Idiopathic hypersomnia with a video recording of a spontaneous sleep attack: A case report.

RATIONALE: Although patients with central disorders of hypersomnolence (CDH) exhibit characteristic symptoms of hypersomnia frequently, it takes 5 to 15 years from the onset for its diagnosis due to the lack of symptom recognition. Here, we present a case of idiopathic hypersomnia (IH), a CDH, wherein early diagnosis was aided by a video footage of a spontaneous sleep attack. PATIENT CONCERNS: A 21-year-old man lost consciousness while driving and experienced an accident. He had complained of excessive daytime sleepiness (EDS) over half a year. During his hospitalization for close monitoring of the loss of consciousness, an in-room surveillance camera captured a 14-minutes long spontaneous sleep attack, during which he experienced general muscle weakness and loss of consciousness without warnings or convulsions leading to a fall from the bed. There were no abnormalities in vital signs. DIAGNOSES: There was no significant cataplexy and less than 2 sleep-onset rapid eye movements (SOREM) in 2 sleep latency tests, with a mean sleep latency of 2.1 and 4.6 minutes. Other sleep deprivation syndromes were excluded from differential diagnosis and finally, a diagnosis of IH was confirmed according to the criteria of the Third Edition of the International Classification of Sleep Disorders. During the course of the disease, attention-deficit/hyperactive disorder (ADHD) and a gaming disorder also diagnosed. INTERVENTIONS: Pharmacological treatment with modafinil was administered for IH and methylphenidate for ADHD. Cognitive behavioral therapy was performed for the gaming disorder. OUTCOMES: The EDS improved, and sleep attacks were no longer observed. The disruption of daily life caused by the gaming disorder was also reduced. LESSONS: Video recordings of sleep attacks are beneficial for identifying the cause of loss of consciousness. Home video recordings may be helpful in the early diagnosis of IH.

A Phase 2, Prospective, Multicenter, Single-Arm Trial of Transarterial Chemoembolization Therapy in Combination Strategy with Lenvatinib in Patients with Unresectable Intermediate-Stage Hepatocellular Carcinoma: TACTICS-L Trial.

Introduction: Transarterial chemoembolization (TACE) is the standard treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC), but recurrence after TACE is common. The present phase 2, prospective, multicenter, single-arm trial, the TACTICS-L trial, investigated the efficacy and safety of TACE plus lenvatinib (LEN), a drug that more strongly promotes vascular normalization and has a better objective response rate (ORR) than sorafenib (jRCTs031180074). Methods: Participants were patients with HCC who had not previously received systemic therapy, hepatic arterial infusion chemotherapy, or immunotherapy and who were ineligible for resection or percutaneous ablation therapy. LEN was to be administered 14-21 days before the first TACE, stopped 2 days before TACE, and resumed 3 days after TACE. Key inclusion criteria were unresectable HCC, Child-Pugh A liver function, 0-2 prior TACE sessions, tumor size ≤10 cm, number of tumors ≤10, and ECOG performance status 0-1. Key exclusion criteria were vascular invasion and extrahepatic spread. The primary endpoint was progression-free survival (PFS) by RECICL, and secondary endpoints were time to untreatable progression, ORR, overall survival (OS), and safety. Results: A total of 62 HCC patients were enrolled in this trial. The median age was 72 years, 77.4% of patients were men, and 95.2% had PS 0. The primary endpoint of median PFS was 28.0 months (90% confidence interval [CI] 25.1-31.0) after a minimum 24 months of follow-up. The secondary endpoint of median OS was not reached (90% CI 35.5 months-NR). LEN-TACE achieved a high response rate and high complete response (CR) rate (4 weeks after the first TACE: ORR 79.0%, CR rate 53.2%; best response: ORR 88.7%, CR rate 67.7%) by RECICL. Exploratory subgroup analyses showed that the characteristics of responders/nonresponders (ORR and CR rate) were similar and that LEN-TACE would be effective in all subgroups, including the population in whom TACE alone would be less likely to be curative (e.g., patients with the non-simple nodular type or a high tumor burden). The relative dose intensity of LEN before the first TACE was important for achieving higher CR rate/ORR by LEN-TACE. No new safety concerns were observed. Conclusion: The results of this trial provide encouraging evidence, supporting the efficacy and favorable safety profile of LEN-TACE in patients who are ineligible for locoregional therapy.

