小谷 和彦

Patients with nonalcoholic fatty liver disease (NAFLD) show dyslipidemia and a high risk for coronary heart disease (CHD). However, conventional atherosclerotic lipids are found at low levels in NAFLD patients with advanced fibrosis, in whom the risk for CHD is extremely high. The aim of the present study was to evaluate the levels of oxidized high-density lipoprotein (oxHDL), an emerging atherosclerotic biomarker, in patients with NAFLD. A total of 32 non-NAFLD subjects and 106 patients with NAFLD were enrolled. The fibrosis grades were stratified using non-invasive methods, including the Fibrosis-4 index and NAFLD fibrosis score. Total cholesterol and low-density lipoprotein (LDL)-cholesterol levels were significantly low in patients with advanced liver fibrosis. In contrast, oxHDL levels were high in NAFLD patients and showed a stepwise increase as fibrosis progressed. These oxHDL levels were independent of the HDL cholesterol levels, and statin use did not influence the oxHDL levels. Obese patients showed no increase in oxHDL levels, whereas patients with a low handgrip strength showed high oxHDL levels in NAFLD with advanced fibrosis. In conclusion, oxHDL is a potential biomarker for assessing the status of patients with NAFLD, including CHD and metabolic/nutritional disturbance, and particular cases with advanced liver fibrosis.

BACKGROUND: Oxidized high-density lipoprotein (oxHDL), unlike native HDL, is characterized by reduced cholesterol efflux capability and anti-inflammatory properties. The ratio of oxHDL to apolipoprotein A-I (oxHDL/apoAI) is a possible marker of dysfunctional HDL. The aim of this study was to evaluate the association between oxHDL/apoAI and coronary plaque characteristics that increase the likelihood of cardiovascular events as determined by coronary computed tomography (CT) angiography. METHODS: A total of 297 patients (mean age; 67 years, men; 63%) who underwent coronary CT angiography for suspected stable coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined by three characteristics: positive remodeling; low-density plaques; and spotty calcification. Significant stenosis was defined as a luminal narrowing of >70%. Serum concentrations of oxHDL were measured using an enzyme-linked immunosorbent assay. RESULTS: Patients with higher oxHDL/ApoAI showed significantly greater prevalence of HRP (p = 0.03) and significant stenosis (p < 0.01) compared with patients with low oxHDL/ ApoAI. The multivariate logistic analysis demonstrated that oxHDL/ApoAI significantly associated with the presence of HRP and significant coronary stenosis (p = 0.01 and < 0.01). In the follow-up study including 243 patients for a median period of 1.8 years, univariate cox regression analysis showed that oxHDL/ApoAI, HRP and significant stenosis were significant predictors of cardiovascular events. CONCLUSIONS: A high oxHDL/apoAI was associated with the presence of HRP and significant stenosis determined by coronary CT angiography, which can lead to cardiovascular events in patients with suspected stable CAD.

Diabetic polyneuropathy (DPN) and endothelial dysfunction are prevalent complications of diabetes mellitus. Currently, there are two non-invasive markers for endothelial dysfunction: flow-mediated dilation and reactive hyperaemia peripheral arterial tonometry (RH-PAT). However, the relationship between diabetic small fibre neuropathy and macroangiopathy remains obscure thus far. Corneal confocal microscopy (CCM) has emerged as a new diagnostic modality to assess DPN, especially of small fibre. To clarify the relationship between diabetic small fibre neuropathy and vascular dysfunction, we aimed to determine the functions of peripheral nerves and blood vessels through clinical tests such as nerve conduction study, coefficient of variation in the R-R interval, CCM, and RH-PAT in 82 patients with type 2 diabetes. Forty healthy control subjects were also included to study corneal nerve parameters. Correlational and multiple linear regression analyses were performed to determine the associations between neuropathy indices and markers for vascular functions. The results revealed that patients with type 2 diabetes had significantly lower values for most variables of CCM than healthy control subjects. RH-PAT solely remained as an explanatory variable significant in multiple regression analysis for several CCM parameters and vice versa. Other vascular markers had no significant multiple regression with any CCM parameters. In conclusion, endothelial dysfunction as revealed by impaired RH-PAT was significantly associated with CCM parameters in patients with type 2 diabetes. This association may indicate that small fibre neuropathy results from impaired endothelial dysfunction in type 2 diabetes. CCM parameters may be considered surrogate markers of autonomic nerve damage, which is related to diabetic endothelial dysfunction. This study is the first to report the relationship between corneal nerve parameter as small fibre neuropathy in patients with type 2 diabetes and RH-PAT as a marker of endothelial dysfunction.

Introduction: Takayasu arteritis (TA) is a chronic vasculitis associated with an increased cardiovascular risk. The measurement of pulse wave velocity (PWV), carotid artery intima-media thickness (CIMT) and flow-mediated dilatation (FMD) are generally used for evaluating the cardiovascular risk. The application of these measurements to TA patients remains undetermined. Material and methods: Clinical studies that reported the PWV, CIMT and FMD levels in TA patients, which were published prior to 2021, were summarized using PubMed. Results: Fifteen studies were eligible. Overall, in TA patients, the PWV and CIMT levels were significantly higher and the FMD levels were significantly lower compared to controls. Part of the studies showed that the disease activity of TA was significantly associated with the PWV, CIMT or FMD levels. Conclusions: The PWV, CIMT and FMD measurements could be useful for evaluating the cardiovascular risk in TA patients. Further studies to determine the proper use of these measurements are warranted.

