Pretreatment Spinal Column Dose Estimation for Spinal SBRT Using Octavius Four-dimensional Phantom and Dose-volume Histograms Four-dimensional Feature: A Dosimetric Analysis.

Aim: The aim of this study was to estimate the spinal column dose for spinal Stereotactic body radiation therapy (SBRT) before patient treatment using the PTW dosimetry Octavius dose-volume histograms (DVH) four-dimensional (4D) feature. Materials and Methods: Twenty-three patients were included in the study, and a volumetric modulated arc therapy plan with 6MV flattening filter-free (6FFF) was generated for each patient in the Eclipse planning system using the Anisotropic Analytical Algorithm (AAA) algorithm (Varian Medical Systems, Palo Alto, CA) for the TrueBeam STx LINAC machine. The Octavius 4D system was used to estimate the spinal cord dose by delivering the plans to the 4D phantom. The measured dose was compared with the Eclipse treatment planning system (TPS) (Varian Medical Systems, Palo Alto, CA) dose. Results: The spinal cord max and mean doses estimated using Varisoft DVH 4D are in close agreement with the TPS calculated max and mean doses. The deviation between measured dose and TPS dose is ±5% for the spinal max dose, and the deviation between measured dose and TPS dose is ± 3% for the spinal mean dose. Conclusions: The study demonstrates that the PTW Octavius 4D phantom and DVH 4D feature can be used as a tool to estimate spinal cord dose before the treatment in spinal SBRT plans. The system provides an independent dose measurement that is comparable to the TPS dose. The close agreement between measured and calculated doses validates the use of this system as a critical organ dose verification tool.

Deletion of cytosolic phospholipase A2 promotes striated muscle growth.

Generation of arachidonic acid by the ubiquitously expressed cytosolic phospholipase A2 (PLA2) has a fundamental role in the regulation of cellular homeostasis, inflammation and tumorigenesis. Here we report that cytosolic PLA2 is a negative regulator of growth, specifically of striated muscle. We find that normal growth of skeletal muscle, as well as normal and pathologic stress-induced hypertrophic growth of the heart, are exaggerated in Pla2g4a-/- mice, which lack the gene encoding cytosolic PLA2. The mechanism underlying this phenotype is that cytosolic PLA2 negatively regulates insulin-like growth factor (IGF)-1 signaling. Absence of cytosolic PLA2 leads to sustained activation of the IGF-1 pathway, which results from the failure of 3-phosphoinositide-dependent protein kinase (PDK)-1 to recruit and phosphorylate protein kinase C (PKC)-zeta, a negative regulator of IGF-1 signaling. Arachidonic acid restores activation of PKC-zeta, correcting the exaggerated IGF-1 signaling. These results indicate that cytosolic PLA2 and arachidonic acid regulate striated muscle growth by modulating multiple growth-regulatory pathways.

Tranexamic acid is associated with less blood transfusion in off-pump coronary artery bypass graft surgery: a systematic review and meta-analysis.

OBJECTIVE: Tranexamic acid reduces blood loss and transfusion in on-pump coronary artery bypass graft (CABG) surgery. Compared with on-pump, off-pump surgery is associated with less blood loss and transfusion. Therefore, tranexamic acid may be less effective for off-pump surgery, and its safety profile may be different in this setting. The aim of this study was to determine the efficacy and safety of tranexamic acid for off-pump CABG surgery. DESIGN: Systematic review and meta-analysis. SETTING: University of Edinburgh. INTERVENTIONS: The administration of tranexamic acid. METHODS: A systematic review of randomized controlled trials administering tranexamic acid to patients undergoing off-pump CABG surgery. A meta-analysis of 24-hour blood loss, postoperative allogeneic transfusion, and thromboembolic events. MEASUREMENTS AND MAIN RESULTS: Eight trials were identified. The lack of appropriate data limited the meta-analysis on blood loss. Tranexamic acid significantly reduced the overall risk of allogeneic blood component transfusion (risk ratio = 0.47; 95% confidence intervals, 0.33-0.66; p < 0.0001) and packed red blood cell transfusions (risk ratio = 0.51; 95% CI, 0.36-0.71; p = 0.0001). No association was found between tranexamic acid and myocardial infarction, stroke, or pulmonary embolism. Population sizes of meta-analyses ranged from 466 to 544. CONCLUSIONS: Tranexamic acid reduces blood transfusion after off-pump surgery. Although no association with adverse events was found, the population sample size was too small to detect rare but clinically significant adverse events. A well-designed randomized controlled trial with an appropriate sample size is required to confirm tranexamic acid effectiveness and safety in off-pump CABG surgery.

Correlation Between Physiological and Performance-Based Metrics to Estimate Pilots' Cognitive Workload.

