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Funding Acknowledgements Type of funding sources: None. Background/Introduction A novel leadless pacemaker enables atrioventricular synchronous pacing. However, there have been still difficulties to obtain high atrioventricular (AV) synchrony due to a mechanical sensing algorithm. We’ve reported a new sensing method for acquiring high AV synchrony regardless of heart rate. Our hypothesis is that this novel sensing method might facilitate better AV synchrony. Purpose The purpose of this study is to investigate the feasibility of our novel sensing method for the patients that ventricular activity completely depends on the ventricular pacing. Methods This study is a retrospective study conducted by 2 centers. From the 1st December, 2021 to the 31th October, 2022, leadless pacemakers with atrioventricular synchronous pacing were implanted to 32 patients in 2 centers. Among the 20 patients with sinus rhythm and complete AV block were analyzed. Two groups were compared in this study. Novel sensing setting was programmed during the hospitalization in Group 1, composed by 9 patients. Auto A3 threshold and auto A3 window end are turned off. An intentionally prolonged A3 window end and a low A3 threshold are programmed in a novel sensing method. Conventional setting (auto A3 threshold, auto A3 window end and auto A4 threshold were turned on) was programmed during the hospitalization in Group 2, composed by 11 patients. Device check was performed at the first outpatient clinic within 3 months after the implantation. Results Overall, 20 patients were analyzed. Baseline characters are described in Table 1. BMI (23.5±0.9 vs 20.4±0.8, p Conclusion Novel sensing method might be a feasible sensing method to obtain higher AV synchrony than conventional algorithm. Further prospective studies will be required.

A linear stress path (LSP) experiment was performed using uniaxial and biaxial tensile tests with a cold-rolled mild steel sheet (SPCD; nominal thickness: 0.8 mm) as the test material. In the LSP experiment, nine LSPs were applied to the specimens to measure the contours of plastic work and the directions of the plastic strain rates, β, for a plastic strain range of 0.002 ≤〖 ε〗_0^p ≤ 0.234. Then, the Yld2000-2d yield function (Barlat et al., 2003) was used to identify a material model that accurately reproduces the experimental data observed in the LSP experiment. Furthermore, a nonlinear stress path (NLSP) experiment was performed. The NLSP consists of two linear stress paths with σ_x:σ_y = 4:1 and 1:1, and a curved stress path connecting the LSPs. The measured work hardening behavior and β values were compared with those calculated using the Yld2000-2d yield function identified from the LSP experiment. It was found that the deformation behavior of the test sample predicted by the material model determined from the LSP experiment clearly shows some deviation from that observed for the NLSP experiment.

Histiocytic sarcoma (HS) is a haematopoietic tumour of histiocyte origin that has been sporadically reported in four-toed hedgehogs (Atelerix albiventris). The present study aimed to investigate clinical, gross, histopathological and immunohistochemical features of HS in eight hedgehogs. Histological and immunohistochemical features of normal histiocytes and Langerhans cells (LCs) of hedgehogs were also investigated. HLA-DR-, Iba-1- and E-cadherin-positive LCs were observed in the epidermis, while Iba-1- and CD204-positive histiocytes were detected in the lymph nodes and spleen of normal hedgehogs. Localized HS (six cases) developed in the skin and spleen, while disseminated HS (two cases) occurred in the intestine. Tumour cells of disseminated HS were also distributed within the mesenteric lymph nodes, liver, kidney, spleen, lung and adrenal glands. Tumour cells of both localized and disseminated HS were composed of histiocytic cells, spindle to pleomorphic cells, multinucleated giant cells and erythrophagocytic cells. Most tumour cells were immunopositive for Iba-1, CD204 and lysozyme. A small number of tumour cells were positive for E-cadherin and CD208, and the tumour cells in one case were positive for HLA-DR. These results suggest that the tumour cells have variable features of histiocyte origin, including dendritic cells, LCs and macrophages. The behaviour of HS in the hedgehog was very aggressive, and 50% of cases died within 90 days of resection. The present study also highlighted the tendency for local tumour recurrence in localized cutaneous HS cases, suggesting a requirement for a long-term follow-up after excision.

