Recurrent nocturnal hypoglycemic hemiplegia: a case report and review of the literature.

A 67-year-old man with type 1 diabetes, Cronkhite-Canada syndrome, and membranous nephropathy who received insulin therapy was admitted to our hospital with right hemiplegia and dysarthria. Brain magnetic resonance imaging revealed a lesion with a high diffusion-weighted imaging signal and low apparent diffusion coefficient signal in the posterior limb of the left internal capsule. He was hypoglycemic with a blood glucose level of 56 mg/dL (3.1 mmol/L). Following glucose administration, the patient's symptoms resolved within several hours. The patient experienced similar transient hypoglycemic hemiplegia at midnight, three times within 10 days. In a literature review of 170 cases of hypoglycemic hemiplegia, 26 cases of recurrent hemiplegia were investigated. Recurrent hypoglycemic hemiplegia occurs more frequently on the right side than on the left side, and most recurrences occur within approximately a week, almost exclusively at midnight and in the early morning. We speculate that hypoglycemia-associated autonomic failure may be involved in the nocturnal recurrence of episodes. In our patient, depleted endogenous insulin secretion and lipodystrophy at the injection site, may have acted as additional factors, leading to severe hypoglycemia despite the absence of apparent autonomic neuropathy. Clinically, it is important to recognize hypoglycemia as a cause of hemiplegia to avoid unnecessary intervention and to maintain an appropriate blood glucose level at midnight and early in the morning to prevent recurrent hypoglycemic hemiplegia.

Comprehensive Cancer Genomic Profiling of Liver Metastasis Led to the Unexpected Identification of Colorectal Cancer.

Comprehensive genomic profiling (CGP) of a metastatic liver tumor biopsy specimen suggested that the patient, who was initially diagnosed with cholangiocarcinoma, had colorectal cancer. The identification of both FBXW7 and APC mutations is deemed characteristic of colorectal cancer. Indeed, subsequent colonoscopy revealed sigmoid colon carcinoma that led to tumor resection followed by systemic chemotherapy. CGP is principally used to identify agents that might potentially benefit the patient. However, results must be interpreted carefully to ensure consistency with the initial diagnosis.

Medium-chain triglycerides (8:0 and 10:0) increase muscle mass and function in frail older adults: a combined data analysis of clinical trials.

Background: Three clinical trials have examined the chronic effects of medium-chain triglycerides (MCTs) on muscle mass and function in frail older adults (mean age 85 years old). However, significant increases in muscle mass and some muscle function relative to long-chain triglycerides (LCTs) have yet to be shown, possibly due to the small number of participants in each trial. Objective: We re-analyzed these previous clinical trials to clarify whether MCT supplementation can increase muscle mass and function. Analysis: After adding post hoc tests to the original report, we compared changes in measurement between the MCT and LCT groups in the first 2 trials and conducted a combined data analysis. Methods: In a combined data analysis, changes from baseline in measurements at the 3 months intervention in the MCTs- and LCTs-containing groups were assessed by analysis of covariance adjusted for baseline values of each measurement, age, sex, BMI, allocation to trial, habitual intakes in energy, protein, leucine, octanoic acid, decanoic acid, and vitamin D during the baseline period. The Mann-Whitney U test was used to analyze data on right and left knee extension times. Results: MCT supplementation for 3 months increased muscle function relative to LCT supplementation with and without an L-leucine (1.2 g) and vitamin D (cholecalciferol, 20 µg)-enriched supplement. In a combined data analysis (n = 29 in MCTs, n = 27 in LCTs), relative to supplementation with 6 g LCTs/day, supplementation with 6 g MCTs/day at dinner for 3 months significantly increased body weight (adjusted mean change from baseline: MCTs 1.2 vs. LCTs 0.2 kg, p = 0.023), right arm muscle area (MCTs 1.4 vs. LCTs-0.7 cm2, p = 0.002), left calf circumference (p = 0.015), right-hand grip strength (MCTs 1.6 vs. LCTs 0.3 kg, p = 0.017), right knee extension time (p = 0.021), left knee extension time (p = 0.034), walking speed (p = 0.002), and number of iterations in leg open and close test (p < 0.001) and decreased right triceps skinfold thickness (p = 0.016). Conclusion: In frail older adults, supplementation for 3 months with a low dose (6 g/day) of MCTs (C8:0 and C10:0) increased muscle mass and function. These findings indicate the potential for the practical use of MCTs in daily life in treating sarcopenia.

Lynch syndrome-associated chordoma with high tumor mutational burden and significant response to immune checkpoint inhibitors.

