Institutional experience report on the target contouring workflow in the radiotherapy department for stereotactic arrhythmia radioablation delivered on conventional linear accelerators.

PURPOSE: In stereotactic arrhythmia radioablation (STAR), the target is defined using multiple imaging studies and a multidisciplinary team consisting of electrophysiologist, cardiologist, cardiac radiologist, and radiation oncologist collaborate to identify the target and delineate it on the imaging studies of interest. This report describes the workflow employed in our radiotherapy department to transfer the target identified based on electrophysiology and cardiology imaging to the treatment planning image set. METHODS: The radiotherapy team was presented with an initial target in cardiac axes orientation, contoured on a wideband late gadolinium-enhanced (WB-LGE) cardiac magnetic resonance (CMR) study, which was subsequently transferred to the computed tomography (CT) scan used for treatment planning-i.e., the average intensity projection (AIP) image set derived from a 4D CT-via an axial CMR image set, using rigid image registration focused on the target area. The cardiac and the respiratory motion of the target were resolved using ciné-CMR and 4D CT imaging studies, respectively. RESULTS: The workflow was carried out for 6 patients and resulted in an internal target defined in standard anatomical orientation that encompassed the cardiac and the respiratory motion of the initial target. CONCLUSION: An image registration-based workflow was implemented to render the STAR target on the planning image set in a consistent manner, using commercial software traditionally available for radiation therapy.

Short-Term Medication Effect on Fall Risk in Multimorbid Inpatients with Dementia.

INTRODUCTION: Dementia increases the risk of falls and fall-related injuries, which may be caused by inappropriate medication use. To date, there is little evidence on which medications are more likely to cause falls. We therefore investigated the effects of medication use and medication changes 48 h before falls in hospitalised patients with dementia. METHODS: This matched case-control study included 74 patients with a mean age of 83 years (38% women) who had been hospitalised for at least 7 days. Information on medications, diagnoses, disease severity, use of walking aids, falls, and demographics was collected from electronic medical records. The effects of the number of medications and psychotropics, equivalent daily doses of antidepressants, antipsychotics and benzodiazepines, anticholinergic burden, medication initiation, dose change, medication discontinuation, as-needed medications, opioid use and the presence of fall-increasing diseases were examined separately for the periods 0 h-24 h and 24 h-48 h before the falls using binomial logistic regression analyses. RESULTS: Falls increased significantly with higher daily antipsychotic doses 24 h before the fall. In addition, the rate of falls increased with higher anticholinergic burden and prevalence of medication discontinuation 24-48 h before the fall. Notably, the total number of medications and psychotropic medications had no effect on the incidence of falls. CONCLUSION: With regard to the short-term effects of medication on fall risk, particular attention should be paid to the daily dose of antipsychotics, anticholinergic burden and medication discontinuation. Further studies with larger samples are needed to confirm the results of this study.

Rectal deformation management with IGRT in prostate radiotherapy: Can it be managed with rigid alignment alone?

PURPOSE: It is challenging to achieve appropriate target coverage of the prostate with Image Guided Radiation Therapy (IGRT) while simultaneously constraining rectal doses within planned values when there is significant variability in rectal filling and shape. We investigated if rectum planning goals can be fulfilled using rigid CBCT-based on-board alignment to account for interfraction rectal deformations. METHODS: Delivered rectal doses corresponding to prostate alignment ("PR") and anterior rectum alignment ("AR") for 239 daily treatments from 13 patients are reported. Rectal doses were estimated by rigidly mapping the planned dose on the daily CT derived from the daily CBCT according to respective alignment shifts. Rectum V95% (rV95%) was used for analyses. RESULTS: Compared to "PR", "AR" alignment increased rV95% for an average of 34.4% across all patients. rV95% (cc) averaged over all fractions was significant from planning values for 10/13 patients for "PR" and for 9/13 for "AR". 3/13 patients had reproducible anatomy. Of patients with non-reproducible anatomy, three had dosimetrically more favorable, while seven had less favorable anatomies. Most shift differences (82.3%) between the "PR" and "AR" alignments larger than 2 mm resulted in rV95% changes larger than 2 cc. Most shift differences (82.2%) of 2 mm or less between the "PR" and "AR" alignments resulted in rV95% changes less than 2 cc. The average percentage of fractions among patients in which anterior or posterior shifts for "AR" and "PR" alignment was larger than the PTV margins was 9.1% (0.0%-37.5%) and 1.3% (0%-10%). CONCLUSION: Rectal deformation and subsequent inconsistent interfraction separation between prostate and rectal wall translate into anatomical changes that cannot always be mitigated with rigid alignment. If systematic differences exist due to a non-reproducible planning anatomy, attempts to restore the planned rectal doses through anterior rectum alignment produce rather small improvements and may result in unacceptable target underdosage.

