Prognostic value of transvalvular flow rate in patients with low-gradient severe aortic stenosis: A dobutamine stress echocardiography study.

BACKGROUNDS: There are limited data on the clinical relevance of transvalvular flow rate (Qmean ) at rest (Qrest) and at peak stress (Qstress ) during dobutamine stress echocardiography (DSE) in patients with low-gradient severe aortic stenosis (LG-SAS). METHODS: We retrospectively analyzed the clinical data of patients with LG-SAS who underwent DSE. LG-SAS was defined as an aortic valve (AV) area index of < .6 cm2 /m2 and a mean AV pressure gradient (AVPG) of < 40 mm Hg. The primary endpoint included all-cause death and heart failure hospitalization. RESULTS: Of 100 patients (mean age 79.5 ± 7.3 years; men, 45.0%; resting left ventricular ejection fraction [LVEF] 52.1% ± 15.9%; resting stroke volume index 35.8 ± 7.7 mL/m2 ; Qrest 171.8 ± 34.9 mL/s), the primary endpoint occurred in 51 patients during a median follow-up of 2.84 (interquartile range 1.01-5.21) years. When the study patients were divided into three subgroups based on Qrest and Qstress , the multivariate analysis showed that Qrest < 200 mL/s and Qstress ≥200 mL/s (hazard ratio 3.844; 95% confidence interval 1.143-12.930; p = .030), as well as Qrest and Qstress < 200 mL/s (hazard ratio 9.444; 95% confidence interval 2.420-36.850; p = .001), were significantly associated with unfavorable outcomes with Qrest and Qstress ≥200 mL/s as a reference after adjusting for resting LVEF, resting mean AVPG, chronic kidney disease, New York Heart Association functional class III/IV, and AV replacement. CONCLUSIONS: Flow conditions based on the combination of Qrest and Qstress are helpful for risk stratification in LG-SAS patients.

Effect of microgravity on mammalian embryo development evaluated at the International Space Station.

Mammalian embryos differentiate into the inner cell mass (ICM) and trophectoderm at the 8-16 cell stage. The ICM forms a single cluster that develops into a single fetus. However, the factors that determine differentiation and single cluster formation are unknown. Here we investigated whether embryos could develop normally without gravity. As the embryos cannot be handled by an untrained astronaut, a new device was developed for this purpose. Using this device, two-cell frozen mouse embryos launched to the International Space Station were thawed and cultured by the astronauts under microgravity for 4 days. The embryos cultured under microgravity conditions developed into blastocysts with normal cell numbers, ICM, trophectoderm, and gene expression profiles similar to those cultured under artificial-1 g control on the International Space Station and ground-1 g control, which clearly demonstrated that gravity had no significant effect on the blastocyst formation and initial differentiation of mammalian embryos.

Post-transplant donor-specific anti-HLA antibodies with a higher mean fluorescence intensity are associated with graft fibrosis in pediatric living donor liver transplantation.

The roles of post-transplant anti-HLA donor specific antibody (DSA) in pediatric liver transplantation (LT), including therapeutic strategies, remain controversial. This study aimed to identify the risks of post-transplant DSA for graft fibrosis progression in pediatric living donor LT (LDLT). We retrospectively evaluated 88 LDLT pediatric cases between December 1995 and November 2019. DSAs were assessed with single antigen bead test. Graft fibrosis was histopathologically scored with METAVIR and the centrilobular sinusoidal fibrosis system. Post-transplant DSAs were detected in 37 (52.9%) cases at 10.8 (1.3-26.9) years post-LDLT. The histopathological examination of 32 pediatric cases with post-transplant DSA revealed that 7 (21.9%) with a high DSA-MFI (≥9,378) showed graft fibrosis progression (≥F2). No graft fibrosis was observed in the subjects with a low DSA-MFI. The risk factors for developing graft fibrosis in pediatric cases with post-transplant DSA were an older graft age (>46.5 years old), lower platelet count (<10.7 × 104/ml) and higher Fib4 index (>0.7807, recipient age; >1.8952, donor age). Limited efficacy of additional immunosuppressants was observed in DSA positive pediatric cases. In conclusion, pediatric cases with a high DSA-MFI and risk factors should undergo a histological examination. The appropriate treatment for post-transplant DSA in pediatric LT needs to be determined.