Post-pulmonary embolism (PE) syndrome is an important clinical condition that can affect the long-term prognosis after acute PE.We aimed to evaluate the prevalence of residual pulmonary thrombi and the thrombotic burden 1 year after acute PE, by using our refined computed tomography (CT) imaging method.In this prospective study, patients diagnosed with acute PE were recruited and examinations were conducted at 1 month, 6 months, and 1 year. Especially at 1 year, patients were evaluated multifacetedly, including by laboratory tests, quality-of-life, 6-min walking test, and enhanced CT.Fifty-two patients were enrolled. Two patients (3.8%) developed chronic thromboembolic pulmonary hypertension. A total of 43 patients completed evaluation at 1 year, among whom (74%) had residual thrombi, with a median modified CT obstruction index (mCTOI) of 10.7%. In multivariate analysis, residual thrombi at 1 month was the only factor significantly related to residual thrombi at 1 year (odds ratio, 103.4; 95% confidence interval, 4.2-2542.1). The tricuspid regurgitation pressure gradient ≥60 mmHg and left ventricular end-diastolic dimension at diagnosis were significantly related to mCTOI at 1 year (β = 0.367, P = .003; and β = -0.435, P = .001, respectively).Using our improved CT imaging protocol, we found a high prevalence of residual thrombi 1 year after acute PE. Furthermore, right ventricular overload was related to the thrombotic burden. The long-term treatment strategy of acute PE could be modified to include precise CT imaging.

Inactivating mutations of Arid1a , a subunit of the Switch/sucrose nonfermentable chromatin remodeling complex, have been reported in multiple human cancers. Intestinal deletion of Arid1a has been reported to induce colorectal cancer in mice; however, its functional role in intestinal homeostasis remains unclear. We investigated the functional role of Arid1a in intestinal homeostasis in mice. We found that intestinal deletion of Arid1a results in loss of intestinal stem cells (ISCs), decreased Paneth and goblet cells, disorganized crypt-villous structures, and increased apoptosis in adult mice. Spheroids did not develop from intestinal epithelial cells deficient for Arid1a . Lineage-tracing experiments revealed that Arid1a deletion in Lgr5 + ISCs leads to impaired self-renewal of Lgr5 + ISCs but does not perturb intestinal homeostasis. The Wnt signaling pathway, including Wnt agonists, receptors, and target genes, was strikingly down-regulated in Arid1a -deficient intestines. We found that Arid1a directly binds to the Sox9 promoter to support its expression. Remarkably, overexpression of Sox9 in intestinal epithelial cells abrogated the above phenotypes, although Sox9 overexpression in intestinal epithelial cells did not restore the expression levels of Wnt agonist and receptor genes. Furthermore, Sox9 overexpression permitted development of spheroids from Arid1a -deficient intestinal epithelial cells. In addition, deletion of Arid1a concomitant with Sox9 overexpression in Lgr5 + ISCs restores self-renewal in Arid1a -deleted Lgr5 + ISCs. These results indicate that Arid1a is indispensable for the maintenance of ISCs and intestinal homeostasis in mice. Mechanistically, this is mainly mediated by Sox9. Our data provide insights into the molecular mechanisms underlying maintenance of ISCs and intestinal homeostasis.

BACKGROUND/PURPOSE The purpose of the present study was to investigate the possibility of reducing clinical impacts of acute necrotic collection (ANC) on patients with acute pancreatitis (AP) using recombinant human soluble thrombomodulin (rTM). METHODS In this retrospective multicenter study, 233 consecutive AP patients with ANC and acute peripancreatic fluid collection (APFC) from 2012 to 2016 were enrolled. To assess clinical impacts of ANC, severity on admission (JPN score, JPN CT grade, and Modified CT severity index), development of walled-off necrosis (WON), imaging costs for follow-up, and mortality were recorded. Finally, we investigated whether rTM could reduce the clinical impacts, adjusting the severity using propensity analysis with Inverse probability of treatment weighting. RESULTS Patients with ANC developed WON with higher ratio than APFC (58/98 [59.2%] vs 20/135 [14.8%], OR = 8.3, P

We investigated the sintering of copper nanoparticles by blue diode laser in atmosphere to apply copper nanoparticles as preformed insert-materials for die bonding of power devices. Copper paste consisting of copper nanoparticles, ethylene glycol, and polyvinylpyrrolidone was formulated. The surface morphology and oxidation state of the sintered copper were evaluated. We found that the higher the laser power, the more the necking between copper particles, and that blue laser sintering successively suppressed oxidation of copper.

Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

Pravastatin is an inhibitor of 3-hydroxy-3-methyl- glutaryl-coenzyme A reductase that has been reported to have therapeutic applications in a range of inflammatory conditions. The aim of the present study was to assess the radioprotective effects of pravastatin in an experimental animal model. Mice were divided into two groups: The control group received ionizing radiation with no prior medication, while the pravastatin group received pravastatin prior to ionizing radiation. Pravastatin was administered orally at 30 mg/kg body weight in drinking water at 24 and 4 h before irradiation. Intestinal crypt epithelial cell survival and the incidence of apoptosis in the intestine and lung were measured post-irradiation. The effect of pravastatin on intestinal DNA damage was determined by immunohistochemistry. Finally, the effect of pravastatin on tumor response to radiotherapy was examined in a mouse mesothelioma xenograft model. Pravastatin increased the number of viable intestinal crypts and this effect was statistically significant in the ileum (P

Background Palliative sedation is a therapeutic option when symptom relief is difficult to achieve at the end-of-life. However, little is known regarding palliative sedation in terminally ill heart failure (HF) patients. Purpose To survey the practice of palliative sedation in terminally ill HF patients at a tertiary referral cardiovascular center, and to investigate the efficacy and safety of sedative agents in HF patients. Methods We retrospectively reviewed consecutive patients who were referred to palliative care team at our institution between September 2013 and August 2018. Patients who were hospitalized for HF and died during hospitalization despite optimal medical therapy were selected and defined as terminally ill HF. We investigated the practice of palliative sedation in terminally ill HF patients and analysed the vital signs and sedation scale before starting sedative agents and about 1 hour afterward. Results Among 95 terminally ill HF patients, 37 were prescribed palliative sedation at the end-of-life (Picture). Of 37 patients (mean age: 70 years, median B-type natriuretic peptide: 1018 pg/ml, median creatinine: 3.0 mg/dl, intravenous inotrope: 81%), 25 were prescribed dexmedetomidine, and 12 were prescribed midazolam as first agent for sedation. Patient's backgrounds were comparable between the two groups. Richmond Agitation-Sedation Scale was significantly reduced (P Table 1. Vital signs and sedation scale Dexmedetomidine group (n=25) Midazolam group (n=12) Baseline After P value Baseline After P value Richmond Agitation-Sedation Scale 1 (0, 1) −1 (−2, 0) Picture. Study flowchart Conclusions Dexmedetomidine and midazolam were commonly used in real-word practice for HF patients at the end-of-life. Although impact on respiratory system differed by treatments, both agents could be prescribed effectively and safely in terminally ill HF patients.

Patient: Female, 39-year-old Final Diagnosis: Anaplastic carcinoma of the pancreas • pancreatic cancer Symptoms: Epigastralgia • jaundice Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology • Oncology Objective: Rare disease Background: Anaplastic carcinoma of the pancreas (ACP) is a rare type of cancer with an extremely poor prognosis. Hereditary pancreatitis is a rare autosomal-dominant disease. It progresses to chronic pancreatitis at a young age, increasing the risk of pancreatic cancer. Case Report: A 39-year-old woman was diagnosed with chronic pancreatitis at the age of 18 years. The patient was referred to our hospital for epigastralgia and jaundice. We identified a tumor mass at the head of the pancreas using contrast computed tomography (CT) and endoscopic ultrasound (EUS) of the abdomen. Tissue biopsy revealed ACP of the spindle cell type. We started the patient on combination chemotherapy using gemcitabine and nanoparticle albumin-bound (nab) -paclitaxel, but she died 1 month after her first visit. An autopsy revealed a mixture of tubular adenocarcinoma and anaplastic carcinoma. We performed genetic analysis using DNA samples from the biopsy tissues but did not find mutations in the PRSS1 and SPINK1 genes associated with hereditary pancreatitis. Conclusions: The risk of pancreatic cancer generally increases in patients with hereditary pancreatitis after 50 years of age. However, in this case, the development of pancreatic cancer occurred at a younger age, suggesting the importance of early detection in such cases. Furthermore, this case suggests that EUS is a useful method for monitoring patients with hereditary pancreatitis and the diagnosis of ACP.

The feasibility of estimating patient-specific dose verification results directly from linear accelerator (linac) log files has been investigated for prostate cancer patients who undergo volumetric modulated arc therapy (VMAT). Twenty-six patients who underwent VMAT in our facility were consecutively selected. VMAT plans were created using Monaco treatment planning system and were transferred to an Elekta linac. During the beam delivery, dynamic machine parameters such as positions of the multi-leaf collimator and the gantry were recorded in the log files; subsequently, root mean square (rms) values of control errors, speeds and accelerations of the above machine parameters were calculated for each delivery. Dose verification was performed for all the plans using a cylindrical phantom with diodes placed in a spiral array. The gamma index pass rates were evaluated under 3%/3 mm and 2%/2 mm criteria with a dose threshold of 10%. Subsequently, the correlation coefficients between the gamma index pass rates and each of the above rms values were calculated. Under the 2%/2 mm criteria, significant negative correlations were found between the gamma index pass rates and the rms gantry angle errors (r = 0.64, p < 0.001) as well as the pass rates and the rms gantry accelerations (r = 0.68, p < 0.001). On the other hand, the rms values of the other dynamic machine parameters did not significantly correlate with the gamma index pass rates. We suggest that the VMAT quality assurance (QA) results can be directly estimated from the log file thereby providing potential to simplify patient-specific prostate VMAT QA procedure.

