Objective: Combination therapy with glecaprevir and pibrentasvir (G/P) has been shown to provide a sustained virologic response (SVR) rate of >97% in patients with chronic hepatitis C virus (HCV) infection in the first published real-world Japanese data. However, a recently published study showed that the treatment was often discontinued in patients ≥75 years old, resulting in low SVR in intention-to-treat (ITT) analysis. Thus, our aim was to evaluate real-world data for G/P therapy in patients ≥75 years of age, the population density of which is high in “rural” regions.Patients and Methods: We conducted a multicenter study to assess the efficacy and safety of G/P therapy for chronic HCV infection, in the North Kanto area in Japan.Results: Of the 308 patients enrolled, 294 (95.5%) completed the treatment according to the protocol. In ITT and per-protocol analyses, the overall SVR12 rate was 97.1% and 99.7%, respectively. The old-aged patients group consisted of 59 participants, 56 of whom (94.9%) completed the scheduled protocol. Although old-aged patients tended to have non-SVR factors such as liver cirrhosis, history of HCC, and prior DAA therapies, the SVR12 rates in old-aged patients were 98.3% and 100% in the ITT and PP analyses, respectively. Of 308 patients enrolled, adverse events were observed in 74 patients (24.0%), with grade ≥3 events in 8 patients (2.6%). There was no significant difference in any grade and grade ≥3 adverse events between the old-aged group and the rest of the study participants. Only one patient discontinued the treatment because of adverse events.Conclusion: G/P therapy is effective and safe for old-aged patients.

  Although body-warming with hot spa-bathing has been proposed to exert medical therapeutic effects on certain diseases, whether body-warming has preventive and promotive effects remains unknown. To clarify this issue, an epidemiological questionnaire study regarding personal hot spa-bathing habits and disease history was carried out in Japan, where individuals engage in daily warm water bathing. Questionnaires regarding hot spa-bathing habits and disease history were randomly sent to 20,000 residents aged ≥65 years living in Beppu, a city in Japan that has the highest concentration of hot spa sources in the world. The results showed that habitual hot spa-bathing exerts preventive or promotive effects on the occurrence of certain diseases, such as hypertension (preventive) and collagen disease (promotive) in women, and cardiovascular diseases (preventive) in men. These findings suggest that habitual body warming is an effective and economical method with beneficial preventive and promotive effects on various diseases.

  Objective: Beppu city is a world-famous resort. Spa bathing has been reported to yield psychophysiological relaxation. Beppu city office planned a health-promoting tour including spa-bathing activities in Beppu for the aging population, which is growing rapidly in Japan. This tour provided spa-bathing experiences, walks through urban districts where old townscapes remain, yoga, mountain hikes and shrine visits. We investigated whether such a short tour brought about a detectable medical effect toward health promotion for the elderly.  Methods: Twenty applicants (mean age: 67.7±3.5 years; male, n＝9 [mean age, 68.9±2.9 years]; female, n＝11 [mean age, 66.7±3.7 years]), joined the tour. These voluntary participants, who were over 60 years of age, participated in a five-day-tour in Oita prefecture. Health checks were conducted on the first and last days of the tour. This tour was conducted in areas containing a gulf, mountain areas, lakeside areas, forests and shrines. Participants visited these areas during the tour.  Outcome Measures: The following parameters of the participants were measured at the beginning and end of tour: stress score, blood pressure, salivary amylase level, serum C-reactive protein level, and serum cortisol level. The results were compared and analyzed by a paired t-test and a simple regression analysis.  Results: The mean values of the following parameters (pre-intervention and post-intervention) showed significant changes after the program: stress score (43.7±8.05 and 39.4±6.57; p-value＝0.005); systolic blood pressure (131±17.8 mmHg and 125±16.2 mmHg; p＝0.018); diastolic blood pressure (73±7.3 mmHg and 70±6.6 mmHg; p＝0.016); serum cortisol (7.7±3.16 µg/dL and 6.1±1.82 µg/dL; p＝0.027). Moreover, the participants’ cortisol levels tended to converge into a normal range.   Conclusion: Tourism in a spa resort can relieve mental and physical stress, reducing blood pressure and correcting the adrenocortical function.