This paper discusses the utilization of pilots' physiological indications such as electroencephalographic (EEG) signals, ocular parameters, and pilot performance-based quantitative metrics to estimate cognitive workload. The study aims to derive a non-invasive technique to estimate pilot's cognitive workload and study their correlation with standard physiological parameters. Initially, we conducted a set of user trials using well-established psychometric tests for evaluating the effectiveness of pupil and gaze-based ocular metrics for estimating cognitive workload at different levels of task difficulty and lighting conditions. Later, we conducted user trials with the NALSim flight simulator using a business class Learjet aircraft model. We analyzed participants' ocular parameters, power levels of different EEG frequency bands, and flight parameters for estimating variations in cognitive workload. Results indicate that introduction of secondary task increases pilot's cognitive workload significantly. The beta frequency band of EEG, nearest neighborhood index specifying distribution of gaze fixation, L1 Norm of power spectral density of pupil diameter, and the duty cycle metric indicated variations in cognitive workload.

Utilization of a Web-Based Conferencing Platform to Improve Global Radiation Oncology Education and Quality-Proof of Principle Through Implementation in India.

PURPOSE: Chartrounds (www.chartrounds.com) was established in the United States in 2010 as a web-based platform for radiation oncologists to review cases with leading disease-site experts. However, the need for access to experts for peer review and education is not unique to the United States, and the Chartrounds platform was therefore adapted for improved global reach. Chartrounds was first expanded to India, and herein we report our initial experience with this initiative. METHODS AND MATERIALS: The US Chartrounds platform was adapted to create Chartrounds India (ind.chartrounds.com). Through collaboration with the Association of Radiation Oncologists of India, India-based specialists were recruited, and the association's membership list was used to announce sessions to potential participants. RESULTS: Between June 2017 and January 2018, 27 Chartrounds India sessions were completed, led by 21 different specialists (representing 10 centers in India) and covering 11 different disease sites/topics. A total of 240 members from 126 centers (private: 56%; teaching: 36%; public: 8%) across 24 states/territories participated in ≥1 session. Of the 240 members who participated in ≥1 session, 159 (66%) participated in ≥2 sessions and 60 (25%) participated in ≥5 sessions. The average number of participants per session was 34 (range, 13-72). On average, 80% of respondents rated the sessions as high or very high quality; 87% and 95% agreed or strongly agreed that the time was used effectively and that the sessions were relevant to daily practice, respectively. Seventy-six percent agreed or strongly agreed that the sessions will result in a change in their practice. The average feedback survey response rate was 32% (range, 17%-49%). CONCLUSIONS: Chartrounds has proven to be an effective resource for US-based radiation oncologists, and our initial experience with Chartrounds India suggests that an online platform for radiation oncology case review and education can be successfully implemented globally with use of local disease site experts.

c-Jun N-terminal kinases mediate reactivation of Akt and cardiomyocyte survival after hypoxic injury in vitro and in vivo.

Akt is a central regulator of cardiomyocyte survival after ischemic injury in vitro and in vivo, but the mechanisms regulating Akt activity in the postischemic cardiomyocyte are not known. Furthermore, although much is known about the detrimental role that the c-Jun N-terminal kinases (JNKs) play in promoting death of cells exposed to various stresses, little is known of the molecular mechanisms by which JNK activation can be protective. We report that JNKs are necessary for the reactivation of Akt after ischemic injury. We identified Thr450 of Akt as a residue that is phosphorylated by JNKs, and the phosphorylation status of Thr450 regulates reactivation of Akt after hypoxia, apparently by priming Akt for subsequent phosphorylation by 3-phosphoinositide-dependent protein kinase. The reduction in Akt activity that is induced by JNK inhibition may have significant biological consequences, as we find that JNKs, acting via Akt, are critical determinants of survival in posthypoxic cardiomyocytes in culture. Furthermore, in contrast to selective p38-mitogen-activated protein kinase inhibition, which was cardioprotective in vivo, concurrent inhibition of both JNKs and p38-mitogen-activated protein kinases increased ischemia/reperfusion injury in the heart of the intact rat. These studies demonstrate that reactivation of Akt after resolution of hypoxia and ischemia is regulated by JNKs and suggest that this is likely a central mechanism of the myocyte protective effect of JNKs.

Aortic valve replacement following coronary artery bypass grafting using bilateral internal mammary arteries.

Aortic valve replacement in patients with a patent internal mammary artery grafts poses two main challenges: Sternal reentry and myocardial protection. Beating heart procedures have been well described in coronary and valve surgery. Herein, we describe a simple reproducible technique of aortic valve replacement that circumvents the main issues highlighted above.

Platypnea-orthodeoxia syndrome: a rare complication after right pneumonectomy.

Platypnea is characterized by breathlessness in the upright position. Orthodeoxia is defined by arterial desaturation on standing. Herein we describe a case of platypnea-orthodeoxia syndrome in a patient who underwent a right pneumonectomy for adenocarcinoma of the lung. Closure of a patent foramen ovale, causing a right-to-left shunt, with an Amplatzer device, produced immediate symptomatic relief.

Prevalence of psychiatric disorder in asymptomatic or minimally symptomatic cancer patients on treatment.