Chordoma is a rare malignant bone tumor arising from notochordal tissue. Conventional treatments, such as radical resection and high-dose irradiation, frequently fail to control the tumor, resulting in recurrence and re-growth. In this study, genetic analysis of the tumor in a 72-year-old male patient with refractory conventional chordoma of the skull base revealed a high tumor mutational burden (TMB) and mutations in the MSH6 and MLH1 genes, which are found in Lynch syndrome. The patient and his family had a dense cancer history, and subsequent germline genetic testing revealed Lynch syndrome. This is the first report of a chordoma that has been genetically proven to be Lynch syndrome. Chordomas usually have low TMB; however, this is an unusual case, because the TMB was high, and immune checkpoint inhibitors effectively controlled the tumor. This case provides a basis for determining the indications for immunotherapy of chordoma based on the genetic analysis. Therefore, further extensive genetic analysis in the future will help to stratify the treatment of chordoma.

Medium-Chain Triglycerides (8:0 and 10:0) Increase Mini-Mental State Examination (MMSE) Score in Frail Elderly Adults in a Randomized Controlled Trial.

BACKGROUND: Supplementation with medium-chain triglycerides (MCTs) was previously shown to increase muscle function in frail elderly individuals. OBJECTIVE: We aimed to assess effects of MCTs on cognition in such individuals. METHODS: We enrolled 64 elderly nursing home residents (85.5 ± 6.8 y; 13 men, 51 women; BMI 18.6 ± 2.5 kg/m2) in a 3-mo randomized, controlled, single-blinded, intervention trial. Participants were randomly allocated to 3 groups: the first group received supplemental L-leucine (1.2 g) and cholecalciferol (20 µg) enriched with 6 g/d of MCTs (LD + MCT group) as a positive control, the second group received 6 g/d of MCTs (MCT group) as the test nutrient, and the third group received 6 g/d of long-chain triglycerides (LCT group) as a negative control. Cognition (secondary outcome) was monitored 4 times: baseline, 1.5 and 3 mo after initiation of the intervention (intervention), and 1.5 mo after termination of the intervention (postintervention follow-up). Cognition scores were assessed by a linear mixed model (intention-to-treat analysis). RESULTS: MCT supplementation increased the Mini-Mental State Examination (MMSE) score by 3.5 points at the 3-mo intervention from baseline (P < 0.001) [intention-to-treat adjusted means: baseline 17.5 points (95% CI: 14.9, 20.2), 3-mo intervention 21.0 points (18.3, 23.7)], whereas LCT supplementation decreased the MMSE score by -0.7 points [baseline 17.0 points (95% CI: 14.4, 19.6), 3-mo intervention 16.3 points (13.6, 18.9)]. At the 3-mo intervention, the difference in MMSE score between the MCT (21.0 points) and LCT (16.3 points) groups became significant (P < 0.05). The increase in MMSE score in response to MCTs was 2.1-fold greater at 3 mo than at 1.5 mo and had returned to baseline value at the 4.5-mo postintervention follow-up visit. CONCLUSION: Supplementation with 6 g MCTs/d may improve the cognition of frail elderly individuals. This trial was registered at umin.ac.jp as UMIN000023302.

Medium-chain triglycerides (8:0 and 10:0) are promising nutrients for sarcopenia: a randomized controlled trial.

BACKGROUND: The combined supplementation of medium-chain triglycerides (MCTs), l-leucine-rich amino acids, and cholecalciferol was previously shown to increase muscle strength and function in frail elderly individuals. OBJECTIVE: We examined whether treatment with MCTs alone is sufficient to increase muscle strength and function and activities of daily living (ADL) in such individuals. METHODS: We enrolled 64 elderly nursing home residents (85.5 ± 6.8 y) in a 3-mo randomized, controlled, single-blinded intervention trial. The participants were randomly assigned to 3 groups: the first group received supplemental l-leucine (1.2 g) and cholecalciferol (20 µg) enriched with 6 g/d of MCTs (LD + MCT group) as a positive control, the second group received 6 g/d of MCTs (MCT group) as a target, and the third group received 6 g/d of long-chain triglycerides (LCT group) as a negative control. Changes in muscle mass, strength, function, and ADL were monitored 4 times: at baseline, at 1.5 and 3 mo after initiation of the intervention (intervention), and 1.5 mo after termination of the intervention (washout). RESULTS: The 64 participants randomly assigned to the 3 groups were included in an intention-to-treat analysis. Forty-eight participants completed the study and were included in a per-protocol analysis. At 3 mo, participants in the MCT group had a 48.1% increase in 10-s leg open and close test performance [intention-to-treat adjusted means: MCT 2.28 n/10 s (1.37, 3.19) compared with LCT -0.59 n/10 s (-1.52, 0.35), P < 0.05], a 27.8% increase in a 30-s repetitive saliva swallowing test [MCT 0.5 n/30 s (0.1, 1.0) compared with LCT -0.5 n/30 s (-0.9, 0.0), P < 0.05], and a 7.5% increase in Functional Independence Measure score, a questionnaire for assessing ADL [MCT 5.6 points (1.3, 9.9) compared with LCT -6.6 points (-11.3, -2.0), P < 0.05]. CONCLUSION: MCTs (6 g/d) could increase the muscle strength and function of frail elderly individuals and also improve their ADL. This trial was registered at the University Hospital Medical Information Network Clinical Trial Registry as UMIN000023302.