Pyrroloquinoline quinone disodium salt improves brain function in both younger and older adults.

Brain function is important for a good quality of life. Pyrroloquinoline quinone disodium salt (PQQ) has been proven to improve brain function and cognition in older adults (above 45 years). In this double-blind, placebo-controlled study, we investigated the effects of PQQ on cognitive function in adults aged between 20 and 65 years. PQQ (20 mg per day) was administered for 12 weeks to the participants. After 12 weeks, the participants showed improvements in composite memory and verbal memory. A further age-stratified analysis was performed. In younger adults (aged 20-40 years), PQQ improved cognitive function (cognitive flexibility, processing speed, and execution speed) after 8 weeks. Only older adults (aged 41-65 years) showed improvements in complex and verbal memory after 12 weeks. In the logistic regression analysis that included the results of all cognitive tests, the changes due to PQQ intake were observed at 8 and 12 weeks in the young and old groups, respectively.

Comprehensive analyses of plant hormones in etiolated pea and maize seedlings grown under microgravity conditions in space: Relevance to the International Space Station experiment "Auxin Transport".

Functional relationships between endogenous levels of plant hormones in the growth and development of shoots in etiolated Alaska pea and etiolated Golden Cross Bantam maize seedlings under different gravities were investigated in the "Auxin Transport" experiment aboard the International Space Station (ISS). Comprehensive analyses of 31 species of plant hormones of pea and maize seedlings grown under microgravity (µg) in space and 1 g conditions were conducted. Principal component analysis (PCA) and a multiple regression analysis with the dataset from the plant hormone analysis of the etiolated pea seedlings grown under µg and 1 g conditions in the presence and absence of 2,3,5-triiodobenzoic acid (TIBA) revealed endogenous levels of auxin correlated positively with bending and length of epicotyls. Endogenous cytokinins correlated negatively with them. These results suggest an interaction of auxin and cytokinins in automorphogenesis and growth inhibition of etiolated Alaska pea epicotyls grown under µg conditions in space. Less polar auxin transport with reduced endogenous levels of auxin increased endogenous levels of cytokinins, resulting in changing the growth direction of epicotyls and inhibiting growth. On the other hand, almost no close relationship between endogenous plant hormone levels and growth and development in etiolated maize seedlings grown was observed under µg conditions in space, as per Schulze et al. (1992). However, endogenous levels of IAA in the seedlings grown under µg conditions in space were significantly higher than those grown on Earth, similar to the cases of polar auxin transport already reported.

Intracardiac Echocardiography Guidance for Percutaneous Transcatheter Closure of Atrial Septal Defects　- Nationwide Registry Data Analysis.

BACKGROUND: Transesophageal echocardiography (TEE) has been used for percutaneous atrial septal defect (ASD) closure, with intracardiac echocardiography (ICE) guidance recently being introduced.Methods and Results: The Japanese Structural Heart Disease Registry was established by the Japanese Association of Cardiovascular Intervention and Therapeutics. This study analyzed data from the Registry for 2,859 consecutive cases undergoing percutaneous ASD closure between January 2015 and December 2020. ASD closure was performed under ICE guidance (n=519; 18.2%), TEE guidance (n=1,428; 49.9%), or TEE plus ICE guidance ("Both"; n=900 cases; 31.5%). The success rates were similar in the TEE, ICE, and both groups (99.0%, 99.2%, vs. 98.0%, respectively; P=0.054), as were complication rates (1.2%, 0.5%, vs. 2.1%, respectively; P=0.24). In the TEE and Both groups, 92.4% and 79.6% of patients required general anesthesia, compared with only 2.9% of patients in the ICE group (P<0.001). Fluoroscopic time was longer in the ICE and Both groups than in the TEE group (median [interquartile range] 19 [14-28] and 21 [13-30] vs. 12 [8-19] min, respectively; P<0.001). Rim deficiency and larger defect diameter were inversely related, whereas hospital volume was positively related to ICE guidance. CONCLUSIONS: Percutaneous transcatheter ASD closure was as feasible under ICE as under TEE guidance. ICE guidance is used for less challenging cases in high-volume centers in Japan.