Optimization of treatment workflow for 0.35T MR-Linac system.

PURPOSE: This study presents a novel and comprehensive framework for evaluating magnetic resonance guided radiotherapy (MRgRT) workflow by integrating the Failure Modes and Effects Analysis (FMEA) approach with Time-Driven Activity-Based Costing (TDABC). We assess the workflow for safety, quality, and economic implications, providing a holistic understanding of the MRgRT implementation. The aim is to offer valuable insights to healthcare practitioners and administrators, facilitating informed decision-making regarding the 0.35T MRIdian MR-Linac system's clinical workflow. METHODS: For FMEA, a multidisciplinary team followed the TG-100 methodology to assess the MRgRT workflow's potential failure modes. Following the mitigation of primary failure modes and workflow optimization, a treatment process was established for TDABC analysis. The TDABC was applied to both MRgRT and computed tomography guided RT (CTgRT) for typical five-fraction stereotactic body RT (SBRT) treatments, assessing total workflow and costs associated between the two treatment workflows. RESULTS: A total of 279 failure modes were identified, with 31 categorized as high-risk, 55 as medium-risk, and the rest as low-risk. The top 20% risk priority numbers (RPN) were determined for each radiation oncology care team member. Total MRgRT and CTgRT costs were assessed. Implementing technological advancements, such as real-time multi leaf collimator (MLC) tracking with volumetric modulated arc therapy (VMAT), auto-segmentation, and increasing the Linac dose rate, led to significant cost savings for MRgRT. CONCLUSION: In this study, we integrated FMEA with TDABC to comprehensively evaluate the workflow and the associated costs of MRgRT compared to conventional CTgRT for five-fraction SBRT treatments. FMEA analysis identified critical failure modes, offering insights to enhance patient safety. TDABC analysis revealed that while MRgRT provides unique advantages, it may involve higher costs. Our findings underscore the importance of exploring cost-effective strategies and key technological advancements to ensure the widespread adoption and financial sustainability of MRgRT in clinical practice.

Exhaled breath condensate identifies metabolic dysregulation in patients with radiation-induced lung injury.

