8x and 12x undersampling factors. MATERIALS AND METHODS: Prospectively undersampled 5D echo-planar J-resolved spectroscopic imaging (EP-JRESI) data were acquired in nine prostate cancer (PCa) patients and three healthy males. The 5D EP-JRESI data were reconstructed using DL and compared with gradient sparsity-based Total Variation (TV) and Perona-Malik (PM) methods. A hybrid reconstruction technique, Dictionary Learning-Total Variation (DLTV), was also designed to further improve the quality of reconstructed spectra. RESULTS: The CS reconstruction of prospectively undersampled (8x and 12x) 5D EP-JRESI data acquired in prostate cancer and healthy subjects were performed using DL, DLTV, TV and PM. It is evident that the hybrid DLTV method can unambiguously resolve 2D J-resolved peaks including myo-inositol, citrate, creatine, spermine and choline. CONCLUSION: Improved reconstruction of the accelerated 5D EP-JRESI data was observed using the hybrid DLTV. Accelerated acquisition of in vivo 5D data with as low as 8.33% samples (12x) corresponds to a total scan time of 14 min as opposed to a fully sampled scan that needs a total duration of 2.4 h (TR = 1.2 s, 32 [Formula: see text]×16 [Formula: see text]×8 [Formula: see text], 512 [Formula: see text] and 64 [Formula: see text]).

The impact of atherosclerotic cardiovascular disease, dyslipidaemia and lipid lowering therapy on Coronavirus disease 2019 outcomes: an examination of the available evidence.

PURPOSE OF REVIEW: Coronavirus Disease 2019 (COVID19) has caused significant global morbidity and mortality, especially in persons with underlying cardiovascular disease. There have been concerns that lipid-lowering therapy (LLT) increases angiotensin-converting enzyme 2 levels. Conversely, pleiotropic effects of statins can theoretically protect against severe COVID19 infection, supporting evidence from other respiratory illnesses in which statin use probably confers benefit. RECENT FINDINGS: There is an abundance of studies that show that statins are safe and potentially protect against severe COVID19 infection (critical illness and death), even when adjustment for potential confounders is undertaken. However, the evidence is limited to retrospective cohorts. The benefit for patients with diabetes is less clear. There is a paucity of evidence for other LLT agents. Available clinical guidelines recommend the ongoing use of LLT in patients with COVID19 (unless specifically contra-indicated) and the data from available studies support these. SUMMARY: In patients with COVID19 infection, LLT should be continued. However, the current findings need substantiating in larger prospective clinical studies with specific examination of the possible mechanisms by which LLT confers benefit from COVID19.

Lipids and peripheral neuropathy.

PURPOSE OF REVIEW: Hyperlipidaemia is associated with the development of neuropathy. Indeed, a mechanistic link between altered lipid metabolism and peripheral nerve dysfunction has been demonstrated in a number of experimental and clinical studies. Furthermore, post hoc analyses of clinical trials of cholesterol and triglyceride-lowering pharmacotherapy have shown reduced rates of progression of diabetic neuropathy. Given, there are currently no FDA approved disease-modifying therapies for diabetic neuropathy, modulation of lipids may represent a key therapeutic target for the treatment of diabetic nerve damage. This review summarizes the current evidence base on the role of hyperlipidaemia and lipid lowering therapy on the development and progression of peripheral neuropathy. RECENT FINDINGS: A body of literature supports a detrimental effect of dyslipidaemia on nerve fibres resulting in somatic and autonomic neuropathy. The case for an important modulating role of hypertriglyceridemia is stronger than for low-density lipoprotein cholesterol (LDL-C) in relation to peripheral neuropathy. This is reflected in the outcomes of clinical trials with the different therapeutic agents targeting hyperlipidaemia reporting beneficial or neutral effects with statins and fibrates. The potential concern with the association between proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy and cognitive decline raised the possibility that extreme LDL-C lowering may result in neurodegeneration. However, studies in murine models and data from small observational studies indicate an association between increased circulating PCSK9 levels and small nerve fibre damage with a protective effect of PCSK9i therapy against small fibre neuropathy. Additionally, weight loss with bariatric surgery leads to an improvement in peripheral neuropathy and regeneration of small nerve fibres measured with corneal confocal microscopy in people with obesity with or without type 2 diabetes. These improvements correlate inversely with changes in triglyceride levels. SUMMARY: Hyperlipidaemia, particularly hypertriglyceridemia, is associated with the development and progression of neuropathy. Lipid modifying agents may represent a potential therapeutic option for peripheral neuropathy. Post hoc analyses indicate that lipid-lowering therapies may halt the progression of neuropathy or even lead to regeneration of nerve fibres. Well designed randomized controlled trials are needed to establish if intensive targeted lipid lowering therapy as a part of holistic metabolic control leads to nerve fibre regeneration and improvement in neuropathy symptoms.