Background: Hepcidin-25 is a 25 amino acid hepatokine and a key regulator of iron metabolism related to iron deficiency anemia. Recent studies have suggested that an elevated hepcidin level is correlated with low energy availability. Leptin is an appetite-suppressing adipokine and has been reported to stimulate hepcidin production in animals and cultured cells. While leptin is modulated by exercise, it is known that endurance runners and sprinters practice different types of exercise. This study investigated and compared the relationships between hepcidin and leptin levels, iron status, and body fat to understand better the risk of iron deficiency anemia in endurance runners and sprinters. Methods: Thirty-six male college track and field athletes (15 endurance runners and 21 sprinters) were recruited for this study. Dietary intake, body composition, and blood levels of ferritin, hepcidin-25, leptin, and adiponectin were measured. Correlations between hepcidin levels and ferritin, body fat, leptin, and adiponectin were evaluated using Pearson's correlation coefficient for each group. Results: The endurance runners had lower hepcidin levels and higher leptin and adiponectin levels compared with sprinters. Ferritin was positively correlated with hepcidin-25 levels in both the endurance and sprinter groups. A positive correlation was observed between hepcidin-25 and body fat or leptin levels only in sprinters. Conclusion: This is the first study investigating the relationship between blood levels of hepcidin and leptin in athletes. The positive correlation between hepcidin-25 and leptin was observed in sprinters but not endurance runners.

Guillain-Barré syndrome (GBS) usually has a good prognosis; however, patients may develop sequelae without prompt treatment. We herein describe an 81-year-old woman who developed acute-onset excruciating thigh pain and weakness in her lower extremities after spinal surgery. We diagnosed acute inflammatory demyelinating polyradiculoneuropathy by a nerve conduction study, which showed findings of demyelination without cerebrospinal fluid analysis because of a spinal prosthesis. Although anti-GM1 and anti-GalNAc-GD1a antibodies were positive, the patient was clinically diagnosed with acute inflammatory demyelinating polyradiculoneuropathy (a subtype of GBS), not acute motor axonal neuropathy. She recovered well with immunoglobulin therapy. A literature review of 18 cases revealed that unexplained weakness, areflexia, and numbness of the extremities after spinal surgery, a shorter time from spinal surgery to symptom onset to general GBS, abnormal nerve conduction study results, normal spinal imaging findings, and the development of atypical symptoms such as cranial and autonomic nerve syndrome and respiratory failure are useful for diagnosing GBS when cerebrospinal fluid examination cannot be performed after spinal surgery.

Lipoprotein(a) (Lp(a)) and low-density lipoprotein cholesterol (LDL-C) are risk factors for cardiovascular disease (CVD). Individuals with familial hypercholesterolemia (FH) have a risk for CVD due to a high LDL-C value. Lp(a) also increases the CVD risk in FH individuals; thus, the Lp(a) value should be carefully managed. The LDL-C value may partly include Lp(a)-cholesterol (Lp(a)-C) in the measurement. Based on the LDL-C value, some individuals are likely misclassified as having FH and/or the status of treatment of FH can be monitored. The present review describes about Lp(a) in FH individuals in terms of the measurement issue of Lp(a) and the related management of FH.

Background: Endoscopic submucosal dissection (ESD) for gastric cancer is increasingly performed worldwide due to its efficacy and safety. This study aimed to assess the evidence of the impact of early vs. delayed feeding after ESD on quality of care, which remains to be fully determined. Methods: Electronic databases (PubMed, the Cochrane Central Register of Controlled Trials, EMBASE) and the trial registries (the World Health Organization International Clinical Trials Platform Search Portal and ClinicalTrials.gov) were searched for studies performed prior to September 2020. Study selection, data abstraction, and quality assessment were independently performed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Self-rated satisfaction and hospital stay were chiefly analyzed. Results: Two randomized controlled trials (239 patients) were included. The early and delayed post-ESD feeding groups had similar rates of post-ESD bleeding (risk ratio 1.90, 95% CI 0.42 to 8.63; I2 = 0%). Early post-ESD feeding resulted in increased patients' satisfaction in comparison to delayed post-ESD feeding (standard mean difference (MD) 0.54, 95% CI 0.27 to 0.81; I2 = 0%) and reduced the length of hospital stay (MD -0.83, 95% CI -1.01 to -0.65; I2 = 0%). Conclusion: Early post-ESD feeding was associated with increased patients' satisfaction and reduced hospital stay in comparison to delayed feeding, while the rate of complications did not differ to a statistically significant extent. As we must acknowledge the limited number of reviewed studies, various trials regarding the quality of care are further needed to determine the benefits of early feeding after ESD.

Background Whether circulating growth differentiation factor 15 (GDF-15) levels differ according to smoking status and whether smoking modifies the relationship between GDF-15 and mortality in patients with coronary artery disease are unclear. Methods and Results Using data from a multicenter, prospective cohort of 2418 patients with suspected or known coronary artery disease, we assessed the association between smoking status and GDF-15 and the impact of smoking status on the association between GDF-15 and all-cause death. GDF-15 was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study (Development of Novel Biomarkers Related to Angiogenesis or Oxidative Stress to Predict Cardiovascular Events). Patients were followed up during 3 years. The age of the patients ranged from 19 to 94 years; 67.2% were men. Never smokers exhibited significantly lower levels of GDF-15 compared with former smokers and current smokers. Stepwise multiple linear regression analysis revealed that the log-transformed GDF-15 level was independently associated with both current smoking and former smoking. In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders. This association was still significant in never smokers, former smokers, and current smokers. However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in current smokers or in former smokers. Conclusions Not only current, but also former smoking was independently associated with higher levels of GDF-15. The prognostic value of GDF-15 on mortality was most pronounced in never smokers among patients with suspected or known coronary artery disease.

