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Study Design: Experimental study., Objective: We sought to elucidate the association between ligamentum flavum thickening and tissue buckling, and the clinical and imaging factors related to buckling by comparing the ligamentum flavum thickness on MRI images and within the actual tissue., Summary of Background Data: Ligamentum flavum thickening is a main contributor to lumbar spinal canal stenosis. Buckling of the tissue may contribute to ligamentum flavum thickening along with tissue hypertrophy; however, this association has not been established conclusively., Materials and Methods: Ligamentum flavum samples (135 ligament samples) from 70 patients with lumbar spinal canal stenosis were evaluated. The ligamentum flavum thicknesses on magnetic resonance imaging (MRI) and in the tissue samples were compared to assess for the presence of buckling. The ligamentum flavum samples were divided into groups with or without buckling based on the difference between their thicknesses on MRI and in the tissues. The Pearson correlation coefficient test was used to assess the relationships between the LF thicknesses on MRI and in the tissues, MRI-tissue difference and LF thickness in the tissues, and MRI-tissue difference and LF thickness on MRI. Further, differences between the buckling+ and buckling- groups were compared using the unpaired t-test (LF thickness on MRI, LF thickness in the tissues, age, disc angle, and disc height) and χ2 (disc level, disc degeneration, and receival/nonreceival of dialysis) test., Results: The ligamentum flavum thickness on MRI and in the tissues had a positive linear relationship, although the thickness was estimated to be significantly larger on MRI than in the tissues themselves. The ligamentum flavum with buckling had a larger thickness on MRI, less tissue hypertrophy, more severe disc degeneration, and was present in patients with a higher rate of dialysis. There were no differences in age and disc height, angle, or level between the two groups., Conclusions: Buckling of the ligamentum flavum coexists with tissue hypertrophy and contributes to perceived ligamentum thickening on imaging. Buckling of the ligamentum flavum tends to occur in less hypertrophied tissues and is associated with the grade of disc degeneration and the presence of other characteristics associated with spinal degeneration., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Experimental study of the ligamentum flavum (LF) thickness among patients with lumbar spinal canal stenosis (LSCS)., Objectives: To elucidate the factors associated with thickening of the LF on magnetic resonance imaging (MRI)., Summary of Background Data: Thickening of the LF is a major contributor to LSCS. This thickening is attributed to tissue hypertrophy or buckling of the ligament, and there may be several associated factors on MRI; however, these factors remain unclear., Methods: We studied the LF in 56 patients (a total of 106 ligaments) with LSCS, who underwent decompressive surgery; among them, 23 were receiving haemodialysis. The Pearson correlation coefficient was used to assess relationships between the thickness of the LF on MRI and the thickness of the LF tissue, age, disc height, disc degeneration, and disc level. Patients were also categorised into 2 groups based on whether they were undergoing haemodialysis, and the relationships were assessed similarly., Results: Among patients with LSCS, the thickness of the LF on MRI showed a significant positive linear relationship with the thickness of the LF tissue, and no association with disc height. Except for in those receiving haemodialysis, the thickness of the LF on MRI showed a significant positive relationship with age, disc degeneration, and disc level among patients with LSCS., Conclusion: In patients with LSCS, thickening of the LF on MRI appears to represent tissue hypertrophy. The association between the thickness of the LF on MRI and age, disc degeneration, and disc level may indicate simultaneous alterations of spine components along with aging that was cancelled by the effects of haemodialysis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Various treatments are available for treating hepatocellular carcinoma (HCC). The immune checkpoint inhibitor combination of atezolizumab plus bevacizumab was recently approved for the treatment of unresectable HCC, but there are few reports on the failure of the combination treatment. Here, we present a case of unresectable HCC with adrenal metastasis that was eventually operated on after lenvatinib (LEN) treatment that followed failed treatment with atezolizumab plus bevacizumab., Patient Concerns: A 68-year-old man was diagnosed with non-alcoholic steatohepatitis-based HCC with adrenal metastasis., Diagnosis: Cirrhosis was classified as Child-Pugh score of 5. HCC was diagnosed as Barcelona Clinic Liver Cancer stage C., Interventions: We initiated treatment with atezolizumab plus bevacizumab. Liver dysfunction appeared 2 days after the first administration but was improved by intravenous rehydration and did not appear after the second course. The HCC shrank, but the adrenal metastasis grew bigger after the fourth course, so we changed the therapy to LEN. After HCC and adrenal metastasis were necrotic by LEN, conversion surgery was performed., Outcomes: After successful conversion therapy, the general condition of the patient was good, and has been carefully followed for 4 months to date without any evidence of further recurrences., Lessons: This case showed that even if atezolizumab plus bevacizumab is not effective, multidisciplinary treatment such as LEN and conversion surgery is possible. Given the efficacy of LEN after atezolizumab plus bevacizumab, it is important to consider that there is a possibility of cure even when first-line treatment is not effective for a patient with unresectable HCC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Bariatric surgery has been reported to improve non-alcoholic steatohepatitis (NASH), which is a frequent comorbidity in morbidly obese patients. We performed a retrospective cohort study to estimate the therapeutic effect of sleeve gastrectomy (SG), the most common bariatric surgery in Japan, on obese patients with NASH by comparing the findings of paired liver biopsies.Eleven patients who underwent laparoscopic SG for the treatment of morbid obesity, defined as body mass index (BMI) > 35 kg/m2, from March 2015 to June 2019 at Hiroshima University Hospital, Japan, were enrolled. All patients were diagnosed with NASH by liver biopsy before or during SG and were re-examined with a second liver biopsy 1 year after SG. The clinical and histological characteristics were retrospectively analyzed.One year after SG, body weight and BMI were significantly reduced, with median reductions in body weight and BMI of-22 kg and -7.9 kg/m2, respectively. Body fat was also significantly reduced at a median of 13.7%. Liver-related enzymes were also significantly improved. On re-examination by paired liver biopsy, liver steatosis improved in 9 of the 11 patients (81.8%), ruling out of the pathological diagnosis of NASH. However, fibrosis stage did not significantly improve 1 year after SG. The non-alcoholic fatty liver disease activity score was significantly reduced in 10 of 11 patients (90.9%).Pathological improvement or remission of NASH could be achieved in most morbidly obese Japanese patients 1 year after SG., Competing Interests: Conflict of interest and source of funding: EM is currently receiving a grant from Grants-in-Aid for Scientific Research and Development from the Ministry of Health, Labor, and Welfare and the Ministry of Education Culture Sports Science and Technology (JSPS KAKENHI grant number 18K15814). KC received a grant from the Japan Agency for Medical Research and Development (grant number JP20fk0210040). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. None of the remaining authors were declared., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The effect of once daily low-dose carvedilol on circadian variations of blood pressure (BP) was studied in Japanese patients with mild or moderate essential hypertension. Thirty-one patients were admitted to hospital whose BP was 150/90 mm Hg/day or greater and they participated in the study. After a placebo period of 1 week, 5 or 10 mg carvedilol was given once daily in the morning for 3 to 7 days, and if BP reduction was not sufficient, the dose was increased to 20 mg daily. The blood pressure variation was monitored before and 1, 2, 4, 6, 8, 10, 12, and 24 h after administration of the drug on the last day of placebo and final dose of carvedilol. Of the 31 cases receiving carvedilol once daily, cumulative effectiveness (13 mm Hg reduction in mean BP) was 48.4% at 10 mg/day and 54.8% at 20 mg/day. Both systolic and diastolic pressures decreased significantly and heart rate decreased slightly. There was no significant difference between the standard deviations of BP on the last days of the control period and the carvedilol treatment. The difference between maximum and minimum BP during the day was not significant between the two periods. Circadian variations of heart rate were also not significantly different for the two periods. This indicates that carvedilol did not have any effect on circadian variations of BP and heart rate. The present study also suggests that low-dose carvedilol once daily may be effective in the treatment of hypertension.

