Acute adverse events of ultra-hypofractionated whole-breast irradiation after breast-conserving surgery for early breast cancer in Japan: an interim analysis of the multi-institutional phase II UPBEAT study.

BACKGROUND: The applicability of ultra-hypofractionated (ultra-HF) whole-breast irradiation (WBI) remains unknown in Japanese women. This study aimed to evaluate the safety and efficacy of this approach among Japanese women and report the results of an interim analysis performed to assess acute adverse events (AEs) and determine whether it was safe to continue this study. METHODS: We enrolled Japanese women with invasive breast cancer or ductal carcinoma in situ who had undergone breast-conserving surgery, were aged ≥ 40 years, had pathological stages of Tis-T3 N0-N1, and had negative surgical margins. Ultra-HF-WBI was delivered at 26 Gy in five fractions over one week. When the number of enrolled patients reached 28, patient registration was paused for three months. The endpoint of the interim analysis was the proportion of acute AEs of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) within three months. RESULTS: Of the 28 patients enrolled from seven institutes, 26 received ultra-HF-WBI, and 2 were excluded due to postoperative infections. No AEs of grade ≥ 3 occurred. One patient (4%) experienced grade 2 radiation dermatitis, and 18 (69%) had grade 1 radiation dermatitis. The other acute grade 1 AEs experienced were skin hyperpigmentation (n = 10, 38%); breast pain (n = 4, 15%); superficial soft tissue fibrosis (n = 3, 12%); and fatigue (n = 1, 4%). No other acute AEs of grade ≥ 2 were detected. CONCLUSIONS: Acute AEs following ultra-HF-WBI were within acceptable limits among Japanese women, indicating that the continuation of the study was appropriate.

Correlation Between Dosimetric Parameters and Local Control in Definitive Radiotherapy for Head and Neck Cancers.

BACKGROUND/AIM: Radiotherapy (RT) outcomes are generally reported based on stage, patient background, and concomitant chemotherapy. This study aimed to investigate the effects of the prescribed dose to gross tumor volume (GTV) and the calculation algorithm on local control in definitive RT for head and neck (H&N) cancers using follow-up images after RT. PATIENTS AND METHODS: This study included 154 patients with H&N cancers treated by Volumetric Modulated Arc Therapy at the Kobe City Medical Center General Hospital. Patients were classified into those receiving definitive RT (70 Gy of irradiation) and those not receiving it. Follow-up images were used to categorize the patients into the responders and non-responders groups. In the non-responders group, follow-up images were imported into the treatment planning system, and the contours of the residual or recurrent areas (local failure) were extracted and fused with computed tomography-simulated images for treatment planning. Dose evaluation parameters included maximum dose, dose administered to 1% of the volume, dose administered to 50% of the volume, dose administered to 99% of the volume (D99%), and minimum dose (Dmin) administered to the GTV. The doses to the GTV were compared between responders and non-responders. RESULTS: D99% exhibited significant differences between local failure and responders and between local failure and non-responders. Dmin showed significant differences between responders and non-responders and between responders and local failure. CONCLUSION: This study emphasizes the importance of verifying dose distribution in all slices of treatment planning, highlighting the need for precise assessment of the dose to the GTV in head and neck cancers.

Population-based asymmetric margins for moving targets in real-time tumor tracking.

BACKGROUND: Both geometric and dosimetric components are commonly considered when determining the margin for planning target volume (PTV). As dose distribution is shaped by controlling beam aperture in peripheral dose prescription and dose-escalated simultaneously integrated boost techniques, adjusting the margin by incorporating the variable dosimetric component into the PTV margin is inappropriate; therefore, geometric components should be accurately estimated for margin calculations. PURPOSE: We introduced an asymmetric margin-calculation theory using the guide to the expression of uncertainty in measurement (GUM) and intra-fractional motion. The margins in fiducial marker-based real-time tumor tracking (RTTT) for lung, liver, and pancreatic cancers were calculated and were then evaluated using Monte Carlo (MC) simulations. METHODS: A total of 74 705, 73 235, and 164 968 sets of intra- and inter-fractional positional data were analyzed for 48 lung, 48 liver, and 25 pancreatic cancer patients, respectively, in RTTT clinical trials. The 2.5th and 97.5th percentiles of the positional error were considered representative values of each fraction of the disease site. The population-based statistics of the probability distributions of these representative positional errors (PD-RPEs) were calculated in six directions. A margin covering 95% of the population was calculated using the proposed formula. The content rate in which the clinical target volume (CTV) was included in the PTV was calculated through MC simulations using the PD-RPEs. RESULTS: The margins required for RTTT were at most 6.2, 4.6, and 3.9 mm for lung, liver, and pancreatic cancer, respectively. MC simulations revealed that the median content rates using the proposed margins satisfied 95% for lung and liver cancers and 93% for pancreatic cancer, closer to the expected rates than the margins according to van Herk's formula. CONCLUSIONS: Our proposed formula based on the GUM and motion probability distributions (MPD) accurately calculated the practical margin size for fiducial marker-based RTTT. This was verified through MC simulations.