Objectives: The role of point-of-care testing (POCT) out of hospital, especially in home care and ambulatory care settings, is an issue meriting further research. We reviewed studies reporting cardiovascular events as a result of the implementation of B-type natriuretic peptide or N-terminal pro B-type natriuretic peptide POCT (BNP/NT-proBNP POCT) for heart disease patients in the settings. Design: Articles were searched via a PubMed engine until May 30, 2020. Results: In total, six studies were selected. Three studies involving ambulatory care used the POCT to refer patients with suspected heart diseases to a specialist. The other three used the tests in home care to monitor patients with heart failure. In ambulatory care, the randomized controlled trials, in which referrals were made to a specialist, showed that the group using POCT had significantly fewer cardiovascular outcomes, such as hospitalizations and deaths, than the non-use group. In home care, adverse outcomes were predicted from changes in BNP levels. Conclusions: In most studies, the use of BNP/NT-proBNP POCT in home care and ambulatory care settings demonstrated favorable results regarding the cardiovascular outcomes. The utility of POCT in the settings is suggested, while more investigations are required.

Early feeding after percutaneous endoscopic gastrostomy (PEG) placement is an accepted practice in the treatment of adult patients and the knowledge is clinically extrapolated in the treatment of children. To verify this treatment in children-as there are some specific features of PEG-related practices in children-the present study aimed to review meta-analyses of early feeding (within 4 h) after PEG placement in children. We searched the PubMed database for articles published until July 2020. A quality assessment was performed using the Grading of Recommendations, Assessment, Development, and Evaluation method. Three randomized controlled trials (208 patients) were eligible for inclusion. No patients died within 72 h. Early feeding resulted in little to no difference in the length of hospital stay (mean difference [MD] -7.47, 95% confidence interval [CI] -25.16 to 10.21; I2 = 95%) and vomiting events (risk ratio 0.84, 95% CI 0.55 to 1.31; I2 = 0%). In a subgroup analysis, early feeding without antibiotics reduced the length of hospital stay in one study (MD -21.60, 95% CI -22.86 to -20.34) but early feeding with antibiotics did not affect the length in two studies (MD 0.28, 95% CI -6.49 to 7.06; I2 = 0%). Overall, the certainty of the evidence was not very high. In summary, early feeding after PEG placement may be a safe alternative to delayed feeding in children. The findings in children seemed similar to those in adults, while there is a need for further studies that specifically investigate PEG placement-related practices in children.

BACKGROUND: Since novel coronavirus disease (COVID-19) emerged, various clinical features of COVID-19 have been reported. METHODS: We conducted a systematic review of published studies reporting the clinical features of COVID-19. Two investigators independently searched PubMed (December 2019-February 2020) for eligible articles. A meta-analysis was performed to measure the frequencies of clinical outcomes and symptoms of COVID-19. A stratified analysis was conducted according to the timeline of outbreak and exposure histories: Group I, most patients were exposed to the Hunan seafood wholesale market and lived in Wuhan, Hubei province; Group II, patients lived in Hubei province but were not directly exposed to the market; and Group III, patients lived outside Hubei. RESULTS: Thirteen studies, all from China, were eligible. The estimated mortality rate among all studies was 2.12%, but that in Group I was 8.66%. The incidence of acute respiratory distress syndrome in Group I was 20.00%. Both fever and cough were major symptoms, and their frequencies were higher in Group I than in Groups II and III, while the frequency of diarrhea in Group I was lower than that in Group III. The estimated frequency of dyspnea in Group I was 37.18%, while those in Groups II and III were 16.95% and 7.03%, respectively. CONCLUSIONS: The trends in the clinical features of COVID-19 changed from December 2019 to February 2020. During this observation period, as the infection continued to spread, the clinical conditions for majority of patients became less severe with the changes in the route of transmission.

OBJECTIVES: Frequent self-weighing is associated with weight loss and maintenance, but the relationship between frequent self-weighing and the incidence of type 2 diabetes (T2D) remains unclear. The study aim was to examine the association between self-weighing frequency and the incidence of T2D in people with impaired fasting glucose (IFG). RESULTS: We tested the hypothesis that self-weighing frequency and the incidence of T2D are associated in 2607 people with IFG (1240 in the intervention arm; 1367 in the self-directed control arm). Both arms received a weighing scale with storage function. Healthcare providers offered a one-year goal-focused lifestyle intervention via phone. Participants were divided into 4 categories based on self-weighing frequency (No data sent [reference group], low: < 2 times/week, middle: 3-4 times/week, and high: 5-7 times/week). The adjusted hazard ratio (AHR) and 95% confidence interval (CI) were calculated. In the intervention arm, middle- and high-frequency self-weighing were associated with a decreased incidence of T2D relative to the reference group (AHR = 0.56, 95% CI [0.32, 0.98] and AHR = 0.43, 95% CI [0.25, 0.74], respectively). In the control arm, high-frequency self-weighing was also associated with a decreased incidence of T2D relative to the reference group (AHR = 0.54, 95% CI [0.35, 0.83]). Trial registration This trial has been registered with the University Hospital Medical Information Network (UMIN000000662).