Radiation-induced lung injury (RILI) is a consequence of therapeutic thoracic irradiation (TR) for many cancers, and there are no FDA-approved curative strategies. Studies report that 80% of patients who undergo TR will have CT-detectable interstitial lung abnormalities, and strategies to limit the risk of RILI may make radiotherapy less effective at treating cancer. Our lab and others have reported that lung tissue from patients with idiopathic pulmonary fibrosis (IPF) exhibits metabolic defects including increased glycolysis and lactate production. In this pilot study, we hypothesized that patients with radiation-induced lung damage will exhibit distinct changes in lung metabolism that may be associated with the incidence of fibrosis. Using liquid chromatography/tandem mass spectrometry to identify metabolic compounds, we analyzed exhaled breath condensate (EBC) in subjects with CT-confirmed lung lesions after TR for lung cancer, compared with healthy subjects, smokers, and cancer patients who had not yet received TR. The lung metabolomic profile of the irradiated group was significantly different from the three nonirradiated control groups, highlighted by increased levels of lactate. Pathway enrichment analysis revealed that EBC from the case patients exhibited concurrent alterations in lipid, amino acid, and carbohydrate energy metabolism associated with the energy-producing tricarboxylic acid (TCA) cycle. Radiation-induced glycolysis and diversion of lactate to the extracellular space suggests that pyruvate, a precursor metabolite, converts to lactate rather than acetyl-CoA, which contributes to the TCA cycle. This TCA cycle deficiency may be compensated by these alternate energy sources to meet the metabolic demands of chronic wound repair. Using an "omics" approach to probe lung disease in a noninvasive manner could inform future mechanistic investigations and the development of novel therapeutic targets.NEW & NOTEWORTHY We report that exhaled breath condensate (EBC) identifies cellular metabolic dysregulation in patients with radiation-induced lung injury. In this pilot study, untargeted metabolomics revealed a striking metabolic signature in EBC from patients with radiation-induced lung fibrosis compared to patients with lung cancer, at-risk smokers, and healthy volunteers. Patients with radiation-induced fibrosis exhibit specific changes in tricarboxylic acid (TCA) cycle energy metabolism that may be required to support the increased energy demands of fibroproliferation.

3D deep convolution neural network for radiation pneumonitis prediction following stereotactic body radiotherapy.

In this study, we investigated 3D convolutional neural networks (CNNs) with input from radiographic and dosimetric datasets of primary lung tumors and surrounding lung volumes to predict the likelihood of radiation pneumonitis (RP). Pre-treatment, 3- and 6-month follow-up computed tomography (CT) and 3D dose datasets from one hundred and ninety-three NSCLC patients treated with stereotactic body radiotherapy (SBRT) were retrospectively collected and analyzed for this study. DenseNet-121 and ResNet-50 models were selected for this study as they are deep neural networks and have been proven to have high accuracy for complex image classification tasks. Both were modified with 3D convolution and max pooling layers to accept 3D datasets. We used a minority class oversampling approach and data augmentation to address the challenges of data imbalance and data scarcity. We built two sets of models for classification of three (No RP, Grade 1 RP, Grade 2 RP) and two (No RP, Yes RP) classes as outputs. The 3D DenseNet-121 models performed better (F1 score [0.81], AUC [0.91] [three class]; F1 score [0.77], AUC [0.84] [two class]) than the 3D ResNet-50 models (F1 score [0.54], AUC [0.72] [three-class]; F1 score [0.68], AUC [0.71] [two-class]) (p = 0.017 for three class predictions). We also attempted to identify salient regions within the input 3D image dataset via integrated gradient (IG) techniques to assess the relevance of the tumor surrounding volume for RP stratification. These techniques appeared to indicate the significance of the tumor and surrounding regions in the prediction of RP. Overall, 3D CNNs performed well to predict clinical RP in our cohort based on the provided image sets and radiotherapy dose information.

Effects of respiratory and cardiac motion on estimating radiation dose to the left ventricle during radiotherapy for lung cancer.

