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Supplemental Digital Content is available in the text., Extracorporeal life support (ECLS) can result in complications due to increased left ventricular (LV) afterload. The percutaneous ventricular assist device (PVAD) and intra-aortic balloon pump (IABP) are both considered to be effective means of LV unloading. This study describes the efficacy of LV unloading and related outcomes with PVAD or IABP during ECLS. From January 2010 to April 2018, all cardiogenic shock patients who underwent ECLS plus simultaneous PVAD or IABP were analyzed. Forty-nine patients received ECLS + PVAD, while 91 received ECLS + IABP. At 48 hours, mean pulmonary artery pressure was significantly reduced in both groups [34 mm Hg to 22, p < 0.01; 32 mm Hg to 21, p < 0.01; ECLS + PVAD and ECLS + IABP group, respectively]. The two groups had similar 30 day survival rates [19 patients (39%) vs. 35 (39%), p = 0.56]. The ECLS + PVAD group had higher incidences of bleeding at the insertion site [11 (22%) vs. 0, p < 0.01] and major hemolysis [9 (18%) vs. 0, p < 0.01]. Both groups had improvement in LV end-diastolic dimension (61 ± 12 mm to 54 ± 12, p = 0.03; 60 ± 12 mm to 47 ± 10, p < 0.01), and LV ejection fraction (16 ± 7% to 22 ± 10, p < 0.01; 22 ± 12% to 29 ± 15, p = 0.01). Both ECLS + PVAD and ECLS + IABP effectively reduced pulmonary artery pressure and improved LV function. Bleeding at the PVAD or IABP insertion site occurred more frequently in the ECLS + PVAD group than the ECLS + IABP group (p < 0.01). Nine patients (18%) in the ECLS + PVAD group experienced major hemolysis, while there was no hemolysis in the ECLS + IABP group (p < 0.01). Careful considerations are required before selecting an additional support to ECLS.

Background There is an ongoing controversy regarding the necessity of single-photon emission computed tomography (SPECT) for patients with ischemic heart diseases after the publication of the results of the ISCHEMIA trial. Purpose We aimed to evaluate the association of the extent of myocardial ischemia with outcomes in patients with suspected coronary artery disease in Japan. Methods From the data of 2780 patients with stable angina who were enrolled prospectively between January 2006 and March 2008 in Japan and had undergone physician-referred non-invasive imaging tests, 1205 patients managed with SPECT were stratified by 10% myocardial ischemia. Major adverse cardiac events (MACEs), including death, myocardial infarction, hospitalization for heart failure, and late revascularization, were followed-up for 1 year. Results Patients with ≥10% myocardial ischemia (n=173) were older than patients with Conclusion The presence of ≥10% myocardial ischemia was significantly associated with the 1-year risk for MACEs in Japanese patients with suspected coronary artery disease. Funding Acknowledgement Type of funding sources: None. Study flowchartOutcomes

STUDY QUESTION After controlled ovarian stimulation (COS) and IUI, is it clinically feasible to recover in vivo conceived and matured human blastocysts by uterine lavage from fertile women for preimplantation genetic testing for aneuploidy (PGT-A) and compare their PGT-A and Gardner scale morphology scores with paired blastocysts from IVF control cycles? SUMMARY ANSWER In a consecutive series of 134 COS cycles using gonadotrophin stimulation followed by IUI, uterine lavage recovered 136 embryos in 42% (56/134) of study cycles, with comparable in vivo and in vitro euploidy rates but better morphology in in vivo embryos. WHAT IS KNOWN ALREADY In vivo developed embryos studied in animal models possess different characteristics compared to in vitro developed embryos of similar species. Such comparative studies between in vivo and in vitro human embryos have not been reported owing to lack of a reliable method to recover human embryos. STUDY DESIGN, SIZE, DURATION We performed a single-site, prospective controlled trial in women (n = 81) to evaluate the safety, efficacy and feasibility of a novel uterine lavage catheter and fluid recovery device. All lavages were performed in a private facility with a specialized fertility unit, from August 2017 to June 2018. Subjects were followed for 30 days post-lavage to monitor for clinical outcomes and delayed complications. In 20 lavage subjects, a single IVF cycle (control group) with the same ovarian stimulation protocol was performed for a comparison of in vivo to in vitro blastocysts. PARTICIPANTS/MATERIALS, SETTINGS, METHODS Women were stimulated with gonadotrophins for COS. The ovulation trigger was given when there were at least two dominant follicles ≥18 mm, followed by IUI of sperm. Uterine lavage occurred 4–6 days after the IUI. A subset of 20 women had a lavage cycle procedure followed by an IVF cycle (control IVF group). Recovered embryos were characterized morphologically, underwent trophectoderm (TE) biopsy, vitrified and stored in liquid nitrogen. Biopsies were analyzed using the next-generation sequencing technique. After lavage, GnRH antagonist injections were administered to induce menstruation. MAIN RESULTS AND THE ROLE OF CHANCE A total of 134 lavage cycles were performed in 81 women. Uterine lavage recovered 136 embryos in 56 (42%) cycles. At the time of cryopreservation, there were 40 (30%) multi-cell embryos and 96 (70%) blastocysts. Blastocysts were of good quality, with 74% (70/95) being Gardener grade 3BB or higher grade. Lavage blastocysts had significantly higher morphology scores than the control IVF embryos as determined by chi-square analysis (P LIMITATIONS, REASON FOR CAUTION The first objective was to evaluate the feasibility of uterine lavage following ovarian stimulation to recover blastocysts for analysis, and that goal was achieved. However, the uterine lavage system was not completely optimized in our earlier experience to levels that were achieved late in the clinical study and will be expected in clinical service. The frequency of chromosome abnormalities of in vivo and IVF control embryos was similar, but this was a small-size study. However, compared to larger historical datasets of in vitro embryos, the in vivo genetic results are within the range of high-quality in vitro embryos. WIDER IMPLICATIONS OF THE FINDINGS Uterine lavage offers a nonsurgical, minimally invasive strategy for recovery of embryos from fertile women who do not want or need IVF and who desire PGT, fertility preservation of embryos or reciprocal IVF for lesbian couples. From a research and potential clinical perspective, this technique provides a novel platform for the use of in vivo conceived human embryos as the ultimate benchmark standard for future and current ART methods. STUDY FUNDING/COMPETING INTEREST(S) Previvo Genetics, Inc., is the sole sponsor for the Punta Mita, Mexico, clinical study. S.M. performs consulting for CooperGenomics. J.E.B. and S.A.C. are co-inventors on issued patents and patents owned by Previvo and ownshares of Previvo. S.N. is a co-author on a non-provisional patent application owned by Previvo and holds stock options in Previvo. S.T.N. and M.J.A. report consulting fees from Previvo. S.T.N., S.M., M.V.S., M.J.A., C.N. and J.E.B. are members of the Previvo Scientific Advisory Board (SAB) and hold stock options in Previvo. J.E.B and S. M are members of the Previvo Board of Directors. A.N. and K.C. are employees of Previvo Genetics. L.V.M, T.M.M, J.L.R and S. S have no conflicts to disclose. TRIAL REGISTRATION NUMBER Protocol Registration and Results System (PRS) Trial Registration Number and Name: Punta Mita Study TD-2104: Clinical Trials NCT03426007.

