Five percent weight loss is a significant 1-year predictor and an optimal 5-year cut-off for reducing the number of obesity-related cardiovascular disease risk components: the Japan Obesity and Metabolic Syndrome Study.

Objective: This study aimed to identify the amount of weight loss needed in patients with obesity to improve metabolic syndrome (MetS), a risk factor for cardiovascular disease (CVD), over a long period of time. Methods: A total of 576 patients with obesity were enrolled in this study. Effects of continuous physician-supervised weight loss on the cumulative MetS components excluding abdominal circumference (defined as obesity-related CVD risk score) were investigated during a 5-year follow-up period. The extent of weight loss required to reduce the obesity-related CVD risk components was assessed using receiver operating characteristic (ROC) curve analyses. Results: Of the 576 participants, 266 completed 5-year follow-up, with 39.1% and 24.1% of them achieving ≥5.0% and ≥7.5% weight loss at the 5-year follow-up, respectively. The area under the ROC curve for reducing the obesity-related CVD risk components was 0.719 [0.662-0.777] at 1 year and 0.694 [0.613-0.775] at 5 years. The optimal cut-off value for weight loss was 5.0% (0.66 sensitivity and 0.69 specificity) and the value with 0.80 specificity was 7.5% (0.45 sensitivity) at 5 years. Greater reductions in weight were associated with greater improvements in the obesity-related CVD risk score at all follow-up periods (P-trend <0.001). Obesity-related CVD risk score was significantly improved by 5.0-7.5% and ≥7.5% weight loss at 1 year (P = 0.029 and P < 0.001, respectively) and ≥7.5% weight loss at 5 years (P = 0.034). Conclusions: A weight loss of ≥5.0% at 1 year and ≥7.5% at 5 years could reduce the number of obesity-related CVD risk components in patients with obesity.

Relationship Between Clinics Offering Telemedicine and Population Density in Japan: An Ecological Study.

Background: The number of clinics offering telemedicine in Japan has been increasing. Regional characteristics such as population density and the number of physicians may be associated with the provision of telemedicine. This study investigated the relationship between clinics offering telemedicine and such regional characteristics for each prefecture in Japan. Methods: Data were collected from publicly available information that included the percentage of clinics offering telemedicine (real-time synchronous type) among all clinics (in 2022), population density, and the number of physicians for each of Japan's 47 prefectures. An ecological study was carried out to determine the correlation between the percentage of clinics offering telemedicine and regional characteristics for each prefecture, and Pearson correlation analysis and multiple regression analysis adjusted for regional characteristics were performed. Results: The min-max and mean levels were, respectively, 3.4-39.2% and 15.6% of clinics offering telemedicine, 66.6-6402.6 and 657.1 people per square kilometer of population density, and 185.2-356.7 and 274.0 physicians per 100,000 people. Geographically, the northeastern regions appeared to show a high percentage of clinics offering telemedicine relative to the southwestern regions. There was a significant negative correlation between the percentage of clinics offering telemedicine and population density (r = -0.31, p < 0.05; ß = -0.31, p < 0.05). Discussion: The negative relationship of the provision of telemedicine in clinics with population density throughout Japan might be a reflection to ensure residents' access to clinics in less populated areas. Although further detailed studies are needed to confirm this, population density might be a useful measure for considering whether to offer telemedicine in clinics in Japan.

Prognostic Biomarkers of Mortality in Older Patients Without Cancer in Home Healthcare.

Introduction The number of patients without cancer who receive home healthcare is increasing; however, prognostic prediction is challenging among them. This study aimed to investigate the prognostic value of generic biomarkers for mortality in patients without cancer who receive home healthcare. Materials and methods The multicenter retrospective cohort study included 114 older patients without cancer, of which 12 (10.5%) died during the study period. The median (interquartile range (IQR)) of the study observation period was 181 (49-293) days. Generic biomarkers included hemoglobin (Hb), albumin (Alb), C-reactive protein (CRP), estimated glomerular filtration rate (eGFR), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). A multivariate-adjusted Cox proportional hazard model on all-cause mortality was used to calculate hazard ratio (HR) and 95% confidence interval (95% CI) for each biomarker. The cut-off values of each biomarker were calculated by receiver operating characteristic curve analysis. The performance of cut-off values was evaluated by time-dependent area under the curves (AUCs). Results The median (IQR) of AST was 13 (10-21) U/L. The biomarkers significantly predictive of mortality were Hb (fully adjusted HR: 0.41; 95% Cl: 0.25 - 0.70), Alb (HR: 0.41; 95% Cl: 0.02 - 0.69), and AST (HR: 1.09; 95% Cl: 1.00 - 1.18), along with male sex (HR: 4.07; 95% Cl: 1.15 - 14.35). The AUC of a cut-off value of AST (> 31 U/L) at 360 days was 0.72 (95% CI 0.71 - 0.72; p < 0.01), which outperformed the AUCs for Hb and Alb. Conclusion AST, in addition to Hb and Alb, may be useful for predicting the prognosis of older patients without cancer, who had a normal-to-mild increased level of AST, in home healthcare settings. Larger-sample and longer follow-up studies will be warranted.

