Frequency of Going Outdoors and Risk of Poor Oral Health Among Older Japanese Adults: A Longitudinal Cohort From the Japan Gerontological Evaluation Study.

BACKGROUND: The association between the frequency of going outdoors and the risk of poor oral health has been reported in several studies; however, the findings have been inconclusive. METHODS: We conducted a 3-year longitudinal study of 19,972 Japanese adults aged ≥65 years who reported no poor oral condition at baseline in 2013. The respondents rated their frequency of going outdoors in three categories (≤1, 2-3, or ≥4 times/week), and the oral conditions reported in 2016 included tooth loss, chewing difficulty, swallowing difficulty, dry mouth, and composite outcomes. The associations between the frequency of going outdoors and the risk of poor oral health were examined as relative risk ratios (RRs) and 95% confidence intervals (CIs) using multivariable Poisson regression, while mediation analysis was performed to investigate indirect effects. RESULTS: During the follow-up, 32.5% of participants developed poor oral health. In the mediation analysis, indirect effects were observed through low instrumental activities of daily living, depressive symptoms, little social network diversity, and underweight. Compared to going outdoors ≥4 times/week, the multivariable RRs of composite poor oral health conditions were 1.12 (95% CI, 1.05-1.20) for 2-3 times/week and 1.22 (95% CI, 1.07-1.39) for ≤1 time/week (P-trend < 0.001). Similar associations were observed for tooth loss, chewing difficulty, and swallowing difficulty; the corresponding RRs were 1.07 (95% CI, 0.97-1.19) and 1.36 (95% CI, 1.13-1.64) (P-trend = 0.002), 1.18 (95% CI, 1.06-1.32) and 1.30 (95% CI, 1.05-1.60) (P-trend < 0.001), and 1.15 (95% CI, 1.01-1.31) and 1.38 (95% CI, 1.08-1.77) (P-trend = 0.002), respectively. CONCLUSION: The frequency of going outdoors was inversely associated with the risk of poor oral health through several modifiable risk factors in the older population.

Impact of Patent Lumbar Arteries on Aneurysm Sac Enlargement with Type II Endoleak after Endovascular Aneurysm Repair.

OBJECTIVE: This study aimed to investigate the impact of the number of patent lumbar arteries (LAs) on sac enlargement after endovascular aneurysm repair (EVAR). METHODS: This was a retrospective cohort single centre registry study. Between January 2006 and December 2019, 336 EVARs were reviewed using a commercially available device excluding type I or type III endoleaks during a follow up of ≥ 12 months. Patients were divided into four groups based on the pre-operative patency of the inferior mesenteric artery (IMA) and high (≥ 4) or low (≤ 3) number of patent LAs: Group 1, patent IMA and high number of patent LAs; Group 2, patent IMA and low number of patent LAs; Group 3, occluded IMA and a high number of patent LAs; Group 4, occluded IMA and low number of patent LAs. RESULTS: Groups 1, 2, 3, and 4 included 124, 104, 45, and 63 patients, respectively. The median follow up duration was 65.1 months. Significant differences in the incidence of overall type II endoleak (T2EL) at discharge between Group 1 and Group 2 (59.7% vs. 36.5%, p < .001) and between Group 3 and Group 4 (33.3% vs. 4.8%, p < .001) were observed. In patients with a pre-operatively patent IMA, the rate of freedom from aneurysm sac enlargement was significantly lower in Group 1 than in Group 2 (69.0% vs. 81.7% five years after EVAR, p < .001). In patients with a pre-operatively occluded IMA, the freedom rate from aneurysm sac enlargement was not significantly different between Groups 3 and Group 4 (95.0% vs. 100% five years after EVAR, p = .075). CONCLUSION: A high number of patent LAs seemed to have a significant role in sac enlargement with T2EL when the IMA was patent pre-operatively, whereas a high number of patent LAs seemed to have limited influence on sac enlargement when the IMA was occluded pre-operatively.

Intravenous methylprednisolone pulse therapy and the risk of in-hospital mortality among acute COVID-19 patients: Nationwide clinical cohort study.