Acute kidney injury is a common complication following heart transplantation, and the factors contributing to acute kidney injury are not well understood. We conducted a retrospective cohort study evaluating patients who underwent heart transplantation between 2009 and 2016 at a single institution. The primary endpoint was incidence of acute kidney injury as defined by Kidney Disease Improving Global Outcomes criteria. Secondary endpoints included 30‐day hospital readmission, 30‐day mortality, and 1‐year mortality. A total of 228 heart transplant patients were included in the study for analysis. In total, 145 (64%) developed acute kidney injury, where 43 (30%) were classified as stage I, 28 (19%) as stage II, and 74 (51%) as stage III. Risk factors found to be associated with the presence of acute kidney injury included increased use of vasopressors and inotropes post‐transplant. Protective factors included cardiopulmonary bypass time

Pneumococcal serotype replacement is an important issue after the introduction of pneumococcal conjugate vaccine (PCV) in children. After the introduction of 13-valent PCV, the incidence of invasive pneumococcal diseases (IPD) caused by Streptococcus pneumoniae serotype 12F (Sp12F) have increased in some countries; however, an outbreak of Sp12F has not reported in the post-13-valent PCV era. We experienced a local outbreak of Sp12F during March through May 2016 in Tsuruoka city, Japan after the introduction of 13-valent PCV in 2013. The IPD patients were two children and seven adults, three of whom died with a rapid disease progress. Although the clear transmission route was not determined, eight of the nine patients (89%) had close contact with children, which suggests that transmitted colonisation of Sp12F among children and adults might be the source of transmission. Continuous monitoring of IPDs, along with the determination of pneumococcal serotypes, is warranted in the post–13-valent PCV era. New IPD control strategies may be needed if this fatal outbreak continues to occur.

Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope (HVJ-E)) have a novel antitumor effect: HVJ-E fused to prostate cancer cells via cell surface receptor causes apoptosis of prostate cancer cells in vitro and in vivo. HVJ-E also induces antitumor immunity by activating natural killer (NK) cells and cytotoxic T cells and suppressing regulatory T cells in vivo. We conducted an open-label, single-arm, phase I/II clinical trial in patients with castration-resistant prostate cancer (CRPC) to determine the safety and efficacy of intratumoral and subcutaneous injection of HVJ-E. Patients with CRPC who were docetaxel-resistant or could not receive docetaxel treatment were eligible. HVJ-E was injected directly into the prostate on day 1 and subcutaneously on days 5, 8 and 12 in two 28-day treatment cycles using a 3+3 dose-escalation design. The primary end points were to evaluate safety and tolerability of HVJ-E. The secondary end points were to analyze tumor immunity and antitumor effect. The study is registered at UMIN Clinical Trials Registry, number UMIN000006142. Seven patients were enrolled, and six patients received HVJ-E. Grade 2 or 3 adverse events (Common Terminology Criteria for Adverse Events Ver. 4.0) were urinary retention and lymphopenia from which the patients recovered spontaneously. No Grade 4 adverse events were observed. Radiographically, three patients had stable disease in the low-dose group, and one patient had stable disease and two had progressive disease in the high-dose group. The prostate-specific antigen (PSA) declined from 14 to 1.9 ng ml−1 in one patient in the low-dose group after two cycles of HVJ-E treatment, and the PSA response rate was 16.6%. NK cell activity was elevated from day 12 to day 28 after HVJ-E administration, whereas serum interleukin-6, interferon (IFN)-α, IFN-β and IFN-γ levels were not affected by HVJ-E treatment. Intratumoral and subcutaneous injections of HVJ-E are feasible and PSA response was observed in a subgroup of CRPC patients.

Purpose Aortic valve incompetence (AI) is a serious complication that develops in 20% of LVAD patients within 12 months of implantation. Many LVAD patients with AI also develop mitral regurgitation (MR). Our goal in this study was to measure systemic flow (Qsys) and LVAD flow (QLVAD) during AI, MR and AI+MR. Methods A mock circulatory loop with a dilated silicone LV and bioprosthetic valves was attached to a HeartMate II LVAD (Abbott Labs), and pressure and flow measured in the LV, LVAD and aorta. A Pre-LVAD ejection fraction of 20% without any valve dysfunction was established, followed LVAD support at speeds of 8, 9.4 and 11krpm. AI and MR were created with small stents that were non-obstructive to forward flow but prevented the leaflets from fully closing. Four conditions were tested: Normal, AI, MR and AI and MR combined. Average flow was obtained from ten cycles of data, and Q calculated as QLVAD/Qsys. Results Pre-LVAD AI, MR and AI+MR produced a 28%, 12% and 45% reduction in Qsys, respectively. LVAD support at 9.4krpm increased Normal Qsys to 3.6 L/min with 95% of flow through the LVAD. MR reduced Qsys by 16% and QLVADby 21%; AI reduced by Qsys by 24% but QLVADby only 5%; and AI+MR reduced Qsys by 25% and QLVADby 7%, which was comparable to AI alone. In all conditions except AI+MR, Q increases with LVAD speed indicating that QLVAD increases faster than Qsys. This trend reverses when MR is present, reducing the impact of AI as LVAD speed is increased. Conclusion The major finding of these studies is that MR does not worsen Qsys when it coincides with AI and LVAD support. AI and MR occur during different phases of the cardiac cycle and sum in the absence of LVAD support. When an LVAD is added without valve dysfunction, QLVADis evenly distributed across systole and diastole. AI and MR reduces systolic and increases diastolic QLVAD, but AI+MR restores the original distribution. AI+MR produces the same overall Qsys but QLVADoccurs more evenly throughout the cardiac cycle resulting in a greater sensitivity to LVAD speed changes.