The purpose of the present study was to determine the risk factors for developing thyroid disorders based on a dose–volume histograms (DVHs) analysis. Data from a total of 116 consecutive patients undergoing 3D conformal radiation therapy for head and neck cancers was retrospectively evaluated. Radiation therapy was performed between April 2007 and December 2010. There were 108 males and 8 females included in the study. The median follow-up term was 24 months (range, 1–62 months). The thyroid function was evaluated by measuring thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels. The mean thyroid dose, and the volume of thyroid gland spared from doses ≥10, 20, 30 and 40 Gy (VS10, VS20, VS30 and VS40) were calculated for all patients. The thyroid dose and volume were calculated by the radiotherapy planning system (RTPS). The cumulative incidences of hypothyroidism were 21.1% and 36.4% at one year and two years, respectively, after the end of radiation therapy. In the DVH analyses, the patients who received a mean thyroid dose

Polaprezinc (PZ), an antiulcer drug, has been reported to have antioxidant properties. The aim of the present study was to assess the feasibility and efficacy of administering PZ for radiation-induced mucositis in head and neck cancer patients. Patients with newly diagnosed head and neck cancer were enrolled in this prospective study. PZ was prepared as an oral rinse. The PZ oral rinse was used four times per day during the course of radiotherapy. Sequential changes in radiation mucositis were assessed during and after radiotherapy according to the Common Terminology Criteria for Adverse Events, version 3.0. Furthermore, a retrospective comparison analysis was performed to assess the efficacy of PZ for radiation-induced mucositis. A total of 32 patients were enrolled in the prospective study of the PZ oral rinse. Radiotherapy was performed up to a total dose of 60-66 Gy using a conventional schedule combined with chemotherapy. Of the 32 patients, 30 (93.8%) reported no complaints due to the PZ oral rinse. In addition, PZ was not associated with severe adverse effects. Among the patients who received PZ, grade 3 mucositis was observed in 29.0% based on the mucosal findings and in 39.3% based on the symptoms. In the patients who did not receive PZ, the incidence of grade 3 mucositis was 40.0% based on the mucosal findings and 60.7% based on the symptoms. Moreover, PZ promoted the recovery from mucositis caused by chemoradiotherapy and was not associated with reduced tumor response to radiotherapy. Therefore, the PZ oral rinse was well tolerated and proved to be efficient for the treatment of radiotherapy-induced oral mucositis.

Introduction In 2013, a total of 1586 kidney transplants were performed in Japan, and 1431 (90.2%) of the organs were from living donors. The purpose of this study is to illuminate the awareness of living kidney donors toward kidney donation after the condition of the recipient changed, thus clarifying the influence of that recognition on the donor. Methods This study design was qualitative descriptive research. Transplant coordinators at 4 hospitals were commissioned to screen subject candidates and hand-deliver printed research explanations to them. Candidates who responded were selected as subjects. I conducted semistructured interviews and analyzed them using the grounded theory approach. This research was approved by the Ethics Research Committee, Faculty of Nursing, Toho University. Results The survey period was from April to November 2014, and consent was obtained from 5 donors and 5 recipients. The outcome of recipients who received kidneys from the 5 donors was as follows: recovered after temporary worsening (n = 3), early graft loss (n = 1), and early death (n = 1). The core category was “to the donor, the meaning of kidney donation is continually redefined.” The donors had a strong interest in the physical condition of the recipient. The 3 changes in the recipients' physical condition, defined as “recovery,” “temporary worsening,” and “complete deterioration,” affected the donor's condition. Conclusion Due to changes in the recipient's physical condition, donors' psychological and physical condition and their definition of the meaning of kidney donation also changed. Health care systems that guarantee lifelong follow-up of the physical and psychological condition of donors after donation are needed.

Objectives: The purpose of this study was to examine the effects of long-term wheel-running on tibia bone properties in T2DM Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods: Ten five-week-old male OLETF rats were used as experimental animals and 5 Long-Evans Tokushima Otsuka (LETO) rats as controls. Half of OLETF rats performed daily voluntary wheel-running for 17 months (OLETF-EXE), while neither the remainder of OLETF nor LETO rats had exercise. At the end of experiment, in addition to serum biochemical and bone formation/resorption marker analyses, bone mass, trabecular bone microarchitecture and cortical bone geometry were analyzed in left tibia, and bone mechanical strength of right tibia was measured. Results: Tibia bone mass, trabecular bone microarchitecture, cortical bone geometry and bone mechanical strength deteriorated in diabetic OLETF rats. However, such deterioration was obviously attenuated in OLETF-EXE rats, which maintained normal levels of blood glucose, HbA1c and blood urea nitrogen. Conclusions: Daily wheel-running could prevent the deterioration of bone properties in OLETF rats. This would be induced mainly by suppressing the development of T2DM. Regular physical exercise may be a potent strategy for preventing not only the development of diabetes but also the deterioration of bone properties in patients with chronic T2DM.