BACKGROUND: Steroids are widely used to modulate the inflammatory reactions associated with coronavirus disease 2019 (COVID-19); however, the optimal upper limit dose of steroid use for acute COVID-19 care remains unclear and currently available data may suffer from a time-dependent bias of no effectiveness or reversed causation given the desperate situation of treatment during this pandemic. Accordingly, the aim of this study was to elucidate the impact of intravenous pulse therapy with methylprednisolone (500 mg or greater per day) on the risk of in-hospital mortality among patients with COVID-19 by controlling for time-dependent bias. METHODS: We performed a prospective cohort study with 67,348 hospitalised acute COVID-19 patients at 438 hospitals during 2020-2021 in Japan. The impact of intravenous methylprednisolone pulse therapy on the risk of in-hospital mortality was examined based on hazard ratios (HRs) and 95% confidence intervals (95% CIs), with stratification according to the status of invasive mechanical ventilation (iMV). Time-dependent bias was controlled for in a marginal structural model analysis, with reference to patients without methylprednisolone therapy. RESULTS: During the study period, 2400 patients died. In-hospital mortality rates of iMV-free patients without or with methylprednisolone pulse therapy were 2.3% and 19.5%, and the corresponding values for iMV-receiving patients were 24.7% and 28.6%, respectively. The marginal structural model analysis showed that intravenous pulse therapy with methylprednisolone was associated with a lower risk of in-hospital mortality among patients receiving-iMV (HR 0.59; 95% CI 0.52-0.68). In contrast, pulse therapy with methylprednisolone increased the risk of in-hospital mortality among iMV-free patients (HR 3.38; 95% CI 3.02-3.79). The benefits of pulse therapy for iMV-receiving patients were greater than in those treated with intermediate/higher doses (40-250 mg intravenously) of methylprednisolone (HR 0.80; 95% CI 0.71-0.89). CONCLUSION: The results of our study suggest that intravenous methylprednisolone showed dose-response efficiencies, and pulse therapy may benefit critically ill patients with acute COVID-19, such as those requiring iMV.

Long-term Weight Loss as a Predictor of Mortality in Hemodialysis Patients.

BACKGROUND: Serial weight decrease can be a prognostic predictor in chronic hemodialysis (HD) patients. We investigated the impact of long-term post-HD body weight (BW) changes on all-cause mortality among HD patients. METHODS: This longitudinal cohort study and post-hoc analysis evaluated participants of a previous randomized controlled trial conducted between 2006 and 2011 who were followed up until 2018. Weight change slopes were generated with repeated measurements every 6 months during the trial for patients having ≥5 BW measurements. Participants were categorized into four groups based on quartiles of weight change slopes; the median weight changes per 6 months were -1.02 kg, -0.25 kg, +0.26 kg, and +0.86 kg for first, second, third, and fourth quartile, respectively. Cox proportional hazard regression was used to evaluate differences in subsequent survival among the four groups. BW trajectories were plotted with a backward time-scale and multilevel regression analysis to visualize the difference in BW trajectories between survivors and non-survivors. RESULTS: Among the 461 patients, 404 were evaluated, and 168 (41.6%) died within a median follow-up period of 10.2 years. The Cox proportional hazard regression adjusted for covariates and baseline BW showed that a higher rate of weight loss was associated with higher mortality. The hazard ratios were 2.02 (95% confidence interval [CI], 1.28-3.20), 1.77 (95% CI, 1.10-2.85), 1.00 (reference), and 1.11 (95% CI, 0.67-1.83) for the first, second, third (reference), and fourth quartiles, respectively. BW trajectories revealed a significant decrease in BW in non-survivors. CONCLUSION: Weight loss elucidated via serial BW measurements every 6 months is significantly associated with higher mortality among HD patients.

Work and Family Conflicts, Depression, and "Ikigai": A Mediation Analysis in a Cross-cultural Study Between Japanese and Egyptian Civil Workers.

BACKGROUND: Total work-family conflicts (TWFCs) could associate with mental health, and having ikigai (a purpose of life) may mediate this association. METHODS: In a cross-cultural study of 4,792 Japanese Aichi Workers' Cohort study participants and 3,109 Egyptian civil workers, the Midlife Development in the United States (MIDUS) questionnaire measured TWFCs and the Center for Epidemiological Studies Depression (CES-D) 11-item scale measured depression. We used logistic regression models to estimate odds ratios (ORs) of having depression and a high-ikigai across levels of TWFCs (low, moderate, and high), and the PROCESS macro of Hayes to test the mediation effect. RESULTS: The prevalence of high TWFCs, depression, and having a high ikigai were 17.9%, 39.4%, and 70.1% in Japanese women, 10.5%, 26.8%, and 70.1% in Japanese men, 23.7%, 58.2%, and 24.7% in Egyptian women, and 19.1%, 38.9%, and 36.9% in Egyptian men, respectively. Compared with participants with low TWFCs, the multivariable ORs of depression in Japanese women and men with high TWFCs were 4.11 (95% confidence interval [CI], 2.99-5.65) and 5.42 (95% CI, 4.18-7.02), and those in Egyptian women and men were 4.43 (95% CI, 3.30-5.95) and 4.79 (95% CI, 3.53-6.48), respectively. The respective ORs of having a high-ikigai were 0.46 (95% CI, 0.33-0.64) and 0.40 (95% CI, 0.31-0.52) in Japanese women and men and were 0.34 (95% CI, 0.24-0.48) and 0.28 (95% CI, 0.20-0.39) in Egyptian women and men. No interaction between TWFCs and country was observed for the associations with depression or ikigai. Ikigai mediated (up to 18%) the associations between the TWFCs and depression, especially in Egyptian civil workers. CONCLUSION: TWFCs were associated with depression, and having low ikigai mediated these associations in Japanese and Egyptian civil workers.