Background:Telemedicine can be performed using a conventional videophone or web conferencing system. Then, joint lesions can only be observed and inferred from two-dimensional images, and it is difficult to perform accurate joint assessments, which is essential for the management of rheumatoid arthritis (RA).Objectives:To develop the next-generation online telemedicine system utilizing mixed reality for RA.Methods:We have developed a system that can assess joints accurately in three-dimensions images in real-time, using Azure Kinect DK (depth sensor)/ HoloLens 2 (headset), which are mixed reality technologies, and Teams (online interview/chat) provided by Microsoft. Furthermore, by applying artificial intelligence (AI), we plan to implement additionally to this system 1) a function to quickly catch and automatically evaluate the patient’s anxiety and changes in facial expressions at the time of examination, 2) a function to record dialogue with the patient in chronological order, 3) a function to support the detection of swollen joints, and 4) function to automatically analyze the questionnaire.Results:This system remotely connects a rheumatologist in the Nagasaki University Hospital (Nagasaki City, urban area) and a patient with RA and a non- rheumatologist in the Goto Central Hospital (Goto Island, rural area). A three-dimensional hologram of the patient’s hand projected in front of a rheumatologist. Using this system, we are able to evaluate joints more accurately than using a conventional videophone or web conferencing system.Conclusion:It is expected that this system will enable remote medical care specializing in rheumatology, which is standardized at a high level even in areas without rheumatologists such as remote islands and remote areas. This system remotely connects Nagasaki City and Goto Island, but due to the performance of the system, it is not limited to these areas and it is possible to connect rheumatologists to any area that can be connected to the network. It is also effective for the purpose of avoiding the risk of infection during long-distance hospital visits under the epidemic of COVID-19 infection.References:[1]Mov Disord. 2020;35:1719-1720.Disclosure of Interests:Shin-ya Kawashiri Speakers bureau: Speaker fees from AbbVie, Asahi Kasei, Astellas, Chugai, Eisai, Eli Lilly, Mitsubishi Tanabe, Novartis, and ONO., Grant/research support from: Research grants from Pfizer., Fumiaki Nonaka: None declared, Shinji Chiba: None declared, Tomoyuki Honda: None declared, Tomohiko Nakajima: None declared, Tomoyuki Ishikawa: None declared, Atsushi Kawakami Speakers bureau: Speaker fees from AbbVie, Actelion, Asahi Kasei, Astellas, Boehringer Ingelheim, Celltrion, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, GSK, Janssen, Kowa, MedPeer, Mitsubishi Tanabe, Novartis, ONO, Pfizer, Taisho, and Takeda., Grant/research support from: Grants and research support from AbbVie, Actelion, Asahi Kasei, Astellas, AYUMI, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa Hakko Kirin, MSD, Neopharma, Novartis, ONO, Sanofi, Taisho, Takeda Science Foundation, and Teijin

The study objective was to investigate the progression of uncorrected mild aortic insufficiency and its impact on survival and functional status after left ventricular assist device implantation.We retrospectively reviewed 694 consecutive patients who underwent implantation of a continuous-flow left ventricular assist device between January 2006 and March 2018. Pre-left ventricular assist device transthoracic echocardiography identified 111 patients with mild aortic insufficiency and 493 patients with trace or no aortic insufficiency. To adjust for differences in preoperative factors, propensity score matching was used, resulting in 101 matched patients in each of the mild aortic insufficiency and no aortic insufficiency groups.Although both groups showed similar survival (P = .58), the mild aortic insufficiency group experienced higher incidence of readmission caused by heart failure (hazard ratio, 2.62; 95% confidence interval, 1.42-4.69; P .01). By using the mixed effect model, pre-left ventricular assist device mild aortic insufficiency was a significant risk factor for both moderate or greater aortic insufficiency and worsening New York Heart Association functional status (P .01).Patients with uncorrected mild aortic insufficiency had a higher risk of progression to moderate or greater aortic insufficiency after left ventricular assist device implantation with worse functional status and higher incidence of readmission caused by heart failure compared with patients without aortic insufficiency. Further investigations into the safety and efficacy of concomitant aortic valve procedures for mild aortic insufficiency at the time of left ventricular assist device implant are warranted to improve patients' quality of life, considering the longer left ventricular assist device use as destination therapy and bridge to transplant with the new US heart allocation system.

Purpose Acute kidney injury (AKI) is a common complication following heart transplant and has been found to be associated with increased morbidity and mortality. The goal of this study is to examine pre- and peri-operative risk factors for AKI post-heart transplant and to identify potentially modifiable risk factors. Methods We conducted a retrospective cohort study evaluating patients who underwent heart transplant between 2009 and 2016 at a single institution. Data were obtained from the Society of Thoracic Surgeons (STS) national database and retrospective chart review. Exclusion criteria were age Results A total of 189 heart transplant patients were included in the study for analysis. In total, 113 (60%) developed AKI, where 37 (33%) were classified as stage I, 23 (20%) as stage II, 53 (47%) as stage III, and 45 patients (24%) required dialysis. Risk factors found to be associated with the presence of AKI included elevated pre-op central venous pressure (CVP) (16 mmHg non-AKI group vs 19 mmHg AKI group, p = 0.020), increased use of vasopressors and inotropes post-transplant, number of blood products transfused (9 vs 11 units, p = 0.009), cardiopulmonary bypass time (163 vs 180 min, p = 0.002), and complications such as delayed sternal closure (19 (29%) vs 48 (45%), p = 0.030). Dialysis after discharge was needed for 7 (8%, p = 0.090) AKI patients. No significant association was found between presence of AKI and hospital readmission, 30-day mortality, and 1-year mortality. Conclusion Risk factors such as elevated pre-op CVP, high use of vasopressors and inotropes, number of blood products transfused, and delayed sternal closure were closely associated with the development of AKI. Delayed sternal closure and number of blood products transfused highlight the impact of bleeding, and the elevated pre-operative CVP is of particular interest due to its potentially modifiable nature.