PURPOSE: Establish a workflow to evaluate radiotherapy (RT) dose variation induced by respiratory and cardiac motion on the left ventricle (LV) and left ventricular myocardium (LVM). METHODS: Eight lung cancer patients underwent 4D-CT, expiratory T1-volumetric-interpolated-breath-hold-examination (VIBE), and cine MRI scans in expiration. Treatment plans were designed on the average intensity projection (AIP) datasets from 4D-CTs. RT dose from AIP was transferred onto 4D-CT respiratory phases. About 50% 4D-CT dose was mapped onto T1-VIBE (following registration) and from there onto average cine MRI datasets. Dose from average cine MRI was transferred onto all cardiac phases. Cumulative cardiac dose was estimated by transferring dose from each cardiac phase onto a reference cine phase following deformable image registration. The LV was contoured on each 4D-CT breathing phase and was called clinical LV (cLV); this structure is blurred by cardiac motion. Additionally, LV, LVM, and an American Heart Association (AHA) model were contoured on all cardiac phases. Relative maximum/mean doses for contoured regions were calculated with respect to each patient's maximum/mean AIP dose. RESULTS: During respiration, relative maximum and mean doses on the cLV ranged from -4.5% to 5.6% and -14.2% to 16.5%, respectively, with significant differences in relative mean doses between inspiration and expiration (P < 0.0145). During cardiac motion at expiration, relative maximum and mean doses on the LV ranged from 1.6% to 59.3%, 0.5% to 27.4%, respectively. Relative mean doses were significantly different between diastole and systole (P = 0.0157). No significant differences were noted between systolic, diastolic, or cumulative cardiac doses compared to the expiratory 4D-CT (P > 0.14). Significant differences were observed in AHA segmental doses depending on tumour proximity compared to global LV doses on expiratory 4D-CT (P < 0.0117). CONCLUSION: In this study, the LV dose was highest during expiration and diastole. Segmental evaluation suggested that future cardiotoxicity evaluations may benefit from regional assessments of dose that account for cardiopulmonary motion.

Shallow kinetics induced by a metronome (SKIM): A novel contactless respiratory motion management.

OBJECTIVES: As an alternative to conventional compression amidst the COVID-19 pandemic, we developed a contactless motion management strategy. By increasing the patient's breathing rate to induce shallow breathing with the aid of a metronome, our hypothesis is that the motion magnitude of the target may be minimized without physical contact or compression. METHODS: Fourteen lung stereotactic body radiation therapy (SBRT) patients treated under fast shallow-breathing (FSB) were selected for inclusion in this retrospective study. Our proposed method is called shallow kinetics induced by a metronome (SKIM). We induce FSB by setting the beats-per-minute (BPM) high (typically in the range of 50-60). This corresponded to a patient breathing rate of 25-30 (breathing) cycles per minute. The magnitude of target motion in 3D under SKIM was evaluated using 4DCT datasets. Comparison with free breathing (FB) 4DCT was also made for a subset for which FB data available. RESULTS: The overall effectiveness of SKIM was evaluated with 18 targets (14 patients). Direct comparison with FB was performed with 12 targets (10 patients). The vector norm mean ± SD value of motion magnitude under SKIM for 18 targets was 8.2 ± 4.1 mm. The mean ± SD metronome BPM was 54.9 ± 4.0 in this group. The vector norm means ± SD values of target motion for FB and SKIM in the 12 target sub-group were 14.6 ± 8.5 mm and 9.3 ± 3.7 mm, respectively. The mean ± SD metronome BPM for this sub-group was 56.3 ± 2.5. CONCLUSION: Compared with FB, SKIM can significantly reduce respiratory motion magnitude of thoracic targets. The difference in maximum motion reduction in the overall vector norm, S-I, and A-P directions was significant (p = 0.033, 0.042, 0.011). Our proposed method can be an excellent practical alternative to conventional compression due to its flexibility and ease of implementation.

Pilot Study Demonstrating the Value of Interdisciplinary Education on the Integration of Radiation Therapy in Lung Cancer Management.