[Successful Atrial Plication in Improving Respiratory Failure due to Bilateral Giant Atria].

Giant atria may trigger respiratory failure, which often requires surgical intervention. We report a patient who presented with respiratory failure due to bilateral giant atria. The patient was a 75-year-old woman with rheumatic heart disease. She had undergone mitral valve replacement and tricuspid annuloplasty at another hospital 17 years ago but recently developed respiratory dysfunction. Compression to the lungs by enlarged atria was diagnosed as the main cause of respiratory dysfunction. Hence, the anterior-to-posterior left atrial wall was plicated by para-annular and superior-half plication, respectively, and the right atrial wall was excised into an ellipse shape. Tricuspid valvuloplasty was performed on four sets of eight artificial chordae with CV5 sutures and an annuloplasty ring. Respiratory failure was alleviated after the surgery.

Crystal Structure of Pyrrolysyl-tRNA Synthetase from a Methanogenic Archaeon ISO4-G1 and Its Structure-Based Engineering for Highly-Productive Cell-Free Genetic Code Expansion with Non-Canonical Amino Acids.

Pairs of pyrrolysyl-tRNA synthetase (PylRS) and tRNAPyl from Methanosarcina mazei and Methanosarcina barkeri are widely used for site-specific incorporations of non-canonical amino acids into proteins (genetic code expansion). Previously, we achieved full productivity of cell-free protein synthesis for bulky non-canonical amino acids, including Nε-((((E)-cyclooct-2-en-1-yl)oxy)carbonyl)-L-lysine (TCO*Lys), by using Methanomethylophilus alvus PylRS with structure-based mutations in and around the amino acid binding pocket (first-layer and second-layer mutations, respectively). Recently, the PylRS·tRNAPyl pair from a methanogenic archaeon ISO4-G1 was used for genetic code expansion. In the present study, we determined the crystal structure of the methanogenic archaeon ISO4-G1 PylRS (ISO4-G1 PylRS) and compared it with those of structure-known PylRSs. Based on the ISO4-G1 PylRS structure, we attempted the site-specific incorporation of Nε-(p-ethynylbenzyloxycarbonyl)-L-lysine (pEtZLys) into proteins, but it was much less efficient than that of TCO*Lys with M. alvus PylRS mutants. Thus, the first-layer mutations (Y125A and M128L) of ISO4-G1 PylRS, with no additional second-layer mutations, increased the protein productivity with pEtZLys up to 57 ± 8% of that with TCO*Lys at high enzyme concentrations in the cell-free protein synthesis.

Intraoperative hemodialysis during open-heart surgery in patients with severe chronic kidney disease: a retrospective cohort study.