Purpose In patients with left ventricular assist device (LVAD), aortic valve insufficiency (AI) could occur in longer period during the cardiac cycle, throughout the diastolic and part of the isovolumetric phases. As the result, the current echocardiographic evaluation of AI grade may underestimate the degree of AI in LVAD patients, especially those with significant AI. In this study, we investigated the differences in AI duration and regurgitant volume before and during LVAD supports (Off and On LVAD) using a mock circulatory loop. Methods All measurements were performed using a mock circulatory system with a dilated silicone LV model attached to a HeartMate II LVAD (Abbott Lab), and pressure and flow measured in the LV, LVAD, and aorta. Baseline condition was established as no LVAD condition (Off LVAD setting) which has 17% ejection fraction, 62 bpm heart rate and 65 mmHg systemic pressure. LVAD condition (On LVAD setting) at 8,800 rpm with same ejection fraction, heart rate and systemic resistance (90 mmHg systemic pressure) was established, followed by testing at three AI severity conditions. AI severity was defined as mild, moderate, or severe based on effective regurgitant orifice area. AI conditions were created with small 3-D printed stents, which were nonobstructive to forward flow, but prevented the leaflets from fully closing. AI durations and regurgitant volumes were determined from the calculated backward flow through the aortic valve. Results With the constant systemic resistance in the On LVAD setting at 8,800 rpm, duration of AI increased by 8.3 % (75 to 83.3%) with mild AI, 5.6% (77.8 to 83.3%) with moderate AI, and 5.6% (77.8 to 83.3%) with severe AI compared to the Off LVAD setting. With the constant systemic resistance in the On LVAD setting at 8,800 rpm, regurgitant volume of AI increased by 0.11 L/min (0.12 to 0.23 L/min, 92%) in mild AI, 0.03 L/min (0.53 to 0.56 L/min, 5.7%) in moderate AI and 0.08L/min (0.78 to 0.86 L/min, 10.3%) with severe AI compared to the Off LVAD setting. Conclusion This mock loop study demonstrated that AI duration was longer and regurgitant volume through the aortic valve was greater during LVAD support compared to same AI degree before LVAD. This suggests that clinical burden of AI may be underestimated in patients with LVAD.

This article focuses on the cause, pathophysiology, differential diagnosis of, and treatment options for vasomotor symptoms. In addition, it summarizes important points for health care providers caring for perimenopausal and postmenopausal women with regard to health maintenance, osteoporosis, cardiovascular disease, and vaginal atrophy. Treatment options for hot flashes with variable effectiveness include systemic hormone therapy (estrogen/progestogen), nonhormonal pharmacologic therapies (selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, clonidine, gabapentin), and nonpharmacologic therapy options (behavioral changes, acupuncture). Risks and benefits as well as contraindications for hormone therapy are further discussed.

Patient: Male, 32 Final Diagnosis: MSSA pneumonia Symptoms: Cough • dyspnea • fever Medication: Meropenem • levofloxacin • vancomycin • peramivir Clinical Procedure: Diagnosed based on CT images • sputum culture • PCR Specialty: Infectious Diseases Objective: Rare disease Background: Increasing evidence has indicated that Staphylococcus aureus pneumonia complicated with influenza virus infection is often fatal. In these cases, disease severity is typically determined by susceptibility to antimicrobial agents and the presence of high-virulence factors that are produced by Staphylococcus aureus, such as Panton-Valentine leukocidin (PVL). Case Report: We describe a rare case of fatal community-acquired pneumonia caused by methicillin-sensitive Staphylococcus aureus (MSSA), which did not secrete major high-virulence factors and coexisted with influenza type B infection. The 32-year-old previously healthy male patient presented with dyspnea, high fever, and cough. His roommate had been diagnosed with influenza B virus infection 3 days earlier. Gram-positive clusters of cocci were detected in the patient’s sputum; therefore, he was diagnosed with severe pneumonia and septic shock, and was admitted to the intensive care unit. Despite intensive antibiotic and antiviral treatment, he died of multiple organ failure 5 days after admission. His blood culture from the admission was positive for MSSA, and further analysis revealed that the strain was negative for major high-virulence factors, including PVL and enterotoxins, although influenza B virus RNA was detected by PCR. Conclusions: Physicians should pay special attention to patients with pneumonia following influenza and Staphylococcus aureus infection, as it may be fatal, even if the Staphylococcus aureus strain is PVL-negative and sensitive to antimicrobial agents.

Objective To assess the efficacy, safety, and tolerability of an extended-duration, combined hormonal oral contraceptive pill (OCP) that reduces the estrogen exposure by almost half compared with other OCPs. Methods This open-label, uncontrolled, multicenter study used an ultra low-dose OCP (1.0 mg norethindrone acetate and 10 micrograms ethinyl E2). The OCP was administered in a regimen of 24 days of a 28-day cycle followed by 10 micrograms ethinyl E2 for 2 days and an inactive tablet for 2 days. The study included healthy, heterosexually active women aged 18-45 years who were at risk of pregnancy. Results The discontinuation rate was 41.7% (692/1,660 patients). Twenty-six pregnancies occurred in 1,555 participants during 15,596 at-risk cycles, resulting in a Pearl Index of 2.2 and a cumulative pregnancy rate of 2.1 for the overall population. Participants experienced an average of 2.6 days of intracyclic (unscheduled) bleeding or spotting per cycle over treatment cycles 213. Intracyclic bleeding was more common in users new to OCPs than in users switching from another OCP and in women aged 18-35 years compared with those aged 36 years or older. The frequency of bleeding episodes decreased after cycle 2 and throughout treatment in all subpopulations. Conclusion The findings of this study demonstrate that this ultra low-dose OCP regimen is effective in preventing pregnancy with a safety and tolerability profile that is comparable with that reported for other low-dose OCPs. Clinical trial registration ClinicalTrials.gov, www.clinicaltrials.gov, NCT00391807. Level of evidence III.