This study aimed to understand baseline knowledge of basic principles of radiation therapy for lung cancer among medical oncology, thoracic surgery, and pulmonology trainees and practicing physicians and also assess whether a didactic lecture will improve objective knowledge and perceived comfort level in making appropriate referrals to radiation oncology (RO). Radiation oncologists at 8 academic institutions offered a presentation covering indications, logistics, efficacy, and toxicity of thoracic radiation. Participants completed a survey to assess their prior exposures to RO and perceived value of the lecture, and objective knowledge gained based on pre/post-lecture questions. Among 121 attendees, 76 completed the pre-test, and 25 the post-test (response rates 62.8% and 20.7%, respectively). Fifty-seven (75.0%) had never previously experienced a RO didactic about lung cancer, 62 (81.6%) had never seen a linear accelerator, and 65 (85.5%) had never rotated in a RO department. The mean pre-test score was 53.5% (SD 17.6%), with a trend (p = 0.066) towards thoracic surgeons (61.5%) performing better than medical oncologists (55.5%) or pulmonologists (48.3%). Level of training (p = 0.130), and prior RO exposures (p = 0.240), did not significantly impact pre-test scores. The mean post-test score of 75.1% (SD 3.6%) was significantly higher than mean pre-test score (p < 0.001). After the lecture, 25 participants (100%) felt more knowledgeable about RO, and 24 (96%) felt more comfortable making appropriate referrals to RO. A didactic lecture about RO for trainees and physicians who treat lung cancer at 8 academic institutions was feasible, filled a gap in exposure, and improved knowledge.

Humor creation during efforts to find humorous cognitive reappraisals of threatening situations.

This interdisciplinary study examined the structure of humor creation in the specific context of efforts to positively reappraise stressful situations for effective coping. In a sample of n = 101 participants, a performance test was used to assess the quantity (fluency, number of generated ideas that qualified as humor) and quality (rated funniness) of humor creation in cognitive reappraisal. Linguistic mechanisms were identified and quantified using cognitive-linguistic methods of corpus analysis, and their employment was correlated with humor production performance on the level of the individual. Almost all individuals were able to come up with reappraisal ideas that qualified as humorous. Depressive symptoms, a negative mood state, and high perceptions of threat did not compromise the participants' capability to create humor. Individuals who were more serious-minded as a trait produced ideas that were rated as less funny, but their basic ability to create humor was unaffected. Metonymy (a contiguity-based principle of meaning extension) emerged as by far the most prominent semantic mechanism in the creation of humorous re-interpretations. Furthermore, its use was related to good humor creation performance in terms of quantity and quality, which is in line with its assumed importance in the extension of meaning in general and the creation of humor in particular. Further effective linguistic mechanisms and conceptual phenomena were identified. The empirical data may be valuable for the development of interventions involving the creation of humorous ideas for cognitive reappraisal.

Quantitative assessment of intra- and inter-modality deformable image registration of the heart, left ventricle, and thoracic aorta on longitudinal 4D-CT and MR images.

PURPOSE: Magnetic resonance imaging (MRI)-based investigations into radiotherapy (RT)-induced cardiotoxicity require reliable registrations of magnetic resonance (MR) imaging to planning computed tomography (CT) for correlation to regional dose. In this study, the accuracy of intra- and inter-modality deformable image registration (DIR) of longitudinal four-dimensional CT (4D-CT) and MR images were evaluated for heart, left ventricle (LV), and thoracic aorta (TA). METHODS AND MATERIALS: Non-cardiac-gated 4D-CT and T1 volumetric interpolated breath-hold examination (T1-VIBE) MRI datasets from five lung cancer patients were obtained at two breathing phases (inspiration/expiration) and two time points (before treatment and 5 weeks after initiating RT). Heart, LV, and TA were manually contoured. Each organ underwent three intramodal DIRs ((A) CT modality over time, (B) MR modality over time, and (C) MR contrast effect at the same time) and two intermodal DIRs ((D) CT/MR multimodality at same time and (E) CT/MR multimodality over time). Hausdorff distance (HD), mean distance to agreement (MDA), and Dice were evaluated and assessed for compliance with American Association of Physicists in Medicine (AAPM) Task Group (TG)-132 recommendations. RESULTS: Mean values of HD, MDA, and Dice under all registration scenarios for each region of interest ranged between 8.7 and 16.8 mm, 1.0 and 2.6 mm, and 0.85 and 0.95, respectively, and were within the TG-132 recommended range (MDA < 3 mm, Dice > 0.8). Intramodal DIR showed slightly better results compared to intermodal DIR. Heart and TA demonstrated higher registration accuracy compared to LV for all scenarios except for HD and Dice values in Group A. Significant differences for each metric and tissue of interest were noted between Groups B and D and between Groups B and E. MDA and Dice significantly differed between LV and heart in all registrations except for MDA in Group E. CONCLUSIONS: DIR of the heart, LV, and TA between non-cardiac-gated longitudinal 4D-CT and MRI across two modalities, breathing phases, and pre/post-contrast is acceptably accurate per AAPM TG-132 guidelines. This study paves the way for future evaluation of RT-induced cardiotoxicity and its related factors using multimodality DIR.