Clinical outcome after cessation of nucleos(t)ide analog treatment in chronic hepatitis B patients who achieved HBsAg seroclearance.

BACKGROUND: We determined the long-term clinical outcome and the durability of treatment cessation after HBsAg seroclearance following nucleos(t)ide analog (NA) therapy in patients with chronic hepatitis B (CHB). METHODS: We analyzed virological relapse (VR), HBsAg reversion, clinical relapse, and changes in HBsAg and HBcrAg levels by iTACT assay after treatment cessation of 90 CHB patients who achieved HBsAg seroclearance by NA treatment. RESULTS: Median age of patients at treatment cessation was 57 years. Median duration of NA treatment and follow-up from cessation of NA were 9.25 and 5.2 years, respectively. Although VR occurred in 19 of 90 (21.1%) patients, HBV DNA levels of 18 patients had temporal elevations and sustained levels under the detection level thereafter. HBsAg reversion using Architect HBsAg QT assay occurred in six patients (6.7%) after cessation of NA. Five patients had temporal HBsAg level elevations and sustained levels under the detection level thereafter. One patient had virological and clinical relapse at 6 months after cessation of NA, and received NA re-treatment. HBsAg levels by iTACT assay from end of treatment (EOT) gradually decreased and in 18 of 28 (64%) patients reached an undetectable level at 5 years after EOT. In contrast, HBcrAg levels by iTACT assay slowly decreased, and in 8 of 29 patients (28%) reached an undetectable level at 5 years after EOT. CONCLUSIONS: Patients receiving NA treatment who achieved HBsAg seroclearance as determined by HBsAg QT assay rarely experienced virological or clinical relapse after the cessation of treatment.

Impact of genetic polymorphism on personalized diet and exercise program for steatotic liver disease.

AIMS: The effects of genetic polymorphism on a personalized diet and exercise program for steatotic liver disease (SLD) are still unclear. METHODS: Participants of this retrospective cohort study were 203 Japanese patients with SLD diagnosed by abdominal ultrasonography. All of them were introduced the personalized diet and exercise treatment. A diet of 25-30 kcal/kg multiplied by ideal body weight (BW) daily and aerobic and resistance exercise (exercise intensity of 4-5 metabolic equivalents daily, respectively) were performed for 6 days. Treatment efficacy was evaluated in terms of the rate of decrease of liver function tests, glycolipid metabolism markers, physical findings, image findings, and cardiovascular disease (CVD) risk score at 6 months compared with baseline. Furthermore, the impact of genetic polymorphism was also investigated. RESULTS: At 6 months compared with baseline, liver function tests (AST, ALT, γGTP), glycolipid metabolism markers (hemoglobin A1c, triglycerides [TG], low-density lipoprotein cholesterol), physical findings (BW, body mass index), image finding (liver stiffness measurement), and CVD risk score (Suita score) improved significantly. There was no significant difference in treatment efficacy, except for the rates of decrease of TG, according to genotype PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs6834314. The rates of decrease of TG with TM6SF2 CT were significantly higher than those with CC or TT, and the rates of TG with HSD17B13 AA were significantly higher than those with AG by multiple comparisons. CONCLUSION: Personalized diet and exercise program for SLD improved liver function tests, physical findings, glycolipid metabolism markers, and CVD risk score. Genetic polymorphism might partially affect treatment efficacy. Further studies should be performed to develop an individualized program for SLD, considering genetic polymorphism.

Efficacy of denosumab in the treatment of hypercalcemic renal dysfunction in sarcoidosis: a case report.