Objectives/Hypothesis The purpose of this study was to estimate the efficacy of superselective arterial chemoradiotherapy for locally advanced carcinomas of the external auditory canal and middle ear. Study Design A retrospective study of clinical data for consecutive patients with locally advanced carcinomas of the external auditory canal and middle ear. Methods Thirteen patients with locally advanced carcinomas of the external auditory canal and middle ear (T3: one patient, T4: 12 patients) were reviewed. The median follow-up duration in the living patients was 33 months. The total dose of radiation therapy was 60 Gy using conventional fractionation. Four, five, or six courses of a superselective arterial infusion (cisplatin 50 mg) were given weekly. Results The overall survival and progression-free survival rates at 2 years, calculated by the Kaplan-Meier method, were 58.7% and 53.8%, respectively. No late-phase adverse effects due to chemoradiation and no adverse effects due to catheterization were observed. Conclusions These results suggest that superselective arterial chemoradiation can be a treatment option for locally advanced carcinomas of the external auditory canal and middle ear. Level of Evidence 4 Laryngoscope, 125:685–689, 2015

The purpose of this study was to investigate the prediction of mechanical error using DICOM-RT plan parameters for volumetric modulated arc therapy (VMAT). We created plans for gantry rotation arcs of 360° and 180° (full-arc and half-arc VMAT) for six maxillary sinus cancer cases using a Monaco treatment planning system, and delivered the doses with a linear accelerator. We calculated DICOM-RT plan parameters, including gantry, multileaf collimator (MLC) positions and Monitor Units (MU). We compared plans with regard to gantry angle per MU (degrees/MU) and MLC travel per MU (mm/MU) for each segment. Calculated gantry angle/MLC position speeds and errors were evaluated by comparison with the log file. On average, the half-arc VMAT plan resulted in 47% and 35% fewer degrees/MU and mm/MU than the full-arc VMAT plan, respectively. The root mean square (r.m.s.) gantry and MLC speeds showed a linear relationship with calculated degrees/MU and mm/MU, with coefficients of determination (R2) of 0.86 and 0.72, respectively. The r.m.s. gantry angle and MLC position errors showed a linear relationship with calculated degrees/MU and mm/MU with R2 of 0.63 and 0.76, respectively. Deviations from plan parameters were related to mechanical error for VMAT, and provided quantitative information without the need for VMAT delivery. These parameters can be used in the selection of treatment planning.

The aim of the present study was to determine the impact of obesity on radiation-induced gastrointestinal (GI) and genitourinary (GU) toxicity. The cases of 54 patients with prostate cancer, treated with three-dimensional conformal radiation therapy (RT), were reviewed. For each patient, the body mass index (BMI), distance between the prostate and rectum (D) on a computerised tomography scan and the dosimetric parameters of the rectum and bladder in the planning data of RT, were analyzed. GI and GU toxicity was assessed during and following RT. The results of the patients with a BMI of

We validated 3D radiochromic film dosimetry for volumetric modulated arc therapy (VMAT) using a newly developed spiral water phantom. The phantom consists of a main body and an insert box, each of which has an acrylic wall thickness of 3 mm and is filled with water. The insert box includes a spiral film box used for dose-distribution measurement, and a film holder for positioning a radiochromic film. The film holder has two parallel walls whose facing inner surfaces are equipped with spiral grooves in a mirrored configuration. The film is inserted into the spiral grooves by its side edges and runs along them to be positioned on a spiral plane. Dose calculation was performed by applying clinical VMAT plans to the spiral water phantom using a commercial Monte Carlo-based treatment-planning system, Monaco, whereas dose was measured by delivering the VMAT beams to the phantom. The calculated dose distributions were resampled on the spiral plane, and the dose distributions recorded on the film were scanned. Comparisons between the calculated and measured dose distributions yielded an average gamma-index pass rate of 87.0% (range, 91.2-84.6%) in nine prostate VMAT plans under 3 mm/3% criteria with a dose-calculation grid size of 2 mm. The pass rates were increased beyond 90% (average, 91.1%; range, 90.1-92.0%) when the dose-calculation grid size was decreased to 1 mm. We have confirmed that 3D radiochromic film dosimetry using the spiral water phantom is a simple and cost-effective approach to VMAT dose verification.