Comparison of the Outcomes of Total Endovascular Aortic Arch Repair Between Branched Endograft and Chimney Endograft Technique in Zone 0 Landing.

PURPOSE: Zone 0 landing in thoracic endovascular aortic repair (TEVAR) has recently gained increasing attention for the treatment of high-risk patients. The aim of this study was to compare the outcomes of total endovascular aortic arch repair between branched TEVAR (bTEVAR) and chimney TEVAR (cTEVAR) in the landing zone (LZ) 0. MATERIALS AND METHODS: This was a single-center, retrospective, and observational cohort study. From January 2010 to March 2020, 40 patients (bTEVAR, n=25; cTEVAR, n=15; median age: 79 years) were enrolled in this study, with a median follow-up period of 4.1 years. These patients were considered unsuitable for open surgical treatment. RESULTS: All procedures were successful and no cases of conversion to open repair were noted during the 30-day postoperative period. The 30-day mortality was 2.5% (n=1; bTEVAR [0 of 25, 0%] vs cTEVAR [1 of 15, 6.7%]; p=0.375), the perioperative stroke rate was 10.0% (n=4; bTEVAR [4 of 25, 16.0%] vs cTEVAR [0 of 15, 0%], p=0.278), and type 1a endoleak rate was 15.0% (n=6; bTEVAR [0 of 25, 0%] vs cTEVAR [6 of 15, 40.0%], p=0.001). The risk factor for stroke was atheroma grade of ≥2 in the brachiocephalic artery (p<0.001). The risk factor for type 1a endoleak was cTEVAR (p=0.001). The 8-year survival rate was 49.9%. The aorta-related death-free rate and aortic event-free rate at 8 years were 94.4% (bTEVAR: 95.5% vs cTEVAR: 93.3%, p=0.504) and 60.7% (bTEVAR: 70.7% vs cTEVAR: 40.0%, p=0.048), respectively. CONCLUSIONS: Total endovascular aortic arch repair using bTEVAR and cTEVAR is feasible for the treatment of aortic arch diseases in high-risk patients who are unsuitable for open surgery. However, as the rate of stroke is high, strict preoperative evaluation to prevent stroke is needed. No rupture of the aneurysm was observed in cTEVAR, but patients should be selected carefully because of the high incidence of type 1a endoleak.

Impact of the Patency of Inferior Mesenteric Artery on 7-Year Outcomes After Endovascular Aneurysm Repair.

PURPOSE: The impact of preoperative patent inferior mesenteric artery (IMA) on late outcomes following endovascular aneurysm repair (EVAR) remains unclear. This study aimed to investigate the specific influence of IMA patency on 7-year outcomes after EVAR. MATERIALS AND METHODS: In this retrospective cohort study, 556 EVARs performed for true abdominal aortic aneurysm cases between January 2006 and December 2019 at our institution were reviewed. Endovascular aneurysm repairs performed using a commercially available device with no type I or type III endoleak (EL) during follow-up and with follow-up ≥12 months were included. A total of 336 patients were enrolled in this study. The cohort was divided into the patent IMA group and the occluded IMA group according to preoperative IMA status. The late outcomes, including aneurysm sac enlargement, reintervention, and mortality rates, were compared between both groups using propensity-score-matched data. RESULTS: After propensity score matching, 86 patients were included in each group. The median follow-up period was 56 months (interquartile range: 32-94 months). The incidence of type II EL at discharge was 50% in the patent IMA group and 19% in the occluded IMA group (p<0.001). The type II EL from IMA and lumbar arteries was significantly higher in the patent IMA group than in the occluded IMA group (p<0.001 and p=0.002). The rate of freedom from aneurysm sac enlargement with type II EL was significantly higher in the occluded IMA group than in the patent IMA group (94% vs 69% at 7 years; p<0.001). The rate of freedom from reintervention was significantly higher in the occluded IMA group than in the patent IMA group (90% vs 74% at 7 years; p=0.007). Abdominal aortic aneurysm-related death and all-cause mortality did not significantly differ between groups (p=0.32 and p=0.34). CONCLUSIONS: Inferior mesenteric artery patency could affect late reintervention and aneurysm sac enlargement but did not have a significant impact on mortality. Preoperative assessment and embolization of IMA might be an important factor for improvement in late EVAR outcomes. CLINICAL IMPACT: The preoperative patency of the inferior mesenteric artery was significantly associated with a higher incidence of sac enlargement and reintervention with type II endoleak following endovascular aneurysm repair, even after adjustment for patient background. Preoperative assessment and embolization of inferior mesenteric artery might be an important factor for improvement in late EVAR outcomes.