BACKGROUND: Acute kidney injury and chronic kidney disease (CKD) after cardiac surgery are associated with poor renal prognosis and increased mortality. The impact of intraoperative hemodialysis (IHD) on postoperative renal function remains unknown. We aimed to evaluate the utility of IHD during open-heart surgery in patients with severe non-dialysis-dependent chronic kidney disease (CKD-NDD) and its association with clinical outcomes. METHODS: This was a single-center retrospective cohort study that employed IHD during non-emergency open-heart surgery in patients with CKD stage G4 or G5. Patients who underwent emergent surgery, chronic dialysis, and/or kidney transplantation were excluded. We retrospectively compared the clinical characteristics and outcomes between patients from the IHD and non-IHD groups. The primary outcomes were 90-day mortality and postoperative initiation of renal replacement therapy (RRT). RESULTS: Twenty-eight patients were categorized into the IHD group and 33 into the non-IHD group. When comparing the IHD and non-IHD groups, men accounted for 60.7 vs. 50.3% of patients, the mean patient age was 74.5 (standard deviation [SD] 7.0) vs. 72.9 (SD 9.4) years (p = 0.744), and the proportion of patients with CKD G4 was 67.9 vs. 84.9% (p = 0.138). Regarding clinical outcomes, no significant differences were observed in the 90-day mortality (7.1 vs. 3.0%; p = 0.482) and 30-day RRT (17.9 vs. 30.3%; p = 0.373) rates between the groups. Among the patients with CKD G4, the IHD group had significantly lower 30-day RRT rates than the non-IHD group (0 vs. 25.0%; p = 0.032). RRT initiation was less likely for patients with CKD G4 (odds ratio 0.07, 95% confidence interval [CI] 0.01-0.37; p = 0.002); however, IHD did not significantly decrease the incidence of poor clinical outcomes (odds ratio 0.20, 95% CI 0.04-1.07; p = 0.061). CONCLUSIONS: IHD during open-heart surgery in patients with CKD-NDD did not improve their clinical outcomes with regards to postoperative dialysis. However, for patients with CKD G4, IHD may be useful for postoperative cardiac management.

Multi-institutional phase II study of ultra-hypofractionated whole-breast irradiation after breast-conserving surgery for breast cancer in Japan: Kyoto Radiation Oncology Study Group (UPBEAT study).

PURPOSE: The UK-FAST-Forward study showed that ultra-hypofractionated whole-breast irradiation (ultra-HF-WBI) involving five fractions of 26 Gy radiation over 1 week was not inferior to HF-WBI. However, it is not used in Japan due to safety concerns. In April 2022, we commenced a multi-institutional, single-arm, phase II trial. Our aim is to confirm the safety of ultra-HF-WBI after breast-conserving surgery (BCS) for breast cancer in Japanese women. METHOD: We plan to enroll 98 patients from 13 institutions. The primary endpoint is the proportion of late adverse events of grades ≥2 within 3 years. DISCUSSION: We believe that this highly promising clinical study can positively impact the Japanese guidelines for breast cancer treatment. The results will help us decide whether or not ultra-HF-WBI can be used as a more convenient alternative to WBI. REGISTRATION NUMBER AND DATE: This trial was registered in the UMIN Clinical Trials Registry (UMIN000047080) on March 4, 2022.

Open surgical treatment of superior vena cava syndrome due to invasive thymoma.

Here we describe a case of open surgery for superior vena cava syndrome due to invasive thymoma. An 85-year-old woman presented with facial swelling and exertional dyspnea. Computed axial tomography revealed a thymoma in the mediastinum, extending to the superior vena cava, right atrium, and bilateral brachiocephalic veins. Endovascular therapy did not seem feasible because superior vena cava appeared totally occluded, and stenting could cause tumor embolism to the pulmonary arteries. Open surgery facilitated macroscopically complete and successful tumor resection. If long-term survival seems possible, open surgery could be a viable treatment option for superior vena cava syndrome that is ineligible for endovascular therapy.

A case of freestyle valve reoperation 23 years after the first operation.

We present a case of redo stentless valve operation in a 73-year-old man who underwent aortic valve replacement via the subcoronary approach with a freestyle aortic bioprosthesis 23 years ago at our institution. He was referred for surgery because an echocardiogram showed severe aortic regurgitation due to structural valve deterioration, and aortic valve replacement was planned. Severe circumferential calcification and adhesion were noted during the surgery between the freestyle and native roots. Redo-aortic valve replacement was successful despite the technical difficulty. In stentless valve reoperations following aortic valve replacement via the subcoronary method, the planning of valve-in-valve transcatheter aortic valve implantation and sutureless valve implantation may be a practical and safe strategy.

Invasive Metastatic Well-Differentiated Liposarcoma to the Heart, Found in Intraoperative Transesophageal Echocardiography.