A 70-year-old female patient was admitted for close examination and treatment of hypercalcemia (corrected serum calcium levels: 3.04 mmol/L) and renal dysfunction (serum creatinine levels: 254.59 µmol/L). The patient had a history of sarcoidosis, diagnosed based on epithelioid cell granulomas in subcutaneous nodule biopsies, uveitis, and bilateral hilar lymphadenopathy, which had spontaneously remitted 10 years before admission. Because the patient was diagnosed with hypercalcemia associated with recurrent sarcoidosis, prednisone (20 mg/day) was initiated, and its dose was tapered following the decrease in serum calcium and creatinine levels. However, the levels of these parameters increased again when the prednisone dose was reduced to ≤ 4 mg/day. We were concerned about glucocorticoid-induced osteoporosis in the patient but hesitated to use first-line bisphosphonates because of renal dysfunction. Therefore, denosumab was initiated to reduce the risk of hypercalcemia, renal dysfunction, and glucocorticoid-induced osteoporosis. Serum creatinine and corrected serum calcium levels subsequently decreased. The prednisone dose could be reduced following repeated denosumab administration.Thus, denosumab can be a multifaceted, beneficial option for sarcoidosis-induced hypercalcemia, as it alleviates renal dysfunction indirectly by normalizing serum calcium levels, facilitates reduction of the glucocorticoid dose, and ameliorates glucocorticoid-induced osteoporosis.

A new imaging classification for safer radial access visceral intervention of the liver and optimal case selection: A preliminary report.

AIM: The aim of this study was to evaluate the use of a new classification for safer transradial access hepatic interventional radiology, based on preoperative evaluation of the location of the left subclavian artery bifurcation in the aortic arch. METHODS: A total of 38 consecutive patients with hepatocellular carcinoma and 74 sessions of radial access for visceral intervention (R.A.V.I.) were reviewed. We classified the location of the left subclavian artery bifurcation in the aortic arch in three areas using an oblique view computed tomography image matched with the curve of the aortic arches according to a new criteria Three Areas Criteria For R.A.V.I. (named "TAC-F-R"), and measured the required time from initial left radial artery arteriography to celiac artery or superior mesenteric artery arteriography. RESULTS: The median time required for left radial artery arteriography to the celiac artery or superior mesenteric artery arteriography in each of the three areas were: area A, 0:11:10 (h, min, s); area B, 0:14:44; and area C, 0:31:51. There were significant differences between each area after Bonferroni correction (p < 0.01; A vs. B, p = 0.086; A vs. C, p = 0.001; and B vs. C, p = 0.045), with areas A and B requiring a significantly shorter time. Finally, no patients showed neurogenic disfunction within 1 week after the R.A.V.I. CONCLUSIONS: The new classification, "TAC-F-R," for safer transradial access hepatic interventional radiology is effective for avoiding difficult cases, and selects more suitable patients with hepatocellular carcinoma for the R.A.V.I.

Two Cases of Advanced Hepatocellular Carcinoma Who Responded Well to the Combination of Durvalumab Plus Tremelimumab After Disease Progression During Atezolizumab Plus Bevacizumab Therapy Under Bevacizumab Withdrawal.

Many systemic chemotherapies, including immune checkpoint inhibitors (ICI), are now available for the treatment of advanced hepatocellular carcinoma. On the other hand, it is often difficult to continue administration of angiogenesis inhibitors in these patients due to various side effects. In the two cases described in this paper, following the introduction of combination therapy with atezolizumab plus bevacizumab (Atezo/Bev), it was difficult to continue bevacizumab treatment due to side effects, such as proteinuria and fluid retention, with disease control in the two patients being ultimately poor. However, both patients experienced treatment success after switching Atezo/Bev to a regimen that included durvalumab, an anti-programmed cell death ligand 1 antibody (anti-PD-L1 antibody) similar to atezolizumab, plus tremelimumab, an anti-cytotoxic T lymphocyte-associated antigen 4 antibody (anti-CTLA-4 antibody) in situations where the continuation of bevacizumab was difficult. The efficacy of subsequent drug sequencing from ICI to another ICI after atezolizumab plus bevacizumab, which is the standard first-line treatment in advanced hepatocellular carcinoma, has not yet been established. We consider that the two cases described in this paper provide valuable information worthy of the report.

Increasing averaging beats improves the test accuracy on Holter-based late potentials in patients with myocardial infarction.

