Ketogenic effects of medium chain triglycerides containing formula and its correlation to breath acetone in healthy volunteers: a randomized, double-blinded, placebo-controlled, single dose-response study.

The efficacy of low-carbohydrate, high-fat diets, such as ketogenic diets, for cancer patients is of research interest. We previously demonstrated the efficacy of the ketogenic diet in a case study in which medium-chain triglycerides (MCTs) or MCT-containing formula (ketogenic formula) was used as a supplement to increase blood ketone bodies. However, little is known about the amounts needed to induce ketogenic effects and about the usefulness of monitoring of breath acetone. To investigate the pharmacokinetics of MCTs and their metabolites, blood ketone bodies and breath acetone, 24 healthy subjects received one of four single oral doses of the ketogenic formula (equivalent to 0, 10, 20, and 30 g of MCTs) under fasting conditions. Total blood ketone bodies, ß-hydroxybutyrate, octanoic acid, and decanoic acid were increased in a dose-dependent manner. The ketogenic effect was considered to depend on octanoic and decanoic acids, because a positive correlation was observed between them. A strong positive correlation was also observed between total serum ketone bodies and breath acetone at each time points. Therefore, monitoring breath acetone levels seems a less invasive method to predict blood concentrations of ketone bodies during ketogenic diet therapy. Clinical trial registration:https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000032634, UMIN-CTR UMIN000032634.

Long-Term Effects of a Ketogenic Diet for Cancer.

A ketogenic diet has been proposed as a potential supportive therapy for cancer patients, although its long-term influence on survival rates remain controversial. In our previous report, we presented promising results for 37 of 55 patients with advanced cancer enrolled between 2013 and 2018 who remained on a ketogenic diet for at least 3 months. We followed all 55 patients until March 2023 and analyzed the data up to March 2022. For the 37 patients with previously reported promising results, the median follow-up period was 25 (range of 3-104) months and 28 patients died. The median overall survival (OS) in this subset of 37 patients was 25.1 months and the 5-year survival rate was 23.9%. We also evaluated the association between the duration of the ketogenic diet and outcome in all 55 patients, except for 2 patients with insufficient data. The patients were divided into two groups: those who followed the diet for ≥12 months (n = 21) and those who followed it for <12 months (n = 32). The median duration of the ketogenic diet was 37 (range of 12-99) months for the ≥12 months group and 3 (range of 0-11) months for the <12 months group. During the follow-up period, 41 patients died (10/21 in the ≥12 months group and 31/32 in the <12 months group). The median OS was 19.9 months (55.1 months in the ≥12 months group and 12 months in the <12 months group). Following the inverse probability of treatment weighting to align the background factors of the two groups and make them comparable, the adjusted log-rank test showed a significantly better OS rate in the group that continued the ketogenic diet for a longer period (p < 0.001, adjusted log-rank test). These results indicate that a longer continuation of the ketogenic diet improved the prognosis of advanced cancer patients.

A multidimensional physical scale is a useful screening test for mild depression associated with childcare in Japanese child-rearing women.

Introduction: Maternal depression is one of the important problems of postpartum women. For its early detection and appropriate treatment, it is necessary to identify women at high risk for depression quickly and easily. Materials and methods: A simple screening scale for depression from physical aspects, the multidimensional physical scale (MDPS), which is a 17-item, self-report, three-step scale (0, 1, 2) according to the theory of Kampo medicine, was developed. The aim of the present study was to develop (n = 785) and validate (n = 350) the MDPS that was designed to rate the risk of depression. The Beck Depression Inventory-Second Edition was used for determination of depression. In the development cohort, the final model was determined using multi-regression logistic analysis. Results: The components of the MDPS for mothers (MDPS-M) were developed, containing the total score of MDPS (0-34 points) and resumption of menstruation or not (-3, 0 points). Receiver-operating characteristic curve analysis of the MDPS-M (-3 to 34) for identifying a high risk of depression showed moderately good discrimination [area under the curve (AUC) = 0.74, 95% confidence interval (CI): 0.70-0.78]. At the cutoff value of MDPS-M (9/10), its sensitivity, specificity, positive predictive value, and negative predictive value were 84.9, 45.7, 36.7, and 89.2%, respectively. External validation of the MDPS-M showed moderately good discrimination (AUC = 0.74, 95% CI: 0.68-0.79) using the same analysis as the development cohort. Conclusion: These results indicate that the MDPS-M is a useful, simple, clinical scale for early identification of mothers at high risk of depression in primary care.

The Japan Frailty Scale is a promising screening test for frailty and pre-frailty in Japanese elderly people.