Development of a new device for manipulating frozen mouse 2-cell embryos on the International Space Station.

Whether mammalian embryos develop normally under microgravity remains to be determined. However, embryos are too small to be handled by inexperienced astronauts who orbit Earth on the International Space Station (ISS). Here we describe the development of a new device that allows astronauts to thaw and culture frozen mouse 2-cell embryos on the ISS without directly contacting the embryos. First, we developed several new devices using a hollow fiber tube that allows thawing embryo without practice and observations of embryonic development. The recovery rate of embryos was over 90%, and its developmental rate to the blastocyst were over 80%. However, the general vitrification method requires liquid nitrogen, which is not available on the ISS. Therefore, we developed another new device, Embryo Thawing and Culturing unit (ETC) employing a high osmolarity vitrification method, which preserves frozen embryos at -80°C for several months. Embryos flushed out of the ETC during thawing and washing were protected using a mesh sheet. Although the recovery rate of embryos after thawing were not high (24%-78%) and embryonic development in ETC could not be observed, thawed embryos formed blastocysts after 4 days of culture (29%-100%) without direct contact. Thus, this ETC could be used for untrained astronauts to thaw and culture frozen embryos on the ISS. In addition, this ETC will be an important advance in fields such as clinical infertility and animal biotechnology when recovery rate of embryos were improved nearly 100%.

Three-dimensionally visualized rhizoid system of moss, Physcomitrium patens, by refraction-contrast X-ray micro-computed tomography.

Land plants have two types of shoot-supporting systems, root system and rhizoid system, in vascular plants and bryophytes. However, since the evolutionary origin of the systems is different, how much they exploit common systems or distinct systems to architect their structures is largely unknown. To understand the regulatory mechanism of how bryophytes architect the rhizoid system responding to environmental factors, we have developed the methodology to visualize and quantitatively analyze the rhizoid system of the moss, Physcomitrium patens, in 3D. The rhizoids having a diameter of 21.3 µm on the average were visualized by refraction-contrast X-ray micro-computed tomography using coherent X-ray optics available at synchrotron radiation facility SPring-8. Three types of shape (ring-shape, line and black circle) observed in tomographic slices of specimens embedded in paraffin were confirmed to be the rhizoids by optical and electron microscopy. Comprehensive automatic segmentation of the rhizoids, which appeared in three different form types in tomograms, was tested by a method using a Canny edge detector or machine learning. The accuracy of output images was evaluated by comparing with the manually segmented ground truth images using measures such as F1 score and Intersection over Union, revealing that the automatic segmentation using machine learning was more effective than that using the Canny edge detector. Thus, machine learning-based skeletonized 3D model revealed quite dense distribution of rhizoids. We successfully visualized the moss rhizoid system in 3D for the first time.

Endothelialization of Amplatzer PFO Occluder Device 12 Months After Implantation: First-in-Human Angioscopic Assessment.

The current guidelines recommend at least 6 months of antithrombotic and antibiotic prophylaxis following atrial septal occluding device placement using the phrase "until endothelialization." However, neo-endothelialization has not been assessed in vivo in humans. Considering the atrial septal defect occluding device, several autopsy cases and device extraction cases only demonstrated insufficient endothelialization beyond 6 months after implantation caused endocarditis and thrombosis. Accordingly, we have successfully developed a method for determining device endothelialization using angioscopy. This method helped us evaluate the endothelialization of a 25 mm Amplatzer PFO occluder device (Abbott) in a 40-year-old man 12 months after implantation. This is the first report evaluating the PFO occluder device in vivo.

Five-Year Psychosocial Impact of Living in Postdisaster Prefabricated Temporary Housing.