Effectiveness of Proximal Landing Zones 0, 1, and 2 Hybrid Thoracic Endovascular Aortic Repair: A Single Centre 12 Year Experience.

OBJECTIVE: Hybrid thoracic endovascular aortic repair (TEVAR) is being accepted increasingly as a first line treatment for arch repair at the present authors' institution. This study aimed to clarify the effectiveness of zones 0, 1, and 2 landing hybrid TEVAR. METHODS: This was a retrospective single centre case series. From April 2008 to March 2020, 348 patients (median age 72 years; interquartile range [IQR] 65, 77 years) were enrolled, with a median follow up period of 5.6 years (IQR 2.6, 8.7 years). The procedures included zone 0 in 135 patients (38.8%), zone 1 in 82 patients (23.6%), and zone 2 proximal landing zone (LZ) hybrid TEVAR in 131 patients (37.6%). The pathologies consisted of dissecting aortic aneurysms in 123 (35.3%) patients. Emergency procedures were performed in 39 (11.2%) patients. RESULTS: The 30 day mortality (n = 2, 0.6%) and hospital deaths (n = 6, 1.7%) were registered. The stroke rate was 1.1% (n = 4), while early and late endoleak rates were 4.8% (n = 17) and 1.7% (n = 6), respectively. Type 1a endoleak and retrograde type A dissection occurred in seven (2.0%) and three (0.9%) patients, respectively. The cumulative survival, freedom from aorta related deaths, and freedom from aortic events in 10 years were 75.0%, 97.2%, and 84.1%, respectively. The freedom from aortic events in each landing zone in 10 years was 82.3%, 81.4%, and 87.9% for zones 0, 1, and 2, respectively. The 10 year survival rates were 82.5% and 73.6%; the 10 year aorta related death free rates were 94.9% and 98.6%, and the 10 year aortic event free rates were 82.3% and 85.5% in the zone 0 and zone 1 and 2 TEVAR, respectively. CONCLUSION: Satisfactory early and long term results of hybrid arch repair at zones 0, 1, and 2 were achieved. To avoid complications and aortic events, the treatment strategy of hybrid arch repair for aortic arch pathologies should be tailored using accurate pre-operative assessment of the ascending aorta and the aortic arch.

Impact of modifiable healthy lifestyle adoption on lifetime gain from middle to older age.

OBJECTIVE: this study explored whether the modification of selected lifestyles is likely to increase life expectancy from middle age onwards, regardless of the presence of major comorbidities. METHODS: we examined a prospective cohort of 20,373 men and 26,247 women aged 40-80 years. Eight modifiable lifestyle factors were assessed: consumption of fruit, fish and milk, walking and/or sports participation, body-mass index, smoking status, alcohol consumption and sleep duration. Modifiable healthy lifestyle factors scored one point each, for a maximum of eight points. The impact of modifiable healthy lifestyle adoption on lifetime gain during the ages of 40-102 years was analysed. FINDINGS: during the median 21 years of follow-up, 8,966 individuals (3,683 men and 5,283 women) died. Life expectancy at 40 years (95% confidence intervals) for 7-8 health lifestyle points was 46.8 (45.6-48.1) and 51.3 (50.0-52.6) years for men and women, respectively. The potential impact of modifiable healthy lifestyle adoption on lifetime gain persisted over the age of 80 years or more, in individuals with ≥5 factors (P < 0.001), particularly older men. The benefits were more pronounced among patients with major comorbidities, such as cardiovascular disease, cancer, hypertension, diabetes, kidney disease and those with multimorbidity throughout all age categories. CONCLUSION: adopting modifiable healthy lifestyles was associated with lifetime gain, even in individuals aged 80 years or more, regardless of the presence of any major comorbidities in each life stage since middle age. The findings imply the importance of improving the one's lifestyle for an increased lifespan, even among older patients and/or those with multimorbidity.

Risk Analysis of Aneurysm Sac Enlargement Caused by Type II Endoleak after Endovascular Aortic Repair.