BACKGROUND: The prevalence of Holter-based late potentials (H-LPs) in cases of fatal cardiac events has increased. Although the noise level of H-LP is higher than that of conventional real-time late potential (LP) recording, a procedure to reduce the noise severity in H-LP by increasing the averaging beats has not been investigated. METHODS: We enrolled 104 patients with post-myocardial infarction (MI) and 86 control participants. Among the patients, 30 reported sustained ventricular tachycardia (VT), and the remaining 74 had unrecorded VT. H-LPs were measured twice in all groups to evaluate the efficacy of increasing the averaging beats for H-LPs. Thereafter, the average of LP was calculated at 250 (default setting), 300, 400, 500, 600, 700, and 800 beats. RESULTS: Across all three groups (MI-VT group, MI non-VT group, and control group), the noise levels significantly decreased in consonance with the increase in averaging beats. In the MI-VT group, the H-LP positive rate considerably increased with the increase in the averaging beats from 250 to 800 both at night and daytime. In the MI-VT group, the LP parameters significantly deteriorated, which led to a positive judgment corresponding to the increment of the averaged night and day beats. The H-LP positive rates were unchanged in the MI non-VT and control groups, while the LP parameters remained consistent, despite the increased averaging beats in the MI non-VT and control groups. CONCLUSION: Increasing the calculated averaging beats in H-LPs can improve the sensitivity of predicting fatal cardiac events in patients with MI.

Effects of Mobilization within 72 h of ICU Admission in Critically Ill Patients: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Previous systematic review and meta-analysis indicates that rehabilitation within a week of intensive care unit (ICU) admission benefits physical function in critically ill patients. This updated systematic review and meta-analysis aim to clarify effects of initiating rehabilitation within 72 h of ICU admission on long-term physical, cognitive, and mental health. We systematically searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi for randomized controlled trials (RCTs) between April 2019 and November 2022 to add to the previous review. Two investigators independently selected and extracted data. Pooled effect estimates for muscle strength, cognitive function, mental health after discharge, and adverse events were calculated. Evidence certainty was assessed via Grading of Recommendations, Assessment, Development, and Evaluations. Eleven RCTs were included in the meta-analysis. Early rehabilitation may improve muscle strength (three trials; standard mean difference [SMD], 0.16; 95% confidence interval [CI], -0.04-0.36) and cognitive function (two trials; SMD, 0.54; 95% CI, -0.13-1.20). Contrastingly, early mobilization showed limited impact on mental health or adverse events. In summary, initiating rehabilitation for critically ill patients within 72 h may improve physical and cognitive function to prevent post-intensive care syndrome without increasing adverse events. The effect on mental function remains uncertain.

Diurnal Variation in and Optimal Time to Measure Holter-Based Late Potentials to Predict Lethal Arrhythmia after Myocardial Infarction.

Background and Objectives: Holter-based late potentials (LPs) are useful for predicting lethal arrhythmias in organic cardiac diseases. Although Holter-based LPs exhibit diurnal variation, no studies have evaluated the optimal timing of LP measurement over 24 h for predicting lethal arrhythmia that leads to sudden cardiac death. Thus, this study aimed to validate the most effective timing for Holter-based LP testing and to explore factors influencing the diurnal variability in LP parameters. Materials and Methods: We retrospectively analyzed 126 patients with post-myocardial infarction (MI) status and 60 control participants who underwent high-resolution Holter electrocardiography. Among the 126 post-MI patients, 23 developed sustained ventricular tachycardia (VT) (the MI-VT group), while 103 did not (the MI-non-VT group) during the observation period. Holter-based LPs were measured at 0:00, 4:00, 8:00, 12:00, 16:00, and 20:00, and heart rate variability analysis was simultaneously performed to investigate factors influencing the diurnal variability in LP parameters. Results: Holter-based LP parameters showed diurnal variation with significant deterioration at night and improvement during the day. Assessment at the time with the longest duration of low-amplitude signals < 40 µV in the filtered QRS complex terminus (LAS40) gave the highest receiver operating characteristics curve (area under the curve, 0.659) and the highest odds ratio (3.75; 95% confidence interval, 1.45-9.71; p = 0.006) for predicting VT. In the multiple regression analysis, heart rate and noise were significant factors affecting the LP parameters in the MI-VT and control groups. In the non-VT group, the LP parameters were significantly influenced by noise and parasympathetic heart rate variability parameters, such as logpNN50. Conclusions: For Holter-based LP measurements, the test accuracy was higher when the LP was measured at the time of the highest or worst value of LAS40. Changes in autonomic nervous system activity, including heart rate, were factors influencing diurnal variability. Increased parasympathetic activity or bradycardia may exacerbate Holter-based LP parameters.