Hematogenous metastasis of liposarcoma to the heart is rare, even though other types of distant metastatic cardiac tumors are relatively more common than primary cardiac tumors. We experienced a case of distant metastasis of liposarcoma to the right interatrial septum, mimicking lipomatous hypertrophy in transesophageal echocardiography (TEE). There were no significant findings in the preoperative transthoracic echocardiography (TTE) or computed tomography (CT). TEE was the only tool to suspect the presence of a cardiac tumor. It also helped evaluate the spread of tumor invasion and make a decision for operation.

Multi-institutional feasibility study of intensity-modulated radiotherapy with chemotherapy for locally advanced non-small cell lung cancer.

BACKGROUND: This multi-institutional clinical trial evaluated the feasibility of intensity-modulated radiotherapy (IMRT) for patients with locally advanced non-small cell lung cancer (NSCLC). METHODS: The major inclusion criteria were clinical stage III NSCLC, age 20-74 years, and Eastern Cooperative Oncology Group performance status 0-1. Patients were treated with either cisplatin + S-1 (CS; four cycles every 4 weeks) or carboplatin + paclitaxel (CP; administered weekly with thoracic radiotherapy [RT], plus two consolidation cycles) concurrently with IMRT (60 Gy in 30 fractions). The primary endpoint was a treatment completion rate, defined as at least two cycles of CS or five cycles of CP during IMRT and completing 60 Gy IMRT within 56 days after the start of treatment, assumed its 90% confidence interval exceeds 60%. RT quality assurance was mandatory for all the patients. RESULTS: Twenty-two patients were registered. One patient withdrew due to pulmonary infection before starting treatment. RT plans were reviewed and none was judged as a protocol violation. Grade 2 and 3 pneumonitis occurred in four (19%) and one (5%) patients, respectively. Seventeen patients met the primary endpoint, with a treatment completion rate of 77.3% (90% confidence interval [CI] 58.0%-90.6%). Four patients failed to complete chemotherapy due to chemotherapy-related adverse events, but 20 patients completed IMRT. There were no treatment-related deaths. The 2-year progression-free and overall survival rates were 31.8% (95% CI 17.3%-58.7%) and 77.3% (95% CI 61.6%-96.9%), respectively. CONCLUSION: The treatment completion rate did not meet the primary endpoint, but 20 of 22 patients completed IMRT.

Development of AI-driven prediction models to realize real-time tumor tracking during radiotherapy.

BACKGROUND: In infrared reflective (IR) marker-based hybrid real-time tumor tracking (RTTT), the internal target position is predicted with the positions of IR markers attached on the patient's body surface using a prediction model. In this work, we developed two artificial intelligence (AI)-driven prediction models to improve RTTT radiotherapy, namely, a convolutional neural network (CNN) and an adaptive neuro-fuzzy inference system (ANFIS) model. The models aim to improve the accuracy in predicting three-dimensional tumor motion. METHODS: From patients whose respiration-induced motion of the tumor, indicated by the fiducial markers, exceeded 8 mm, 1079 logfiles of IR marker-based hybrid RTTT (IR Tracking) with the gimbal-head radiotherapy system were acquired and randomly divided into two datasets. All the included patients were breathing freely with more than four external IR markers. The historical dataset for the CNN model contained 1003 logfiles, while the remaining 76 logfiles complemented the evaluation dataset. The logfiles recorded the external IR marker positions at a frequency of 60 Hz and fiducial markers as surrogates for the detected target positions every 80-640 ms for 20-40 s. For each logfile in the evaluation dataset, the prediction models were trained based on the data in the first three quarters of the recording period. In the last quarter, the performance of the patient-specific prediction models was tested and evaluated. The overall performance of the AI-driven prediction models was ranked by the percentage of predicted target position within 2 mm of the detected target position. Moreover, the performance of the AI-driven models was compared to a regression prediction model currently implemented in gimbal-head radiotherapy systems. RESULTS: The percentage of the predicted target position within 2 mm of the detected target position was 95.1%, 92.6% and 85.6% for the CNN, ANFIS, and regression model, respectively. In the evaluation dataset, the CNN, ANFIS, and regression model performed best in 43, 28 and 5 logfiles, respectively. CONCLUSIONS: The proposed AI-driven prediction models outperformed the regression prediction model, and the overall performance of the CNN model was slightly better than that of the ANFIS model on the evaluation dataset.

