Heart failure with preserved ejection fraction is a socioeconomic burden in Japan as well as other developed countries. Diuretics are widely used to attenuate symptoms and signs of congestion in both heart failure with preserved and reduced ejection fraction, although their effects on long-term prognosis of both phenotypes of heart failure have not been demonstrated because of an ethical difficulty in designing a randomized and prospective clinical trial. Guidelines do not provide any guidance on therapy choice, and physicians blindly choose furosemide among loop diuretics in current clinical settings. However, several clinical studies have suggested that the effects of loop diuretics are not consistent, and that furosemide is not necessarily preferable as compared with other loop diuretics. We should pay attention to the choice of loop diuretics. Regarding the improvement of long-term prognosis, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, mineralocorticoid receptor blocker and β-blocker are proven effective for heart failure with reduced ejection fraction. However, none of these drugs have improved prognosis of heart failure with preserved ejection fraction in clinical trials. Observational studies and subanalysis of clinical trials suggest the benefits of these drugs in this phenotype of heart failure. All of clinical trials and observational studies present facts to us, and let us recognize that “one size fits all approach” may be a cause for a lack of evidence about the therapeutic strategy of heart failure with preserved ejection fraction until now. We have to make efforts to clarify characteristics of patients with heart failure and preserved ejection fraction to whom the administration of each drug provides benefits or do not.

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One of the most critical social problems in Japan is the remarkable increase in the aging population. Elderly patients with a variety of complications and issues other than biomedical problems such as dementia and life support with nursing care have been also increasing. Ever since the Japanese economy started to decline after the economic bubble burst of 1991 and the Lehman Brothers bankruptcy in 2008, how we can resolve health problems of the elderly at a lower cost has become one of our most challenging social issues. On the other hand, the appropriate supply of medical and welfare resources is also a fundamental problem. The disparity of physician distribution leads to a marked lack of medical services especially in remote and rural areas of Japan. The government has been attempting to recruit physicians into rural areas through a regional quota system. Based on this background, the medical field pays a great amount of attention to community-based family medicine (CBFM). CBFM requires basic knowledge of community health and family medicine. The main people involved in CBFM are expected to be a new type of general practitioner that cares for residents in targeted communities. To improve the performance of CBFM doctors, we need to establish a better CBFM education system and assess it appropriately when needed. Here, we review the background of CBFM development and propose an effective education system.

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Background Oxidative stress plays an important role in the pathogenesis of bronchial asthma. Antioxidant nutrition and supplementation have been used to reduce oxidative stress. However, a clinical trial with antioxidant supplementation showed no beneficial effects in patients with asthma. On the other hand, physical activity is related to the prognosis of chronic obstructive pulmonary disease (COPD) and is also related to oxidant status. We investigated the relationships between oxidative stress, serum levels of vitamins, dietary vitamin intake, daily activities, and pulmonary functions in patients with asthma.
Methods Eighteen patients with bronchial asthma were enrolled in this study. Reactive oxidative stress was assessed by measuring organic hydroperoxides (diacron reactive oxygen metabolites: dROM) in sera and by measuring H₂O₂ levels in exhaled breath condensates. The biological antioxidant capacity in serum was evaluated by measuring antioxidant potential capacity against ferric ion. We also assessed pulmonary functions, fraction of exhaled nitric oxide, serum levels of vitamins, dietary vitamin intake, and physical activities.
Results There were no relationships between the index of oxidative stress (dROM and H₂O₂ in exhaled breathe condensates) and pulmonary functions, serum levels of vitamins, daily vitamin intakes, and activity levels in patients with asthma.
Conclusion The status of transient oxidative stress may not be related to daily activities, vitamin levels, and pulmonary functions in patients with asthma in a real-life setting. However, our results were obtained in the short-term period from a small number of subjects, so a large longitudinal study is required to ascertain the relationships between oxidative stress, physical activity and vitamin intake in patients with asthma.