High density lipoprotein-associated miRNA is increased following Roux-en-Y gastric bypass surgery for severe obesity.

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight-loss procedures, but how severe obesity and RYGB affect circulating HDL-associated microRNAs (miRNAs) remains unclear. Here, we aim to investigate how HDL-associated miRNAs are regulated in severe obesity and how weight loss after RYGB surgery affects HDL-miRNAs. Plasma HDLs were isolated from patients with severe obesity (n = 53) before and 6 and 12 months after RYGB by immunoprecipitation using goat anti-human apoA-I microbeads. HDLs were also isolated from 18 healthy participants. miRNAs were extracted from isolated HDL and levels of miR-24, miR-126, miR-222, and miR-223 were determined by TaqMan miRNA assays. We found that HDL-associated miR-126, miR-222, and miR-223 levels, but not miR-24 levels, were significantly higher in patients with severe obesity when compared with healthy controls. There were significant increases in HDL-associated miR-24, miR-222, and miR-223 at 12 months after RYGB. Additionally, cholesterol efflux capacity and paraoxonase activity were increased and intercellular adhesion molecule-1 (ICAM-1) levels decreased. The increases in HDL-associated miR-24 and miR-223 were positively correlated with an increase in cholesterol efflux capacity (r = 0.326, P = 0.027 and r = 0.349, P = 0.017, respectively). An inverse correlation was observed between HDL-associated miR-223 and ICAM-1 at baseline. Together, these findings show that HDL-associated miRNAs are differentially regulated in healthy participants versus patients with severe obesity and are altered after RYGB. These findings provide insights into how miRNAs are regulated in obesity before and after weight reduction and may lead to the development of novel treatment strategies for obesity and related metabolic disorders.

Bariatric surgery leads to an improvement in small nerve fibre damage in subjects with obesity.

INTRODUCTION: Subjects with obesity have metabolic risk factors for nerve fibre damage. Because bariatric surgery improves these risk factors we have assessed whether this can ameliorate nerve fibre damage. METHODS: Twenty-six obese subjects without diabetes (age: 46.23 ± 8.6, BMI: 48.7 ± 1.5, HbA1c: 38.0 ± 4.5) and 20 controls (age: 48.3 ± 6.2, BMI: 26.8 ± 4.2, HbA1c: 39.1 ± 2.6) underwent detailed assessment of neuropathy at baseline and 12 months after bariatric surgery. RESULTS: Obese subjects had normal peroneal (45.9 ± 5.5 vs. 48.1 ± 4.5, P = 0.1) and sural (46.9 ± 7.6 vs. 47.9 ± 10.6, P = 0.1) nerve conduction velocity, but a significantly higher neuropathy symptom profile (NSP) (4.3 ± 5.7 vs. 0.3 ± 0.6, P = 0.001), vibration perception threshold (VPT) (V) (10.2 ± 6.8 vs. 4.8 ± 2.7, P < 0.0001), warm threshold (C°) (40.4 ± 3.5 vs. 37.2 ± 1.8, P = 0.003) and lower peroneal (3.8 ± 2.2 vs. 4.9 ± 2.2, P = 0.02) and sural (8.9 ± 5.8 vs. 15.2 ± 8.5, P < 0.0001) nerve amplitude, deep breathing-heart rate variability (DB-HRV) (beats/min) (21.7 ± 4.1 vs. 30.1 ± 14, P = 0.001), corneal nerve fibre density (CNFD) (n/mm2) (25.6 ± 5.3 vs. 32.0 ± 3.1, P < 0.0001), corneal nerve branch density (CNBD) (n/mm2) (56.9 ± 27.5 vs. 111.4 ± 30.7, P < 0.0001) and corneal nerve fibre length (CNFL) (mm/mm2) (17.9 ± 4.1 vs. 29.8 ± 4.9, P < 0.0001) compared to controls at baseline. In control subjects there was no change in neuropathy measures over 12 months. However, 12 months after bariatric surgery there was a significant reduction in BMI (33.7 ± 1.7 vs. 48.7 ± 1.5, P = 0.001), HbA1c (34.3 ± 0.6 vs. 38.0 ± 4.5, P = 0.0002), triglycerides (mmol/l) (1.3 ± 0.6 vs. 1.6 ± 0.8, P = 0.005) and low-density lipoprotein cholesterol (mmol/l) (2.7 ± 0.7 vs. 3.1 ± 0.9, P = 0.02) and an increase in high-density lipoprotein cholesterol (mmol/l) (1.2 ± 0.3 vs. 1.04 ± 0.2, P = 0.002). There was a significant improvement in NSP (1.6 ± 2.7 vs. 4.3 ± 5.7, P = 0.004), neuropathy disability score (0.3 ± 0.9 vs. 1.3 ± 2.0, P = 0.03), CNFD (28.2 ± 4.4 vs. 25.6 ± 5.3, P = 0.03), CNBD (64.7 ± 26.1 vs. 56.9 ± 27.5, P = 0.04) and CNFL (20.4 ± 1.2 vs. 17.9 ± 4.1, P = 0.02), but no change in cold and warm threshold, VPT, DB-HRV or nerve conduction velocity and amplitude. Increase in CNFD correlated with a decrease in triglycerides (r = -0.45, P = 0.04). CONCLUSION: Obese subjects have evidence of neuropathy, and bariatric surgery leads to an improvement in weight, HbA1c, lipids, neuropathic symptoms and deficits and small nerve fibre regeneration without a change in quantitative sensory testing, autonomic function or neurophysiology.

