Prognostic significance of baseline low-density lipoprotein cholesterol in patients undergoing coronary revascularization; a report from the CREDO-Kyoto registry.

BACKGROUND: The impact of very low baseline levels of low-density lipoprotein cholesterol (LDL-C) on patients with coronary artery disease remains unclear. METHOD: We enrolled 39,439 patients of the pooled population from the CREDO-Kyoto registries Cohorts 1, 2, and 3. The study population consisted of 33,133 patients who had undergone their first coronary revascularization. We assessed the risk for mortality and cardiovascular events according to quintiles of the baseline LDL-C levels. RESULTS: Patients in the very low LDL-C quintile (<85 mg/dL) had more comorbidities than those in the other quintiles. Lower LDL-C levels were strongly associated with anemia, thrombocytopenia, and end-stage renal disease. The cumulative 4-year incidence of all-cause death increased as LDL-C levels decreased (very low: 19.4 %, low: 14.5 %, intermediate: 11.1 %, high: 10.0 %, and very high: 9.2 %; p < 0.001), which was driven by both the early and late events. After adjusting for baseline characteristics, the adjusted risks of the very low and low LDL-C quintiles relative to the intermediate LDL-C quintile remained significant for all-cause death (very low: HR 1.29, 95 % CI 1.16-1.44, p < 0.001; low: HR 1.15, 95 % CI 1.03-1.29, p = 0.01). The excess adjusted risks of the lowest LDL-C quintile relative to the intermediate LDL-C quintile were significant for clinical outcomes such as cardiovascular death (HR 1.17, 95 % CI 1.01-1.35), non-cardiovascular death (HR 1.35, 95 % CI 1.15-1.60), sudden death (HR 1.44, 95 % CI 1.01-2.06), and heart failure admission (HR 1.11 95 % CI 1.01-1.22), while there was no excess risk for the lowest LDL-C quintile relative to the intermediate LDL-C quintile for myocardial infarction and stroke. CONCLUSIONS: Lower baseline LDL-C levels were associated with more comorbidities and a significantly higher risk of death, regardless of cardiovascular or non-cardiovascular causes, in patients who underwent coronary revascularization.

Validity and reliability of the 2-min step test in individuals with stroke and lower-limb musculoskeletal disorders.

Introduction: We investigated the reliability and validity of the 2-min step test (2MST) for assessing the exercise endurance of individuals with stroke and lower-limb musculoskeletal disorders. Participants and methods: The participants were 39 individuals with stroke and 42 with lower-limb musculoskeletal disorders (mainly hip fractures) from the convalescent rehabilitation wards of four hospitals. The concurrent validity and congruence between the 2MST and the 6-min walk test (6MWT) and construct validity by hypotheses testing, including mobility and lower limb muscle strength, were also confirmed. A subset of participants (stroke-group, n = 15; musculoskeletal-group, n = 19) underwent a retest 2MST for our evaluation of relative and absolute reliability using the intraclass correlation coefficient (ICC1,1) and Bland-Altman plot. Results: Both groups showed a moderate correlation between the 2MST and 6MWT (ρ = 0.55-0.60), but the congruence was not sufficient. The 6MWT was correlated with mobility in both groups and with muscle strength in the stroke group, whereas the 2MST did not show a significant correlation with mobility. The relative reliability was excellent in both groups (ICC1,1 > 0.9). In terms of absolute reliability, the width of the limit of agreement was 18.8% for the stroke group and 15.4% for the musculoskeletal group, relative to their respective sample means of 2MST. A fixed bias was identified in the stroke group, in which step counts increased by 6.5 steps upon retesting. Discussion: Our analyses revealed that the 2MST is a valid and reliable tool for assessing the exercise endurance of individuals with stroke or lower-limb musculoskeletal disorders. However, it is necessary to validate the absolute reliability observed herein by using a larger sample size. In addition, when assessing the exercise endurance of individuals with stroke, it may be necessary to consider the potential bias of an increased step count during retesting.

Shared decision-making in physiotherapy: a cross-sectional study of patient involvement factors and issues in Japan.