Validation and verification framework and data integration of biosensors and in vitro diagnostic devices: a position statement of the IFCC Committee on Mobile Health and Bioengineering in Laboratory Medicine (C-MBHLM) and the IFCC Scientific Division.

Advances in technology have transformed healthcare and laboratory medicine. Biosensors have emerged as a promising technology in healthcare, providing a way to monitor human physiological parameters in a continuous, real-time, and non-intrusive manner and offering value and benefits in a wide range of applications. This position statement aims to present the current situation around biosensors, their perspectives and importantly the need to set the framework for their validation and safe use. The development of a qualification framework for biosensors should be conceptually adopted and extended to cover digitally measured biomarkers from biosensors for advancing healthcare and achieving more individualized patient management and better patient outcome.

Relationship of Thyroid Function with Renal Hemodynamics and Cholesterol Metabolism in Proteinuric Kidney Disease: A Pilot Study.

Nephrotic syndrome and hypothyroidism are respectively reported to influence renal hemodynamics and hypercholesterolemia. However, the relationship of proteinuria-associated thyroid function with renal hemodynamics and cholesterol metabolism has yet to be determined in a simultaneous analysis of thyroid, renal, and cholesterol variables. We investigated the hypothesis that the changes in thyroid hormones by proteinuria may contribute to changes in cholesterol metabolism and renal hemodynamics by proteinuria. Twenty-nine patients (17 men and 12 women) with proteinuric kidney disease (mean age 46 years) were enrolled in a pilot study. Data for serum free triiodothyronine (FT3), free thyroxine (FT4), total cholesterol, and filtration fraction (FF; assessed by para-aminohippuric acid clearance) were used in variable-adjusted correlation analyses. The patients had the following data (mean ± standard deviation): urinary protein 5.18 ± 3.28 g/day, FT3 2.18 ± 0.44 pg/mL, FT4 1.03 ± 0.26 ng/dL, FF 0.27 ± 0.07, and total cholesterol 327 ± 127 mg/dL. There was a significant positive correlation of FT3 with FF (ß = 0.58, p = 0.01) and a significant inverse correlation of FT4 with total cholesterol (ß = -0.40, p = 0.01). A positive correlation of FT3 with FF and an inverse correlation of FT4 with total cholesterol were demonstrated in patients with proteinuric kidney disease. The proteinuria-associated reduction in serum thyroid hormone levels was correlated with hypercholesterolemia and the reduced glomerular FF. Further studies of these relationships are required.

Diagnostic Accuracy of Highest-Grade or Predominant Histological Differentiation of T1 Colorectal Cancer in Predicting Lymph Node Metastasis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Treatment guidelines for colorectal cancer (CRC) suggest 2 classifications for histological differentiation-highest grade and predominant. However, the optimal predictor of lymph node metastasis (LNM) in T1 CRC remains unknown. This systematic review aimed to evaluate the impact of the use of highest-grade or predominant differentiation on LNM determination in T1 CRC. METHODS: The study protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO, registration number: CRD42023416971) and was published in OSF ( https://osf.io/TMAUN/ ) on April 13, 2023. We searched 5 electronic databases for studies assessing the diagnostic accuracy of highest-grade or predominant differentiation to determine LNM in T1 CRC. The outcomes were sensitivity and specificity. We simulated 100 cases with T1 CRC, with an LNM incidence of 11.2%, to calculate the differences in false positives and negatives between the highest-grade and predominant differentiations using a bootstrap method. RESULTS: In 42 studies involving 41,290 patients, the differentiation classification had a pooled sensitivity of 0.18 (95% confidence interval [CI] 0.13-0.24) and 0.06 (95% CI 0.04-0.09) ( P < 0.0001) and specificity of 0.95 (95% CI 0.93-0.96) and 0.98 (95% CI 0.97-0.99) ( P < 0.0001) for the highest-grade and predominant differentiations, respectively. In the simulation, the differences in false positives and negatives between the highest-grade and predominant differentiations were 3.0% (range 1.6-4.4) and -1.3% (range -2.0 to -0.7), respectively. DISCUSSION: Highest-grade differentiation may reduce the risk of misclassifying cases with LNM as negative, whereas predominant differentiation may prevent unnecessary surgeries. Further studies should examine differentiation classification using other predictive factors.