Simulated Acute Hypobaric Hypoxia Effects on Cognition in Helicopter Emergency Medical Service Personnel - A Randomized, Controlled, Single-Blind, Crossover Trial.

OBJECTIVE: To evaluate, under replicable, blinded and standardised conditions, the effect of acute exposure to hypobaric hypoxia (HH) (equivalent to 200 or 3000 or 5000 m above sea level (asl)) on selected cognitive domains and physiological parameters in personnel of helicopter emergency medical service (HEMS). METHODS: We conducted a randomized clinical trial using a single-blind crossover design in an environmental chamber (terraXcube) to induce HH in 48 HEMS personnel. Participants performed cognitive tests (CT) before the ascent, after 5 min at altitude, and after simulated cardiopulmonary resuscitation (SCR). CT evaluated: sustained attention using the psychomotor vigilance test (PVT) that included measurement of reaction time (RT); risky decision making using the balloon analogue risk task (BART), and attention and speed of processing using the digit symbol substitution test (DSST). CT performance was subjectively rated with a visual analogue scale (VAS). Physiological data were recorded with a physiological monitoring system. Data were analysed using a linear mixed model and correlation analysis. RESULTS: Mean reaction time was significantly slower (p = 0.002) at HH (5000 m asl), but there were no independent effects of HH on the other parameters of the PVT, BART or DSST. Participants did not detect subjectively the slower RT at altitude since VAS performance results showed a positive correlation with mean RT (p = 0.009). DSST results significantly improved (p = 0.001) after SCR. CONCLUSION: Acute exposure of HEMS personnel to HH induced a slower RT but no changes in any other investigated measures of cognition. The reduced RT was not detected subjectively by the participants. Trial number 3489044136, ClinicalTrials.gov trial registration.

Formyl-Peptide Receptors in Infection, Inflammation, and Cancer.

Formyl-peptide receptors (FPRs) recognize bacterial and mitochondrial formylated peptides as well as endogenous non-formylated peptides and even lipids. FPRs are expressed on various host cell types but most strongly on neutrophils and macrophages. After the discovery of FPRs on leukocytes, it was assumed that these receptors predominantly govern a proinflammatory response resulting in chemotaxis, degranulation, and oxidative burst during infection. However, it is clear that the activation of FPRs has more complex consequences and can also promote the resolution of inflammation. Recent studies have highlighted associations between FPR function and inflammatory conditions, including inflammatory disorders, cancer, and infection. In this review we discuss these recent findings.

Body Mass Index Predicts Decline in Executive Function in Bipolar Disorder: Preliminary Data of a 12-Month Follow-up Study.

INTRODUCTION: Obesity and associated risk factors have been linked to cognitive decline before. OBJECTIVES: In the present study, we evaluated potential cumulative negative effects of overweight and obesity on cognitive performance in euthymic patients with bipolar disorder (BD) in a longitudinal design. METHODS: Neurocognitive measures (California Verbal Learning Test, Trail Making Test [TMT] A/B, Digit-Symbol-Test, Digit-Span, d2 Test), anthropometrics (e.g., body mass index [BMI]), and clinical ratings (Hamilton Depression Scale, Young Mania Rating Scale) were collected over a 12-month observation period. Follow-up data of 38 patients with BD (mean age 40 years; 15 males, 23 females) were available. RESULTS: High baseline BMI predicted a decrease in the patient's performance in the Digit-Span backwards task measuring working memory performance. In contrast, cognitive performance was not predicted by increases in BMI at follow-up. Normal weight bipolar patients (n = 19) improved their performance on the TMT B, measuring cognitive flexibility and executive functioning, within 1 year, while overweight bipolar patients (n = 19) showed no change in this task. CONCLUSIONS: The results suggest that overweight can predict cognitive performance changes over 12 months.