BACKGROUND/AIMS: This study aimed to predict sustained viral response (SVR) to low-dose pegylated interferon (PEG-IFN) plus ribavirin of elderly and/or cirrhotic patients with genotype 2 hepatitis C virus (HCV) using viral response within 2 weeks. METHODS: Low-dose PEG-IFN-α-2b plus ribavirin was administered to 50 elderly and/or cirrhotic patients with genotype 2 HCV for 24 weeks. The dynamics of HCV RNA and HCV core antigen levels within 2 weeks were measured. RESULTS: The patients' median age was 66 years. There were 21 male and 29 female patients. The median baseline HCV RNA level was 5.7 log IU/mL. Rapid viral response was achieved in 17 patients (34%), SVR in 28 (56%), and two (4%) discontinued treatment. Univariate analysis of factors contributing to SVR showed significant differences for sex, baseline virus level, and response within 4 weeks. When 40 fmol/L was set as the cutoff value for the core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 93%, 75%, 84%, 88%, and 85%, respectively. CONCLUSIONS: Low-dose PEG-IFN plus ribavirin was a safe and cost-effective treatment for elderly and/or cirrhotic patients with genotype 2 HCV, and the viral response within 2 weeks was a useful predictor of SVR.
Aged* ; Female ; Genotype* ; Hepacivirus* ; Hepatitis C* ; Hepatitis* ; Humans ; Interferons* ; Liver Cirrhosis ; Male ; Ribavirin* ; RNA ; Sensitivity and Specificity

Purpose: The aim of present study was to investigate the endothelial function of immersion of patients with diabetes in carbon dioxide (CO2)-enriched water Methods: Sixteen diabetic patients with minor complications were immersed in CO2-enriched water for 4 weeks, and 8 patients were immersed in normal spa water for the same duration. To assess endothelial function, forearm flow-mediated dilation (FMD) was measured in those patients, and %FMD at pre-immersion was compared to that at post-immersion in CO2-enriched water. The pulse wave velocity (PWV) was also measured to determine whether vascular stiffness was affected in those patients. The percent coefficient of variation of R-R intervals was examined as CVR-R (%). All patients were medicated with antidiabetic drugs, which were not changed during the study. Results: %FMD showed no significant difference in any patients between pre- and post-CO2-enriched water bathing. However, %FMD was significantly increased in patients under 8.0% of HbA1c after CO2-enriched water bathing (p<0.05), but it was not significantly increased in patients over 8.0 of HbA1c. PWV and CVR-R (%) were significantly reduced in all patients after CO2-enriched water bathing. Conclusion: CO2-enriched water immersion had a positive effect on endothelial function, and reduced arterial wall stiffness in patients with diabetes. These findings suggest that CO2-enriched water bathing may improve microcirculation, as well as subjective symptoms, in patients with controlled diabetes.

We describe a 38-year-old, severely emaciated female with slowly progressive type 1 diabetes mellitus (SPIDDM), who had hypoglycemia due to fasting and an extremely low energy intake. After being diagnosed with diabetes mellitus (DM), she took in only 300-500 kcal per day and her weight had decreased to 30 kg, with a body mass index (BMI) of 11.4 kg/m². She was admitted with hypoglycemia, and SPIDDM was confirmed by nearly-completely ceased insulin secretion and seropositivity towards anti-GAD antibody. After appropriate dietary therapy and insulin administration, she recovered from a state of emaciation and her glucose metabolism was restored. With this patient it proved very effective for the general physician to coordinate treatment for both diabetes and an eating disorder.