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Background To explore new factors that are predictive of post-partial nephrectomy (PN) renal global function, we analyzed various clinico-pathological factors with a special focus on renal volume measured via three-dimensional imaging technology and histopathological parameters in non-neoplastic parenchyma.
Methods Estimated glomerular filtration rate (eGFR) and computed tomography (CT) scan were examined pre- and 6 months. post-operatively in 52 patients treated by PN. The post-operative percent eGFR decline was employed as the measure of global renal functional deterioration. The novel factors analyzed included the percent renal parenchymal volume decline of the diseased side, contralateral and bilateral sides and the global glomerulosclerosis (GS) extent in non-neoplastic parenchyma. Renal parenchymal volumetry by CT scan was performed using SYNAPSE VINCENT (Fujifilm). Additional factors analyzed included patient demographics and comorbidities, surgical factors and tumor pathology. All factors demonstrating significant tendencies (P < 0.1) in univariate analyses were subjected to multivariate logistic regression analysis.
Results Two groups were categorized according to the degree of eGFR decline. Groups A and B were categorized as less than 15% and greater than 15% decline, respectively. Pre-operative eGFR was significantly lower in group B than in group A. Greater than 10% global GS extent in non-neoplastic parenchyma, male gender and proteinuria were significantly more frequent in in group B than in group A. The renal volume change was not statistically significant. In multivariate logistic regression analysis, greater than 10% global GS extent in non-neoplastic parenchyma was the sole independent affecting factor for Group B.
Conclusion Our study suggested that host factors rather than surgical factors may be useful for the prediction of post-PN renal global function. The evaluation of the global GS extent in non-neoplastic parenchyma is a promising biomarker of post-PN renal global function.

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Background Previously, we had performed a clinical study using human leukocyte antigen (HLA)-A24-binding peptide vaccines containing a combination of novel cancer-testis antigens and anti-angiogenic peptides derived from DEPDC1, URLC10, FOXM1, KIF20A and VEGFR1 for advanced gastric cancer (AGC) patients who were refractory to chemotherapy. We applied the cocktail vaccine to the combination therapy with S-1 for patients with AGC as a post-operative adjuvant therapy and performed this clinical pilot study.
Methods AGC patients who had curative surgery and were classified as pathologically stage III were enrolled. At each 6-week treatment cycle, patients received weekly subcutaneous administration of the cocktail vaccine with 5 continuous injections and one break for the first 4 cycles and with bi-weekly injections for the following 4 cycles. S-1 (80 mg/m²) was administered orally for 4 weeks with 2-week rest for all 8 cycles. The primary endpoint was the safety of the combination therapy and the secondary was the relative dose intensity for S-1.
Results Fourteen patients were enrolled. Six patients with HLA-A*2402 had received S-1 plus the cocktail vaccine as an adjuvant therapy and the remaining 8 had S-1 monotherapy for eight cycles. Five out of 6 patients subjected to the combination group completed the therapy and one patient discontinued because of Grade 3 injection-site reaction. No adverse events of grade 3 or higher were observed except injection-site reactions shown in 5 out of 6 patients who had vaccine therapy. The mean and median relative dose intensities for S-1 were 75.5% and 88% in the combination group and 67% and 80.5% in S-1.
Conclusion The vaccine therapy combined with S-1 was manageable and safe adjuvant therapy for stage III gastric cancer. Furthermore, the optimal relative dose intensity of S-1 was achieved in combination group, although the injection-site reaction should be considered.

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Background Hepatocellular carcinoma (HCC) in patients without hepatitis B (HBV) and -C virus (HCV) infection are increasing in Japan. Method for detecting high-risk liver diseases of HCC in general population has still not been established. Liver stiffness measurement (LSM) and Controlled Attenuation Parameter (CAP) using transient elastography (TE; FibroScan System) are useful for detecting liver fibrosis and steatosis. The aim of this study is to clarify TE for risk assessment of HCC in general population.
Methods This cross-sectional study was performed for residents aged ≥ 40 years in an intermountain town in Japan with a population of 3,493. Blood laboratory testing included tumor markers, abdominal ultrasound (AUS), and TE was performed.
Results Among 175 subjects (64 men, 111 women), TE was evaluated and three patients with HCC were detected by AUS. For detecting HCC, the cut-off value of LSM was 5.3 kPa sensitivity 100%, specificity 75%, AUROC 0.88). The combination of LSM and CAP (LSM > 5.3 kPa with any CAP and CAP > 248 dB/m with any LSM) could detect the high-risk liver diseases of HCC (HCC, nonalcoholic fatty liver/steatohepatitis, HBV or HCV related chronic viral hepatitis with alanine transaminase (ALT) > 30 IU/L for men or > 19 IU/L for women or cirrhosis of any cause) with high sensitivity (sensitivity 90%, specificity 55%, positive predictive value 10%, negative predictive value 99%, P = 0.006).
Conclusion The combination of LSM and CAP can be useful in detecting high-risk liver diseases of HCC out of general population.