BACKGROUND: Cancer not only affects organ systems physically but can also affect the mind as a psychiatric disorder. Appropriate treatment can be clinically efficacious and cost-effective. With this background, a study was conducted in a regional cancer center to assess the prevalence of psychiatric disorder amongst cancer patients and correlate it with socio-demographic parameters. MATERIALS AND METHODS: Asymptomatic or minimally symptomatic cancer patients on active anticancer treatment, fulfilling inclusion criteria, were served psychiatric assessment questionnaire. The demographic and the medical data were obtained from subjects and their medical records. Correlation of prevalence of psychiatric disorder with socio-demographic parameters was done using the Chi-square test. RESULTS: Thirty-eight patients returned the questionnaire duly filled. Of them, 24 (63%) had some psychiatric disorder. All these 24 patients were suffering from depression--15 (63%) from major depression and 9 (37%) from minor depression. Only 6 (25%) patients had anxiety disorder. The prevalence of psychiatric disorder in patients aware of the diagnosis and prognosis was 58 and 55% respectively. This was significantly higher as compared to the patients who were not aware of their diagnosis and prognosis (P-value 0.019 and 0.05 respectively). CONCLUSION: High prevalence of psychiatric disorder, especially depression, amongst the cancer patients--particularly in those who were aware of the diagnosis and prognosis. A majority of these disorders are eminently treatable. Routine psychiatric evaluation of all cancer patients is a matter of debate that needs to be addressed in larger prospective surveys.

Mitral valve replacement for mitral stenosis secondary to Hunter's syndrome.

Hunter's syndrome is a rare, X-linked recessive, mucopolysaccharidosis. Survival into adulthood is uncommon. Mitral valve disease, predominantly regurgitation, has been reported in these patients. We have found no reports of mitral valve replacement for mitral stenosis secondary to Hunter's syndrome in the English literature. We report that mitral valve replacement for this pathology is a viable treatment option in an adult patient; however, specific precautions must be considered.

Stabilization of beta-catenin by a Wnt-independent mechanism regulates cardiomyocyte growth.

beta-Catenin is a transcriptional activator that regulates embryonic development as part of the Wnt pathway and also plays a role in tumorigenesis. The mechanisms leading to Wnt-induced stabilization of beta-catenin, which results in its translocation to the nucleus and activation of transcription, have been an area of intense interest. However, it is not clear whether stimuli other than Wnts can lead to important stabilization of beta-catenin and, if so, what factors mediate that stabilization and what biologic processes might be regulated. Herein we report that beta-catenin is stabilized in cardiomyocytes after these cells have been exposed to hypertrophic stimuli in culture or in vivo. The mechanism by which beta-catenin is stabilized is distinctly different from that used by Wnt signaling. Although, as with Wnt signaling, inhibition of glycogen synthase kinase-3 remains central to hypertrophic stimulus-induced stabilization of beta-catenin, the mechanism by which this occurs involves the recruitment of activated PKB to the beta-catenin-degradation complex. PKB stabilizes the complex and phosphorylates glycogen synthase kinase-3 within the complex, inhibiting its activity directed at beta-catenin. Finally, we demonstrate via adenoviral gene transfer that beta-catenin is both sufficient to induce growth in cardiomyocytes in culture and in vivo and necessary for hypertrophic stimulus-induced growth. Thus, in these terminally differentiated cells, beta-catenin is stabilized by hypertrophic stimuli acting via heterotrimeric G protein-coupled receptors. The stabilization occurs via a unique Wnt-independent mechanism and results in cellular growth.

Glycogen synthase kinase-3beta regulates growth, calcium homeostasis, and diastolic function in the heart.

Glycogen synthase kinase (GSK) 3beta is a negative regulator of stress-induced cardiomyocyte hypertrophy. It is not clear, however, if GSK-3beta plays any role in regulating normal cardiac growth and cardiac function. Herein we report that a transgenic mouse expressing wild type GSK-3beta in the heart has a dramatic impairment of normal post-natal cardiomyocyte growth as well as markedly abnormal cardiac contractile function. The most striking phenotype, however, is grossly impaired diastolic relaxation, which leads to increased filling pressures of the left ventricle and massive atrial enlargement. This is due to profoundly abnormal calcium handling, leading to an inability to normalize cytosolic [Ca2+] in diastole. The alterations in calcium handling are due at least in part to direct down-regulation of the sarcoplasmic reticulum calcium ATPase (SERCA2a) by GSK-3beta, acting at the level of the SERCA2 promoter. These studies identify GSK-3beta as a regulator of normal growth of the heart and are the first of which we are aware, to demonstrate regulation of expression of SERCA2a, a critical determinant of diastolic function, by a cytosolic signaling pathway, the activity of which is dynamically modulated. De-regulation of GSK-3beta leads to severe systolic and diastolic dysfunction and progressive heart failure. Because down-regulation of SERCA2a plays a central role in the diastolic and systolic dysfunction of patients with heart failure, these findings have potential implications for the therapy of this disorder.