Volumetric intensity-modulated Arc (RapidArc) therapy for primary hepatocellular carcinoma: comparison with intensity-modulated radiotherapy and 3-D conformal radiotherapy

<p>Abstract</p> <p>Background</p> <p>To compare the RapidArc plan for primary hepatocellular carcinoma (HCC) with 3-D conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) plans using dosimetric analysis.</p> <p>Methods</p> <p>Nine patients with unresectable HCC were enrolled in this study. Dosimetric values for RapidArc, IMRT, and 3DCRT were calculated for total doses of 45~50.4 Gy using 1.8 Gy/day. The parameters included the conformal index (CI), homogeneity index (HI), and hot spot (V_107%) for the planned target volume (PTV) as well as the monitor units (MUs) for plan efficiency, the mean dose (D_mean) for the organs at risk (OAR) and the maximal dose at 1% volume (D_1%) for the spinal cord. The percentage of the normal liver volume receiving ≥ 40, > 30, > 20, and > 10 Gy (V_{40 Gy}, V_{30 Gy}, V_{20 Gy}, and V_{10 Gy}) and the normal tissue complication probability (NTCP) were also evaluated to determine liver toxicity.</p> <p>Results</p> <p>All three methods achieved comparable homogeneity for the PTV. RapidArc achieved significantly better CI and V_107%values than IMRT or 3DCRT (<it>p </it>< 0.05). The MUs were significantly lower for RapidArc (323.8 ± 60.7) and 3DCRT (322.3 ± 28.6) than for IMRT (1165.4 ± 170.7) (<it>p </it>< 0.001). IMRT achieved a significantly lower D_meanof the normal liver than did 3DCRT or RapidArc (<it>p </it>= 0.001). 3DCRT had higher V_{40 Gy}and V_{30 Gy}values for the normal liver than did RapidArc or IMRT. Although the V_{10 Gy}to the normal liver was higher with RapidArc (75.8 ± 13.1%) than with 3DCRT or IMRT (60.5 ± 10.2% and 57.2 ± 10.0%, respectively; <it>p </it>< 0.01), the NTCP did not differ significantly between RapidArc (4.38 ± 2.69) and IMRT (3.98 ± 3.00) and both were better than 3DCRT (7.57 ± 4.36) (<it>p </it>= 0.02).</p> <p>Conclusions</p> <p>RapidArc provided favorable tumor coverage compared with IMRT or 3DCRT, but RapidArc is not superior to IMRT in terms of liver protection. Further studies are needed to establish treatment outcome differences between the three approaches.</p

Efficacy of telemedicine for the management of cardiovascular disease: a systematic review and meta-analysis

BACKGROUND: Telemedicine has been increasingly integrated into chronic disease management through remote patient monitoring and consultation, particularly during the COVID-19 pandemic. We did a systematic review and meta-analysis of studies reporting effectiveness of telemedicine interventions for the management of patients with cardiovascular conditions. METHODS: In this systematic review and meta-analysis, we searched PubMed, Scopus, and Cochrane Library from database inception to Jan 18, 2021. We included randomised controlled trials and observational or cohort studies that evaluated the effects of a telemedicine intervention on cardiovascular outcomes for people either at risk (primary prevention) of cardiovascular disease or with established (secondary prevention) cardiovascular disease, and, for the meta-analysis, we included studies that evaluated the effects of a telemedicine intervention on cardiovascular outcomes and risk factors. We excluded studies if there was no clear telemedicine intervention described or if cardiovascular or risk factor outcomes were not clearly reported in relation to the intervention. Two reviewers independently assessed and extracted data from trials and observational and cohort studies using a standardised template. Our primary outcome was cardiovascular-related mortality. We evaluated study quality using Cochrane risk-of-bias and Newcastle-Ottawa scales. The systematic review and the meta-analysis protocol was registered with PROSPERO (CRD42021221010) and the Malaysian National Medical Research Register (NMRR-20–2471–57236). FINDINGS: 72 studies, including 127 869 participants, met eligibility criteria, with 34 studies included in meta-analysis (n=13 269 with 6620 [50%] receiving telemedicine). Combined remote monitoring and consultation for patients with heart failure was associated with a reduced risk of cardiovascular-related mortality (risk ratio [RR] 0·83 [95% CI 0·70 to 0·99]; p=0·036) and hospitalisation for a cardiovascular cause (0·71 [0·58 to 0·87]; p=0·0002), mostly in studies with short-term follow-up. There was no effect of telemedicine on all-cause hospitalisation (1·02 [0·94 to 1·10]; p=0·71) or mortality (0·90 [0·77 to 1·06]; p=0·23) in these groups, and no benefits were observed with remote consultation in isolation. Small reductions were observed for systolic blood pressure (mean difference –3·59 [95% CI –5·35 to –1·83] mm Hg; p<0·0001) by remote monitoring and consultation in secondary prevention populations. Small reductions were also observed in body-mass index (mean difference –0·38 [–0·66 to –0·11] kg/m(2); p=0·0064) by remote consultation in primary prevention settings. INTERPRETATION: Telemedicine including both remote disease monitoring and consultation might reduce short-term cardiovascular-related hospitalisation and mortality risk among patients with heart failure. Future research should evaluate the sustained effects of telemedicine interventions. FUNDING: The British Heart Foundation