Metabolic and cardiovascular outcomes of bariatric surgery.

PURPOSE OF REVIEW: Bariatric surgery is an effective therapy for morbid obesity that also improves weight-related metabolic parameters and reduces morbidity and mortality. The purpose of this review is to consolidate our current understanding of metabolic, macrovascular and microvascular benefits of bariatric surgery and to provide an update. RECENT FINDINGS: Early resolution of insulin resistance and type 2 diabetes mellitus (T2DM) varies by type of bariatric surgery and appears to be mediated by changes in secretion of gut hormones, metabolism of bile acids, expression of glucose transporters and the gut microbiome. Dyslipidaemia, atherosclerosis, microvascular complications of obesity and diabetes, systemic and tissue-level inflammation show evidence of regression and hypertension improves significantly after bariatric surgery. SUMMARY: Bariatric surgery leads to improvements in obesity-related metabolic comorbidities such as dyslipidaemia, HDL functionality, hypertension, T2DM, insulin resistance and inflammation. It slows the atherosclerotic process and reduces cardiovascular and all-cause mortality. Recent data have demonstrated regression of the microvascular complications of obesity and diabetes including the regeneration of small nerve fibres. The magnitude of change in short-term metabolic effects depends on the surgical procedure whilst longer term effects are related to the amount of sustained excess weight loss.

Modeling Elekta VersaHD using the Varian Eclipse treatment planning system for photon beams: A single-institution experience.

The aim of this study was to report a single-institution experience and commissioning data for Elekta VersaHD linear accelerators (LINACs) for photon beams in the Eclipse treatment planning system (TPS). Two VersaHD LINACs equipped with 160-leaf collimators were commissioned. For each energy, the percent-depth-dose (PDD) curves, beam profiles, output factors, leaf transmission factors and dosimetric leaf gaps (DLGs) were acquired in accordance with the AAPM task group reports No. 45 and No. 106 and the vendor-supplied documents. The measured data were imported into Eclipse TPS to build a VersaHD beam model. The model was validated by creating treatment plans spanning over the full-spectrum of treatment sites and techniques used in our clinic. The quality assurance measurements were performed using MatriXX, ionization chamber, and radiochromic film. The DLG values were iteratively adjusted to optimize the agreement between planned and measured doses. Mobius, an independent LINAC logfile-based quality assurance tool, was also commissioned both for routine intensity-modulated radiation therapy (IMRT) QA and as a secondary check for the Eclipse VersaHD model. The Eclipse-generated VersaHD model was in excellent agreement with the measured PDD curves and beam profiles. The measured leaf transmission factors were less than 0.5% for all energies. The model validation study yielded absolute point dose agreement between ionization chamber measurements and Eclipse within ±4% for all cases. The comparison between Mobius and Eclipse, and between Mobius and ionization chamber measurements lead to absolute point dose agreement within ±5%. The corresponding 3D dose distributions evaluated with 3%global/2mm gamma criteria resulted in larger than 90% passing rates for all plans. The Eclipse TPS can model VersaHD LINACs with clinically acceptable accuracy. The model validation study and comparisons with Mobius demonstrated that the modeling of VersaHD in Eclipse necessitates further improvement to provide dosimetric accuracy on par with Varian LINACs.