Diastolic Dysfunction Contributes to Impaired Cardiorespiratory Fitness in Patients with Lung Cancer and Reduced Lung Function Following Chest Radiation.

Cardiorespiratory fitness (CRF) is a robust and independent predictor of cardiovascular health and overall mortality. Patients with lung cancer often have chronic lung disease, contributing to impaired CRF. Radiation to the heart during lung cancer treatment may further reduce CRF. The determinants of CRF in this population are not well understood. We prospectively evaluated 12 patients with lung cancer without known cardiovascular disease with reduced lung function receiving curative intent thoracic radiotherapy to determine whether cardiac diastolic function, as assessed by Doppler echocardiography and N-terminal pro-brain natriuretic peptide (NTproBNP) levels, correlate with CRF measured by peak oxygen consumption (VO2). Doppler-derived measures of diastolic function and serum NTproBNP levels inversely correlated with peak VO2. In a multivariate regression model, NTproBNP was the strongest independent variable associated with peak VO2. These results suggest that diastolic dysfunction further contributes to reduced CRF in patients with lung cancer who have received radiotherapy.

Attitudes and Perceptions Towards Radiation Therapy in Breast Cancer Patients: The Role of a Multidisciplinary Care Team.

Previous studies have shown that breast cancer patients' beliefs regarding radiation therapy (RT) are influenced by a multitude of factors encompassing demographic, socioeconomic, cultural, and healthcare-related domains. The association between consultation with a multidisciplinary care team and breast cancer patients' attitudes towards RT, however, remains understudied. Using survey and medical record data from 185 women with invasive, non-metastatic breast cancer who received breast conserving surgery, we aimed to characterize the relationship between the number and type of oncological specialties consulted and women's belief in RT's ability to decrease the likelihood of breast cancer recurrence. Using multivariable models, we found that compared to women who discussed RT with only one oncologist (medical, radiation, or surgical), women who discussed RT with all three oncologists were more likely to report increased agreement with RT's ability to reduce cancer recurrence. No single specialty of oncology, including radiation oncology, showed increased associations with women's beliefs regarding RT's efficacy. We conclude that women's beliefs in the ability of radiation therapy to reduce breast cancer recurrence are associated with an increased number of oncologic physicians consulted.

Formyl-Peptide Receptor Activation Enhances Phagocytosis of Community-Acquired Methicillin-Resistant Staphylococcus aureus.

BACKGROUND: Formyl-peptide receptors (FPRs) are important pattern recognition receptors that sense specific bacterial peptides. Formyl-peptide receptors are highly expressed on neutrophils and monocytes, and their activation promotes the migration of phagocytes to sites of infection. It is currently unknown whether FPRs may also influence subsequent processes such as bacterial phagocytosis and killing. Staphylococcus aureus, especially highly pathogenic community-acquired methicillin-resistant S aureus strains, release high amounts of FPR2 ligands, the phenol-soluble modulins. METHODS: We demonstrate that FPR activation leads to upregulation of complement receptors 1 and 3 as well as FCγ receptor I on neutrophils and, consequently, increased opsonic phagocytosis of S aureus and other pathogens. RESULTS: Increased phagocytosis promotes killing of S aureus and interleukin-8 release by neutrophils. CONCLUSIONS: We show here for the first time that FPRs govern opsonic phagocytosis. Manipulation of FPR2 activation could open new therapeutic opportunities against bacterial pathogens.