The current coronavirus disease 2019 (COVID-19) pandemic presents a global challenge for managing acutely ill patients and complications from viral infection. Systemic inflammation accompanied by a "cytokine storm," hemostasis alterations and severe vasculitis have all been reported to occur with COVID-19, and emerging evidence suggests that dysregulation of lipid transport may contribute to some of these complications. Here, we aim to summarize the current understanding of the potential mechanisms related to COVID-19 dyslipidemia and propose possible adjunctive type therapeutic approaches that modulate lipids and lipoproteins. Specifically, we hypothesize that changes in the quantity and composition of high-density lipoprotein (HDL) that occurs with COVID-19 can significantly decrease the anti-inflammatory and anti-oxidative functions of HDL and could contribute to pulmonary inflammation. Furthermore, we propose that lipoproteins with oxidized phospholipids and fatty acids could lead to virus-associated organ damage via overactivation of innate immune scavenger receptors. Restoring lipoprotein function with ApoA-I raising agents or blocking relevant scavenger receptors with neutralizing antibodies could, therefore, be of value in the treatment of COVID-19. Finally, we discuss the role of omega-3 fatty acids transported by lipoproteins in generating specialized proresolving mediators and how together with anti-inflammatory drugs, they could decrease inflammation and thrombotic complications associated with COVID-19.

Background: Aspiration pneumonia (AsP), a phenotype of community-acquired pneumonia (CAP), is a common and problematic disease with symptomless recurrence and fatality in old adults. Characteristic factors for distinguishing AsP from CAP need to be determined to manage AsP. No such factorial markers in oldest-old adults, who are often seen in the primary-care settings, have yet been established. Methods: From the database of our Primary Care and General Practice Study, including the general backgrounds, clinical conditions and laboratory findings collected by primary care physicians and general practitioners, the records of 130 patients diagnosed with either AsP (n = 72) or CAP (n = 58) were extracted. Characteristic factors associated with the diagnosis of AsP were statistically compared between AsP and CAP. Results: The patients were older in the AsP group (median 90 years old) than in the CAP group (86 years old). The body temperature, heart rate, and diastolic blood pressure were lower in the patients with AsP than in those with CAP. Witnessed meal dysphagia by families and caregivers was reported only in AsP. Living in a nursing home, comorbidities of cerebral infarction and dementia (as positive factors) and hypertension (as a negative factor) were considered predictive to diagnose AsP in a stepwise logistic regression analysis. Conclusions: Among oldest-old adults in primary-care settings, living in a nursing home and the dysphagia risks are suggested to be characteristic factors for diagnosing AsP. Age and some relevant clinical information may help manage AsP and also be useful for families and caregivers.

Background VEGF-D (vascular endothelial growth factor D) and VEGF-C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF-C level is inversely and independently associated with all-cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF-D had distinct relationships with mortality and cardiovascular events in those patients. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF-D was measured. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3-year follow-up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N-terminal pro-B-type natriuretic peptide, cardiac troponin-I, and high-sensitivity C-reactive protein), and VEGF-C, the VEGF-D level was significantly associated with all-cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF-D, either alone or in combination with VEGF-C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all-cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old. Conclusions In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF-D value seems to independently predict all-cause mortality.

BACKGROUND: Kimura's disease (KD) is known to be dominant among young Asian men, but it can also occur in middle- and advanced-aged people. The clinical characteristics of KD, especially by age, are not well known. AIM: This study was performed to investigate the effects of age on the clinical characteristics of KD. DESIGN: We conducted a case series study. METHODS: All case studies of patients diagnosed with KD were collected via a PubMed search of studies published until August 2018. The data were analyzed by age group. RESULTS: In total, 215 studies were reviewed (238 patients; mean age of 36 years). The male:female ratio was 4:1 overall, 17:1 in patients aged <20 years, 4:1 in patients aged 20-39 years and 2:1 in patients aged ≥40 years (P = 0.01). The percentage of patients with pruritus was 15.4% overall, 3.8% in patients aged <20 years, 15.5% in patients aged 20-39 years and 21.7% in patients aged ≥40 years (P = 0.02). The time to diagnosis was 5.3 years overall, 3.2 years in patients aged <20 years, 4.7 years in patients aged 20-39 years and 7.1 years in patients aged ≥40 years (P < 0.01). CONCLUSIONS: The proportion of female patients affected the incidence of pruritus, and the time to diagnosis increased as the patients' age increased. There were no significant age-related differences in region/race, complications, multiplicity, laterality, anatomical distribution, maximum size, eosinophil count, immunoglobulin E level, initial treatment, recurrence or outcomes. This may be useful information for the diagnosis of KD.