BACKGROUND: Although the preoperative risk factors associated with the occurrence of type II endoleak (ETII) after endovascular aortic repair (EVAR) have gradually become more evident, the preoperative risk factors associated with aneurysm sac enlargement caused by ETII remain unclear. This study aimed to determine the preoperative risk factors associated with aneurysm sac enlargement caused by ETII after EVAR. METHODS: This retrospective cohort study reviewed 519 EVARs performed for true abdominal aortic aneurysm between January 2006 and December 2018 at our institution. EVARs using commercially available bifurcated devices with no type I or III endoleaks during follow-up and with ≥12 months follow-up were included. A total of 320 patients were enrolled in the study. To identify the preoperative risk factors of sac enlargement after EVAR, Cox regression analysis was used to assess preoperative data. RESULTS: The median follow-up period was 60.8 months. Overall, 135 of 320 patients (42%) had ETII during follow-up, and 47 of 135 patients (35%) developed aneurysm sac enlargement. Multivariate analysis revealed that chronic kidney disease (CKD) stage ≥4 (hazard ratio [HR], 4.65; 95% confidence interval [CI], 2.13-10.15; P = 0.001), patent inferior mesenteric artery (IMA) (HR, 17.85; 95% CI, 2.46-129.73; P< 0.001), and number of patent lumbar arteries (LAs) (HR, 1.37; 95% CI, 1.13-1.68; P= 0.002) were risk factors of aneurysm sac enlargement caused by ETII. CONCLUSIONS: CKD stage ≥4, patent IMA, and number of patent LAs were independent risk factors for aneurysm sac enlargement after EVAR. In particular, patent IMA had the highest HR and seemed to have the greatest impact on long-term aneurysm sac enlargement. Hence, taking preoperative measures to address a patent IMA appears to be important in reducing the incidence of sac enlargement.

Microvascular Dysfunction Related to Progressive Left Ventricular Remodeling due to Chronic Occlusion of the Left Anterior Descending Artery in an Adult Porcine Heart.

Occlusion of a major coronary artery induces myocardial infarction (MI), leading to left ventricle (LV) remodeling due to progressive microvasculature dysfunction. Irreversible impairment in microvascular function has been suggested to extend from the infarcted region into the infarct-border or remote regions, depending on the time to revascularization. Our aim was to determine whether the occlusion of a major coronary artery induces microvascular dysfunction in the adjacent area perfused by intact coronary arteries using a porcine model for chronic total occlusion of the left anterior descending artery (LAD). MI was induced via an ameroid constrictor ring around the LAD in adult Göttingen pigs (Sus scrofa domesticus, n = 5). Age-matched normal pigs were treated as controls (n = 3). Cardiac magnetic resonance showed reduced systolic regional wall motion in the left circumflex (LCx) and right coronary artery (RCA) territories, with a progressively worsening motion in the infarction-adjacent area over an eight-week period. On 13N-ammonia positron emission tomography (PET), myocardial blood flow (MBF) during hyperemia was significantly greater in the LCx and RCA territories (particularly in the infarction-adjacent area) compared to that in the LAD territory at four weeks after infarct induction. Subsequently, the flow significantly decreased, approaching that in the LAD territory at eight weeks after infarct induction. Fluoroscopy-guided pressure-wire studies showed significantly higher microvascular resistance in the LCx area at eight weeks compared to that in controls. Electron microscopy showed endothelium swelling and microvasculature disruption in areas adjacent to the LCx and RCA territories. Anterior MI caused coronary microvascular dysfunction in the adjacent area, associated with a reduced MBF and regional wall motion.

Relationship Between Bacteremia and Hemorrhagic Stroke in Patients With Continuous-Flow Left Ventricular Assist Device.

BACKGROUND: Blood stream infection is thought to increase the risk of hemorrhagic stroke, a major adverse event with devastating outcome, in patients with continuous-flow left ventricular assist devices (LVADs). We analyzed the risk factors of hemorrhagic stroke in LVAD patients, as well as the time relationship between systemic bacteremia and hemorrhagic stroke.Methods and Results:We evaluated the incidence of systemic bacteremia and stroke in 164 patients who underwent continuous-flow LVAD implantation between 2005 and 2016. At 1 and 2 years after implantation, the incidence of bacteremia was 29% and 36%, and the incidence of hemorrhagic stroke was 22% and 22% in patients without bacteremia, and 32% and 44% in those with bacteremia, respectively (P=0.035). This higher prevalence of hemorrhagic stroke in patients with bacteremia was notable particularly in the chronic phase (>90 days after implantation). Multivariate analysis revealed that bacteremia was an independent risk factor of hemorrhagic stroke in the chronic phase [hazard ratio, 2.36 (1.02-5.62); P=0.044]. The hazard rate was the highest immediately after the onset of bacteremia, and the risk steadily declined by 90 days after the last episode of bacteremia and flattened thereafter. CONCLUSIONS: Bacteremia was an independent risk factor of hemorrhagic stroke in patients in the chronic phase, with the highest risk seen in the early phase following an episode of bacteremia.