Aim ‘Predict, resect and discard’ strategies for diminutive and small colonic polyps are considered to be cost effective for treating colorectal cancers. The aim of this study was to determine, retrospectively, the histological features of colonic polyps resected by endoscopic procedures or surgery using an updated database. Method We retrospectively analysed the clinicopathological features of colorectal polyps, less than 20 mm in size, which were removed by endoscopy from January 2009 to November 2011 at the National Cancer Center Hospital (NCCH) in Tokyo, Japan. Results Less than 1% of diminutive polyps (≤ 5 mm) were classified as mucosal high-grade neoplasia (Category 4), and no submucosal invasion by carcinoma (Category 5) lesions were noted. However, 3% of small polyps (6–9 mm) were classified as Category 5; of these, 6% were submucosal deep invasive cancers. Morphologically, depressed components were observed more frequently in carcinomas than in adenomas in both small and large polyps (10–20 mm). Conclusion In light of the ‘predict, resect and discard’ strategies for small polyps, we should pay attention to the possible clinical malignancy of small and large polyps. We recommend that these strategies should be applied selectively and that they should be informed by accurate endoscopic evaluations.

We report on the operation of a 25.8 Gbit/s DML TOSA over a wide temperature range (WTR) with extremely high eye-mask margin for Ethernet applications. The TOSA is comprised of a co-axial TO-CAN package with an LC-type receptacle for the optical connector and an FPC for the electrical interface. By combining a wide bandwidth InGaAlAs WTR-DFB chip and a novel TOSA design, extremely high Ethernet mask margins exceeding 30% at 25.8 Gbit/s over a case temperature of -- 5 degC to 75 degC is achieved. This TOSA enables small form factor modules, such as SFP+, to operate at up to 70 degC.

Objective To study the association between paternal medical comorbidities and the outcomes of assisted reproductive technology (ART). Design Retrospective cohort study. Setting Academic reproductive medicine center. Patient(s) We analyzed fresh ART cycles uszing freshly ejaculated sperm from the male partner of couples undergoing ART cycles from 2004 until 2014. We recorded patient and partner demographic characteristics. The cohort was linked to hospital billing data to obtain information on selected male partners' comorbidities identified using ICD-9-CM codes. Intervention(s) None. Main Outcome Measure(s) Fertilization, clinical pregnancy, miscarriage, implantation, and live-birth rates as well as birth weights and gestational ages. Result(s) In all, we identified 2,690 men who underwent 5,037 fresh ART cycles. Twenty-seven percent of men had at least one medical diagnosis. Men with nervous system diseases had on average lower pregnancy rates (23% vs. 30%) and live-birth rates (15% vs. 23%) than men without nervous system diseases. Lower fertilization rates were also observed among men with respiratory diseases (61% vs. 64%) and musculoskeletal diseases (61% vs. 64%) relative to those without these diseases. In addition, men with diseases of the endocrine system had smaller children (2,970 vs. 3,210 g) than men without such diseases. Finally, men with mental disorders had children born at an earlier gestational age (36.5 vs. 38.0 weeks). Conclusion(s) The current report identified a possible relationship between a man's health history and IVF outcomes. As these are potentially modifiable factors, further research should determine whether treatment for men's health conditions may improve or impair IVF outcomes.

A method is presented for configuration optimization of frames that have specified properties on nodal displacements, stresses, and reaction forces against static loads. The conventional ground structure approach is first used for topology optimization. A feasible solution with a small number of members satisfying all the design requirements except the stress constraints is obtained by assigning artificially small upper-bound displacement, or by penalizing the stiffness of a thin member. This way, the well-known difficulty in topology optimization under stress constraints is successfully avoided. The nodal locations and cross-sectional areas of the feasible solution are next optimized to obtain an approximate optimal configuration under stress constraints. The proposed method is applied to the design of self-fastening clamping members for membrane structures modeled using frame elements. An optimization result is also presented for a clamping member that adjusts deformation of membrane by applying a clamping force with a vertically attached bolt.

In plant and industrial complex, further energy saving can be realized by DC interconnection between the ends of AC radial distribution system. We fabricated a power system simulator to verify that the DC interconnection is effective for energy saving in the distribution system. An YBCO toroidal coil composed of eight double pancake coils was fabricated and adopted in the simulator as a DC reactor. Harmonic current with DC-offset component were observed in the YBCO toroidal coil and the frequency component ratio of harmonic current depended on the inductance of the toroidal coil. Energy loss in the YBCO toroidal coil during the DC interconnection in the power system simulator decreased with the inductance of the YBCO toroidal coil because the magnitude of harmonic current component decreased with the inductance. To clarify the loss characteristics in the YBCO toroidal coil, we investigated influence of the magnitude of harmonic-frequency component and DC-offset component on the transport current loss in YBCO tape conductor. The transport current lose was independent of the magnitude of DC-offset component. The energy loss characteristics in the YBCO toroidal coil were closely related to the transport current loss in the YBCO tape conductor with harmonic current.