Favorable Impact of Serum TERT C228T for Prognosis after Surgical Resection for Liver Cancer.

INTRODUCTION: Personalized medicine and molecular therapies with the diagnosis of somatic genetic alterations are expected to be developed for liver cancer. Nevertheless, it is unknown whether a mutation in the telomere reverse transcriptase promoter (TERT C228T) in serum cfDNA might be useful for making prognostic predictions after surgical resection for primary liver cancer. METHODS: This cohort study retrospectively investigated 111 patients who had undergone surgical resection of liver cancer for the first time. We investigated the differences between clinicopathological features and prognosis according to classification of three tumor markers, including AFP, PIVKAII, and TERT C228T. RESULTS: Multivariate analysis identified etiology (fatty liver disease vs. HBV odds ratio [OR] 6.853) and fibrosis stage (2-4, OR: 0.137) as determinants of TERT C228T-positive liver cancer with normal levels of AFP and PIVKAII (TERT single positive liver cancer). TERT single positive (Yes, OR: 0.301), fibrosis (FIB)-4 index (≥3.25, OR: 2.038), Child-Pugh classification (B, OR: 4.975), and number of tumors (≥2, OR: 4.098) were identified as determinants of the recurrence of liver cancer. TERT single positive (Yes, OR: 3.311), FIB-4 index (≥3.25, OR: 0.433), and number of tumors (≥2, OR: 0.262) were identified as determinants of disease-free survival. CONCLUSIONS: Our results highlight the impact of classification of prognostic tumor markers. TERT single positive is one predictor of favorable prognosis after surgical resection for liver cancer.

Impact of fibrosis on liver-related event incidence in nonalcoholic fatty liver disease: A multicenter observational study.

AIM: There are few reports on the prognosis of liver-related events in Japanese patients with nonalcoholic fatty liver disease (NAFLD). We undertook an observational study to compare the prognosis between fibrotic and nonfibrotic groups in Japanese NAFLD patients. METHODS: Prognosis in 393 NAFLD patients who underwent liver biopsy between April 2013 and April 2015 at multiple centers were investigated. The time to onset of liver-related events, cardiovascular events, development of extrahepatic cancers, and death were compared between the pathologically fibrotic nonalcoholic steatohepatitis (NASH) group and nonalcoholic fatty liver (NAFL) + nonfibrotic NASH group. A similar analysis was carried out based on the fibrotic classification diagnosed using four noninvasive fibrosis prediction models. RESULTS: The mean age and body mass index at the time of liver biopsy was 55.7 years old and 28.04 kg/m2 , respectively The cumulative incidence of liver-related events at 1080 days after liver biopsy was 5.79% in the pathologically fibrotic NASH group and 0% in the NAFL + nonfibrotic NASH group, with a significant difference (p = 0.0334). The cumulative incidence of liver-related events was significantly higher in the positive group for the prediction model than in the negative group in all four models (all p values were <0.0001). There was no significant difference between the pathologically fibrotic NASH group and NAFL + nonfibrotic NASH group in terms of cumulative incidence of cardiovascular events, development of extrahepatic cancers, and death. CONCLUSIONS: The incidence of liver-related events was significantly higher in the fibrotic NASH group than that of the NAFL + nonfibrotic NASH group in Japanese NAFLD patients.

Efficacy of the Combination of Systemic Sequential Therapy and Locoregional Therapy in the Long-Term Survival of Patients with BCLC Stage C Hepatocellular Carcinoma.