Background To clarify the influence of hypertension and blood pressure ( BP ) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐ RHYTHM Registry was performed. Methods and Results A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05–2.21, P =0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73–1.52, P =0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up (Q1, CI 1.75–4.74, P CI 1.02–2.53, P =0.041) after adjustment for components of CHA 2 DS 2 ‐ VAS c score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage. Conclusions BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation. Clinical Trial Registration URL : http://www.umin.ac.jp/ctr . Unique identifier: UMIN 000001569.

The purpose of our study was to assess the feasibility of radiotherapy (RT) for locally advanced paranasal sinus carcinomas in late elderly patients (aged ≥75 years) from a single institution in Japan. From 2000 to 2015, we retrospectively analyzed 14 patients (11 maxillary and 3 ethmoid sinus carcinoma patients) who underwent RT for pathologically confirmed paranasal sinus carcinomas. RT was performed without unexpected cessations. Two patients, however, developed Grade 3 mucositis. The median follow-up duration was 13 months (range 2-54 months). The 1- and 2-year overall survival (OS) rates were 81.8 and 54.5 %, respectively. The local response rate after the initial treatment was 85.7 %. The 1- and 2-year progression-free survival (PFS) rates were 46.2 and 24.8 %, respectively. Univariate analysis of different clinicopathological parameters was conducted to identify associations with OS and PFS. We demonstrated that intensity modulated radiation therapy (IMRT) of >60 Gy with concomitant intra-arterial (cisplatin-based) infusion chemoradiotherapy led to improved OS and PFS rates, although no statistical significance was observed. Moreover, none of the squamous cell carcinoma (SCC) patients who received 33 fractions of 66 Gy in IMRT died during the median follow-up period of 13 months (range 12-25 months). In conclusion, RT with concomitant intra-arterial (cisplatin-based) infusion chemoradiotherapy can be considered an effective, well-tolerated, and feasible treatment option for late elderly patients with paranasal sinus carcinomas. In addition, >60 Gy of RT in IMRT led to improved survival outcomes in elderly paranasal sinus carcinoma patients.

The effect of oxygen partial pressure on the phase transformation of Al2O3 scale on various Fe–Al alloys with and without very thin (∼100 nm) Fe coating was investigated. Fe-coating on Fe–Al alloys can effectively suppress metastable Al2O3 formation, but little effect was observed when the samples were oxidized in a low partial pressure of oxygen. Under the low atmosphere, metastable to stable α-Al2O3 scale phase transformation on both Fe-coated and non-coated Fe–Al alloys was significantly delayed. The lattice spacing of α-Al2O3 scale formed in air decreased with increasing alloy Al content. Further decrease in the lattice spacing of α-Al2O3 scale was observed when the alloy was oxidized in low . The results obtained clearly indicated that the formation of Fe2O3 or Fe3+ in metastable Al2O3 accelerated the metastable to stable α-Al2O3 scale transformation.

We compared the efficiency and accuracy of full-arc and half-arc volumetric-modulated arc therapy (VMAT) delivery for maxillary cancer. Plans for gantry rotation angles of 360° and 180° (full-arc and half-arc VMAT) were created for six maxillary cancer cases with the Monaco treatment planning system, and delivered using an Elekta Synergy linear accelerator. Full-arc and half-arc VMAT were compared with regard to homogeneity index (HI), conformity index (CI), mean dose to normal brain, total monitor units (MU), delivery times, root mean square (r.m.s.) gantry accelerations (°/s(2)), and r.m.s. gantry angle errors (°). The half-arc VMAT plans achieved comparable HI and CI to the full-arc plans. Mean doses to the normal brain and brainstem with the half-arc VMAT plans were on average 16% and 17% lower than those with the full-arc VMAT plans. For other organs at risk (OARs), no significant DVH differences were observed between plans. Half-arc VMAT resulted in 11% less total MU and 20% shorter delivery time than the full-arc VMAT, while r.m.s. gantry acceleration and r.m.s. gantry angle error during half-arc VMAT delivery were 30% and 23% less than those during full-arc VMAT delivery, respectively. Furthermore, the half-arc VMAT plans were comparable with the full-arc plans regarding dose homogeneity and conformity in maxillary cancer, and provided a statistical decrease in mean dose to OAR, total MU, delivery time and gantry angle error. Half-arc VMAT plans may be a suitable treatment option in radiotherapy for maxillary cancer.