Frailty is one of the most important problems in a super-aged society. It is necessary to identify frailty quickly and easily at the bedside. We developed a simple patient-reported frailty screening scale, the Japan Frailty Scale (JFS), based on the aging concept of Kampo medicine. Eight candidate questions were prepared by Kampo medicine experts, and a simple prediction model was created in the development cohort (n = 434) and externally validated in an independent validation cohort (n = 276). The physical indicators and questionnaires associated with frailty were also comprehensively evaluated. The reference standard for frailty or pre-frailty was determined based on the Kihon checklist. In the development cohort, four questions, nocturia (0-2), lumbago (0-2), cold sensitivity (0-2), exhaustion (0-4), and age (0-1) were selected by multivariable logistic regression analysis. The total JFS score is 0-11. Receiver-operating characteristic curve analysis of the JFS for identifying frailty status showed moderately good discrimination (area under the curve (AUC) = 0.78, 95 % confidence interval (CI): 0.73-0.82). At the JFS cutoff value of 3/4 for frailty or pre-frailty, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 86.9 %, 53.3 %, 62.8 %, and 81.7 %, respectively. External validation of the JFS showed moderately good discrimination (AUC = 0.76, 95 % CI: 0.70-0.81). The sensitivity, specificity, PPV, and NPV were 79.9 %, 61.4 %, 69.3 %, and 73.7 %, respectively. These results indicate that the JFS is a promising patient-reported clinical scale for early identification of pre-frail/frail patients at the bedside in primary care.

Clinical Importance of Body Composition in Improving Bone Mineral Density of Femoral Neck After Denosumab Therapy in Patients With Rheumatoid Arthritis or Collagen Diseases.

BACKGROUND/AIM: To investigate factors associated with increased bone mineral density (BMD) of the neck of femur in rheumatoid arthritis or collagen diseases receiving denosumab, focusing on body composition calculated by bioelectrical impedance analysis (n=90, 78 females). PATIENTS AND METHODS: We defined Δfemur as BMD (12 months minus baseline), using dual-energy X-ray absorptiometry after denosumab therapy. Factors associated with Δfemur were retrospectively investigated. RESULTS: Low skeletal muscle index (SMI) was observed in 6 males and 32 females. There was a significant difference in phase angle (PhA) of the left leg (LL) between the Δfemur ≥0 (n=70) and Δfemur <0 (n=20) groups (p=0.040) but not in SMI (p=0.310). Multiple regression analysis indicated that PhA of LL was significantly related to Δfemur (p=0.0398). CONCLUSION: PhA appears to be a clinically significant indicator of improvement of Δfemur in patients receiving denosumab.

Ketogenic Effects of Multiple Doses of a Medium Chain Triglycerides Enriched Ketogenic Formula in Healthy Men under the Ketogenic Diet: A Randomized, Double-Blinded, Placebo-Controlled Study.

Ketogenic diets, which are carbohydrate-restricted high-fat diets, may have therapeutic effects on various diseases, including cancer. However, ketogenic diets are often not standardized and, therefore, results are difficult to interpret. We previously investigated the usefulness of ketogenic diets in cancer therapy, where ketogenic formulas (KF) were used as supplements to enhance blood ketone bodies; however, the amount of KF was determined empirically with reference to blood ketone bodies levels. Here, to determine a standardized optimal amount of KF, we investigated temporal changes in blood ketone bodies (acetoacetic acid (AcAc), ß-hydroxybutyrate (BHB)) and safety in 20 healthy individuals when KF was taken repeatedly under the conditions of a ketogenic diet (UMIN000034216). The diurnal variation in total ketone bodies, and AcAc and BHB levels significantly increased after lunch and after dinner, on the 4th day of KF administration. There were no significant safety issues related to KF in the context of anthropometric, metabolic, nutritional, urological and gastrointestinal parameters. In addition, ketogenic diets lead to changes in gut microbiota. KF showed a decrease in phylum Firmicutes. Our study provides baseline data of the usefulness of KF in a ketogenic diet.

Right atrial blood cyst with total occlusion of the right coronary artery.

Cardiac blood cysts are rarely seen in adult patients and in the right atrium. The origin of cardiac blood cysts is not understood, and several hypotheses have been proposed. We present a rare case of right atrial blood cyst with total occlusion of the right coronary artery (RCA). Inflammatory processes may have played an important role in the development of the cyst, because infiltration of inflammatory cells was observed in the cystic wall. Additionally, total obstruction of the proximal RCA indicated that ischemia and/or infarction in the right atrium might be related to formation of the cyst.

Regional postsystolic shortening in patients with hypertrophic cardiomyopathy: its incidence and characteristics assessed by strain imaging.