OBJECTIVE: This study aims to evaluate the long-term impact of living in postdisaster prefabricated temporary housing on social interaction activities and mental health status. METHODS: A total of 917 adult residents in a coastal town, whose residences were destroyed by the tsunami caused by the Great East Japan Earthquake (GEJE), were enrolled for the assessment held 5 y after the disaster. They answered questions about their experience and consequence of living in prefabricated temporary housing after the disaster. Their present scores on 5 types of self-reported measures regarding the psychosocial or psychiatric status and their present and recalled social interaction activities were cross-sectionally collected. RESULTS: A total of 587 (64.0%) participants had a history of living in prefabricated temporary housing, while the other 330 (36.0%) had not. The prevalence of social interaction activities significantly decreased after the GEJE. However, the experience of living in prefabricated temporary housing did not adversely affect the subsequent social interaction activities or mental conditions of the participants 5 y after the disaster. CONCLUSIONS: Living in postdisaster prefabricated temporary housing may not negatively impact subsequent psychosocial conditions or social interaction activities 5 y later.

Impact of type of reconstructed residence on social participation and mental health of population displaced by disasters.

After disasters, people are often forced to reconstruct or move to new residences. This study aimed to reveal the association between the types of reconstructed residences and psychosocial or psychiatric conditions among the population. A total of 1071 adult residents in a coastal town, whose houses were destroyed by the tsunami caused by the Great East Japan Earthquake, enrolled in the study five years after the disaster. The type of reconstructed post-disaster residences (reconstructed on the same site/disaster-recovery public condominium/mass-translocation to higher ground/privately moving to remote areas) and the current psychosocial indicators were investigated. The results revealed that individuals living in public condominiums showed significantly worse scores on the Lubben Social Network Scale-6 (p < 0.0001) and the Center for Epidemiologic Studies Depression Scale (p < 0.0001), and slightly worse scores on the Kessler Psychological Distress Scale (p = 0.035) and the Impact of Event Scale-Revised (p = 0.028). Lower psychosocial indicator scores in the public condominium group were more remarkable in younger adults aged < 65 years. Insomnia evaluated using the Athens Insomnia Scale was not different among the four residential types. In summary, residents moving into disaster-recovery public condominiums are likely to have less social interaction, be more depressed, and may need additional interventions.

Angioscopic Evaluation of Atrial Septal Defect Closure Device Neo-Endothelialization.

Background Current guidelines recommend at least 6 months of antithrombotic therapy and antibiotic prophylaxis after septal-occluding device deployment in transcatheter closure of atrial septal defect. It has been estimated that it takes ≈6 months for complete neo-endothelialization; however, neo-endothelialization has not previously been assessed in vivo in humans. Methods and Results The neointimal coverage of septal occluder devices was evaluated 6 months after implantation in 15 patients by angioscopy from the right atrium. Each occluder surface was divided into 9 areas; the levels of endothelialization in each area were semiquantitatively assessed by 4-point grades. Device neo-endothelialization was sufficient in two thirds of patients, but insufficient in one third. In the comparison between patients with sufficiently endothelialized devices of average grade score ≥2 (good endothelialization group, n=10) and those with poorly endothelialized devices of average grade score <2 (poor endothelialization group, n=5), those in the poor endothelialization group had larger devices deployed (27.0 mm [25.0-31.5 mm] versus 17.0 mm [15.6-22.5 mm], respectively) and progressive right heart dilatation. The endothelialization was poorer around the central areas. Moreover, the prevalence of thrombus formation on the devices was higher in the poorly endothelialized areas than in the sufficiently endothelialized areas (Grade 0, 94.1%; Grade 1, 63.2%; Grade 2, 0%; Grade 3, 1.6%). Conclusions Neo-endothelialization on the closure devices varied 6 months after implantation. Notably, poor endothelialization and thrombus attachment were observed around the central areas and on the larger devices.

Resting echocardiographic predictors for true-severe aortic stenosis in patients with low-gradient severe aortic stenosis: A dobutamine stress echocardiography study.