Effects of colorectal endoscopic submucosal dissection on postoperative abdominal symptoms: a prospective observational study.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective procedure to resect large superficial gastrointestinal neoplasms. In gastric ESD, several studies showed the relationship between postoperative abdominal symptoms and endoscopic treatment. However, the influence of colorectal ESD on abdominal symptoms after treatment is still unknown. To the best of our knowledge, this is the first prospective multicenter study performed to investigate the impact of colorectal ESD on postoperative abdominal symptoms. This study aimed to clarify the association between change of abdominal symptoms and ESD. METHODS: This study was a prospective multicenter observational trial that enrolled 141 out of 171 patients who underwent colorectal ESD and answered the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire from March 2015 to August 2019. We evaluated abdominal symptoms in the patients using the GSRS questionnaire before ESD and a few weeks after ESD. RESULTS: Comparing the GSRS before and after ESD, overall scores changed from 1.58 ± 0.58 to 1.48 ± 0.48, and the five subscales (reflux syndrome, abdominal pain, indigestion syndrome, diarrhea syndrome, and constipation syndrome) were slightly improved. Overall scores, indigestion syndrome, and constipation syndrome were statistically significantly different before and after ESD (P < 0.05). CONCLUSIONS: In GSRS, a score of ≥ 3 is often treated as a clinically significant symptom. Therefore, our findings indicated that there was no clinically significant difference. For this reason, colorectal ESD does not affect postoperative abdominal symptoms and is considered a minimally invasive treatment. The analysis of the impact of colon ESD on gastrointestinal symptoms UMIN000016914.

Multi-institutional dose-segmented dosiomic analysis for predicting radiation pneumonitis after lung stereotactic body radiation therapy.

PURPOSE: To predict radiation pneumonitis (RP) grade 2 or worse after lung stereotactic body radiation therapy (SBRT) using dose-based radiomic (dosiomic) features. METHODS: This multi-institutional study included 247 early-stage nonsmall cell lung cancer patients who underwent SBRT with a prescribed dose of 48-70 Gy at an isocenter between June 2009 and March 2016. Ten dose-volume indices (DVIs) were used, including the mean lung dose, internal target volume size, and percentage of entire lung excluding the internal target volume receiving greater than x Gy (x = 5, 10, 15, 20, 25, 30, 35, and 40). A total of 6,808 dose-segmented dosiomic features, such as shape, first order, and texture features, were extracted from the dose distribution. Patients were randomly partitioned into two groups: model training (70%) and test datasets (30%) over 100 times. Dosiomic features were converted to z-scores (standardized values) with a mean of zero and a standard deviation (SD) of one to put different variables on the same scale. The feature dimension was reduced using the following methods: interfeature correlation based on Spearman's correlation coefficients and feature importance based on a light gradient boosting machine (LightGBM) feature selection function. Three different models were developed using LightGBM as follows: (a) a model with ten DVIs (DVI model), (b) a model with the selected dosiomic features (dosiomic model), and (c) a model with ten DVIs and selected dosiomic features (hybrid model). Suitable hyperparameters were determined by searching the largest average area under the curve (AUC) value in the receiver operating characteristic curve (ROC-AUC) via stratified fivefold cross-validation. Each of the final three models with the closest the ROC-AUC value to the average ROC-AUC value was applied to the test datasets. The classification performance was evaluated by calculating the ROC-AUC, AUC in the precision-recall curve (PR-AUC), accuracy, precision, recall, and f1-score. The entire process was repeated 100 times with randomization, and 100 individual models were developed for each of the three models. Then the mean value and SD for the 100 random iterations were calculated for each performance metric. RESULTS: Thirty-seven (15.0%) patients developed RP after SBRT. The ROC-AUC and PR-AUC values in the DVI, dosiomic, and hybrid models were 0.660 ± 0.054 and 0.272 ± 0.052, 0.837 ± 0.054 and 0.510 ± 0.115, and 0.846 ± 0.049 and 0.531 ± 0.116, respectively. For each performance metric, the dosiomic and hybrid models outperformed the DVI models (P < 0.05). Texture-based dosiomic feature was confirmed as an effective indicator for predicting RP. CONCLUSIONS: Our dose-segmented dosiomic approach improved the prediction of the incidence of RP after SBRT.