Covariance J-resolved spectroscopy: Theory and application in vivo.

Magnetic resonance spectroscopy (MRS) is a powerful tool capable of investigating the metabolic status of several tissues in vivo. In particular, single-voxel-based 1 H spectroscopy provides invaluable biochemical information from a volume of interest (VOI) and has therefore been used in a variety of studies. Unfortunately, typical one-dimensional MRS data suffer from severe signal overlap and thus important metabolites are difficult to distinguish. One method that is used to disentangle overlapping resonances is the two-dimensional J-resolved spectroscopy (JPRESS) experiment. Due to the long acquisition duration of the JPRESS experiment, a limited number of points are acquired in the indirect dimension, leading to poor spectral resolution along this dimension. Poor spectral resolution is problematic because proper peak assignment may be hindered, which is why the zero-filling method is often used to improve resolution as a post-processing step. However, zero-filling leads to spectral artifacts, which may affect visualization and quantitation of spectra. A novel method utilizing a covariance transformation, called covariance J-resolved spectroscopy (CovJ), was developed in order to improve spectral resolution along the indirect dimension (F1 ). Comparison of simulated data demonstrates that peak structures remain qualitatively similar between JPRESS and the novel method along the diagonal region (F1 = 0 Hz), whereas differences arise in the cross-peak (F1 ≠0 Hz) regions. In addition, quantitative results of in vivo JPRESS data acquired on a 3T scanner show significant correlations (r2 >0.86, p<0.001) when comparing the metabolite concentrations between the two methods. Finally, a quantitation algorithm, 'COVariance Spectral Evaluation of 1 H Acquisitions using Representative prior knowledge' (Cov-SEHAR), was developed in order to quantify γ-aminobutyric acid and glutamate from the CovJ spectra. These preliminary findings indicate that the CovJ method may be used to improve spectral resolution without hindering metabolite quantitation for J-resolved spectra.

Accelerated five-dimensional echo planar J-resolved spectroscopic imaging: Implementation and pilot validation in human brain.

PURPOSE: To implement an accelerated five-dimensional (5D) echo-planar J-resolved spectroscopic imaging sequence combining 3 spatial and 2 spectral encoding dimensions and to apply the sequence in human brain. METHODS: An echo planar readout was used to acquire a single spatial and a single spectral dimension during one readout. Nonuniform sampling was applied to the two phase-encoded spatial directions and the indirect spectral dimension. Nonlinear reconstruction was used to minimize the ℓ1-norm or the total variation and included a spectral mask to enhance sparsity. Retrospective reconstructions at multiple undersamplings were performed in phantom. Ten healthy volunteers were scanned with 8× undersampling and compared to a fully sampled single slice scan. RESULTS: Retrospective reconstruction of fully sampled phantom data showed excellent quality at 4×, 8×, 12×, and 16× undersampling using either reconstruction method. Reconstruction of prospectively acquired in vivo scans with 8× undersampling showed excellent quality in the occipito-parietal lobes and good quality in the frontal lobe, consistent with the fully sampled single slice scan. CONCLUSION: By utilizing nonuniform sampling with nonlinear reconstruction, 2D J-resolved spectra can be acquired over a 3D spatial volume with a total scan time of 20 min, which is reasonable for in vivo studies.

3D spatially encoded and accelerated TE-averaged echo planar spectroscopic imaging in healthy human brain.