BACKGROUND: Evidence-based medicine education has not focused on how clinicians involve patients in decision-making. Although shared decision-making (SDM) has been investigated to address this issue, there are insufficient data on SDM in physiotherapy. This study aimed to clarify the issues concerning patient involvement in Japan, and to examine whether SDM is related to perceptions of patient involvement in decision-making. METHODS: The study participants were recruited from among acute and sub-acute inpatients and community residents receiving physiotherapy outpatient care, day care, and/or home rehabilitation. The Control Preference Scale (CPS) was used to measure the patients' involvement in decision-making. The nine-item Shared Decision-Making Questionnaire (SDM-Q-9) was used to measure SDM. In analysis I, we calculated the weighted kappa coefficient to examine the congruence in the CPS between the patients' actual and preferred roles. In analysis II, we conducted a logistic regression analysis using two models to examine the factors of patient involvement. RESULTS: Analysis I included 277 patients. The patients' actual roles were as follows: most active (4.0%), active (10.8%), collaborative (24.6%), passive (35.0%), and most passive (25.6%). Their preferred roles were: most active (3.3%), active (18.4%), collaborative (39.4%), passive (24.5%), and most passive (14.4%). The congruence between actual and preferred roles by the kappa coefficient was 0.38. Analysis II included 218 patients. The factors for patient involvement were the clinical environment, the patient's preferred role, and the SDM-Q-9 score. CONCLUSIONS: The patients in Japan indicated a low level of decision-making involvement in physiotherapy. The patients wanted more active involvement than that required in the actual decision-making methods. The physiotherapist's practice of SDM was revealed as one of the factors related to perceptions of patient involvement in decision-making. Our results demonstrated the importance of using SDM for patient involvement in physiotherapy.

Dedifferentiation maintains melanocyte stem cells in a dynamic niche.

For unknow reasons, the melanocyte stem cell (McSC) system fails earlier than other adult stem cell populations1, which leads to hair greying in most humans and mice2,3. Current dogma states that McSCs are reserved in an undifferentiated state in the hair follicle niche, physically segregated from differentiated progeny that migrate away following cues of regenerative stimuli4-8. Here we show that most McSCs toggle between transit-amplifying and stem cell states for both self-renewal and generation of mature progeny, a mechanism fundamentally distinct from those of other self-renewing systems. Live imaging and single-cell RNA sequencing revealed that McSCs are mobile, translocating between hair follicle stem cell and transit-amplifying compartments where they reversibly enter distinct differentiation states governed by local microenvironmental cues (for example, WNT). Long-term lineage tracing demonstrated that the McSC system is maintained by reverted McSCs rather than by reserved stem cells inherently exempt from reversible changes. During ageing, there is accumulation of stranded McSCs that do not contribute to the regeneration of melanocyte progeny. These results identify a new model whereby dedifferentiation is integral to homeostatic stem cell maintenance and suggest that modulating McSC mobility may represent a new approach for the prevention of hair greying.

CFD simulation of CVD reactors in the CH3SiCl3(MTS)/H2 system using a two-step MTS decomposition and one-step SiC growth models.

In this study, we report on a computational fluid dynamics (CFD) simulation of the chemical vapor deposition reactor of silicon carbide (SiC) in the methyltrichlorosilane (MTS, CH3SiCl3)/H2 system. The formation of SiC thin film is controlled by various process parameters, such as temperature and pressure. In this study, we propose a reaction mechanism of MTS decomposition to SiC growth on a substrate surface for CVD reactors in the CH3SiCl3(MTS)/H2 system. The reaction mechanism has two gas-phase pyrolysis reactions and one SiC film formation reaction. However, we individually build and validate MTS decomposition and SiC growth models to reduce uncertainty. An in-house version of reactingFoam, a reactive flow solver within OpenFOAM v2006, was used as the simulation tool. Our model accurately reproduced MTS decomposition for T = 1100-1350 K and [H2]/[MTS] = 2.65-14 at p = 101,325 Pa. Then, the MTS decomposition model was coupled with the SiC growth model, and the coupled model was applied to the SiC deposition data. The model could reproduce multiple datasets through validation studies.

[Two Cases of Transfusion-Free Hepatectomy Following Chemotherapy for H3 Grade of Simultaneous Liver Metastases].

We report 2 cases of transfusion-free treatment for H3 grade of simultaneous liver metastases of the colon which were treated with the chemotherapy followed by R0 liver resection. Case 1 was a 67-year-old woman bearing ascending colon cancer and a metastatic mass occupying the left lobe of the liver with 160 mm in diameter. Laparoscopic ileocecal resection and 30-day left hepatectomy were performed after the 7 courses of FOLFOX plus bevacizumab(BEV). Case 2 was a 72- year-old woman bearing transverse colon cancer with more than 10 foci of liver metastases ranging from 21 mm to 100 mm in diameter. After the transverse colon resection and 12 months of chemotherapy from FOLFOX plus BEV to FOLFIRI plus panitumumab, partial liver resection was performed for each of size-reduced foci. In both patients who declined blood transfusion, optimization of red cells and autologous transfusion with hemodilution contributed to the safe liver resection with no postoperative complications.