Socioeconomic Status Transition Throughout Life and Risk of Dementia.

Importance: Socioeconomic status (SES) is associated with dementia. However, the role of SES transitions in dementia is less explored; such evidence would be useful to understand whether social mobility is associated with healthy longevity at older ages. Objective: To investigate the association of lifetime SES transition with risk of dementia. Design, Setting, and Participants: This prospective cohort study, conducted from August 2010 to December 2016, used data from the Japan Gerontological Evaluation Study for participants aged 65 years or older from 31 different areas in Japan. Individuals with missing SES values, loss of follow-up, or new dementia onset 1 year or less from baseline were excluded. Data analysis was performed from April 2022 to April 2023. Exposure: Transitions in SES across the life course. Main Outcomes and Measures: The main outcome was risk of dementia incidence and corresponding loss or gain of dementia-free periods in a lifespan. The incidence of dementia was identified with a national registry of long-term nursing care services. Results: A total of 9186 participants (4703 men [51.2%]) were included. The mean (SD) age at baseline was 74.2 (6.0) years. Six SES transitions were identified: upward, stable-high, upper-middle, lower-middle, downward, and stable-low. During the follow-up period, 800 cases of dementia were identified. Many dementia risk factors, including lifestyle behaviors, comorbidities, and social factors, were associated with SES transition patterns. Compared with lower-middle SES, the lowest risk of dementia was observed for upward transition (hazard ratio [HR], 0.66; 95% CI, 0.57-0.74) followed by stable-high (HR, 0.77; 95% CI, 0.69-0.86), downward (HR, 1.15; 95% CI, 1.09-1.23), and stable-low (HR 1.45; 95% CI, 1.31-1.61) transition (P < .001 for linearity); there was no association of upper-middle transition with risk of dementia (HR, 0.91; 95% CI, 0.79-1.03). The greatest increases in dementia-free years in the lifespan were also associated with upward SES transition (eg, 1.8 years [95% CI, 1.4-2.2 years] at age 65 years), while the downward transition was associated with the largest loss in lifetime dementia-free years at 75 years or older (eg, -1.4 years [95% CI, -2.4 to -0.4 years] at age 85 years). Conclusions and Relevance: This cohort study of Japanese older adults identified that upward and downward SES transitions were associated with risk of dementia and the length of dementia-free periods over the lifespan. The results may be useful to understand the association between social mobility and healthy longevity.

Efficacy of Pharmacotherapy for Seasonal Influenza in Young and Middle-aged Adults: A Systematic Review and Network Meta-analysis.

Background Seasonal influenza affects healthcare demand. However, the efficacy of anti-influenza drugs, particularly among young patients at a low risk of complications, has rarely been evaluated. Therefore, we evaluated the efficacy of anti-influenza drugs against seasonal influenza in healthy young and middle-aged adults. Methods A systematic review and network meta-analysis were conducted. The Cochrane Central Register of Controlled Trials and Medical Literature Analysis and Retrieval System Online were searched for original articles reporting double-blind, randomized controlled trials published up to the end of July 2023. Clinical trials that tested the efficacy of anti-influenza drugs in young and middle-aged patients with seasonal influenza were also included. The primary outcome was time to fever alleviation. The efficacy and adverse effects of these treatments were estimated using a Bayesian hierarchical random-effects model and a Markov chain Monte Carlo simulation. Results In total, 24 articles with 34 treatments and 8,949 individuals were included. Oseltamivir (300 mg/day for 5 days) showed the largest reduction in time to fever alleviation by -19.1 (95% confidence interval [CI]: -29.4, -10.7) h compared with a placebo. Baloxavir marboxil (40 mg/day) reduced the time to symptom alleviation by -28.2 (95% CI: -42.7, -13.7) h, and peramivir (300 mg/day) administered by intravenous infusion for 1 day reduced the time to resumption of usual activities by -43.5 (95% CI: -72.8, -14.2) h. Conclusion Several pharmaceutical treatments were able to reduce the recovery time for fever and symptom alleviation and resumption of usual activities in young and middle-aged adults with seasonal influenza without increasing the risk of complications.

Pleiotropic effects of extracellular vesicles from induced pluripotent stem cell-derived cardiomyocytes on ischemic cardiomyopathy: A preclinical study.