INTRODUCTION: Many medical professionals unofficially use quick methods for saving time. However, the evidence of such assessments is limited. The main aim of this article is verifying the agreement of these methods. OBJECTIVES: Overall, 106 out-patients were simultaneously evaluated with respect to the respiratory time measurement (RTM; 60 divided by the single respiratory time), 15 seconds period quadruple respiratory rate (15secRR; 15 seconds respiratory rate multiplied by 4), and 1-min respiratory rate (1minRR; gold standard respiratory rate). METHOD: We assessed the correlation, Bland-Altman plot, kappa value, and normalized root mean square error of the quick methods for the respiratory rate, with 1minRR as the gold standard. RESULTS: The mean ± SD of 1minRR, RTM, and 15secRR are 20.4 ± 5.6, 19.1 ± 5.7, and 21.4 ± 6.5 breathes per minute, respectively. The correlation between RTM and 1minRR was 0.85 (95% confidence interval [95% CI]: 0.79-0.90), while that between 15secRR and 1minRR was 0.81 (95% CI: 0.74-0.87). The kappa coefficients between RTM and 1minRR, between 15secRR and 1minRR, and between RTM and 15secRR were 0.57 (95% CI: 0.41-0.72), 0.59 (95% CI: 0.43-0.74), and 0.37 (95% CI: 0.20-0.53), respectively. The normalized root mean square error between RTM and 1minRR was 16.9% and that between 15secRR and 1minRR was 15.0%. The Bland Altman plot demonstrated that RTM and 15secRR showed contrasting characteristics. CONCLUSION: Compared to the gold standard, RTM tends to underestimate, while 15secRR tends to overestimate the respiratory rate. Therefore, health care professionals should be aware of this methodological tendency to assess vital signs properly.

BACKGROUND: The cardiovascular relevance of isolated low levels of high-density lipoprotein cholesterol (HDL-C) is yet to be determined. Stroke often leads to long-term disability, and thus, not only stroke mortality but also stroke incidence is a topic of research. Although isolated low HDL-C level has been found to be a predictor for stroke mortality previously, whether it can predict stroke incidence is unknown. METHODS: In the Jichi Medical School cohort study, 11 025 community-living residents without a history of stroke were examined. Hazard ratios (HRs) for isolated and non-isolated low HDL-C levels were calculated relative to those for normal HDL-C levels in stroke patients using Cox's regression models. RESULTS: During the mean follow-up period of 10.7 years, 412 residents had their first-ever stroke. The multivariable-adjusted HRs for the levels of isolated and non-isolated low HDL-C were 1.11 (95% confidence interval, 0.85-1.44) and 1.35 (1.01-1.81), respectively, when compared to that for normal HDL-C. CONCLUSION: Low HDL-C levels with other dyslipidemias may contribute to the incidence of stroke, not isolated low HDL-C.

BACKGROUND: Following community clinical placements, medical students use reflective writing to discover the story of their journey to becoming medical professionals. However, because of assessor bias analyzing these writings qualitatively to generalize learner experiences may be problematic. This study uses a process-oriented text mining approach to better understand meanings of learner experiences by connecting key concepts in extended student reflective essays. METHODS: Text mining quantitative analysis is used on self-evaluative essays (n = 47, unique word count range 43-575) by fifth-year students at a regional quota-system university in Japan that specializes in training general practitioners for underserved communities. First, six highly-occurring key words were identified: patient, systemic treatment, locale, hospital, care, and training. Then, standardized keyword frequency analysis robust to overall essay length and keyword volume used individual keywords as "nodes" to calculate per-keyword values for each essay. Finally, Principle Components Analysis and regression were used to analyze key word relationships. RESULTS: Component loadings were strongest for the keyword area, indicating most shared variance. Multiply regressing three of the remaining keywords hospital, systemic treatment, and training yielded R2 = 0.45, considered high for this exploratory study. In contrast, direct patient experience for students was difficult to generalize. CONCLUSIONS: Impressions of the practicing area environment were strongest in students, and these impressions were influenced by hospital workplace, treatment provision, and training. Text mining can extract information from larger samples of student essays in an efficient and objective manner, as well as identify patterns between learning situations to create models of the learning experience. Possible implications for community-based clinical learning may be greater understanding of student experiences for on-site precepts benefitting their roles as mentors.

Safe obstetric care is a worldwide requirement. In Japan, a reduced number of obstetricians has prompted the centralization of obstetric facilities, and Japan's islands are expected to experience problems in handling deliveries. Although many pregnant women "move" to the mainland at later gestational weeks, "transport" from the island to the mainland may be occasionally needed when disorders manifest before the "move." Other women plan within-island deliveries; however, transport is required when complications arise. Managing delivery- or pregnancy-related problems may differ in transport by the population size of islands. We investigated the following issues in relation to the population size of Japan's islands: 1) How were deliveries handled on islands? 2) How many pregnant women were transported to the mainland? 3) What was the reason for and what affected transport? A total of 142 municipalities were selected to participate in a questionnaire survey, and 108 institutions from 106 municipalities responded. A comparative analysis by island size was performed using 2014 data: small-sized (population < 1,000), mid-sized (1,000 to 5,000), and large-sized (≥ 5,000). The percentage of women transported to the mainland from small-sized islands was significantly higher than that from large-sized islands (6.8 vs. 2.6% of all births in a year, respectively, P < 0.01). Transport was mainly in response to threatened preterm labor. Adverse weather was the most frequent factor affecting transport reliability. Our findings may contribute to a more detailed understanding of the state of obstetric care on Japan's islands.