BACKGROUND: The aim of this study was to evaluate the clinical impact of a combination of systemic sequential therapy and locoregional therapy on the long-term survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC). METHODS: Sixty-four consecutive patients with intrahepatic target nodules who had initially received systemic therapy (lenvatinib and atezolizumab plus bevacizumab) were reviewed. The clinical impact of the combined use of systemic sequential therapy and locoregional therapy was evaluated by determining overall survival (OS). The combined use of systemic sequential therapy with more than two agents and locoregional treatment was defined as multidisciplinary combination therapy (MCT), while only systemic sequential therapy and repeated locoregional-treatment was defined as a single treatment procedure (STP). RESULTS: R0 resection, MCT, and STP resulted in significantly better OS compared with no additional treatment (median OS, not reached vs. 18.2 months and 12.6 vs. 8.1 months, respectively; p = 0.002). Multivariate analysis confirmed that the use of R0 resection and MCT were associated with better OS (hazard ratio [HR]; 0.053, p = 0.006 and 0.189, p < 0.001, respectively) compared with that for STP (HR; 0.279, p = 0.003). CONCLUSIONS: MCT is may effective in patients with BCLC stage C HCC and intrahepatic target nodules who have previously received systemic therapy-based treatment.

Effect of Neuromuscular Electrical Stimulation in Patients With Critical Illness: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Neuromuscular electrical stimulation (NMES) is used in the rehabilitation of patients with critical illness. However, it is unclear whether NMES prevents ICU-acquired weakness (ICU-AW). For this purpose, we conducted an updated systematic review and meta-analysis. DATA SOURCES: We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases from April 2019 to November 2022 to identify new randomized controlled trials to the previous meta-analysis. STUDY SELECTION: We systematically searched the literature for all randomized controlled trials on the effect of NMES in patients with critical illness. DATA EXTRACTION: Two authors independently selected the studies and extracted data. They calculated the pooled effect estimates associated with the occurrence of ICU-AW and adverse events as primary outcomes and muscle mass change, muscle strength, length of ICU stay, mortality, and quality of life as secondary outcomes. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Overall, eight studies were added to the previous 10 studies. Evidence suggests that the use of NMES reduces the occurrence of ICU-AW (six trials; risk ratio [RR], 0.48; 95% CI, 0.32-0.72); however, NMES may have little to no effect on pricking sensation in patients (eight trials; RR, 6.87; 95% CI, 0.84-56.50). NMES is likely to reduce the change in muscle mass (four trials; mean difference, -10.01; 95% CI, -15.54 to -4.48) and may increase muscle strength (six trials; standardized mean difference, 0.43; 95% CI, 0.19-0.68). Further, NMES may result in little to no difference in the length of ICU stay, and the evidence is uncertain about the effect on mortality and quality of life. CONCLUSIONS: This updated meta-analysis revealed that the use of NMES may result in a lower occurrence of ICU-AW in patients with critical illness, but its use may have little to no effect on pricking sensation in patients.

Age-related reference intervals for ambulatory electrocardiographic parameters in healthy individuals.

Background: The advent of novel monitoring technologies has dramatically increased the use of ambulatory electrocardiography (AECG) devices. However, few studies have conducted detailed large-scale investigations on the incidence of arrhythmias over 24 h, especially ectopy, in healthy individuals over a wide age range. Objectives: This study aimed to investigate the incidence of arrhythmias detected using AECG and associated factors, in healthy individuals, over a wide age range. Methods: In this cross-sectional study, we performed AECG on 365 healthy volunteers (median [interquartile range]: 48 [36, 67], 20-89 years, 165 men) under free-running conditions for 24 h. Ultrasonic echocardiography and heart rate variability analysis were performed to explore the factors associated with the incidence of arrhythmias. Results: The 97.5th percentile of single ventricular ectopy (VE) was 149/day, 254/day, and 1,682/day in the 20-39-, 40-59- and 60-89-year age groups, respectively; that of single supraventricular ectopy (SVE) was 131/day, 232/day, and 1,063/day, respectively. Multivariate analysis revealed that aging was the only independent significant factor influencing the frequency of VE (ß = 0.207, P = 0.001). Age (ß = 0.642, P < 0.001), body mass index (BMI) (ß = -0.112, P = 0.009), and the root mean square of successive differences in RR intervals (ß = 0.097, P = 0.035) were factors significantly associated with SVE frequency. Conclusions: Age-specific reference intervals of VE and SVE in a large population of healthy participants over a wide age range were generated. VE and SVE increased with age; SVE was influenced by BMI and the aging-induced decrease in parasympathetic tone activity.