BACKGROUND: Postsystolic shortening (PSS) is considered myocardial shortening after the point of aortic valve closure and can be observed physiologically in healthy individuals. However, the incidence and magnitude of PSS in myocardial disorders have not been investigated. OBJECTIVES: We performed strain imaging to characterize PSS in patients with hypertrophic cardiomyopathy (HCM) versus healthy individuals. METHODS: Thirty patients with HCM (22 men and 8 women; mean age 62+/-6 years) and 30 control subjects (20 men and 10 women; mean age 61 +/- 9 years) were studied. For both groups, patterns of myocardial strain curves were assessed by the 18-segment model using apical 2-chamber, 4-chamber, and long-axis views. PSS was defined if the peak strain existed beyond aortic valve closure. The severity of PSS was assessed as postsystolic index (strain amplitude beyond aortic closure divided by whole strain amplitude) for each segment. RESULTS: As compared with control subjects, patients with HCM had a greater isovolumic relaxation time (105 +/- 31 vs 74 +/- 28 milliseconds, P < .001), despite the comparable value of left ventricular ejection fraction (65 +/- 6% vs 65 +/- 4%, P = not significant). The number of segments having PSS was greater in patients with HCM than in control subjects (12.6 +/- 3.0 vs 8.4 +/- 3.7, P < .001). This was associated with greater values of postsystolic index in all segments for patients with HCM. In patients with HCM, the number of segments having PSS correlated significantly with the isovolumic relaxation time (r = 0.36, P < .05). CONCLUSIONS: Patients with HCM have more pathologic PSS, which may have etiologic contribution to the functional heterogeneity of this disease entity, especially diastolic dysfunction.

Acute effects of diltiazem on regional left ventricular diastolic filling dynamics in patients with hypertrophic cardiomyopathy as assessed by color kinesis.

BACKGROUND: The effect of calcium antagonists on regional left ventricular (LV) filling dynamics in patients with hypertrophic cardiomyopathy (HCM) is not well known, so the present study evaluated the results of echocardiography with color kinesis (CK) analysis during diltiazem infusion. METHODS AND RESULTS: Nineteen patients (16 men, 3 women; mean age 55+/-15 years) underwent echocardiography with CK analysis during intravenous diltiazem (10 mg/2 min). Using the quantitative CK software the LV short-axis image was divided into 6 segments and the percent endocardial expansion at the early, mid- and late-diastolic filling time was averaged for all segments, with the standard deviation of the mean used as an index of diastolic asynchrony (asynchrony index). The regional mean filling time was also measured for the corresponding segments. As global diastolic parameters, the global filling time, peak filling rate, and the time-to-peak filling were calculated. After the administration of diltiazem, the asynchrony index was decreased for all three diastolic filling times. Diltiazem shortened the mean filling time overall, especially in the posterior and lateral wall segments. These findings were associated with significant improvement in the CK-derived global diastolic parameters. CONCLUSIONS: Diltiazam has a favorable effect on LV diastolic asynchrony, which may account for the acute changes in global LV relaxation.

Forearm hyperemia is a better marker than carotid intima-media thickness or ankle-brachial index for coronary artery disease in Japanese males under 65.

Forearm hyperemia, carotid intima-media thickness (IMT), and ankle-brachial pressure index (ABI) are subclinical markers associated with coronary artery disease (CAD). However, it is not known which marker is most highly correlated with CAD. We therefore compared these three parameters in the same patients under 65 years of age. In 40 males with documented CAD (mean age, 53 years), we measured forearm hyperemia by plethysmography, carotid IMT by B-mode ultrasound, and ABI by Doppler ultrasonography. Microalbuminuria, serum lipids, glucose and C-reactive protein (CRP) were also measured. Thirteen normal males served as controls (mean age, 49 years). Compared with normal subjects, CAD patients had lower hyperemia (42 vs. 92%; p < 0.001) and greater carotid IMT (0.81 vs. 0.67 mm; p < 0.01), but ABI was similar. The sensitivity of forearm hyperemia (72%) was higher than that of carotid IMT (22%) or ABI (3%) (abnormal criteria: forearm hyperemia < 60%, carotid IMT 21.0 mm, and ABI < 0.9). The patients had higher serum low-density lipoprotein (LDL) cholesterol, glucose and CRP, and lower high-density lipoprotein (HDL) cholesterol than the controls. Albuminuria was present in 49% of patients. Subclinical markers were further analyzed by age (35-54 vs. 55-64 years). The sensitivity of carotid IMT was lower in the younger patients (4% vs. 33%), while that of forearm hyperemia (69% vs. 75%) and albuminuria (47% vs. 52%) did not change with age. While carotid ultrasound was useful in older patients ( > or = 55 years), forearm hyperemia and microalbuminuria were sensitive markers irrespective of age. ABI was not useful in the Japanese men with CAD under age 65.