We aimed to investigate the relationship between high-density lipoprotein cholesterol (HDL-C) concentration and the incident stroke subtypes. We enrolled 11 027 participants between the ages of 18 and 90 years without a history of stroke in 12 Japanese communities. Cox's regression models were used for stroke subtypes, adjusted for traditional risk factors, according to the categories based on HDL-C concentrations: 1.04 to 1.55 mmol/L, ≥1.56 mmol/L, and <1.03 mmol/L (as the reference). During a mean follow-up of 10.7 years, 412 stroke events had occurred. However, HDL-C was not significantly associated with the incidence of cerebral infarction and subarachnoid hemorrhage. High HDL-C concentration was associated with a decreased incidence of intracerebral hemorrhage in women (hazard ratio = 0.23; 95% confidence interval = 0.06-0.89), but not in men (hazard ratio = 0.73; 95% confidence interval = 0.27-1.97). Therefore, high HDL-C concentration might have a protective effect on the incidence of intracerebral hemorrhage, particularly in women.

Background: The importance of management of metabolic syndrome (MetS) for risk reduction of cardiovascular disease (CVD) has been recognized worldwide. Because of the comparatively unique characteristics of bodily figure/obesity and incident CVD in Japan, the relevance of MetS on CVD can be still discussed among Japanese people. The present study aimed to review briefly the relationship of MetS with CVD morbidity/mortality among general Japanese people. Methods: Population-based prospective cohort studies evaluating the predictive value of MetS on CVD morbidity/mortality via a PubMed search up to 2019 were summarized. Results: We identified two studies on morbidity that reported MetS to predict CVD morbidity. We identified three studies on mortality, and these studies showed an increased direction of hazard ratio (HR) of CVD mortality, while one study reported an insignificant prediction of MetS for CVD mortality. In the meta-analysis method, MetS significantly predicted CVD morbidity (HR=1.71 [95% confidence interval=1.34-2.18] in men and HR=1.89 [95% confidence interval=1.45-2.46] in women) as well as CVD mortality (HR=1.68 [95% confidence interval=1.37-2.06] in men and HR=1.73 [95% confidence interval=1.39-2.15] in women). Conclusion: Among general Japanese people, MetS can be a positive predictor of CVD morbidity/mortality. Since the studies are limited, more research is needed to establish the findings.

OBJECTIVES: Using annual health check-up data, the aim of this study was to identify target populations for lifestyle interventions to effectively prevent diabetes in a real-world setting. METHODS: The Japan Diabetes Outcome Intervention Trial-1, a prospective, cluster-randomized controlled trial, was launched to test if year-long telephone-delivered lifestyle support by health professionals can prevent the development of type 2 diabetes (T2D) in people with impaired fasting glucose (IFG) identified at health check-ups. A total of 2607 participants aged 20-65 years with IFG were randomized to an intervention arm (n = 1240) or a control arm (n = 1367). We performed subgroup analysis to examine the effects of the intervention on the incidence of T2D in participants with body mass index (BMI) ≥25, metabolic syndrome (MetS), and non-alcoholic or alcoholic elevated liver enzymes at the baseline. Cox regression analysis adjusted for sex was used to calculate the hazard ratios (HRs). RESULTS: In addition to IFG, the presence of BMI ≥25, MetS, and elevated liver enzymes increased the incidence of diabetes by two- or three-fold. During a median follow-up period of 4.9 years, only the non-alcoholic elevated liver enzyme group showed a low incidence rate owing to lifestyle interventions (adjusted HR: 0.42, 95% confidence interval: 0.18-0.98). CONCLUSION: The results suggest that people who have IFG and non-alcoholic elevated liver enzymes are a good target population for lifestyle interventions to effectively reduce the incidence of diabetes in a real-world setting.

Introduction: Lipoprotein(a) (Lp[a]) is a risk factor of cardiovascular disease (CVD). Familial hypercholesterolemia (FH), which exhibits high low-density lipoprotein cholesterol (LDL-C) levels, is a risk factor of CVD. The relationship of Lp(a) with CVD has been characterized in populations specific to FH. Material and methods: Studies reporting on the relationship of Lp(a) with CVD among FH subjects via PubMed up to 2020 were reviewed. Results: Eight studies were identified as eligible. In the meta-analyses, a high Lp(a) level was significantly and predictively associated with CVD compared to a low Lp(a) level in 2 cross-sectional studies (odds ratio = 2.57; 95% confidence interval (CI): 1.16-5.73) and 6 cohort studies (risk/hazard ratio = 1.91; 95% CI: 1.50-2.43). The totally integrated relative risk of these studies was 1.97 (95% CI: 1.57-2.46). Conclusions: FH subjects with high Lp(a) levels can have a high CVD risk, and besides LDL-C, attention should be paid to Lp(a) levels in FH subjects.

A 60-year-old man was admitted to our hospital with bilateral post auricular masses, first noticed 1 year earlier. Blood tests showed eosinophilia and high immunoglobulin E (IgE) levels, and cervical computed tomography showed 10-mm soft tissue masses with scattered lymphadenopathy. The tumors showed intermediate and high signal intensity on T1- and T2-weighted cervical magnetic resonance imaging, respectively. After mass resection, the tumors were diagnosed as Kimura's disease (KD). Generally, KD affects young men; however, even in older patients, KD should be included as a differential diagnosis for head and neck tumors in patients with eosinophilia and high IgE.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The frequency of use of emergency telephone consultation (ETC) services, which is a telephone triage system in Japan, was explored to determine age- and sex-related trends on symptoms/events among Japanese adults. Data were obtained from records of the initial year of ETC services in Saitama Prefecture (from October 2014 to September 2015). Residents who used the ETC services were divided into four age groups (20-39, 40-64, 65-74, and ≥75 years old). The number of calls per 1000 persons (call rate, CR) was compared between the groups. The annual CR for the top 10 symptoms/events were assessed. The annual CR was 2.6/1000 persons. The annual CR was significantly higher for women (2.9) than for men (2.3) (p < 0.05). ETC use was the highest in the 20-39 age group for both sexes (3.3 and 4.4 in men and women, respectively). All groups had fever, abdominal pain, and nausea/vomiting in common. In older adults, the frequency of events such as bruises and head injury was high. Women and younger adults tended to use ETC services. There were similarities and differences in symptoms/events among the groups, which should be recognized by call centers to help foster call center staff.