BACKGROUND: Stem cell-secreted extracellular vesicles (EVs) play essential roles in intercellular communication and restore cardiac function in animal models of ischemic heart disease. However, few studies have used EVs derived from clinical-grade stem cells and their derivatives with stable quality. Moreover, there is little information on the mechanism and time course of the multifactorial effect of EV therapy from the acute to the chronic phase, the affected cells, and whether the effects are direct or indirect. METHODS: Induced pluripotent stem cell-derived cardiomyocytes (iPSCM) were produced using a clinical-grade differentiation induction system. EVs were isolated from the conditioned medium by ultracentrifugation and characterized in silico, in vitro, and in vivo. A rat model of myocardial infarction was established by left anterior descending artery ligation and treated with iPSCM-derived EVs. RESULTS: iPSCM-derived EVs contained microRNAs and proteins associated with angiogenesis, antifibrosis, promotion of M2 macrophage polarization, cell proliferation, and antiapoptosis. iPSCM-derived EV treatment improved left ventricular function and reduced mortality in the rat model by improving vascularization and suppressing fibrosis and chronic inflammation in the heart. EVs were uptaken by cardiomyocytes, endothelial cells, fibroblasts, and macrophages in the cardiac tissues. The pleiotropic effects occurred due to the direct effects of microRNAs and proteins encapsulated in EVs and indirect paracrine effects on M2 macrophages. CONCLUSIONS: Clinical-grade iPSCM-derived EVs improve cardiac function by regulating various genes and pathways in various cell types and may have clinical potential for treating ischemic heart disease.

Associations between Supper Timing and Mortality from Cardiovascular Disease among People with and without Hypertension.

AIM: Less is known about the impact of supper time on cardiovascular disease (CVD) risk among hypertensives and nonhypertensives. We aimed to explore this issue in a cohort study. METHODS: We analyzed the data of 72,658 participants (15,386 hypertensives and 57,272 nonhypertensives) aged 40-79 years without a history of CVD at baseline (1988-1990) under the Japan Collaborative Cohort study. Supper time was assessed based on self-reported questionnaires categorized as before 17:00, between 17:00 and 20:00, after 20:00, irregular supper time, and reference supper time (17:00-20:00). Hazard ratios (HRs) and 95% confidence intervals (95% CI) of CVD mortality were calculated according to supper time after adjustment for potential confounders, stratified by hypertensive status and age group (＜65 and ≥ 65 years). RESULTS: During a median of 19.4 years of follow-up, 4,850 CVD deaths were recorded. Compared with the reference time, the risk of CVD mortality was higher for irregular supper time for the total population, either hypertensives or nonhypertensives, more specifically hypertensives aged ≥ 65 years; the multivariable HR (95% CI) of CVD mortality in the total population was 1.28 (1.11-1.50, P＜0.01). The supper time of ＞20:00 tended to be associated with the higher risk only for hypertensives; the multivariable HR was 1.39 (0.98-1.96, P=0.06). CONCLUSION: Irregular supper time was associated with an increased risk of CVD mortality. Supper timing could be a surrogate marker for CVD risk.

Early achievement of walkability after cardiac surgery and the risk of cardiovascular disease after hospital discharge.

AIMS: This study aimed to investigate the association between the time to achieve walkability after cardiac surgery and the risk of cardiovascular disease after hospital discharge. METHODS: We conducted a prospective cohort study involving 553 ambulatory patients aged 71.5 (range, 64.0-77.0) years who underwent cardiac surgery. All patients were divided into five groups based on the time to achieve walkability ≥100 m within 1, 2, 3, 4 or 5 days after cardiac surgery. We examined the risk of post-cardiovascular disease outcomes, including readmission due to heart failure, ischaemic heart disease and other cardiovascular disease, according to the time to achieve walkability with reference to 5 days using the Fine and Gray regression model, considering competing risks. RESULTS: In the survival curve analysis, we examined the time to experience post-cardiovascular disease incidence after hospital discharge. During a median of 3.3 years of follow-up, 118 patients developed cardiovascular disease. We observed a positive association between the time to achieve walkability and cardiovascular disease risk, particularly heart failure. The multivariate hazard ratios (95% confidence intervals) for heart failure readmission were N/A (not assessed due to the sample size being too small) for 1 day, 0.31 (0.10-0.99) for 2 days, 0.60 (0.21-1.79) for 3 days and 0.76 (0.22-2.72) for 4 days (P for trend = 0.032). CONCLUSIONS: The shorter walkability achievement time was associated with a lower risk of cardiovascular diseases, more specifically heart failure readmission, among patients who underwent cardiac surgery. The time required to achieve walkability is a useful predictor for cardiovascular diseases after hospital discharge.

Accuracy of breathing and radial pulse assessment by non-medical persons: an observational cross-sectional study.