Several different pathologies, including many neurodegenerative disorders, affect the energy metabolism of the brain. Glutamate, a neurotransmitter in the brain, can be used as a biomarker to monitor these metabolic processes. One method that is capable of quantifying glutamate concentration reliably in several regions of the brain is TE-averaged (1) H spectroscopic imaging. However, this type of method requires the acquisition of multiple TE lines, resulting in long scan durations. The goal of this experiment was to use non-uniform sampling, compressed sensing reconstruction and an echo planar readout gradient to reduce the scan time by a factor of eight to acquire TE-averaged spectra in three spatial dimensions. Simulation of glutamate and glutamine showed that the 2.2-2.4 ppm spectral region contained 95% glutamate signal using the TE-averaged method. Peak integration of this spectral range and home-developed, prior-knowledge-based fitting were used for quantitation. Gray matter brain phantom measurements were acquired on a Siemens 3 T Trio scanner. Non-uniform sampling was applied retrospectively to these phantom measurements and quantitative results of glutamate with respect to creatine 3.0 (Glu/Cr) ratios showed a coefficient of variance of 16% for peak integration and 9% for peak fitting using eight-fold acceleration. In vivo scans of the human brain were acquired as well and five different brain regions were quantified using the prior-knowledge-based algorithm. Glu/Cr ratios from these regions agreed with previously reported results in the literature. The method described here, called accelerated TE-averaged echo planar spectroscopic imaging (TEA-EPSI), is a significant methodological advancement and may be a useful tool for categorizing glutamate changes in pathologies where affected brain regions are not known a priori. Copyright © 2016 John Wiley & Sons, Ltd.

Correlated spectroscopic imaging of calf muscle in three spatial dimensions using group sparse reconstruction of undersampled single and multichannel data.

PURPOSE: To implement a 5D (three spatial + two spectral) correlated spectroscopic imaging sequence for application to human calf. THEORY AND METHODS: Nonuniform sampling was applied across the two phase encoded dimensions and the indirect spectral dimension of an echo planar-correlated spectroscopic imaging sequence. Reconstruction was applied that minimized the group sparse mixed ℓ2,1-norm of the data. Multichannel data were compressed using a sensitivity map-based approach with a spatially dependent transform matrix and utilized the self-sparsity of the individual coil images to simplify the reconstruction. RESULTS: Single channel data with 8× and 16× undersampling are shown in the calf of a diabetic patient. A 15-channel scan with 12× undersampling of a healthy volunteer was reconstructed using 5 virtual channels and compared to a fully sampled single slice scan. Group sparse reconstruction faithfully reconstructs the lipid cross peaks much better than ℓ1 minimization. CONCLUSION: COSY spectra can be acquired over a 3D spatial volume with scan time under 15 min using echo planar readout with highly undersampled data and group sparse reconstruction.

Accelerated echo planar J-resolved spectroscopic imaging in prostate cancer: a pilot validation of non-linear reconstruction using total variation and maximum entropy.

The overlap of metabolites is a major limitation in one-dimensional (1D) spectral-based single-voxel MRS and multivoxel-based MRSI. By combining echo planar spectroscopic imaging (EPSI) with a two-dimensional (2D) J-resolved spectroscopic (JPRESS) sequence, 2D spectra can be recorded in multiple locations in a single slice of prostate using four-dimensional (4D) echo planar J-resolved spectroscopic imaging (EP-JRESI). The goal of the present work was to validate two different non-linear reconstruction methods independently using compressed sensing-based 4D EP-JRESI in prostate cancer (PCa): maximum entropy (MaxEnt) and total variation (TV). Twenty-two patients with PCa with a mean age of 63.8 years (range, 46-79 years) were investigated in this study. A 4D non-uniformly undersampled (NUS) EP-JRESI sequence was implemented on a Siemens 3-T MRI scanner. The NUS data were reconstructed using two non-linear reconstruction methods, namely MaxEnt and TV. Using both TV and MaxEnt reconstruction methods, the following observations were made in cancerous compared with non-cancerous locations: (i) higher mean (choline + creatine)/citrate metabolite ratios; (ii) increased levels of (choline + creatine)/spermine and (choline + creatine)/myo-inositol; and (iii) decreased levels of (choline + creatine)/(glutamine + glutamate). We have shown that it is possible to accelerate the 4D EP-JRESI sequence by four times and that the data can be reliably reconstructed using the TV and MaxEnt methods. The total acquisition duration was less than 13 min and we were able to detect and quantify several metabolites.

Evaluation of anxiety-like behaviour in a rat model of acute postoperative pain.