Elucidating the perceptions of residents regarding medical group practice (GP) among rural communities (GP-R) in Japan will be useful for establishing this system in such communities. A survey by questionnaire, as made by experts in rural health, was conducted in 2017. The self-administered questionnaire inquired about the perceptions of residents for accepting the GP-R into the community's healthcare using seven major elements of GP-R. The questionnaire was randomly distributed to 400 adult residents who lived in rural communities with a recently launched GP and had access to clinics within the communities. Among the 321 respondents, comparisons were made between younger (≤sixties) and older (≥seventies) residents, and a stepwise multiple regression analysis was performed to extract the factors influencing acceptance of the GP-R system. The results showed that older residents had a greater disapprove of being treated by different physicians daily or weekly in clinics (p < 0.001) and the use of telemedicine (p < 0.001) compared with younger residents. Younger residents showed a greater disapproval of clinics closing on weekdays than older residents (p = 0.007). Among all respondents, regardless of age groups, over half of residents approved of the involvement of nurse practitioners in the GP-R. Living with family and children was also extracted as an independent factor influencing a positive perception of the GP-R. These data suggest that the promotion of GP-R should consider generation gaps in the approach to medical practice as well as the family structures of residents. The involvement of nurse practitioners can also encourage the acceptance of GP-R in Japan.

Resolution of regional disparities in cancer mortality is global challenge. Establishing an equal system of cancer treatment throughout the country is required under the Cancer Control Act in Japan. The types of treated cancer may reflect practical experience at the institutions and cooperation to other institutions. This study investigated the types treated at the institutions in rural communities of Japan. A questionnaire survey was conducted for 811 public rural institutions (clinics and small-to-middle-sized hospitals [< 200 beds]) in 2013. The survey's items included the types of treated cancer (14 categories: stomach, colon, breast, liver, biliary tract, pancreatic, prostate, esophageal, lung, renal, urinary tract, testicular, hematopoietic, and others) and the first five types were defined as major cancers. The data were analyzed between hospitals and clinics. The response rate was about 60%, and of 177 hospitals and 281 clinics, 54 hospitals (30%) and 10 clinics (3%) reported the types of cancer. The median number of cancer types in hospitals was significantly greater than that of clinics (4 [interquartile range 3.0-7.8]) vs. 1 [1.0-1.8], P < 0.01). The prevalence of hospitals treating at least one of five major cancers was significantly greater than that of clinics (96% vs. 30%, P < 0.01). The prevalence of clinics treating prostate cancer was significantly greater than that of hospitals (31% vs. 70%, P = 0.03). In conclusion, most types of cancer are treated at small-to-middle-sized hospitals, except for prostate cancer, providing basic information about cancer treatment in rural communities of Japan.

AIMS: A functional abnormality in high-density lipoprotein (HDL) particles rather than a quantitative abnormality in HDL cholesterol levels has been suggested to promote atherosclerosis. The modification of HDL may underlie functional changes to HDL such as gaining the ability to bind and activate the lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1). We aimed to develop a novel method for measuring modified HDL on the basis of its binding to LOX-1. METHODS: We designed a LOX-1 binding-based enzyme-linked immunosorbent assay (ELISA) with recombinant LOX-1 and anti-apoAI antibody. A lipid-free standard was devised by making a chimeric fusion protein containing anti-LOX-1 antibody and human apoAI fragment. We used this system to detect modified HDL, designated as LOX-1 ligand containing apoAI (LAA). RESULTS: With our ELISA system, we detected HDL modified by copper oxidation, hypochlorous acid, 4-hydroxynonenal, and potassium cyanate, but not native HDL. Upon oxidation, HDL showed increased LOX-1 binding activity and decreased cholesterol efflux and paraoxonase-1 activities. In the ELISA, the chimeric fusion protein standard showed minimal variation in reference binding curves in contrast to copper-oxidized HDL preparations, suggesting better quality control of the chimeric fusion protein as the standard for measuring modified HDL activity. LAA was detectable in the plasma of healthy individuals and of mice fed a high-fat diet. CONCLUSION: We have developed a novel ELISA by using recombinant LOX-1 and anti-apoAI antibody to measure the activity of modified HDL in plasma.