OBJECTIVE: Dobutamine stress echocardiography (DSE) is not always feasible in patients with low-gradient severe aortic stenosis (LG-SAS), and there are limited data available on the resting echocardiographic predictors for true-severe aortic stenosis (TSAS). This study investigated resting echocardiographic predictors for TSAS. METHODS: Clinical data of 106 LG-SAS patients who underwent DSE were retrospectively analyzed. LG-SAS was defined as an aortic valve area index (AVAi) < .6 cm2 /m2 , and a mean AV pressure gradient < 40 mm Hg. The velocity ratio (VR) was calculated as the peak left ventricular outflow tract velocity/peak AV velocity. TSAS was defined as a projected AVAi < .6 cm2 /m2 . RESULTS: The mean age was 79.3 ± 7.3 years, and 45 (42.5%) were men. The resting AV data were as follows: AVAi, .50 ± .07 cm2 /m2 ; mean AV pressure gradient, 23.0 ± 7.4 mm Hg; and VR, .25 ± .05. The projected AVAi was .58 ± .09 cm2 /m2 , and TSAS was documented in 65 (61.3%) patients. In multivariate analysis, the independent predictors of TSAS were AVAi (p = 0.012) and VR (p = 0.004) with respective best cut-off values of .52 cm2 /m2 and .25 on receiver-operating characteristic curve analysis. According to incremental numbers of the predictors, correct classification percentages of TSAS significantly increased with the Cochran-Armitage trend test (16.2% in no predictors, 65.2% in one predictor, and 95.7 % in two predictors; p < 0.001). CONCLUSIONS: Resting AVAi and VR were independent predictors of TSAS in LG-SAS patients. The true severity might be predictable using the combination of resting parameters.

Five-year Psychosocial Impact of Living in Post-Disaster Prefabricated Temporary Housing.

OBJECTIVE: This study aims to evaluate the long-term impact of living in post-disaster prefabricated temporary housing on social interaction activities and mental health status. METHODS: A total of 917 adult residents in a coastal town, whose residences were destroyed by the tsunami caused by the Great East Japan Earthquake (GEJE), were enrolled for the assessment held five years after the disaster. They answered questions about their experience and consequence of living in prefabricated temporary housing after the disaster. Their present scores on five types of self-reported measures regarding the psychosocial or psychiatric status and their present and recalled social interaction activities were cross-sectionally collected. RESULTS: A total of 587 (64.0%) participants had a history of living in prefabricated temporary housing, while the other 330 (36.0%) had not. The prevalence of social interaction activities significantly decreased after the GEJE. However, the experience of living in prefabricated temporary housing did not adversely affect the subsequent social interaction activities or mental conditions of the participants five years after the disaster. CONCLUSIONS: Living in post-disaster prefabricated temporary housing may not negatively impact subsequent psychosocial conditions or social interaction activities five years later.

Evaluating the long-term effect of space radiation on the reproductive normality of mammalian sperm preserved on the International Space Station.

Space radiation may cause DNA damage to cells and concern for the inheritance of mutations in offspring after deep space exploration. However, there is no way to study the long-term effects of space radiation using biological materials. Here, we developed a method to evaluate the biological effect of space radiation and examined the reproductive potential of mouse freeze-dried spermatozoa stored on the International Space Station (ISS) for the longest period in biological research. The space radiation did not affect sperm DNA or fertility after preservation on ISS, and many genetically normal offspring were obtained without reducing the success rate compared to the ground-preserved control. The results of ground x-ray experiments showed that sperm can be stored for more than 200 years in space. These results suggest that the effect of deep space radiation on mammalian reproduction can be evaluated using spermatozoa, even without being monitored by astronauts in Gateway.

Influence of coronary artery disease and percutaneous coronary intervention on mid-term outcomes in patients with aortic valve stenosis treated with transcatheter aortic valve implantation.