Onishi H, Arakawa S, Nakajima T, Izumi Y. Levels of specific immunoglobulin G to the forsythia detaching factor of Tannerella forsythia in gingival crevicular fluid are related to the periodontal status. J Periodont Res 2010; 45: 672–680. © 2010 John Wiley & Sons A/S Background and Objective: Forsythia detaching factor (FDF) is a putative virulence factor of Tannerella forsythia that induces detachment of adherent cells and interleukin-8 production in human fibroblasts. The objective of the present study was to clarify the relationship between anti-FDF IgG levels in gingival crevicular fluid and the clinical status in patients with periodontitis and in healthy subjects. Material and Methods: Gingival crevicular fluid and subgingival plaque samples were obtained from both the diseased and healthy sites of 37 patients with periodontitis and from 30 healthy subjects. Anti-FDF IgG levels were evaluated, and both the fdf gene and T. forsythia 16S ribosomal RNA (rRNA) were detected using the PCR. Results: Anti-FDF IgG levels (of both diseased and healthy sites) of patients with periodontitis were significantly higher than those of healthy subjects. Among the patients with periodontitis, anti-FDF IgG levels of healthy sites were significantly higher than those of diseased sites and the levels showed negative correlations with probing pocket depth and clinical attachment level. Among the patients with periodontitis, T. forsythia 16S rRNA was detected in 18 of 37 diseased sites and in 5 of 29 healthy sites, and the fdf gene was detected in 19 of 37 diseased sites and in 7 of 29 healthy sites. By contrast, no healthy subjects were positive for T. forsythia 16S rRNA or the fdf gene. Conclusion: These data suggest that anti-FDF IgG levels in gingival crevicular fluid are related to the periodontal status.

Endoscopic mucosal resection (EMR) is a minimally invasive technique for effective treatment of early stage colorectal lesions with no invasive potential. However, the high frequency of local recurrence after piecemeal EMR for large lesions is considered a serious problem. In contrast, endoscopic submucosal dissection (ESD) allows en-bloc resection, irrespective of the lesion's size. ESD has been established as a standard method for the endoscopic removal of early cancers in the upper gastrointestinal tract in Japan. Although the use of ESD for colorectal lesions has been studied clinically, ESD is not yet established as a standard therapeutic method. We define the indications for en-bloc resection, based on extensive clinicopathological analyses, as a laterally spreading tumor (LST) non-granular type (LST-NG) lesion greater than 20 mm and an LST granular (LST-G) type lesion greater than 40 mm. Both of these lesions had a high submucosal invasion rate. Especially, LST-NG type lesions greater than 20 mm are technically difficult to remove completely even by piecemeal EMR and are considered a "definite indication for en-bloc resection". The ESD procedure is undoubtedly an ideal method to achieve en-bloc resection, however, the prevalences of suitable lesions among all neoplastic lesions and among all early cancers were not high (1.0% and 5.0%, respectively). Therefore, it is crucial to master more fundamental therapeutic techniques and have knowledge of surveillance strategy after endoscopic treatment.

Aims Clinically serosa-positive (T3–4) gastric cancer has a poor prognosis. This phase II trial explored the feasibility and safety of preoperative chemotherapy followed by D2 or D3 gastrectomy in this type of gastric cancer. Methods Patients with T3–4 gastric cancer received one course of S-1 (80 mg/m 2 daily for 3 weeks) and cisplatin (60 mg/m 2 on day 8) chemotherapy and then underwent D2 or D3 gastrectomy with curative intent. Primary endpoint was toxicities. Results Of 50 patients enrolled, 49 were eligible and received the treatment protocol. Chemotherapy-related toxicities were mild; grade 3 neutropenia in 2 patients, anorexia in 3, and nausea in 2, and no grade 4 toxicities. Clinical response was achieved in 13 of 34 evaluable patients. Of the 49 patients, 39 underwent D2 or D3 dissection. There was no surgical mortality. Operative morbidity occurred in 5 of 49 patients, including pancreatic fistula in 1 and abdominal abscess in 2. Conclusion This multi-modality treatment seems to be feasible and safe for T3–4 gastric cancer.

A case of large cell neuroendocrine carcinoma (LCNEC) of the tongue base is described. It was characterized by solid tumor nests with central necrosis and rosette formation resembling basaloid squamous cell carcinoma. Immunohistochemical examination revealed that this tumor had neuroendocrine differentiation. It was diagnosed as LCNEC of the tongue base. Pulmonary LCNEC is a well-established entity, but LCNEC also occurs in other organs. This is the first report of mucosal LCNEC in the oral cavity. Basal cells in the normal squamous epithelium around the tumor indicated positivity for neural cell adhesion molecule and N-cadherin. These cells were considered neuroendocrine-related cells in the lingual squamous epithelium, which are related to the tumorigenesis of mucosal LCNEC in the tongue base.

Palm oil has the important advantage of productivity compared with other vegetable oils such as rapeseed oil and soybean oil. However, the cold flow performance of palm oil methyl ester (PME) is poorer than other vegetable-oil-based biodiesel fuels. Previous research by the current authors has shown that ethanol blending into PME improves the cold flow performance and considerably reduces smoke emission. The reduced smoke may be expected to allow an expansion in the exhaust gas recirculation (EGR) limit and lead to reduced oxides of nitrogen (NO x). This paper experimentally analyses the influence of EGR on smoke and NO x emissions with ethanol-blended PME. The results show that the combination of ethanol blending and EGR is effective in reducing NO x and smoke simultaneously without the thermal efficiency deteriorating. The smoke reduction can be attributed to an improved fuel—air mixing by an increased ignition delay owing to the low cetane number of ethanol and by a promoted fuel spray atomization caused by the low boiling point of ethanol. The increase in the oxygen content also leads to lower soot emission. The decrease in local equivalence ratio by ethanol blending was also suggested by the flame observation in which flame with high luminosity, high temperature, and high KL factor shrinks.

Involvement of celiac nodes is defined as distant metastasis in the TNM classification for thoracic esophageal carcinoma. Some textbooks, however, describe dissection of these nodes as a standard technique. The present study was, therefore, undertaken to clarify which celiac nodes are regional for thoracic esophageal carcinoma and whether or not celiac node dissection would provide a survival benefit. Eight hundred and five patients who underwent R0 resection (no residual tumor) with systematic lymphadenectomy including the celiac axis area for thoracic esophageal carcinoma were retrospectively investigated. The frequency of metastasis and the therapeutic value of dissecting celiac nodes were compared to those associated with the left gastric artery area. The frequencies of left gastric and celiac nodal involvement were 15.4% and 9.6%, respectively, for thoracic esophageal carcinoma. As for tumor location, the incidences of metastasis around left gastric artery and celiac axis from the upper, middle and lower portion were 6.7% and 1.0%; 12.3% and 7.7%; and 25.7% and 17.4%, respectively. The 5-year survivals of patients with celiac but not left gastric metastasis were 36.3% and 41.8% for the middle and lower portions, respectively, while the corresponding values with left gastric involvement but no celiac metastasis were 24.1% and 27.9%. These differences were not significant. The frequency of celiac node involvement was not low. And, their dissection has equivalent therapeutic value to that of left gastric nodes. Revision of the TNM classification to account for celiac node involvement in thoracic esophageal carcinoma, especially of the middle and lower portions, is needed.