The purpose of the present study was to establish an experimental rat model for late radiation proctitis, and to examine the assessment strategy for late radiation proctitis. A total of 57 Wistar rats were used. Fourty-five of the rats were exposed to selective rectal irradiation with a single fraction of 25 Gy. These rats were sacrificed at the 4(th), 12(th), 24(th), and 37(th) week following irradiation. The remaining 12 rats comprised the control group without irradiation. The rectal mucosa of each rat was evaluated macroscopically and pathologically. The number of vessels in the rectal mucosa was counted microscopically. In addition, the vascular stenosis was evaluated. In the results, the degree of clinical and macroscopic findings decreased following acute proctitis and developed later. In the pathological examination, mucosal changes and microangiopathy were followed up, as well. The absolute number of vessels in the rectum was the greatest at the 12(th) week following irradiation and was the lowest in the control group. The severity of the microangiopathy was also well evaluated. To conclude, we established an animal experimental model of late radiation proctitis, and also established an assessment strategy to evaluate objectively the severity of late radiation proctitis with focusing on microangiopathy using an animal experimental model. This model can be used as an animal experimental model of radiation-induced microangiopathy.

Purpose The purpose of the present study was to standardize the experimental rat model of radiation proctitis and to examine the efficacy of polaprezinc on radiation proctitis. Methods and Materials A total of 54 female Wistar rats (5 weeks old) were used. The rats were divided into three groups: those treated with polaprezinc (PZ+), those treated with base alone, exclusive of polaprezinc (PZ−), and those treated without any medication (control). All the rats were irradiated to the rectum. Polaprezinc was prepared as an ointment. The ointment was administered rectally each day after irradiation. All rats were killed on the 10th day after irradiation. The mucosal changes were evaluated endoscopically and pathologically. The results were graded from 0 to 4 and compared according to milder or more severe status, as applicable. Results According to the endoscopic findings, the proportion of mild changes in the PZ+, PZ−, and control group was 71.4%, 25.0%, and 14.3% respectively. On pathologic examination, the proportion of low-grade findings in the PZ+, PZ−, and control group was 80.0%, 58.3%, and 42.9% for mucosal damage, 85.0%, 41.7%, and 42.9% for a mild degree of inflammation, and 50.0%, 33.3%, and 4.8% for a shallow depth of inflammation, respectively. The PZ+ group tended to have milder mucosal damage than the other groups, according to all criteria used. In addition, significant differences were observed between the PZ+ and control groups regarding the endoscopic findings, degree of inflammation, and depth of inflammation. Conclusions This model was confirmed to be a useful experimental rat model for radiation proctitis. The results of the present study have demonstrated the efficacy of polaprezinc against acute radiation-induced rectal disorders using the rat model.

Summary. Approximately 30% of patients who have recurrent hepatitis C after liver transplantation achieve sustained virological response (SVR) by taking a combination therapy of pegylated interferon and ribavirin. For the remaining non-SVR patients, an effective management treatment has not yet been established. In this study, efficacy of long-term peginterferon maintenance therapy for non-SVR patients was evaluated. Forty patients who had previously received the combination therapy for hepatitis C after living donor liver transplantation were classified into one of the following three groups: the SVR group (n = 11); the non-SVR-IFN group (n = 17), which received low-dose peginterferon maintenance therapy for non-SVR patients; and the non-SVR-Withdrawal group (n = 12), which discontinued the interferon treatment. We then compared histological changes among these three groups after 2 or more years follow-up. Activity grade of liver histology improved or remained stable in patients in the SVR and non-SVR-IFN groups, but deteriorated in half of the patients in the non-SVR-Withdrawal group. Fibrosis improved or remained stable in 10 of 11 SVR patients and in 13 of 17 non-SVR-IFN patients, but deteriorated in all non-SVR-Withdrawal patients. Mean changes in fibrosis stage between pretreatment and final liver biopsy were −0.18, +0.06 and +2.2 in the SVR, non-SVR-IFN and non-SVR-Withdrawal groups, respectively. Fibrosis stage deteriorated to F3 or F4 significantly more rapidly in the non-SVR-Withdrawal group than in the other two groups. In conclusion, continuing long-term maintenance therapy with peginterferon prevented histological progression of hepatitis C in patients who had undergone living donor liver transplantation.