Low-intensity resistance training to improve knee extension strength in community-dwelling older adults: Systematic review and meta-analysis of randomized controlled studies.

AIM: The purpose of this systematic review and meta-analysis was to investigate the effects of low-intensity resistance training on knee extension strength with respect to intensity, frequency, duration and training site in community-dwelling older adults. METHODS: A literature search was conducted for articles published up to December 2018 on PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Physiotherapy Evidence Database (PEDro), OTseeker and Ichushi-Web. Randomized controlled trials involving resistance training with <60 % one repetition maximum (1RM) in community-dwelling older adults aged 60 years and older were eligible. RESULTS: In total, 7 studies involving 275 participants were included in the meta-analysis. The results showed significant improvements in knee extension strength with low-intensity resistance training [standardized mean difference (SMD) 0.62, 95 % confidence interval (CI) 0.32 to 0.91]. In subgroup analyses, significant improvements were observed in the group with intensity at 50-60 % 1RM (0.83, 0.46 to 1.19), but not in the group at 40 % or less 1RM (0.30, 95%CI: -0.08 to 0.68). Concerning frequency, there were significant improvements in knee strength for those receiving training three times (0.90, 0.52 to 1.27) and two times (0.36, 0.03 to 0.69) per week, with a significant difference between the groups (p = 0.04). CONCLUSIONS: Low-intensity resistance training should be considered as an effective intervention to improve knee extension strength in community-dwelling older adults. Older adults may show more improvement in knee extension strength if intensity of the training is set at 50-60 % 1RM and frequency of training is three times per week.

Efficacy of Therapeutic Exercise on Activities of Daily Living and Cognitive Function Among Older Residents in Long-term Care Facilities: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVES: This study aimed to systematically analyze the efficacy of therapeutic exercise on activities of daily living (ADL) and cognitive function among older residents in long-term care facilities. DATA SOURCES: PubMed, Cochrane Central of Register Trials, Physiotherapy Evidence Database, OTseeker, and Ichushi-Web were searched from inception until December 2018. STUDY SELECTION: Databases were searched to identify randomized controlled trials (RCTs) of therapeutic exercise for long-term care facility residents aged 60 years and older, focusing on ADL and cognitive function as outcomes. DATA EXTRACTION: Two independent reviewers extracted the key information from each eligible study. Two reviewers independently screened and assessed all studies for eligibility, extracting information on study participants, details of interventions, outcome characteristics, and significant outcomes. Any discrepancies were resolved by a third reviewer. DATA SYNTHESIS: A total of 11 RCTs with 1280 participants were eligible for analyses. Therapeutic exercise had a significant benefit on ADL (standard mean difference [SMD]=0. 22, 95% confidence interval [CI]: 0.02, 0.42, P=.03). Subgroup analyses indicated that interventions conducted ≥3 days per week [SMD=0.42, 95% CI 0.02, 0.82, P=.04] had a significant benefit on ADL. For cognitive function, group exercise and ≥3 days/week of intervention had a significant benefit (group exercise: mean difference [MD]=3.36, 95% CI 0.91, 5.80, P=.007; ≥3 days/week of intervention: MD=2.28, 95% CI 0.07, 4.49, P=.04). CONCLUSIONS: Therapeutic exercise conducted 3 or more days per week may be effective for improving ADL and cognitive function among older residents in long-term care facilities. This meta-analysis suggested that group exercise for cognitive functions was effective. However, the effective method of intervention delivery for ADL was unclear.

Modifiers of the Risk of Diabetes for Long-Term Outcomes After Coronary Revascularization: CREDO-Kyoto PCI/CABG Registry.