Medium-Chain Triglycerides in Combination with Leucine and Vitamin D Benefit Cognition in Frail Elderly Adults: A Randomized Controlled Trial.

The combined supplementation of medium-chain triglycerides (MCTs), L-leucine-rich amino acids, and cholecalciferol (vitamin D3) increase muscle strength and function in frail elderly individuals. However, their effects on cognition are unknown. We enrolled 38 elderly nursing home residents (mean age±SD, 86.6±4.8 y) in a 3-mo randomized, controlled, parallel group trial. The participants were randomly allocated to 3 groups: the first group received a L-leucine (1.2 g)- and cholecalciferol (20 µg)-enriched supplement with 6 g of MCT (LD+MCT); the second group received the same supplement with 6 g of long-chain triglycerides (LD+LCT); and the third group did not receive any supplements (control). Cognition was assessed at baseline and after the 3-mo intervention. The difference in changes among the groups was assessed with ANCOVA, adjusting for age and the baseline value as covariates. After 3 mo, the Mini-Mental State Examination (MMSE) score in the LD+MCT group increased by 10.6% (from 16.6 to 18.4 points, p<0.05). After 3 mo, the Nishimura geriatric rating scale for mental status (NM scale) score in the LD+MCT group increased by 30.6% (from 24.6 to 32.2 points, p<0.001), whereas that in the LD+LCT and control groups decreased by 11.2% (from 31.2 to 27.7 points, p<0.05) and 26.1% (from 27.2 to 20.1 points, p<0.001), respectively. The combined supplementation of MCTs (6 g), L-leucine-rich amino acids, and cholecalciferol may improve cognitive function in frail elderly individuals.

Medium-Chain Triglycerides in Combination with Leucine and Vitamin D Increase Muscle Strength and Function in Frail Elderly Adults in a Randomized Controlled Trial.

BACKGROUND: Sarcopenia, the loss of skeletal muscle mass, strength, and function, is common in elderly individuals but difficult to treat. OBJECTIVE: A combination of nutrients was investigated to treat sarcopenia in very frail elderly adults. METHODS: We enrolled 38 elderly nursing home residents (11 men and 27 women with a mean ± SD age of 86.6 ± 4.8 y) in a 3-mo randomized, controlled, single-blind, parallel group trial. The participants were randomly allocated to 3 groups. The first group received a daily l-leucine (1.2 g) and cholecalciferol (20 µg)-enriched supplement with 6 g medium-chain triglycerides (TGs) (MCTs) (LD + MCT); the second group received the same leucine and cholecalciferol-enriched supplement with 6 g long-chain TGs (LD + LCT); and the third group did not receive any supplements (control). The supplement and oils were taken at dinner, and changes in muscle mass, strength, and function were monitored. RESULTS: The increase in body weight in the LD + MCT (1.1 ± 1.0 kg) and LD + LCT (0.8 ± 1.1 kg) groups was greater than that in the control group (-0.5 ± 0.9 kg) (P < 0.05). After 3 mo, participants in the LD + MCT group had a 13.1% increase in right-hand grip strength (1.2 ± 1.0 kg, P < 0.01), a 12.5% increase in walking speed (0.078 ± 0.080 m/s, P < 0.05), a 68.2% increase in a 10-s leg open-and-close test performance (2.31 ± 1.68 n/10 s, P < 0.001), and a 28.2% increase in peak expiratory flow (53 ± 59 L/min, P < 0.01). No significant improvements in muscle mass, strength, or function were observed in the LD + LCT or control groups. CONCLUSION: The combined supplementation of MCTs (6 g), leucine-rich amino acids, and cholecalciferol at dinner may improve muscle strength and function in frail elderly individuals. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN000017567.