Asian Variant Intravascular Lymphoma: A Look at the Laboratory Data of Lactase Dehydrogenase and Soluble Interleukin-2 Receptor.

Asian variant intravascular lymphoma (AIVL) is a rare type of intravascular lymphoma that occurs in Asian populations. Syndrome of inappropriate antidiuretic hormone selection (SIADH) frequently occurs in patients with AIVL. Because it remains difficult to diagnose and has a poor prognosis, markers for early diagnosis are required. Although lactase dehydrogenase (LD) and soluble interleukin-2 receptor (sIL-2R) are diagnostic candidates, these markers do not appear to have been used often in prior studies. We present the case of an 87-year-old Japanese man with AIVL complicated by unexplained SIADH with a complaint of anorexia. Computer tomography showed splenomegaly but no lymphadenopathy. Elevated LD and sIL-2R were detected in the blood. The patient was diagnosed with AIVL through a random skin biopsy and was successfully treated with chemotherapy. When a patient presents with SIADH, we should actively look at or measure blood LD and sIL-2R for early diagnosis of ALVL. Further cases are warranted to determine these observations.

Regional Variations in Coronavirus Disease 2019 Mortality in Japan: An Ecological Study.

Introduction: As the characteristics of coronavirus disease 2019 (COVID-19) vary across regions and countries, the relationship between regional characteristics, such as the distribution of physicians and hospital beds, and COVID-19 mortality was assessed in the 47 prefectures of Japan. Methods: This ecological study was based on the number of patients with COVID-19 by prefecture during the seventh wave of COVID-19 in Japan (June-October 2022). COVID-19 mortality was indexed as the number of COVID-19 deaths divided by the number of new COVID-19 cases. Data on regional factors, such as population size, number of physicians, and hospital beds by prefecture, were obtained from government statistics. Correlations between regional characteristics and COVID-19 mortality index were analyzed by dividing the 47 prefectures into two groups at the median level of population size (more populated group [MPG] ≥ 1.6 million and less populated group [LPG] < 1.6 million). Results: The COVID-19 mortality index (mean 12.7, minimum-maximum: 4.7-25.7) was correlated negatively with the number of physicians per hospital bed (r = -0.386, p = 0.007) and positively with the number of long-term care facilities per 10,000 population (r = 0.397, p = 0.006) and aging rate (the proportion of population aged ≥ 65 years) (r = 0.471, p = 0.001). The two groups varied with respect to the number of physicians (28.7 physicians in the LPG vs. 26.1 physicians in the MPG, p = 0.038) and hospital beds (156 beds in the LPG vs. 119 beds in the MPG, p < 0.001) per 10,000 population. In the multiple regression analysis, the COVID-19 mortality index was correlated negatively with the number of physicians per hospital bed (ß = -0.543, p = 0.024) and positively with the aging rate (ß = 0.434, p = 0.032) in the LPG, with nonsignificant correlations in the MPG. Conclusions: The data may suggest a need of improvement in the distribution of physicians and hospital beds in the healthcare system in regions with smaller and older populations to reduce the rate of COVID-19.

Factors associated with regional retention of physicians: a cross-sectional online survey of medical students and graduates in Japan.

BACKGROUND: Physician shortage and maldistribution is an urgent health policy issue requiring resolution. Determination of factors associated with regional retention and development of effective policy interventions will help to solve this issue. The purpose of the present study was to identify factors associated with regional retention and discuss their policy implications. METHODS: We conducted a cross-sectional online survey from February to March of 2022 for graduates from regional quotas (special quotas for medical schools to select students engaged in community medicine) and Jichi Medical University (JMU) and students at 10 medical schools including JMU. Completed surveys were obtained from 375 graduates and 1153 students. Questions included intention to continue to work in their home prefecture in the future, as well as background information and potential factors associated with regional retention. In the analyses, regional quotas and JMU were referred to as community medicine-oriented programs and schools (CMPS). We performed logistic regression analyses to identify factors associated with regional retention. RESULTS: Among the students, scholarship-bonded obligatory service, satisfaction with current life, intention to belong to ikyoku (a traditional physician allocation/training system in Japanese medical schools), and interest in general practice/family medicine were significantly positively associated with regional retention. Among the graduates, satisfaction with training environment, intention to belong to ikyoku, and recommending their program to high school students were significantly positively associated with regional retention. For students of CMPS, satisfaction with the career development program was positively associated with future regional retention. For graduates, this association was observed only in the crude analysis. CONCLUSIONS: In addition to known factors such as interest in general practice/family medicine, intention to belong to ikyoku had a substantial impact on regional retention. The present results suggest that the career support system represented by ikyoku as well as a career development program are of potential importance for increasing regional retention through the mechanisms of a sense of belonging and a life-long education system. These findings provide useful information for the development of further policy interventions that interweave traditional and new systems to maximize their effectiveness.