Diagnosis and treatment approaches for simultaneous onset of subarachnoid hemorrhage and thyroid storm: a case report.

BACKGROUND: Subarachnoid hemorrhage and thyroid storm are similar in their clinical symptomatology, and diagnosis of these conditions, when they occur simultaneously, is difficult. Here, we report a rare case of concurrent subarachnoid hemorrhage and thyroid storm we encountered at our hospital. CASE PRESENTATION: The patient was a 52-year-old woman. While bathing at home, the patient experienced a sudden disturbance of consciousness and was brought to our hospital. The main physical findings upon admittance were Glasgow Coma Scale score of E1V2M4, elevated blood pressure (208/145 mmHg), and tachycardia with atrial fibrillation (180 bpm) along with body temperature of 36.1 °C. Brain computed tomography revealed subarachnoid hemorrhage associated with a ruptured aneurysm of the posterior communicating artery branching from the left internal carotid artery, and aneurysm clipping was performed. Blood tests upon admission revealed high levels of free T3 and free T4 and low levels of thyroid-stimulating hormone. Upon determining that the patient had hyperthyroidism, thiamazole was administered. However, due to continuous impaired consciousness, fever, and persistence of tachycardia, the patient was diagnosed with thyroid storm. Oral potassium iodide and hydrocortisone were added to the treatment. The treatment was successful as the patient's symptoms improved, and she became lucid. In this case, we believe that in the presence of untreated hyperthyroidism, the onset of subarachnoid hemorrhage induced thyroid storm. Tachycardia of 130 bpm or higher, which is the diagnostic criterion for thyroid storm, rarely occurs with subarachnoid hemorrhage. Therefore, we believe it is an important factor for recognizing the presence of the thyroid storm. In this case, clipping surgery was prioritized which resulted in a favorable outcome. However, it is possible that invasive surgery may have exacerbated thyroid storm, suggesting that treatment should be tailored as per patient's condition. CONCLUSION: If a pulse rate of 130 bpm or higher is observed alongside subarachnoid hemorrhage, we recommend considering the possibility of concomitant thyroid storm and testing for thyroid hormone. If concomitant thyroid storm is present, we believe that a treatment plan tailored to the patient's condition is critical, and early diagnosis will lead to a favorable outcome for the patient.

Treatment efficacy of diet and exercise program for fatty liver and pretreatment predictors.

AIMS: Both diet and exercise counseling are recommended for patients with fatty liver, including nonalcoholic fatty liver disease (NAFLD), to achieve weight loss goals. However, data evaluating treatment efficacy are limited. METHODS: The subjects of this retrospective cohort study were 186 consecutive Japanese cases with fatty liver diagnosed by abdominal ultrasonography. Treatment efficacy and predictive factors of "Hospitalization Program for Improvement Purpose for Fatty Liver" as a combined diet and aerobic and resistance exercise program were evaluated according to the hospitalization group (153 cases) or the no hospitalization group (33 cases). To balance the confounding biases, treatment efficacy was evaluated using propensity score-matched analysis. In the hospitalization group, a diet of 25-30 kcal/kg multiplied by ideal body weight (BW) daily and aerobic and resistance exercise (exercise intensity of 4-5 metabolic equivalents daily, respectively) were performed for 6 days. RESULTS: In liver function tests and BW at 6 months compared with baseline, the rates of decrease of the hospitalization group (24 cases) were significantly higher than those of the no hospitalization group (24 cases), using propensity score-matched analysis. In markers of glycolipid metabolism and ferritin levels, the rates of the hospitalization group were not different from those of the no hospitalization group. In the hospitalization group (153 cases), multivariate regression analysis identified the etiology of non-NAFLD, the presence of diabetes mellitus, and large waist circumference as independent predictors of decreased rates of hemoglobin A1c levels. CONCLUSION: The diet and exercise program for fatty liver improved liver function tests and BW. Further study should be performed to develop a feasible and suitable program.