Intensity modulated radiotherapy for elderly bladder cancer patients

<p>Abstract</p> <p>Background</p> <p>To review our experience and evaluate treatment planning using intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) for the treatment of elderly patients with bladder cancer.</p> <p>Methods</p> <p>From November 2006 through November 2009, we enrolled 19 elderly patients with histologically confirmed bladder cancer, 9 in the IMRT and 10 in the HT group. The patients received 64.8 Gy to the bladder with or without concurrent chemotherapy. Conventional 4-field "box" pelvic radiation therapy (2DRT) plans were generated for comparison.</p> <p>Results</p> <p>The median patient age was 80 years old (range, 65-90 years old). The median survival was 21 months (5 to 26 months). The actuarial 2-year overall survival (OS) for the IMRT vs. the HT group was 26.3% <it>vs </it>.37.5%, respectively; the corresponding values for disease-free survival were 58.3% <it>vs</it>. 83.3%, respectively; for locoregional progression-free survival (LRPFS), the values were 87.5% <it>vs</it>. 83.3%, respectively; and for metastases-free survival, the values were 66.7% <it>vs</it>. 60.0%, respectively. The 2-year OS rates for T1, 2 <it>vs</it>. T3, 4 were 66.7% <it>vs</it>. 35.4%, respectively (<it>p </it>= 0.046). The 2-year OS rate was poor for those whose RT completion time greater than 8 weeks when compared with the RT completed within 8 wks (37.9% vs. 0%, <it>p </it>= 0.004).</p> <p>Conclusion</p> <p>IMRT and HT provide good LRPFS with tolerable toxicity for elderly patients with invasive bladder cancer. IMRT and HT dosimetry and organ sparing capability were superior to that of 2DRT, and HT provides better sparing ability than IMRT. The T category and the RT completion time influence OS rate.</p

S100A8 and S100A9 Are Associated with Doxorubicin-Induced Cardiotoxicity in the Heart of Diabetic Mice

© 2016 Pei, Tam, Sin, Wang, Yung, Chan, Wong, Ying, Lai and Siu. Cardiomyopathy is a clinical problem that occurs in the hearts of type 2 diabetic patients as well as cancer patients undergoing doxorubicin chemotherapy. The number of diabetic cancer patients is increasing but surprisingly the cardiac damaging effects of doxorubicin, a commonly used chemotherapeutic drug, on diabetic hearts have not been well-examined. As the signaling mechanisms of the doxorubicin-induced cardiomyopathy in type 2 diabetic heart are largely unknown, this study examined the molecular signaling pathways that are responsible for the doxorubicin-induced cardiotoxicity in type 2 diabetic hearts. Male 14- to 18-week-old db/db mice were used as the type 2 diabetic model, and age-matched non-diabetic db/+ mice served as controls. The db/+ non-diabetic and db/db diabetic mice were randomly assigned to the following groups: db/+CON, db/+DOX-5d, db/+DOX-7d, db/dbCON, db/dbDOX-5d, and db/dbDOX-7d. Mice assigned to doxorubicin (DOX) group were exposed to an intraperitoneal (i.p.) injection of DOX at a dose of 15 mg/kg to induce cardiomyopathy. Mice in control (CON) groups were i.p. injected with the same volume of saline instead of DOX. Mice were euthanized by overdose of ketamine and xylazine 5 or 7 days after the DOX injection. Microarray analysis was adopted to examine the changes of the whole transcriptional profile in response to doxorubicin exposure in diabetic hearts. Ventricular fractional shortening was examined as an indicator of cardiac function by transthoracic echocardiography. The presence of diabetic cardiomyopathy in db/db mice was evident by the reduction of fractional shortening. There was a further impairment of cardiac contractile function 7 days after the DOX administration in db/db diabetic mice. According to our microarray analysis, we identified a panel of regulatory genes associated with cardiac remodeling, inflammatory response, oxidative stress, and metabolism in the DOX-induced cardiac injury in diabetic heart. The microarray results of selected genes were confirmed by real time PCR. Notably, S100A8 and S100A9 were found to have a unique specific expression pattern that was coincident with the DOX-induced cardiomyopathy in diabetic hearts. Correspondingly, NF-κB expression in diabetic hearts was increased together with the elevation of S100A8/9 and activation of p38 MAPK signaling after DOX administration, which induced cardiac inflammation as demonstrated by the elevation of cardiac IL-6 level. These findings provide novel pre-clinical information for revealing the S100A8/A9-associated molecular signaling pathways that mediate the doxorubicin-induced cardiotoxicity in diabetic hearts.Link_to_subscribed_fulltex