AdipoR agonist increases insulin sensitivity and exercise endurance in AdipoR-humanized mice.

Adiponectin receptors, AdipoR1 and AdipoR2 exert anti-diabetic effects. Although muscle-specific disruption of AdipoR1 has been shown to result in decreased insulin sensitivity and decreased exercise endurance, it remains to be determined whether upregulation of AdipoR1 could reverse them in obese diabetic mice. Here, we show that muscle-specific expression of human AdipoR1 increased expression levels of genes involved in mitochondrial biogenesis and oxidative stress-detoxification to almost the same extents as treadmill exercise, and concomitantly increased insulin sensitivity and exercise endurance in obese diabetic mice. Moreover, we created AdipoR-humanized mice which express human AdipoR1 in muscle of AdipoR1·R2 double-knockout mice. Most importantly, the small-molecule AdipoR agonist AdipoRon could exert its beneficial effects in muscle via human AdipoR, and increased insulin sensitivity and exercise endurance in AdipoR-humanized mice. This study suggests that expression of human AdipoR1 in skeletal muscle could be exercise-mimetics, and that AdipoRon could exert its beneficial effects via human AdipoR1.

Human adiponectin receptor AdipoR1 assumes closed and open structures.

The human adiponectin receptors, AdipoR1 and AdipoR2, are key anti-diabetic molecules. We previously reported the crystal structures of human AdipoR1 and AdipoR2, revealing that their seven transmembrane helices form an internal closed cavity (the closed form). In this study, we determined the crystal structure of the D208A variant AdipoR1, which is fully active with respect to the major downstream signaling. Among the three molecules in the asymmetric unit, two assume the closed form, and the other adopts the open form with large openings in the internal cavity. Between the closed- and open-form structures, helices IV and V are tilted with their intracellular ends shifted by about 4 and 11 Å, respectively. Furthermore, we reanalyzed our previous wild-type AdipoR1 diffraction data, and determined a 44:56 mixture of the closed and open forms, respectively. Thus, we have clarified the closed-open interconversion of AdipoR1, which may be relevant to its functional mechanism(s).

Clinical impact of evaluation of frailty in endoscopic submucosal dissection for early gastric cancer in elderly patients.

AIMS: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is performed safely and effectively in elderly patients; however, whether ESD for EGC in elderly patients with frailty is safe and improves prognosis remains unclear. METHODS: In total, 142 patients aged ≥80 years who underwent ESD for EGC between September 2008 and September 2014 were included. We compared outcomes between patients with frailty and those without frailty. Frailty was assessed using the Clinical Frailty Scale (CFS) based on a patient's status before admission. Study endpoints were short- and long-term clinical outcomes after ESD. RESULTS: Patients were allocated into two groups: no frailty (CFS 1-3, n = 101) versus frailty (CFS 4-7, n = 41). Short-term clinical outcomes, specifically, adverse events and curability, did not differ between the two groups. For the long-term clinical outcomes, patients with frailty had significantly worse outcomes after ESD than those without frailty (the 3-year overall survival rates were 73.2% vs. 93.1%; P < 0.001 with log-rank test). The Cox proportional hazards model showed that frailty was only an independent risk factor for poor prognosis. CONCLUSIONS: ESD for EGC is safe for elderly patients with or without frailty. However, elderly patients with frailty have a significantly poorer prognosis than those without frailty after ESD. Our results indicate that the frailty evaluation may be helpful to determine whether ESD for EGC should be performed. Geriatr Gerontol Int 2020; 20: 461-466.

A feasibility study of independent verification of dose calculation for Vero4DRT using a Clarkson-based algorithm.