BACKGROUND: Unrelieved acute postoperative pain can lead to a wide range of adverse effects, such as anxiety, depression, restlessness and sleep deprivation. OBJECTIVE: To investigate anxiety-like behaviour in a postoperative pain model. INTERVENTIONS AND MAIN OUTCOME MEASURES: Mechanical hypersensitivity was assessed with an electronic von Frey device, whereas anxiety-like behaviour was measured with light/dark testing and elevated plus maze testing. RESULTS: Rats developed significant mechanical hyperalgesia on 1, 3 and 8 days postsurgery compared with sham-operated rats. There was no reduction in motility between preincision and postincision when animals were allowed to move freely in an open field locomotion test. In light-dark tests, incised animals spent significantly less time than sham rats in the light compartment on the 1st and 3rd postoperative days. However, in an elevated plus maze test, differences between sham and incised rats were only observed on the 8th postoperative day as they spent significantly more time in the open arms. Pretreatment with morphine significantly increased withdrawal thresholds compared with treatment with saline (0.9% NaCl), but had no effect on light or open arm avoidance behaviour. CONCLUSION: We report that a rat model of acute postoperative pain is associated with anxiety-like increased light and open arm avoidance behaviour.

Rosacea - the ophthalmic perspective.

CONTEXT: Rosacea is a chronic cutaneous inflammatory disorder with variable presentations. Although primarily considered a skin disease, rosacea may involve the eyes in a significant number of patients leading to ocular complications. It has been recognized that many patients of ocular rosacea in dermatological outpatient department (OPD) go unnoticed as the physicians don't ask about eye symptoms. Same holds true in ophthalmic OPD's where the doctors usually don't consider this diagnosis. The diagnosis of ocular rosacea primarily relies on observation of ophthalmic clinical features but it can be easily missed if accompanying cutaneous features are subtle or inconsistent. The subject diagnosis if not diagnosed and treated promptly, may cause varying degrees of ocular morbidity and may impair vision secondary to corneal involvement. OBJECTIVE: To review published literature and provide an overview on different pathophysiologic mechanisms of ocular rosacea and clinical features required for its diagnosis. As well as to highlight various treatment modalities available for ocular rosacea. MATERIALS AND METHODS: In our study Medline and Google Scholar were the key search engines to find literature using keywords like epidemiology, pathogenesis, clinical features, management and complications of ocular rosacea.

Magnetic Resonance Spectroscopy for Cervical Cancer: Review and Potential Prognostic Applications.

This review article investigates the utilization of MRS in the setting of cervical cancer. A variety of different techniques have been used in this space including single-voxel techniques such as point-resolved spectroscopy (PRESS) and stimulated echo acquisition mode spectroscopy (STEAM). Furthermore, the experimental parameters for these acquisitions including field strength, repetition times (TR), and echo times (TE) vary greatly. This study critically examines eleven MRS studies that focus on cervical cancer. Out of the eleven studies, ten studies utilized PRESS acquisition, while the remaining study used STEAM acquisition. These studies generally showed that the choline signal is altered in cervical cancer (4/11 studies), the lipid signal is generally increased in cervical cancer or the lipid distribution is changed (5/11 studies), and that diffusion-weighted imaging (DWI) can quantitatively detect lower apparent diffusion coefficient (ADC) values in cervical cancer (2/11 studies). Two studies also investigated the role of MRS for monitoring treatment response and demonstrated mixed results regarding choline signal, and one of these studies showed increased lipid signal for non-responders. There are several new MRS technologies that have yet to be implemented for cervical cancer including advanced spectroscopic imaging and artificial intelligence, and those technologies are also discussed in the article.

Acute Toxicity of Total Body Irradiation Using Volumetric Arc Therapy With a Focus on the Effect of Lung Dose Rate.

Purpose: To report adverse effects of high dose total body irradiation (TBI) delivered using a volumetric arc therapy (VMAT) technique and to assess pulmonary toxicity at dose rates of 40 and 100 monitor units per minute (MU/min). Methods and Materials: This retrospective study included patients >18 years old who received ≥8 Gy TBI using a VMAT technique. The TBI dose was prescribed to a planning target volume consisting of a 0.5 cm retraction of the body with the lungs subtracted. The objective function specified planning target volume coverage goals of D100% ≥ 90% and Dmax <130%. A lung dose control structure consisting of a 1 cm retraction of the lung volume was limited to Dmean <75%. Treatments were initially delivered with a dose rate of 40 MU/min for the thoracic isocenters and 100 MU/min for the other isocenters. Beginning in January 2021, a dose rate of 100 MU/min was used for all isocenters. All treatments were administered in 2 Gy fractions delivered twice daily. Acute toxicity was assessed for 30 days after TBI. Results: A total of 29 patients were included in this analysis who received TBI between January 2019 and October 2021. Prescription dose ranged from 8 to 12 Gy. Mean lung dose was 7.9 Gy (SD, 1.4 Gy) for patients treated at 40 MU/min and for patients treated at 100 MU/min 7.1 Gy (SD, 1.3 Gy). Mucositis was the most common grade 3 toxicity and occurred in 10 (34%) patients. Only 1 instance of pneumonitis was observed and occurred in a patient who received a mean lung dose of 10.1 Gy delivered at 40 MU/min. Conclusions: In this cohort of patients who received high dose TBI using a VMAT technique, the composite rate of acute toxicity was not unexpectedly high. We did not observe an increase in lung toxicity after increasing the dose rate of the thoracic isocenters from 40 MU/min to 100 MU/min.