Cortical and Subcortical Neural Correlates for Respiratory Sensation in Response to Transient Inspiratory Occlusions in Humans

Cortical and subcortical mechanosensation of breathing can be measured by short respiratory occlusions. However, the corresponding neural substrates involved in the respiratory sensation elicited by a respiratory mechanical stimulus remained unclear. Therefore, we applied the functional magnetic resonance imaging (fMRI) technique to study cortical activations of respiratory mechanosensation. We hypothesized that thalamus, frontal cortex, somatosensory cortex, and inferior parietal cortex would be significantly activated in response to respiratory mechanical stimuli. We recruited 23 healthy adults to participate in our event-designed fMRI experiment. During the 12-min scan, participants breathed with a specialized face-mask. Single respiratory occlusions of 150 ms were delivered every 2–4 breaths. At least 32 successful occlusions were collected for data analysis. The results showed significant neural activations in the thalamus, supramarginal gyrus, middle frontal gyrus, inferior frontal triangularis, and caudate (AlphaSim corrected p &lt; 0.05). In addition, subjective ratings of breathlessness were significantly correlated with the levels of neural activations in bilateral thalamus, right caudate, right supramarginal gyrus, left middle frontal gyrus, left inferior triangularis. Our results demonstrated cortical sources of respiratory sensations elicited by the inspiratory occlusion paradigm in healthy adults were located in the thalamus, supramarginal gyrus, and the middle frontal cortex, inferior frontal triangularis, suggesting subcortical, and cortical neural sources of the respiratory mechanosensation are thalamo-cortical based, especially the connections to the premotor area, middle and ventro-lateral prefrontal cortex, as well as the somatosensory association cortex. Finally, level of neural activation in thalamus is associated with the subjective rating of breathlessness, suggesting respiratory sensory information is gated at the thalamic level

GRAIL Refinements to Lunar Seismic Structure

A method to enhance and detect subtle seismic arrivals typically used in terrestrial seismology, is to stack seismograms that have been time shifted to the predicted arrival time of a hypothetical phase of interest. We previously applied this array processing approach to the Apollo lunar seismic data, providing the first direct constraint on the size and state of the Moon's core. The method used travel time predictions made from pre-existing estimates of the crust and mantle velocities and densities and assumed that each of the Moons layers ia a uniform shell with no lateral variation or heterogeneity. In reality the structural properties of the Moon are likely inhomogeneous and vary both laterally and with depth

Multi-Modality Imaging of Atheromatous Plaques in Peripheral Arterial Disease: Integrating Molecular and Imaging Markers

Peripheral artery disease (PAD) is a common and debilitating condition characterized by the narrowing of the limb arteries, primarily due to atherosclerosis. Non-invasive multi-modality imaging approaches using computed tomography (CT), magnetic resonance imaging (MRI), and nuclear imaging have emerged as valuable tools for assessing PAD atheromatous plaques and vessel walls. This review provides an overview of these different imaging techniques, their advantages, limitations, and recent advancements. In addition, this review highlights the importance of molecular markers, including those related to inflammation, endothelial dysfunction, and oxidative stress, in PAD pathophysiology. The potential of integrating molecular and imaging markers for an improved understanding of PAD is also discussed. Despite the promise of this integrative approach, there remain several challenges, including technical limitations in imaging modalities and the need for novel molecular marker discovery and validation. Addressing these challenges and embracing future directions in the field will be essential for maximizing the potential of molecular and imaging markers for improving PAD patient outcomes

Structural insights into the electron/proton transfer pathways in the quinol:fumarate reductase from Desulfovibrio gigas

The membrane-embedded quinol:fumarate reductase (QFR) in anaerobic bacteria catalyzes the reduction of fumarate to succinate by quinol in the anaerobic respiratory chain. The electron/proton-transfer pathways in QFRs remain controversial. Here we report the crystal structure of QFR from the anaerobic sulphate-reducing bacterium Desulfovibrio gigas (D. gigas) at 3.6 Å resolution. The structure of the D. gigas QFR is a homo-dimer, each protomer comprising two hydrophilic subunits, A and B, and one transmembrane subunit C, together with six redox cofactors including two b-hemes. One menaquinone molecule is bound near heme b_L in the hydrophobic subunit C. This location of the menaquinone-binding site differs from the menaquinol-binding cavity proposed previously for QFR from Wolinella succinogenes. The observed bound menaquinone might serve as an additional redox cofactor to mediate the proton-coupled electron transport across the membrane. Armed with these structural insights, we propose electron/proton-transfer pathways in the quinol reduction of fumarate to succinate in the D. gigas QFR

Structural insights into the electron/proton transfer pathways in the quinol : fumarate reductase from Desulfovibrio gigas

Guan, H., Hsieh, Y., Lin, P. et al. Structural insights into the electron/proton transfer pathways in the quinol : fumarate reductase from Desulfovibrio gigas. Sci Rep 8, 14935 (2018) doi:10.1038/s41598-018-33193-