Dose verification for a gimbal-mounted image-guided radiotherapy system, Vero4DRT (Mitsubishi Heavy Industries Ltd., Tokyo, Japan) is usually carried out by pretreatment measurement. Independent verification calculations using Monte Carlo methods for Vero4DRT have been published. As the Clarkson method is faster and easier to use than measurement and Monte Carlo methods, we evaluated the accuracy of an independent calculation verification program and its feasibility as a secondary check for Vero4DRT. Computed tomography (CT)-based dose calculation was performed using a modified Clarkson-based algorithm. In this study, 120 patients' treatment plans were collected in our institute. The treatments were performed using conventional irradiation for lung and prostate, 3-dimensional (3D) conformal stereotactic body radiotherapy (SBRT) for the lung, and intensity-modulated radiation therapy (IMRT) for the prostate. Differences between the treatment planning system (TPS) and the Clarkson-based independent dose verification software were computed, and confidence limits (CLs, mean ± 2 standard deviation %) for Vero4DRT were compared with the CLs for the C-arms linear accelerators in the previous study. The results of the CLs, the conventional irradiation, SBRT, and IMRT showed 2.2 ± 3.5% (CL of the C-arms linear accelerators: 2.4 ± 5.3%), 1.1 ± 1.7% (-0.3 ± 2.0%), 4.8 ± 3.7% (5.4 ± 5.3%), and -0.5 ± 2.5% (-0.1 ± 3.6%) differences, respectively. The dose disagreement between the TPS and CT-based independent dose verification software was less than the 5% action level of American Association of Physicists in Medicine (AAPM) Task Group 114 (TG114). The CLs for the gimbal-mounted Vero4DRT were similar to the deviations for C-arms linear accelerators.

Prognostic implications of preoperative chronic kidney disease and anemia in patients undergoing coronary artery bypass graft surgery.

PURPOSE: Chronic kidney disease (CKD) and anemia are independent preoperative risk factors for coronary artery bypass graft (CABG) surgery. We evaluated the implications of the coexistence of these two factors and their associated prognosis for CABG surgery. METHODS: We analyzed, retrospectively, consecutive patients who underwent elective CABG surgery between 2004 and 2014. The patients were classified into four groups depending on the presence or absence of preoperative CKD and anemia. We assessed the major adverse cardiac and cerebrovascular event (MACCE), defined as composite outcomes of cardio- and cerebrovascular death, revascularization through surgery or percutaneous intervention, hospitalization for congestive heart failure, and cerebral infarction. RESULTS: The study population consisted of 510 patients (73 % male; median age 71 years old), followed up for a median period of 2.8 years. Multivariate analysis indicated that neither the CKD/no-anemia group [hazard ratio (HR) 0.98, 95 % confidence interval (CI) 0.39-2.51, P = 0.973] nor the no-CKD/anemia group (HR 1.20, 95 % CI 0.69-2.09, P = 0.512) had significantly poorer prognoses than the no-CKD/no-anemia group. However, the CKD/anemia group had a significantly higher risk of a MACCE (HR 2.01, 95 % CI 1.01-3.98, P = 0.046). CONCLUSION: The presence of both CKD and anemia in patients undergoing CABG for coronary artery disease is synergistically associated with a worse outcome.

Endothelial-mesenchymal transition in human atrial fibrillation.

BACKGROUND: Atrial fibrosis is a hallmark of atrial structural remodeling leading to the persistence of atrial fibrillation. Although fibroblasts play a major role in atrial fibrosis, their source in the adult atrium is unclear. We tested the hypothesis that endothelial cells contribute to fibroblast accumulation through an endothelial-mesenchymal transition in the atrium of patients with atrial fibrillation. METHODS AND RESULTS: The study group consisted of patients with atrial fibrillation and valvular disease or atrial septal defect who underwent left atrial appendectomy during cardiac surgery (n=38). The amount of fibrotic depositions in the left atrium positively correlated with left atrial dimension. Furthermore, snail and S100A4, indicative of endothelial-mesenchymal transition, were quantified in the left atrium using western blot analysis, which showed statistically significant correlations with left atrial dimension. Immunofluorescence assay of the left atrial tissue identified snail and S100A4 being expressed within the endocardium which is composed of CD31+ cells. The snail-positive endocardium also showed the expression of membrane type 1-matrix metalloproteinase. Immunofluorescence multi-labeling experiments identified that heat shock protein 47, prolyl-4-hydroxylase, and procollagen type 1 co-localized with snail and S100A4 within the endothelial cells of the left atrium, indicating the mesenchymal phenotype to produce collagen. CONCLUSIONS: In this study, we showed that the endothelial-mesenchymal transition occurs in the atrium of patients with atrial fibrillation. This observation should help in constructing a novel therapeutic approach for preventing atrial structural remodeling.