A 55-year-old woman underwent living-donor liver transplantation (LDLT). She had no history of autoimmune diseases. Spleen was preserved. Steroids were withdrawn at 3 months after LDLT. Epstein-Barr virus (EBV) infection occurred at 3.5 years after LDLT. Recurrent hepatitis C virus infection was confirmed at 4.5 years after LDLT, and pegylated interferon was introduced. Diagnosis of EBV-positive post-transplant lymphoproliferative disorder (PTLD) was made at 4.8 years after LDLT, and tacrolimus (Tac) was stopped completely. Then, unconsciousness, convulsion, and cervical stiffness appeared suddenly. Electroencephalography, cerebrospinal fluid analysis, and image studies revealed normal or only nonspecific findings. The patient was in a state of exhaustion; therefore, steroid pulse therapy (SPT) was attempted. Surprisingly, her general condition, including consciousness disturbance, was improved markedly, and Hashimoto's encephalopathy (HE) was suspected, based on this reaction to SPT. Elevations of anti-thyroglobulin antibody and anti-thyroid peroxidase antibody were confirmed. After withdrawal of Tac, and treatment with acyclovir and steroids, EBV-positive PTLD and HE improved, although they recurred at 5.1 years after LDLT. SPT improved only neurological symptoms. Molecular-targeted therapy was given for recurrent PTLD, based on analysis of sampling specimens. This therapy was effective, but tumor lysis syndrome occurred, and the patient died at 5.3 years after LDLT.

Herpes simplex virus (HSV) hepatitis has a fatal impact on the outcome of organ transplanted recipients. Here, we present a thought-provoking case of HSV hepatitis in a high-risk recipient after living-related liver transplantation (LRLT). A 1-month-old female newborn infant was affected by HSV encephalitis. Fulminant hepatic failure (FHF) of unknown etiology occurred suddenly at 4.4 years of age. Viral infections were ruled out as the cause of FHF. Intensive care including plasma exchange (PE) was started, and the preoperative treatments for ABO incompatibility were performed. Thereafter, LRLT was performed emergently. Although strong immunosuppression for ABO incompatibility was continued after LRLT, antibody-mediated rejection (AMR) occurred on postoperative day (POD) 4. PE was repeated and improvements were obtained. However, liver dysfunction appeared on POD 8. Histopathological findings of liver needle biopsy clearly revealed HSV hepatitis, although the results of HSV DNA and antibody titer in blood sample did not clearly indicate HSV infection. On POD 21, thrombotic microangiopathy (TMA) occurred and the plasma and immunoglobulin were replenished. Our pediatric recipient recovered successfully from AMR, HSV hepatitis, TMA, and repeated sepsis. We conclude that well considered therapy based on the real-time detection of HSV hepatitis is indispensable for the further improvements of outcome in HSV hepatitis after LRLT.

Background & Aims The ARID1A gene encodes a protein that is part of the large adenosine triphosphate (ATP)-dependent chromatin remodeling complex SWI/SNF and is frequently mutated in human pancreatic ductal adenocarcinomas (PDACs). We investigated the functions of ARID1A during formation of PDACs in mice. Methods We performed studies with Ptf1a-Cre;KrasG12D mice, which express activated Kras in the pancreas and develop pancreatic intraepithelial neoplasias (PanINs), as well as those with disruption of Aird1a (Ptf1a-Cre;KrasG12D;Arid1af/f mice) or disruption of Brg1 (encodes a catalytic ATPase of the SWI/SNF complex) (Ptf1a-Cre;KrasG12D; Brg1f/fmice). Pancreatic ductal cells (PDCs) were isolated from Arid1af/f mice and from Arid1af/f;SOX9OE mice, which overexpress human SOX9 upon infection with an adenovirus-expressing Cre recombinase. Pancreatic tissues were collected from all mice and analyzed by histology and immunohistochemistry; cells were isolated and grown in 2-dimensional and 3-dimensional cultures. We performed microarray analyses to compare gene expression patterns in intraductal papillary mucinous neoplasms (IPMNs) from the different strains of mice. We obtained 58 samples of IPMNs and 44 samples of PDACs from patients who underwent pancreatectomy in Japan and analyzed them by immunohistochemistry. Results Ptf1a-Cre;KrasG12D mice developed PanINs, whereas Ptf1a-Cre;KrasG12D;Arid1af/f mice developed IPMNs and PDACs; IPMNs originated from PDCs. ARID1A-deficient IPMNs did not express SOX9. ARID1A-deficient PDCs had reduced expression of SOX9 and dedifferentiated in culture. Overexpression of SOX9 in these cells allowed them to differentiate and prevented dilation of ducts. Among mice with pancreatic expression of activated Kras, those with disruption of Arid1a developed fewer PDACs from IPMNs than mice with disruption of Brg1. ARID1A-deficient IPMNs had reduced activity of the mTOR pathway. Human IPMN and PDAC specimens had reduced levels of ARID1A, SOX9, and phosphorylated S6 (a marker of mTOR pathway activation). Levels of ARID1A correlated with levels of SOX9 and phosphorylated S6. Conclusions ARID1A regulates expression of SOX9, activation of the mTOR pathway, and differentiation of PDCs. ARID1A inhibits formation of PDACs from IPMNs in mice with pancreatic expression of activated KRAS and is down-regulated in IPMN and PDAC tissues from patients.