Early recognition of cardiopulmonary arrest (CPA) expedites emergency calls and resuscitation and improves the survival rate of unresponsive individuals. However, the accuracy of breathing and radial artery pulse assessment by non-medical persons is poorly understood. The aim of this study was to determine the accuracy of breathing assessment and radial pulse palpation among 450 non-medical personnel using a high-fidelity simulator. We examined the accuracy of 10 second's assessment for breathing and radial pulse using a high-fidelity mannequin simulator, included 496 non-medical participants (school teachers) between 2016-2018. For a primary results, the sensitivity for the detection of the presence of the breathing and radial pulse was 96.2% (97.5% for sensitivity and 92.0% for specificity) and 91.7% (99.1% for sensitivity and 56.8% for specificity), respectively. Futher, breathing rate and radial pulse rate were strongly correlated with the assessments, with Spearman's correlation coefficients of 0.813 (P < 0.001) and 0.719 (P < 0.001), respectively. In contrast, radial pulse strength was weakly correlated with the assessment (coefficient of 0.288, P < 0.001). Our results suggested that non-medical persons would show high accuracy in detecting and measuring respiration and radial pulse, although they did not accurately determine radial pulse strength for the early recognition of CPA.

Cardiomyocyte deoxyribonucleic acid damage and cardiac recovery in paediatric dilated cardiomyopathy.

OBJECTIVES: The goal of this study was to identify the clinical significance of the deoxyribonucleic acid (DNA) damage response marker, phosphorylated H2A histone variant X, on the bridge to recovery in low-weight paediatric patients with dilated cardiomyopathy (DCM) after having a Berlin Heart EXCOR implanted. METHODS: Consecutive paediatric patients with DCM who had an EXCOR implanted for DCM at our hospital between 2013 and 2021 were reviewed. Patients were classified into 2 groups according to the degree of DNA damage in the left ventricular cardiomyocytes-the low DNA damage group and the high DNA damage group-using the median value as the threshold. We examined and compared the preoperative factors and histologic findings associated with cardiac functional recovery following the explant procedure in the 2 groups. RESULTS: Competing outcome analysis of 18 patients (median body weight, 6.1 kg) showed that the incidence of an EXCOR explant was 40% at 1 year after the implant procedure. Serial echocardiography revealed significant left ventricular functional recovery in the low DNA damage group 3 months after the implant. The univariable Cox proportional hazards model revealed that the percentage of phosphorylated H2A histone variant X-positive cardiomyocytes was the significant factor associated with cardiac recovery and the EXCOR explant (hazard ratio, 0.16; 95% confidence interval, 0.027-0.51; P = 0.0096). CONCLUSIONS: The degree of DNA damage response to the EXCOR implant may aid in predicting the bridge to recovery with EXCOR among low-weight paediatric patients with DCM.

Risk factors for atrial arrhythmia recurrence after atrial arrhythmia surgery with pulmonary valve replacement.

Objectives: Atrial arrhythmias are a significant cause of late morbidity and mortality in patients after tetralogy of Fallot repair. However, reports on their recurrence following atrial arrhythmia surgery are limited. We aimed to identify the risk factors for atrial arrhythmia recurrence after pulmonary valve replacement (PVR) and arrhythmia surgery. Methods: We reviewed 74 patients with repaired tetralogy of Fallot who underwent PVR for pulmonary insufficiency at our hospital between 2003 and 2021. Twenty-two patients (mean age, 39 years) underwent PVR and atrial arrhythmia surgery. A modified Cox-maze III was performed in 6 patients with chronic atrial fibrillation, and a right-sided maze was performed in 12 with paroxysmal atrial fibrillation, 3 with atrial flutter, and 1 with atrial tachycardia. Atrial arrhythmia recurrence was defined as any documented sustained atrial tachyarrhythmia requiring intervention. The influence of preoperative parameters on recurrence was assessed with the Cox proportional-hazards model. Results: The median follow-up period was 9.2 years (interquartile range, 4.5-12.4). Cardiac death and redo-PVR due to prosthetic valve dysfunction were not observed. Eleven patients had atrial arrhythmia recurrence after discharge. Atrial arrhythmia recurrence-free rates were 68% at 5 years and 51% at 10 years after PVR and arrhythmia surgery. Multivariable analysis revealed that right atrial volume index (hazard ratio, 1.04; 95% confidence interval, 1.01-1.08, P = .009) was a significant risk factor for atrial arrhythmia recurrence after arrhythmia surgery and PVR. Conclusions: Preoperative right atrial volume index was associated with atrial arrhythmia recurrence, which may assist in planning the timing of atrial arrhythmia surgery and PVR.