Mitigating Risks in Cone Beam Computed Tomography Guided Online Adaptive Radiation Therapy: A Preventative Reference Planning Review Approach.

Purpose: Online adaptive radiation therapy (oART) treatment planning requires evaluating the temporal robustness of reference plans and anticipating the potential changes during treatment courses that may even lead to risks unique to the adaptive workflow. This study conducted a risk analysis of the cone beam computed tomography guided adaptive workflow and is the first to assess an adaptive-specific reference planning review that mitigates risk in the planning process to prevent events and treatment deficiencies during adaptation. Methods and Materials: A quality management team of medical physicists, residents, physicians, and radiation therapists performed a fault tree analysis and failure mode and effects analysis. Fault trees were created for under/overdosing targets and treatment deficiencies and assisted in identifying failure modes for the failure mode and effects analysis. Treatment deficiency was defined as a nonideal oART plan resulting in treatment with a lower quality plan (either oART or scheduled plan), treatment delay, or canceling treatment for the day. A reference planning checklist was created to catch failure modes before reaching the patient. Risk priority numbers (RPNs = severity * detectability * occurrence) were scored with and without the reference planning checklist to quantify risk mitigation. A root cause analysis was conducted for an event where an adaptive plan failed to generate. Results: The reference planning checklist (with items covering patient background, contouring/planning robustness for anatomy variability, and machine limitations) reduced the RPN for all failure modes. Only 1 failure mode with an RPN > 150 occurred with the reference planning checklist compared with 29 failure modes without, including 14 adaptive-specific failure modes. Contouring, planning, setup, scheduling, and documentation errors were identified during the fault tree analysis. Twenty-nine of 70 errors were adaptive-specific. The reference planning checklist could address 23 of 33 errors for over- or underdosing and 28 of 37 errors for treatment deficiency. The root cause analysis highlighted the need to check the setup prior to adaptive plan delivery and the time-out checklist. Conclusions: The reference planning checklist improved the detection of the failure modes and improved the quality and robustness of the plans produced for oART. It is ideally performed before the physician plan review to prevent last-minute replan (before or after first adaptive treatment) and delay of patient start. The checklist presented can be modified based on failures specific to individual clinics and used at various planning steps based on available resources.

The accuracy of artificial intelligence deformed nodal structures in cervical online cone-beam-based adaptive radiotherapy.

Background and Purpose: Online cone-beam-based adaptive radiotherapy (ART) adjusts for anatomical changes during external beam radiotherapy. However, limited cone-beam image quality complicates nodal contouring. Despite this challenge, artificial-intelligence guided deformation (AID) can auto-generate nodal contours. Our study investigated the optimal use of such contours in cervical online cone-beam-based ART. Materials and Methods: From 136 adaptive fractions across 21 cervical cancer patients with nodal disease, we extracted 649 clinically-delivered and AID clinical target volume (CTV) lymph node boost structures. We assessed geometric alignment between AID and clinical CTVs via dice similarity coefficient, and 95% Hausdorff distance, and geometric coverage of clinical CTVs by AID planning target volumes by false positive dice. Coverage of clinical CTVs by AID contour-based plans was evaluated using D100, D95, V100%, and V95%. Results: Between AID and clinical CTVs, the median dice similarity coefficient was 0.66 and the median 95 % Hausdorff distance was 4.0 mm. The median false positive dice of clinical CTV coverage by AID planning target volumes was 0. The median D100 was 1.00, the median D95 was 1.01, the median V100% was 1.00, and the median V95% was 1.00. Increased nodal volume, fraction number, and daily adaptation were associated with reduced clinical CTV coverage by AID-based plans. Conclusion: In one of the first reports on pelvic nodal ART, AID-based plans could adequately cover nodal targets. However, physician review is required due to performance variation. Greater attention is needed for larger, daily-adapted nodes further into treatment.