Objectives: The purpose of this study was to examine the beneficial effects of balneotherapy in patients with chronic heart failure (CHF).
Background: Some reports have shown that balneotherapy reduces systemic blood pressure in healthy volunteers. However, it is not clear whether balneotherapy improves the status of CHF. We hypothesized that hyperthermia using hot water would improve cardiac and peripheral endothelial function and clinical symptoms.
Methods: Twenty-six patients with chronic systolic heart failure classified as New York Heart Association (NYHA) functional status II or III were divided into two groups. In the balneotherapy group, patients were immersed in a hot spring at 40°C for 10min daily for two weeks; in the control group, patients took a daily shower. We measured plasma brain natriuretic peptide (BNP) and asymmetric dimethylarginine (ADMA). The left ventricular ejection fraction (LVEF) and cardiothoracic ratio (CTR) were evaluated by echocardiography and chest radiography, respectively. Brachial-ankle pulse-wave velocity (baPWV) was measured non-invasively using an automatic device.
Results: Clinical symptoms were improved after two weeks of hot spring therapy. Although heart rate and CTR did not change, clinical symptom and LVEF improved and mean blood pressure, BNP, ADMA and PWV significantly decreased.
Conclusions: Repeated immersion in a hot spring improves peripheral vascular endothelial function, thus leading to improvement of clinical activity and symptoms in patients with CHF.

A 53-year-old man presented with a painful, non-healing ischemic ulcer of the left fifth toe. The patient was initially treated conservatively for 4 months with local debridement and medication with antiplatelet therapy but his symptoms and the ulcer was refractory. A computed tomography revealed a bulky, irregular, gritty, localized calcification of the infra-renal aorta and was compatible with the so-called “coral reef aorta”. Angiography confirmed the findings of the CT scan, and there was no evidence of occlusive lesions in the distal runoff vessels. A diagnosis of blue toe syndrome secondary to infra-renal coral reef aorta was made. In order to prevent further embolization, the patient underwent aortic excision with PTFE grafting via a retroperitoneal incision. In order to increase the microcirculation of the toe and to aid in the healing of the ulcer, a lumbar sympathectomy was performed simultaneously. The ulcer healed completely on postoperative day 47. The treatment method for coral reef aorta depends on the presence or absence of global ischemia of the lower extremity and embolic complications.

AIMTo perform quality control studies on testicular volume measurements for a multi-center epidemiological study of male reproductive function.

METHODSWe constructed a data matrix with a balanced assignment for 2 consecutive days by ten investigators (andrological career: 4-21 years) from five institutions and 12 male volunteers aged 20-26 years. Testicular volume was measured by Prader's orchidometer. A skilled technician also performed an ultrasound estimate of testicular volume.

RESULTSA statistically significant inter-investigator variation was found for both testes (P < 0.05). In addition, there was a statistically significant investigator-by-volunteer interaction in testicular volume measurement (P < 0.01). However, there was no statistically significant difference in the two measurements performed on consecutive days for either testis. The testicular volumes for both the right and left testes as estimated by ultrasonography were smaller than results using the orchidometer. However, there was no statistical significance (P > 0.05). The difference in experiences of the investigators did not significantly correlate with accuracy of measurements in either testis.

CONCLUSIONThe present study revealed significant differences in the results of estimation of testicular volume among the ten investigators, but intra-investigator variation was not considerable. Improved training and proper standardization of the measurement will be necessary before starting a multi-center study based on an andrological examination.

Patients with mechanical valve prosthesis must receive long-term oral anticoagulant therapy, thus it is important to set the optimal international normalized ratio of prothrombin time (PT-INR) that effectively prevented thromboembolic complications without excessive bleeding. In this study, anticoagulant therapy was evaluated in terms of the activity of coagulation and fibrinolysis in 137 patients after isolated mechanical valve replacement. With a lower target range of 1.5-2.0 for the PT-INR, thrombin antithrombin III complex (TAT) increased to more than 3.0ng/ml in 30 cases, and the activity of coagulation appeared to increase due to insufficient anticoagulant therapy. After the target range was raised to 2.0-2.5 in all cases, the PT-INR increased significantly from 1.63 to 2.25 (p<0.01) and TAT decreased significantly from 7.58 to 2.81ng/ml (p<0.01). This showed that activity of coagulation and fibrinolysis was suppressed by high intensity anticoagulation. It is necessary to review the individual activity of coagulation and fibrinolysis to determine the intensity of anticoagulation. We recommend 2.0-2.5 as the target range for the PT-INR.