AIM: Clinical prediction scores for older patients are inaccurate, partially because they do not account for the effects of aging on the respiratory rate. The principal aim of the present study was to assess the effects of aging on the normal respiratory rate in older patients in a clinical setting. METHODS: We recruited 634 participants aged >59 years to <100 years who presented to our hospital (Iwakuni Municipal Miwa Hospital, for regular appointments without any new symptoms. We assessed the relationship between age and respiratory rate using Pearson's correlation coefficient and the Jonckheere-Terpstra test. We carried out multiple linear regression analysis, with sex, age, blood pressure, heart rate and 14 comorbidities as dependent variables, and respiratory rate as the independent variable. RESULTS: The mean ± standard deviation respiratory rate for all for all participants was 16.1 ± 4.28. The mean ± standard deviation respiratory rates for individuals aged in their 60s, 70s, 80s and 90s were 14.8 ± 4.28, 15.5 ± 3.62, 16.37 ± 4.48 and 17.1 ± 4.45, respectively. Pearson's correlation coefficient between age and respiratory rate was 0.17 (95% confidence interval 0.10-0.25). The Jonckheere-Terpstra test and multiple linear regression analysis showed a significant positive trend between age group and respiratory rate (P < 0.001). CONCLUSIONS: Although the correlation coefficient between age and respiratory rate was low (R = 0.17), aging was a statistically significant factor in determining the normal respiratory rate in older patients. Furthermore, the respiratory rate increased with age. Geriatr Gerontol Int 2019; 19: 1179-1183.

Circulating ApolipoproteinL1 (ApoL1) is a component of pre-β-high-density lipoprotein (HDL), however little is known about the relationship of ApoL1 with cardiometabolic factors. Considering previous studies reporting the correlation of ApoL1 to triglyceride, we have hypothesized that ApoL1 associates with insulin-related metabolism. The current study examined their associations in 126 non-diabetic subjects and 36 patients with type 2 diabetes (T2DM). Non-diabetic subjects demonstrated triglyceride (standardized coefficients [s.c.] = 0.204, p < 0.05), body mass index (s.c. =0.232, p < 0.05) and HDL cholesterol (s.c. = -0.203, p < 0.05) as independent determinant of ApoL1 levels, and the significant elevation of ApoL1 in metabolic syndrome. Lipoprotein fractionation analysis revealed the predominant distribution of ApoL1 in large HDL fraction, and the significant increase of ApoL1 in large LDL fraction in high ApoL1 samples with insulin resistance. In T2DM, ApoL1 was higher in T2DM with metabolic syndrome, however ApoL1 was lower with β cell dysfunction. Insulin significantly promotes ApoL1 synthesis and secretion in HepG2 cells. In conclusion, circulating ApoL1 may be associated with abnormal HDL metabolism in insulin resistant status. This may suggest a regulation of insulin signal on the ApoL1 level, leading to offer a novel insight to the ApoL1 biology.

The ratio of oxidized lipoprotein(a) to native lipoprotein(a) (oxLp(a)/Lp(a)) may be a reasonable index for assessing endothelial dysfunction in type 2 diabetes mellitus (T2DM). The present study investigated whether the oxLp(a)/Lp(a) level is correlated with the endothelial function using the Endo-PATTM, a newly developed device, in patients with T2DM. A total of 63 patients with T2DM (mean age: 59 years old) were enrolled in the study. The patients' serum Lp(a) and oxLp(a) levels were measured using an enzyme-linked immunosorbent assay. The reactive hyperemia index (RHI) level was measured using an Endo-PATTM 2000. A correlation analysis between the measured variables was conducted. Among the patients, the mean hemoglobin A1c was 7.8%. The median level of oxLp(a)/Lp(a) was 0.28 (interquartile range: 0.07-0.54), and the mean RHI was 1.8 (standard deviation: 0.4). In a multiple linear regression analysis, the oxLp(a)/Lp(a) level was an independent, significant, and inverse variable for the RHI level (β = -0.26, p < 0.05), along with male gender. A high oxLp(a)/Lp(a) level may reflect endothelial dysfunction, as assessed by the Endo-PATTM, in patients with T2DM. Further studies are warranted to confirm the observed findings.

Background: Evidence of the long-term benefits of telephone-delivered lifestyle interventions is limited. This study investigated the ability of telephone-delivered lifestyle intervention to reduce the incidence of metabolic syndrome (MetS) in subjects diagnosed with impaired fasting glucose (IFG) during health checkups. Methods: Our subjects were participants in the Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1), a prospective, cluster-randomized controlled trial designed to investigate whether goal-focused lifestyle coaching over the telephone can effectively reduce the incidence of type 2 diabetes development in high-risk individuals in a primary health care setting. We extracted 753 and 844 J-DOIT1 participants from the intervention and controls arms, respectively, who had IFG but did not meet the MetS criteria at baseline. The intervention arm received goal-focused lifestyle support delivered by health care providers via telephone over a 1-year period. The endpoint was the development of incident MetS, defined based on the Adult Treatment Panel III criteria modified for Japan. Results: During the median follow-up period of 4.9 years, 8.0% of the intervention arm and 12.0% of the control arm developed MetS. Overall, the hazard ratio (HR) for the development of MetS was 0.75 [95% confidence interval (CI), 0.52-1.09; P = 0.14] in the intervention arm. However, the HR in overweight or obese [body mass index (BMI) ≥23 kg/m2] individuals was significantly reduced to 0.63 (95% CI, 0.41-0.95; P = 0.029), but not in lean (BMI <23 kg/m2) individuals. Conclusion: Telephone-delivered lifestyle intervention effectively reduced the incidence of MetS in overweight and obese subjects in a real-world setting. Clinical trial registration number: UMIN000000662 (registered March 30, 2007; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000000798).