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Background The aim of this paper was to evaluate the validity of tumor volume measurement using diffusion-weighted (DW) imaging in cervical cancer.
Methods In this retrospective study, 22 patients, who underwent preoperative 3.0 T MR examinations with DW imaging were evaluated. Tumor volume measurement by oblique axial (short axis to the uterine cervix) T2-weighted imaging was performed by manually outlining the tumor on the monitor. The area of tumor in each slice was multiplied by the slice profile (slice thickness plus intersection gap), and the total tumor volume was calculated by summation of these obtained volumes. Meanwhile, one experienced radiological technologist generated three-dimensional DW images of cervical cancer using a volume-rendering algorithm at a computer workstation, and tumor volume was automatically calculated in the workstation. Analysis via the intraclass correlation coefficient (ICC) and Bland-Altman plots were used to assess the validity and reliability of these methods.
Results Between tumor volumes measured by T2-weighted imaging methods and DW imaging methods, the ICC was excellent (0.962). The 95% limits of agreement of volume measurement were –52.7 and 35.7 mL (mean difference, –8.5 mL). In regards to intra-observer variability, the ICC was excellent (0.963). The 95% limits of agreement of volume measurement were –42.2 and 47.4 mL (mean difference, 2.6 mL).
Conclusion DW imaging can be used to measure cervical cancer volume.

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Background There is accumulating evidence that shows cell-mediated immunity regulated by T cells is impaired in cancer patients. Unfortunately, the mechanisms by which B cells participate in tumor immunity are only partially understood.
Methods The serum concentration of Immunoglobulin G (IgG) was measured by Enzyme-Linked ImmunoSorbent Assay (ELISA) in patients with gastric cancer. Immunohistochemistry was also performed using the anti- cluster of differentiation (CD)134 antibody to evaluate the number of plasma cells in the tumor tissue.
Results The total serum IgG concentration was significantly lower in patients with lymph node metastasis compared with patients without metastasis. The serum concentration of total IgG at stage III/IV was significantly lower compared with tumors classified as stage I/II. A decreased serum concentration of total IgG and IgG1 was significantly related to a poor prognosis for gastric cancer patients. Furthermore, multivariate analysis indicated that the serum concentration of IgG and lymph node metastasis were independent prognostic indicators for poorer survival. The number of plasma cells was significantly lower in gastric cancer tissue compared with non-cancerous gastric mucosa.
Conclusion A decreased serum concentration of IgG was closely related to poor prognosis, indicating the possibility that impaired antibody-mediated immunity is associated with tumor progression in patients with gastric cancer.

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Background Remnant gastric cancer (RGC) is an uncommon form of gastric cancer. The aim of this study was to investigate factors influencing the prognosis of patients with RGC.
Methods A total of 49 patients diagnosed with RGC and 214 patients with primary upper third gastric cancer (PUGC) at our institution between January 1990 and December 2014 were included. The clinicopathological characteristics, prognosis, and factors influencing prognosis were compared.
Results The body mass index (BMI) of RGC was significantly lower than that for PUGC (P < 0.0001). Multivariate analysis revealed that BMI and the depth of tumor invasion were independent prognostic factors in RGC. ROC analysis indicated that an optimal cut-off value for BMI was 20.6. Based on this value, patients were divided into two groups: BMI^High (≥ 20.6) and BMI^Low (< 20.6). The 5-year survival rates of patients with BMI^High early gastric cancer, BMI^High advanced gastric cancer, BMI^Low early gastric cancer, and BMI^Low advanced gastric cancer were 90%, 83.3%, 64.3% and 33.8%, respectively, and the difference was statistically significant (P = 0.00023).
Conclusion Our retrospective study indicated a poor prognosis of RGC compared with PUGC, and that BMI could predict the prognosis of RGC. The prognosis of patients with BMI^Low advanced RGC was extremely poor.

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Pulse oximeters are used to noninvasively measure oxygen saturation in arterial blood (SaO₂). Although arterial oxygen saturation measured by pulse oximeter (SpO₂) is usually indicated in 1% increments, the value of SaO₂ from arterial blood gas analysis is not an integer. We have developed a new pulse oximeter that can measure SpO₂ to one digit after the decimal point. The values of SpO₂ from the newly developed pulse oximeter are highly correlated with the values of SaO₂ from arterial blood gas analysis (SpO₂ = 0.899 × SaO₂ + 9.944, r = 0.887, P < 0.0001). This device may help improve the evaluation of pathological conditions in patients.

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