Background: Diabetes is a well-known risk factor for adverse outcomes after coronary revascularization. Objectives: This study sought to determine high-risk subgroups in whom the excess risks of diabetes relative to nondiabetes are particularly prominent and thus may benefit from more aggressive interventions. Methods: The study population consisted of 39,427 patients (diabetes: n = 15,561; nondiabetes: n = 23,866) who underwent first percutaneous coronary intervention (n = 33,144) or coronary artery bypass graft (n = 6,283) in the pooled CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Graft) registry. The primary outcome measure was major adverse cardiovascular and cerebral endpoints (MACCE), which was defined as a composite of all-cause death, myocardial infarction, and stroke. Results: With median follow-up of 5.6 years, diabetes was associated with significantly higher adjusted risks for MACCE. The excess adjusted risks of diabetes relative to nondiabetes for MACCE increased with younger age (≤64 years: adjusted HR: 1.30; 95% CI: 1.19-1.41; P < 0.001; 64-73 years: adjusted HR: 1.24; 95% CI: 1.16-1.33; P < 0.001; >73 years: adjusted HR: 1.17; 95% CI: 1.10-1.23; P < 0.001; P interaction < 0.001), mainly driven by greater excess adjusted mortality risk of diabetes relative to nondiabetes in younger tertile. No significant interaction was observed between adjusted risk of diabetes relative to nondiabetes for MACCE and other subgroups such as sex, mode of revascularization, and clinical presentation of acute myocardial infarction. Conclusions: The excess risk of diabetes relative to nondiabetes for MACCE was profound in the younger population. This observation suggests more aggressive interventions for secondary prevention in patients with diabetes might be particularly relevant in younger patients.

Percutaneous coronary intervention using new-generation drug-eluting stents versus coronary arterial bypass grafting in stable patients with multi-vessel coronary artery disease: From the CREDO-Kyoto PCI/CABG registry Cohort-3.

AIMS: There is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease. METHODS AND RESULTS: The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04-1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96-1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79-1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05-2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06-3.43, P<0.0001). CONCLUSIONS: In this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD.

Ruptured Abdominal Aortic Aneurysm Complicated with Occlusion of Bilateral Common Iliac Arteries.

We report a case of ruptured abdominal aortic aneurysm complicated with occlusion of bilateral common iliac arteries. A 68-year-old man complained of sudden onset of lower abdominal and back pain. A contrast-enhanced computed tomography showed ruptured abdominal aortic aneurysm of about 80 mm in diameter and a giant retroperitoneal hematoma, as well as occlusion of both common iliac arteries. We performed Y-grafting, concomitant with thrombectomy of both iliac arteries from inside the aneurysm. Postoperative course was uneventful without ischemic findings of the legs and the patient was discharged on the 17th postoperative day.

The Role of KEAP1-NRF2 System in Atopic Dermatitis and Psoriasis.

The Kelch-like erythroid cell-derived protein with cap'n'collar homology-associated protein 1 (KEAP1)-nuclear factor erythroid-2-related factor 2 (NRF2) system, a thiol-based sensor-effector apparatus, exerts antioxidative and anti-inflammatory effects and maintains skin homeostasis. Thus, NRF2 activation appears to be a promising treatment option for various skin diseases. However, NRF2-mediated defense responses may deteriorate skin inflammation in a context-dependent manner. Atopic dermatitis (AD) and psoriasis are two common chronic inflammatory skin diseases caused by a defective skin barrier, dysregulated immune responses, genetic predispositions, and environmental factors. This review focuses on the role of the KEAP1-NRF2 system in the pathophysiology of AD and psoriasis and the therapeutic approaches that utilize this system.

Effect of education on physical and occupational therapists' perceptions of clinical practice guidelines and shared decision making: a randomized controlled trial.

[Purpose] This study aimed to investigate the influence of the evidence practice gap on physiotherapist and occupational therapists through shared decision making using the clinical practice guidelines. [Participants and Methods] A randomized controlled trial was used. The participants included 126 therapists from three institutions. The inclusion criteria was permanent employment in these institutions. Participants' characteristics were masked from the allocator, evaluator, and analyzer. For the intervention group, a workshop on shared decision making was conducted using clinical practice guidelines. Two control groups were set. One group received a lecture on the knowledge of clinical practice guidelines, and the other group received a lecture on the knowledge of shared decision making. The primary outcomes were "education, attitudes and beliefs, and interest and perceived role in evidence-based practice" scale. [Results] The primary outcomes showed a significant difference between the clinical practice guidelines with shared decision making group and the clinical practice guidelines group (mean ± standard deviation, pre/post; clinical practice guidelines with shared decision making group, 2.4 ± 0.9/4.4 ± 1.7; clinical practice guidelines group, 3.0 ± 1.5/3.5 ± 2.0; shared decision making group, 2.6 ± 1.2/ 3.3 ± 1.8). [Conclusion] Shared decision making education using the clinical practice guidelines improves evidence-based practice of self-efficacy in physiotherapists and occupational therapists.

Relationship between exercise motivation and social support in a support facility for persons with disabilities in Japan.