Target volume definition for staple line recurrences of non-small cell lung cancer.

BACKGROUND: Staple line (SL) recurrences of non-small cell lung cancer (NSCLC) are commonly treated with radiotherapy (RT), but the target volume definition - whole SL versus focused on recurrence - is unclear. The aim of the study was to determine the appropriate target volume for RT of SL recurrences. MATERIALS AND METHODS: Twenty-two consecutive patients (20 stage I, 2 stage II) treated with salvage RT for SL recurrences were retrospectively analyzed. Imaging features at the time of SL recurrence were evaluated to guide target volume definition. RESULTS: Surgery: All patients had complete tumor resection (wedge resection in 10 (45%) and lobectomy in 12 (55%) patients). 14 (64%) patients had risk factors for recurrence, including surgical margins ≤ 2 cm, angiolymphatic and visceral pleural invasion.Salvage RT: After a median 26 months (9-67), all 22 patients developed SL recurrence which was metabolically active on PET in all and biopsy-confirmed in 18/22 (82%) patients. All patients underwent RT targeting the location of the SL recurrence only. 13/22 (59%) patients had additional PE T-negative nodular or linear SL changes that were not included in the irradiated volume.Recurrence after RT: After a median 17 months (9-34) 10/22 (45%) patients recurred either regionally 6/10 (60%), in the lungs 4/10 (40%) or distally 3/10 (30%). No patient recurred at the SL. Two-year overall and disease-free survival rates after RT were 71% and 65%, respectively. CONCLUSION: RT to SL recurrences alone results in excellent local control. Additional treatment to reduce regional and distant recurrences should be considered.

Humor comprehension and creative cognition: Shared and distinct neurocognitive mechanisms as indicated by EEG alpha activity.

Humor comprehension is increasingly recognized as showing parallels to more conventional creative cognition; yet our understanding of brain mechanisms underlying creative cognition in a humorous context is still limited. The present study addressed this issue by investigating functional patterns of EEG alpha activity while 93 participants viewed nonverbal humorous cartoons until they indicated having recognized the punch line, and subsequently vocalized their idea as to what constituted it. In a similar fashion, EEG was also assessed during performance of the Alternate Uses Task (AUT), in order to identify similarities and differences in EEG alpha activity implicated in conventional creative cognition vs. humor comprehension. Analyses revealed a pattern of robust task-related alpha power increases in both tasks, which were markedly more right-lateralized at ventral fronto-temporal sites in the humor task as compared to the AUT. Findings are interpreted in line with recent literature on the functional role of alpha activity in the creativity domain. Altogether, this study adds further evidence to the particular role of EEG alpha oscillations in creative cognition and supports the idea that conventional creative ideation and the comprehension of humor share neural mechanisms affiliated to creative cognition.

Functional coupling of brain networks during creative idea generation and elaboration in the figural domain.

The neuroscientific investigation of creative cognition has advanced by considering the functional connectivity between brain regions and its dynamic changes over time, which are consistent with stages in the ideation process. Surprisingly, although the communication between neuronal networks takes place in a time-scale of milliseconds, EEG studies investigating a time-course in cortico-cortical communication during creative ideation are rare and findings are typically restricted to the verbal domain. Therefore, this study examined functional coupling using EEG (task-related phase-locking in the upper-alpha range) during creative thinking in the figural domain. Using an innovative computerized experimental paradigm, we specifically investigated the stage of idea generation and the stage of idea elaboration in an adapted picture completion task. The findings confirmed a hypothesized increase of functional coupling from idea generation to elaboration, which was most pronounced in frontal-central as well as frontal-temporal networks. The connectivity in the frontal-parietal/occipital network already increased during idea generation and remained constant during elaboration. Importantly, more original participants generally showed higher functional connectivity in all brain networks. This elevated functional coupling with frontal brain regions might reflect increased executive processes related to internal attention, motor planning, and semantic selection processes supporting highly original thought in the figural domain.