Hypofractionated stereotactic body radiotherapy (SBRT) for pulmonary lesions provides a high local control rate, allows completely painless ambulatory treatment, and is not associated with adverse reactions in most cases. Here we report a 70-year-old lung cancer patient with slight focal pulmonary honeycombing in whom subclinical idiopathic pulmonary fibrosis was exacerbated by SBRT. This experience has important implications for the development of selection criteria prior to SBRT for pulmonary lesions. For SBRT candidates with lung tumors, attention must be paid to the presence of co-morbid interstitial pneumonia even if findings are minimal. Such patients must be informed of potential risks, and careful decision-making must take place when SBRT is being considered.

Background This prospective randomized study compared the survival of patients with tumour node metastasis (TNM) stage T2 N1–2 gastric cancer treated by gastrectomy alone or gastrectomy followed by uracil–tegafur. Methods Patients were randomly assigned to surgery alone or to surgery and postoperative uracil–tegafur 360 mg per m2 per day orally for 16 months. The primary endpoint was overall survival. Relapse-free survival and site of recurrence were secondary endpoints. Results Of 190 registered patients, 95 were randomized to each group; two patients with early cancer were subsequently excluded from the chemotherapy group. The trial was terminated before the target number of patients was reached because accrual was slower than expected. Drug-related adverse effects were mild, with no treatment-related deaths. At a median follow-up of 6·2 years, overall and relapse-free survival rates were significantly higher in the chemotherapy group (hazard ratio for overall survival 0·48, P = 0·017; hazard ratio for relapse-free survival 0·44, P = 0·005), confirming the survival benefit shown in an interim analysis performed 2 years earlier. Conclusion Interim and final analyses revealed a significant survival benefit for postoperative adjuvant chemotherapy with uracil–tegafur in patients with serosa-negative, node-positive gastric cancer. Registration number: NCT00152243 (http://www.clinicaltrials.gov).

Objective To identify the current and future state of the practice of reproductive medicine. Design Cross-sectional survey. Setting Not applicable. Patient(s) None. Intervention(s) Not applicable. Main Outcome Measure(s) The survey included 57 questions designed to assess practice patterns/metrics and professional satisfaction and morale. Result(s) A total of 336/1,100 (31%) responded, and they were 38% women, 61% men, and 76% Caucasian, with a mean age of 54. Respondents averaged 2.3 jobs and averaged 53 hours of work per week: 44% work in academia and 50% in private groups. Average practice size was 5.5, with an average of 470 fresh IVF cycles performed per year. Percent effort included 63% infertility, 10% endocrinology, 10% surgery, and 9% research. Respondents performed an average of 13 major surgeries, 69 minor surgeries, and 128 oocyte retrievals per year. A total of 60% were salaried, and 40% were equity partners. Compensation was highly skewed. Greater than 84% had a positive morale and had a positive view of the future, and 92% would again choose REI as a career. The most satisfying areas of employment were patient interactions, intellectual stimulation, interactions with colleagues, and work schedule. The least satisfying areas were work schedule and financial compensation. Training was felt to be too focused on female factor infertility and basic research with insufficient training on embryology, genetics, male factor infertility, and clinical research. In the next 5 years, 57% suggested that the need for specialists would stay the same, while 20% predicted a decrease. A total of 58% felt we are training the correct number of fellows (37% felt we are training a surplus). Compared with academia, those in private practice reported higher compensation, less major surgery, more IVF, less endocrinology, and less research. Men worked more hours, conducted more surgery and IVF cycles, and had higher compensation than women. Morale was similar across age, gender, practice type, and geography. Conclusion(s) Our subspecialty has an extremely high morale. We are a middle-aged subspecialty with disparate compensation and a focused practice. Some respondents sense a need for a change in our training, and most anticipate only mild growth in our field.

Objectives Safe and effective contraceptive options for obese women are becoming more important due to the obesity epidemic within the United States. This study evaluated the impact of body mass index (BMI) on efficacy, safety and bleeding patterns during use of an ultra-low-dose combined oral contraceptive (COC). Study Design Data are from a Phase 3 clinical efficacy and safety study of an ultra-low-dose COC containing 1.0-mg norethindrone acetate and 10-mcg ethinyl estradiol. Pearl Indices, adverse events and bleeding profile were calculated for BMI ranges of 30 kg/m 2 . Results Of the 1581 participants included in the analysis, 28.3% were overweight, and 18.0% were obese. For women aged 18–45 years, the Pearl Indices were 2.49, 2.32 and 1.89 for women with a BMI 30 kg/m 2 , respectively. The ultra-low dose of ethinyl estradiol did not impact scheduled bleeding or intensity of bleeding, but we observed a slight decline in amenorrhea and slight increase in unscheduled bleeding in obese women compared with other BMI categories. Conclusions Our analysis of an ultra-low-dose COC did not find clinically important differences in contraceptive failure rates, adverse events or bleeding profile with increasing BMI. Implications Our analysis of an ultra-low ethinyl estradiol dose COC did not find clinically important differences in contraceptive failure rates, adverse events or bleeding profile with increasing BMI. An ultra-low-dose COC provides another safe and effective contraceptive option for obese women.

A 1/1.8-inch 6.4 MPixel 60 frames/s CMOS image sensor fabricated in a 0.18-mum single-poly triple-metal (1P3M) process is described. A zigzag-shaped 1.75 T/pixel architecture and a 10-bit counter-type column parallel ADC enables 2.5times2.5 mum2 pixels. The resulting pixel has 38% fill factor and 12ke-/lux.s sensibility. In addition, full frame and 2times2 binning modes are interchangeable without an extra invalid frame

It is known that women who smoke cigarettes and use oral contraceptives are more likely to have breakthrough bleeding than women who do not smoke. In this article, we review possible mechanisms by which cigarette smoke and its constituents may contribute to irregular bleeding, highlight differences in the activities of nicotine and cigarette smoke, and postulate further studies in the area.