PURPOSE: Exercise motivation (EM) is related to individual capabilities and social support. However, in support facilities for people with disabilities, it is susceptible to a lack of social support. In this study, we classified EM into Autonomous Motivation (AM) and controlled motivation (CM) and then examined the influence of social support. METHOD: Thirty-three residents from a support facility for people with disabilities in Japan participated in this study. We conducted a hierarchical multiple regression analysis in which age, gender and time since admission were entered in Step 1, mobility and self-efficacy as individual capabilities in Step 2, and family support, facility support and peer support as social support in Step 3. RESULT: A significant increase in variance from Step 2 to Step 3 was found for both AM (ΔR2 = 0.504, ΔF = 12.18, p < .001) and CM (ΔR2 = 0.269, ΔF = 3.491, p = .031). The results also showed that AM was higher among those with high family and facility support, and CM was higher among those with low family and high peer support. CONCLUSIONS: Social support was a more significant predictor of EM among participants than individual capabilities.KEY MESSAGESAmong residents of support facilities for people with disabilities, assessing not only individual capabilities but also social support status can lead to better understandings of exercise motivation (EM).To enhance facility residents' autonomous motivation (AM), it is necessary to intervene after evaluating family and facility support.When family support is not readily available among facility residents, efforts should be made to encourage residents to interact with each other to increase peer support.

Loricrin and NRF2 Coordinate Cornification.

Cornification involves cytoskeletal cross-linkages in corneocytes (the brick) and the secretion of lipids/adhesion structures to the interstitial space (the mortar). Because the assembly of lipid envelopes precedes corneocyte maturation, loricrin is supposed to be dispensable for the protection against desiccation. Although the phenotypes of Lor knockout (LKO) mice are obscure, the antioxidative response on the KEAP1/NRF2 signaling pathway compensates for the structural defect in utero. In this study, we asked how the compensatory response is evoked after the defects are repaired. To this end, the postnatal phenotypes of LKO mice were analyzed with particular attention to the permeability barrier function primarily maintained by the mortar. Ultrastructural analysis revealed substantially thinner cornified cell envelopes and increased numbers of lamellar granules in LKO mice. Superficial epidermal damages triggered the adaptive repairing responses that evoke the NRF2-dependent upregulation of genes associated with lamellar granule secretion in LKO mice. We also found that corneodesmosomes are less degraded in LKO mice. The observation suggests that loricrin and NRF2 are important effectors of cornification, in which proteins need to be secreted, cross-linked, and degraded in a coordinated manner.

Concomitant Mitral Regurgitation in Severe Aortic Stenosis　- A Report From the CURRENT AS Registry.

BACKGROUND: The clinical significance of concomitant mitral regurgitation (MR) has not been well addressed in patients with severe aortic stenosis (AS).Methods and Results:We analyzed 3,815 patients from a retrospective multicenter registry of severe AS in Japan (CURRENT AS registry). We compared the clinical outcomes between patients with moderate/severe MR and with none/mild MR according to the initial treatment strategy (initial aortic valve replacement [AVR] or conservative strategy). The primary outcome measure was a composite of aortic valve-related death or heart failure hospitalization. At baseline, moderate/severe MR was present in 227/1,197 (19%) patients with initial AVR strategy and in 536/2,618 (20%) patients with a conservative strategy. The crude cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with moderate/severe MR than in those with none/mild MR, regardless of the initial treatment strategy (25.2% vs. 14.4%, P<0.001 in the initial AVR strategy, and 63.3% vs. 40.7%, P<0.001 in the conservative strategy). After adjusting confounders, moderate/severe MR was not independently associated with higher risk for the primary outcome measure in the initial AVR strategy (hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.67-1.83, P=0.69), and in the conservative strategy (HR 1.13, 95% CI 0.93-1.37, P=0.22). CONCLUSIONS: Concomitant moderate/severe MR was not independently associated with higher risk for the primary outcome measure regardless of the initial treatment strategy.

NRF2 in the Epidermal Pigmentary System.

Melanogenesis is a major part of the environmental responses and tissue development of the integumentary system. The balance between reduction and oxidation (redox) governs pigmentary responses, for which coordination among epidermal resident cells is indispensable. Here, we review the current understanding of melanocyte biology with a particular focus on the "master regulator" of oxidative stress responses (i.e., the Kelch-like erythroid cell-derived protein with cap'n'collar homology-associated protein 1-nuclear factor erythroid-2-related factor 2 system) and the autoimmune pigment disorder vitiligo. Our investigation revealed that the former is essential in pigmentogenesis, whereas the latter results from unbalanced redox homeostasis and/or defective intercellular communication in the interfollicular epidermis (IFE). Finally, we propose a model in which keratinocytes provide a "niche" for differentiated melanocytes and may "imprint" IFE pigmentation.