The role of glutathione in the central nervous system in regulating blood pressure (BP) and sympathetic nerve activity (SNA) was investigated in rats. Intracerebroventricular (ICV) injection of glutathione disulfide (GSSG: 1.7-33 nmol) resulted in a dose-dependent increase in BP [delta mean BP: 17 +/- 1 mm Hg (n = 7) for 33-nmol dose] together with a marked increase in SNA [163 +/- 13 to 672 +/- 70 spikes/10 s (n = 7), p less than 0.001]. Intracerebroventricular administration of its reduced form (GSH, 33 nmol) produced a vasodepressor response (delta mean BP: -9 +/- 2 mm Hg) accompanied by a corresponding decrease in SNA [192 +/- 15 to 54 +/- 22 spikes/10 s (n = 6), p less than 0.01]. These responses were not due to a leakage into the systemic circulation, since intravenous injection of GSSG or GSH (33 nmol) did not show any cardiovascular effects. Electrical stimulation of the posterior hypothalamus induced hypertension with a significant decrease of GSSG in the brain stem. The results indicate that GSSG has a stimulatory control over the sympathetic nervous system while GSH has an inhibitory effect on SNA. Glutathione disulfide and GSH may act within the central nervous system to modulate the tone of the sympathetic nervous system.

The effect of brain glutathione reductase activity on blood pressure regulation was investigated. The intravenous administration of the glutathione reductase inhibitor, nitrofurantoin (0.1-0.3 mg/rat), to seven normotensive Wistar rats caused dose-dependent rises in blood pressure and the heart rate (delta mean blood pressure 17 +/- 1 mmHg; delta heart rate 89 +/- 7 beats/min for 0.3 mg). Rats treated with 0.3 mg nitrofurantoin showed a 50% decrease in glutathione reductase activity with a twofold increase in the ratio of glutathione disulphide to reduced glutathione in the hypothalamus and brainstem, and a 1.5-fold increase in plasma noradrenaline and plasma renin activity compared with controls. These nitrofurantoin-induced effects were totally abolished by pretreatment with a sympathetic ganglion blocker (4 mg pentolinium tartrate, administered subcutaneously) except for the increased ratio of glutathione disulphide to reduced glutathione and the decreased glutathione reductase activity in the brain. These results suggest that the blood pressure elevation caused by inhibition of brain glutathione reductase activity occurs through activation of the sympathetic nervous system and the renin-angiotensin system.

The effect of renin inhibitor ES-1005 on renin gene expression was investigated in sodium-depleted marmosets. The kidneys were removed after continuous infusion of ES-1005 (12 mg/kg per h) for 2 h. The relative amount of kidney renin messenger (m)RNA was measured by densitometric Northern blot analysis using an alpha-32P-labelled human renin complementary (c)DNA fragment as a hybridization probe. Plasma renin activity was completely inhibited by ES-1005. The level of kidney renin mRNA decreased significantly to about one-third of the normal control value. We also investigated the inhibitory potency of the renin inhibitor ES-6864 on the renin-like activity in dog tissues (adrenal glands, aorta and brainstem). ES-6864 inhibited the tissue renin-like activity with an IC50 of 10(-7) to 10(-8) mol/l in vitro. Renin inhibitors not only inhibit the activity of plasma and tissue renin, but also suppress the synthesis of renin in the kidney.