BACKGROUND: A high frequency of coronary artery disease (CAD) is reported in patients with severe aortic valve stenosis (AS) who undergo transcatheter aortic valve implantation (TAVI). However, the optimal management of CAD in these patients remains unknown. HYPOTHESIS: We hypothesis that AS patients with TAVI complicated by CAD have poor prognosis. His study evaluates the prognoses of patients with CAD and severe AS after TAVI. METHODS: We divided 186 patients with severe AS undergoing TAVI into three groups: those with CAD involving the left main coronary (LM) or proximal left anterior descending artery (LAD) lesion (the CAD[LADp] group), those with CAD not involving the LM or a LAD proximal lesion (the CAD[non-LADp] group), and those without CAD (Non-CAD group). Clinical outcomes were compared among the three groups. RESULTS: The CAD[LADp] group showed a higher incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) and all-cause mortality than the other two groups (log-rank p = .001 and p = .008, respectively). Even after adjustment for STS score and percutaneous coronary intervention (PCI) before TAVI, CAD[LADp] remained associated with MACCE and all-cause mortality. However, PCI for an LM or LAD proximal lesion pre-TAVI did not reduce the risk of these outcomes. CONCLUSIONS: CAD with an LM or LAD proximal lesion is a strong independent predictor of mid-term MACCEs and all-cause mortality in patients with severe AS treated with TAVI. PCI before TAVI did not influence the outcomes.

Divergence in red light responses associated with thermal reversion of phytochrome B between high- and low-latitude species.

Phytochromes play a central role in mediating adaptive responses to light and temperature throughout plant life cycles. Despite evidence for adaptive importance of natural variation in phytochromes, little information is known about molecular mechanisms that modulate physiological responses of phytochromes in nature. We show evolutionary divergence in physiological responses relevant to thermal stability of a physiologically active form of phytochrome (Pfr) between two sister species of Brassicaceae growing at different latitudes. The higher latitude species (Cardamine bellidifolia; Cb) responded more strongly to light-limited conditions compared with its lower latitude sister (C. nipponica; Cn). Moreover, CbPHYB conferred stronger responses to both light-limited and warm conditions in the phyB-deficient mutant of Arabidopsis thaliana than CnPHYB: that is Pfr CbphyB was more stable in nuclei than CnphyB. Our findings suggest that fine tuning Pfr stability is a fundamental mechanism for plants to optimise phytochrome-related traits in their evolution and adapt to spatially varying environments, and open a new avenue to understand molecular mechanisms that fine tune phytochrome responses in nature.

Impact of Prosthesis-Patient Mismatch on Hemodynamics During Exercise in Patients With Aortic Stenosis After Transcatheter Aortic Valve Implantation With a Balloon-Expandable Valve.

BACKGROUND: There is no evidence of hemodynamic performance during exercise in patients with aortic stenosis (AS) after transcatheter aortic valve implantation (TAVI). This study aimed to investigate the changes in kinematic hemodynamics during exercise and determine the impact of prosthesis-patient mismatch (PPM) on the hemodynamics of transcatheter heart valves using exercise stress echocardiography (ESE) in AS patients after TAVI. METHODS AND RESULTS: This study enrolled 77 consecutive patients (mean age 82 ± 5 years, 50.6% male) who underwent ESE 3-6 months after TAVI with a balloon-expandable valve. The effective orifice area index at rest was significantly correlated with the mean pressure gradient (PG) during exercise (p <0.001). The patients were divided into two groups according to the presence of PPM (PPM and non-PPM groups). During exercise, the patients with PPM had a higher left ventricular ejection fraction (74.6 ± 6.1% vs. 69.7 ± 9.6%, p = 0.048), a lower stroke volume index (47.2 ± 14.0 ml/m2 vs. 55.6 ± 14.5 ml/m2, p = 0.037), a significantly higher mean transvalvular PG (21.9 ± 9.1 mmHg vs. 12.2 ± 4.9 mmHg, p = 0.01) and an increased mean PG from rest to exercise (5.7 ± 3.5 mmHg vs. 2.3 ± 2.8 mmHg, p <0.001) compared with patients without PPM. Patients with PPM had a higher pulmonary artery systolic pressure (SPAP) during exercise (57.3 ± 13.8 mmHg vs. 49.7 ± 10.9 mmHg, p = 0.021) and a higher incidence of exercise-induced pulmonary hypertension (43.8 vs. 15.0%, p = 0.037) than patients without PPM. PPM was strongly associated with exercise-induced pulmonary hypertension (hazard ratio: 3.570, p = 0.013). CONCLUSIONS: AS patients with PPM after TAVI showed a disproportionate increase in the transvalvular PG and SPAP during exercise, and PPM was associated with exercise-induced pulmonary hypertension.