Differences in metabolic characteristics between Metabolically Healthy Obesity (MHO) and Metabolically Unhealthy Obesity (MUO) in weight reduction therapy.

Metabolically Healthy Obesity (MHO) is generally recognized as the absence of any metabolic disorders and cardiovascular diseases, including type 2 diabetes, dyslipidemia, and hypertension, in obese individuals; however, it is not clearly defined. Therefore, the present study investigated differences in metabolic characteristics between individuals with MHO and Metabolically Unhealthy Obesity (MUO) during weight reduction therapy. The key factors defining MHO and the importance of weight reduction therapy for MHO were also examined. Cohort data from the Japan Obesity and Metabolic Syndrome (JOMS) study were analyzed. Subjects were divided into the MHO (n = 25) and MUO (n = 120) groups. Prior to weight reduction therapy, serum adiponectin levels were significantly higher in the MHO group than in the MUO group. Serum adiponectin levels also negatively correlated with the area of subcutaneous adipose tissue (SAT) and Homeostasis model assessment (HOMA)-R in the MHO group, but not in the MUO group. Collectively, the present results suggest the importance of adiponectin for maintaining metabolic homeostasis in the MHO group. On the other hand, no significant differences were observed in inflammatory markers between the MHO and MUO groups, suggesting the presence of chronic inflammation in both groups. Furthermore, a positive correlation was noted between changes in serum cystatin C levels and waist circumference in the MHO group, which indicated that despite the absence of metabolic disorders, the MHO group exhibited anti-inflammatory responses during weight reduction therapy. These results underscore the significance of weight reduction even for individuals with MHO.

Additional staining for lymphovascular invasion is associated with increased estimation of lymph node metastasis in patients with T1 colorectal cancer: Systematic review and meta-analysis.

OBJECTIVES: Lymphovascular invasion (LVI) is a critical risk factor for lymph node metastasis (LNM), which requires additional surgery after endoscopic resection of T1 colorectal cancer (CRC). However, the impact of additional staining on estimating LNM is unclear. This systematic review aimed to evaluate the impact of additional staining on determining LNM in T1 CRC. METHODS: We searched five electronic databases. Outcomes were diagnostic odds ratio (DOR), assessed using hierarchical summary receiver operating characteristic curves, and interobserver agreement among pathologists for positive LVI, assessed using Kappa coefficients (κ). We performed a subgroup analysis of studies that simultaneously included a multivariable analysis for other risk factors (deep submucosal invasion, poor differentiation, and tumor budding). RESULTS: Among the 64 studies (18,097 patients) identified, hematoxylin-eosin (HE) and additional staining for LVI had pooled sensitivities of 0.45 (95% confidence interval [CI] 0.32-0.58) and 0.68 (95% CI 0.44-0.86), specificities of 0.88 (95% CI 0.78-0.94) and 0.76 (95% CI 0.62-0.86), and DORs of 6.26 (95% CI 3.73-10.53) and 6.47 (95% CI 3.40-12.32) for determining LNM, respectively. In multivariable analysis, the DOR of additional staining for LNM (DOR 5.95; 95% CI 2.87-12.33) was higher than that of HE staining (DOR 1.89; 95% CI 1.13-3.16) (P = 0.01). Pooled κ values were 0.37 (95% CI 0.22-0.52) and 0.62 (95% CI 0.04-0.99) for HE and additional staining for LVI, respectively. CONCLUSION: Additional staining for LVI may increase the DOR for LNM and interobserver agreement for positive LVI among pathologists.

The Attributes of Physicians Assigned to Rural Clinics Designated for Areas without Physicians in Japan.