KAATSU training is a novel training, which is performed under conditions of restricted blood flow. It can induce a variety of beneficial effects such as increased muscle strength, and it has been adopted by a number of facilities in recent times. The purpose of the present study is to know the present state of KAATSU training in Japan and examine the incidence of adverse events in the field. The data were obtained from KAATSU leaders or instructors in a total of 105 out of 195 facilities where KAATSU training has been adopted. Based on survey results, 12,642 persons have received KAATSU training (male 45.4%, female 54.6%). KAATSU training has been applied to all generations of people including the young ( 80 years old). The most popular purpose of KAATSU training is to strengthen muscle in athletes and to promote the health of subjects, including the elderly. It has been also applied to various kinds of physical conditions, cerebrovascular diseases, orthopedic diseases, obesity, cardiac diseases, neuromuscular diseases, diabetes, hypertension and respiratory diseases. In KAATSU training, various types of exercise modalities (physical exercise, walking, cycling, and weight training) are used. Most facilities have used 5-30 min KAATSU training each time, and performed it 1-3 times a week. Approximately 80% of the facilities are satisfied with the results of KAATSU training with only small numbers of complications reported. The incidence of side effects was as follows; venous thrombus (0.055%), pulmonary embolism (0.008%) and rhabdomyolysis (0.008%). These results indicate that the KAATSU training is a safe and promising method for training athletes and healthy persons, and can also be applied to persons with various physical conditions.

Colorectal cancer is the third most prevalent cause of cancer-related mortality in Japan, and the incidence of submucosal colorectal cancer is increasing. To reduce colorectal cancer mortality, however, not only is early detection of colorectal cancer required but also adequate depth diagnosis is needed. Current endoscopes provide high-resolution imaging that produces clear, vivid features of detected lesions. In particular, when combined with image enhancement, high-magnification endoscopy can provide a detailed analysis of the morphological architecture of pit pattern and the capillary pattern in a simple and quick manner. Characteristic colonoscopic findings obtained by a combination of conventional colonoscopy, magnifying chromoendoscopy, and narrow-band imaging (NBI) with magnification are useful for determining the depth of invasion of early stage colorectal cancers, an essential factor in selecting a treatment modality. This article is part of an expert video encyclopedia.

Mast cell-derived prostaglandin D(2) (PGD(2)) is one of the essential modulators of eosinophilic airway inflammation in asthma and allergic rhinitis. Two G protein-coupled receptors for PGD(2), prostaglandin D(2) receptor (DP) and chemoattractant receptor-homologous molecule expressed on Th(2) cells (CRTH2), are both expressed on the surface of eosinophils, and CRTH2 has been demonstrated to mediate PGD(2)-induced eosinophil mobilization in vitro. However, it has not yet been determined whether PGD(2) and its receptors mediate in vivo eosinophil trafficking into the airways or other organs. We demonstrated that intratracheal administration of PGD(2) in rats pretreated with systemic interleukin-5 (IL-5) injection induced marked airway eosinophilia, determined by the differential counts of cells in bronchoalveolar lavage (BAL) fluid and lung histology, within 2 h. Systemic IL-5 alone significantly increased the number of eosinophils in the peripheral blood but showed no effect on airway eosinophilia. Three CRTH2-specific agonists (13,14-dihydro-15-keto-PGD(2), 11-deoxy-11-methylene-15-keto-PGD(2), and indomethacin) demonstrated equivalent induction of BAL eosinophilia to that of PGD(2), but a DP agonist (BW 245C [5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl)-hydantoin]) or a thromboxane A(2) receptor (TP) agonist ([1S-1alpha,2beta(5Z), 3alpha(1E,3R*),4alpha)]-7-[3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo-[2.2.1]heptan-2-yl]-5-heptenoic acid) showed no effect. PGD(2) or CRTH2 agonist-induced BAL eosinophilia was almost completely inhibited by pretreatment with a CRTH2/TP antagonist, ramatroban [BAY-u3405; (+)-(3R)-3-(4-fluorobenzenesulfonamido)-1,2,3,4-tetra-hydrocarbazole-9-propionic acid], whereas a TP-specific antagonist, SQ29,548 (5-heptenoic, 7-[3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]-hept-2-yl]-[1S-[1alpha,2alpha(Z),3alpha,4alpha]]), or a DP-specific antagonist, BW A868C [3-benzyl-5-(6-carboxyhexyl)-1-(2-cyclohexy-2-hydroxyethylamino)-hydantoin], did not inhibit the effects of PGD(2). These results suggest that CRTH2 plays a significant role in the eosinophil trafficking from the bloodstream into the airways in PGD(2)-related airway inflammation.

Our understanding of asthma severity was advanced by the identification of biomarkers which account for differences in lung function impairment. We tried to examine the effects of corticosteroid treatment on known correlates of asthma severity including peripheral eosinophil counts, total IgE, IL-5, and eotaxin Levels in plasma. We compared these biomarkers among groups of stable asthmatics categorized by the dose of corticosteroid (N: steroid-free, n = 25; L: low-dose inhaled, n = 27; MH: medium or high-dose inhaled, n= 19; O: inhaled plus oral, n= 8). Next we compared these markers and peak expiratory flow rate (PEFR) in unstable asthmatics before and after treatment with steroids (n = 22). Eotaxin levels in the O group were higher than those in the N and MH groups (P0.05). Logistic regression analysis demonstrated that plasma eotaxin level was correlated with the severity of asthma defined by treatment intensity (P = 0.01) and % FEV1 (P = 0.04) while the other markers were not. Eotaxin levels did not change after steroid treatment in unstable patients, whereas eosinophil counts decreased in parallel with PEFR. Among biomarkers of asthma severity studied, plasma eotaxin level was not significantly affected by corticosteroid treatment, and was associated with the severity even in the presence of steroid therapy.