Prognostic impact of transcatheter mitral valve repair in patients with exercise-induced secondary mitral regurgitation.

AIMS: Although exercise-induced secondary mitral regurgitation (MR) is known to have a poor prognosis, the therapeutic strategy towards this condition remains to be investigated. In the present study, we aimed to investigate the prognostic impact of transcatheter mitral valve repair (TMVr) using the MitraClip in patients with exercise-induced secondary MR. METHODS AND RESULTS: Of the 200 consecutive patients with secondary MR who underwent exercise stress echocardiography, 46 (23%) that presented with exercise-induced secondary MR [i.e. increase in effective regurgitant orifice area (EROA) of ≥ 0.13 cm2] were enrolled in the present investigation. The composite endpoints of all-cause mortality and hospitalization for heart failure were evaluated. Of the 46 patients included in the current cohort, 19 (41%) underwent TMVr and 27 (59%) were medically managed (control group). Although the TMVr group tended to present with a greater EROA at rest (0.26 ± 0.10 vs. 0.20 ± 0.08 cm2, P = 0.047), there were no differences in the EROA changes during exercise between the two groups (0.18 ± 0.10 vs. 0.18 ± 0.04 cm2, P = 0.940). While the TMVr group reported a higher event-free survival rate after the 13-month follow-up period (log-rank P = 0.017), the Cox proportional-hazard analysis suggested the TMVr to be associated with clinical outcomes (hazard ratio: 0.419, P = 0.044). CONCLUSION: As opposed to the medical management, TMVr treatment was associated with a lower risk of composite endpoints in patients with exercise-induced secondary MR. Exercise stress echocardiography is considered to have played an important role in decision-making for secondary MR.

Determinants of Physicians' Attitudes Toward the Management of Infectious Diseases in Terminally Ill Patients With Cancer.

OBJECTIVES: Antimicrobials are frequently prescribed to terminally ill patients with cancer; however, physicians' practice patterns regarding antimicrobial use vary widely. This study aimed to systematically identify factors that determine physicians' attitudes toward the management of infectious diseases in terminally ill patients with cancer. METHODS: A nationwide cross-sectional survey involving 600 oncologists, 600 infectious diseases physicians, 600 palliative care physicians, and 220 home care physicians was conducted between November 2017 and January 2018. The primary endpoint was physicians' attitudes toward the management of infectious diseases in terminally ill patients with cancer with a few weeks of prognosis. Physicians' beliefs regarding management of infectious diseases as well as physician-perceived "good death" were also assessed (1 = strongly disagree to 6 = strongly agree). RESULTS: There were 895 (44.3%) analyzable response, and average scores of physicians' attitudes ranged between 2.69 and 4.32. In total, 241 (27%; 95% CI = 24-30) to 691 (78%; 95% CI = 75-81) respondents showed proactive attitudes toward various infectious diseases management. In linear regression analysis, determinants of proactive attitudes included the following: physicians' belief that examination and treatment will improve quality of life and prognosis and reduce suffering (ß = 0.32, t = 9.99, P = 0.00); greater physician-perceived importance on receiving enough treatment (ß = 0.09, t = 2.88, P = 0.00) and less importance on dying a natural death (ß = -0.07, t = -2.14, P = 0.03) for a "good death"; working at a tertiary care hospital (ß = 0.16, t = 4.40, P = 0.00); and not being a home care physician (ß = -0.20, t = -5.51, P = 0.00) or palliative care physician (ß = -0.12, t = -3.64, P = 0.00). CONCLUSIONS: Physicians have divergent attitudes toward the management of infectious diseases in terminally ill patients with cancer. Reflection by physicians on their own beliefs and perceptions regarding infectious disease management and a "good death" may help provide the best end-of-life care.