In Japan, there are rural clinics designated for areas without physicians to ensure the availability of medical care for rural area residents. The purpose of this study was to clarify the attributes of physicians working in the rural clinics. Using the 2018 Ministry of Health, Labour and Welfare data in Japan, we compared the attributes and board certifications of physicians in rural clinics with those of physicians in other clinics. The age group with the highest percentage of physicians was the over 70 group (16%) and the early 30s group (15%) at rural clinics; however, the highest percentage of physicians at other clinics was the 70 over group (20%) and the early 60s group (16%). The number of physicians working in the internal medicine field at rural clinics was 550 (89%). There were 147 (27%) board-certified physicians in that field. Among them, the number of board certifications in internal medicine, surgery, and other than internal medicine or surgery were 79 (54%), 17 (12%), and 51 (35%), respectively. The proportion of board-certified surgery physicians within the internal medicine field in rural clinics was significantly higher than in other clinics (5%). In rural clinics, the age distribution of physicians was different from that in other clinics, and many of the physicians worked in the internal medicine field, but some of them seemed to have a mismatch between their board-certifications and their fields of practice. Further studies are necessary to clarify what the mismatches mean in rural practice.

Association of oxidized ApoB and oxidized ApoA-I with high-risk coronary plaque features in cardiovascular disease.

BACKGROUND: Oxidized apolipoprotein B (oxLDL) and oxidized ApoA-I (oxHDL) are proatherogenic. Their prognostic value for assessing high-risk plaques by coronary computed tomography angiography (CCTA) is missing. METHODS: In a prospective, observational study, 306 participants with cardiovascular disease (CVD) had extensive lipoprotein profiling. Proteomics analysis was performed on isolated oxHDL, and atherosclerotic plaque assessment was accomplished by quantitative CCTA. RESULTS: Patients were predominantly White, overweight men (58.5%) on statin therapy (43.5%). Increase in LDL-C, ApoB, small dense LDL-C (P < 0.001 for all), triglycerides (P = 0.03), and lower HDL function were observed in the high oxLDL group. High oxLDL associated with necrotic burden (NB; ß = 0.20; P < 0.0001) and fibrofatty burden (FFB; ß = 0.15; P = 0.001) after multivariate adjustment. Low oxHDL had a significant reverse association with these plaque characteristics. Plasma oxHDL levels better predicted NB and FFB after adjustment (OR, 2.22; 95% CI, 1.27-3.88, and OR, 2.80; 95% CI, 1.71-4.58) compared with oxLDL and HDL-C. Interestingly, oxHDL associated with fibrous burden (FB) change over 3.3 years (ß = 0.535; P = 0.033) when compared with oxLDL. Combined Met136 mono-oxidation and Trp132 dioxidation of HDL showed evident association with coronary artery calcium score (r = 0.786; P < 0.001) and FB (r = 0.539; P = 0.012) in high oxHDL, whereas Met136 mono-oxidation significantly associated with vulnerable plaque in low oxHDL. CONCLUSION: Our findings suggest that the investigated oxidized lipids are associated with high-risk coronary plaque features and progression over time in patients with CVD. CLINICALTRIALS: gov NCT01621594. FUNDING: National Heart, Lung, and Blood Institute at the NIH Intramural Research Program.

The framework for modern community medicine in Japan.

Along with the transition to depopulation and an aging society in Japan, the modification of community medicine and its related systems is required. With this in mind, the Japanese government has recently advocated two major plans: 'Community Healthcare Vision' and 'Community-based Integrated Care System'. This paper proposes a theoretical framework to understand modern community medicine based on the ongoing government plans. The key viewpoints consisting of the framework are 'community and/or region', 'care systematization,' and 'coworking with residents (citizens)'. This is expected to be useful for capturing and monitoring the whole picture of modern community medicine in Japan. Such modeling might aid in the future development of medicine and medical science, as in other developed countries.

The Relationship between the Distribution of Home Medical Clinics and Home Care Service Offices in Japan.

The increasing number of older people in Japan has led to a need for cooperation between home medical and care services. The collaboration between medical and care provisions in home settings is thus a matter for concern. The present study examines the distribution of and relationship between the number of home medical clinics (HMCs) and home care service offices (HCOs) in Japan. We used national data, detailing the total population, percentage of older adults, and number of HMCs and HCOs. Overall, 23,428 HMCs and 35,612 HCOs were identified nationwide. While the southwestern region of Japan had a high number of HMCs relative to the northeastern region, there was not such a clear difference in the regional distribution of number of HCOs. A linear regression analyses, adjusted for the percentage of older people, revealed a significant positive correlation between the number of HMCs per 10,000 older people and HCOs per 10,000 older people (ß = 0.58, p < 0.001). These findings may allow us to understand advances in cooperation between home medical and care services in Japan.