Urate Transporter ABCG2 Function and Asymptomatic Hyperuricemia: A Retrospective Cohort Study of CKD Progression.

RATIONALE & OBJECTIVE: Treatment of asymptomatic hyperuricemia is not commonly implemented. However, it is unclear whether urate deposition that begins during asymptomatic hyperuricemia can induce nephropathy. Dysfunction of ATP-binding cassette subfamily G member 2 (ABCG2), a urate efflux transporter, leads to elevated serum uric acid concentration (SUA). We investigated the association between asymptomatic hyperuricemia and decreased estimated glomerular filtration rate (eGFR), and the impact of ABCG2 on this relationship. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 1,885 Japanese adults undergoing routine health care follow-up between 2007 and 2017 who had eGFR ≥60 mL/min/1.73 m2, of which 311 had asymptomatic hyperuricemia (SUA >7.0 mg/dL). Study participants were classified into 3 categories of estimated ABCG2 function (full, 75%, and ≤50% function). PREDICTORS: Baseline SUA and estimated ABCG2 function. OUTCOME: Change in eGFR over time. ANALYTICAL APPROACH: Linear mixed-effect models were used to analyze the relationship between asymptomatic hyperuricemia, ABCG2 function, and eGFR decline. RESULTS: Asymptomatic hyperuricemia was negligibly associated with eGFR decline overall. However, among those with eGFR 60-89 mL/min/1.73 m2 and ≤50% ABCG2 function, eGFR decline was associated with asymptomatic hyperuricemia (P = 0.03). ABCG2 was not associated with eGFR reductions when the SUA was <6.0 mg/dL. Among participants with SUA ≥6.0 mg/dL and eGFR 60-89 mL/min/1.73 m2, ≤50% ABCG2 function was associated with approximately 1.2-fold faster eGFR decline compared with fully functional ABCG2 (P = 0.02). Among the participants with SUA ≥6.0 mg/dL and eGFR 60-89 mL/min/1.73 m2, the adjusted eGFR slopes (given as mean ± standard error of the mean, in mL/min/1.73 m2 per year) were -0.946 ± 0.049, -1.040 ± 0.046, and -1.148 ± 0.069 for full, 75%, and ≤50% ABCG2 function, respectively. LIMITATIONS: Lack of measurement of urinary urate and uremic toxins that are known to be transported by ABCG2, and no independent validation cohort. CONCLUSIONS: Asymptomatic hyperuricemia was not associated with eGFR decline, except when in the presence of ≤50% ABCG2 function. PLAIN-LANGUAGE SUMMARY: The urate transporter ABCG2 is a protein that regulates serum urate concentrations; when dysfunctional, it can lead to elevated serum concentrations of this compound (ie, hyperuricemia). Although persistent hyperuricemia induces gout and kidney injury, the effects on organs during the asymptomatic phase have yet to be established. Therefore, to clarify the relationship between ABCG2, asymptomatic hyperuricemia, and kidney function, we conducted a retrospective cohort study of 1,885 healthy participants, including 311 participants with asymptomatic hyperuricemia. We found that the coexistence of asymptomatic hyperuricemia and severe ABCG2 dysfunction was associated with the age-dependent decline in kidney function. We concluded that asymptomatic hyperuricemia represents a risk factor for chronic kidney disease, at least in individuals with highly dysfunctional ABCG2. This new finding highlights the potential importance of ABCG2 in the pathogenesis of hyperuricemia-induced kidney injury.

The Impact of Lenvatinib on Tumor Blood Vessel Shrinkage of Hepatocellular Carcinoma during Treatment: An Imaging-Based Analysis.

INTRODUCTION: When lenvatinib is administered to people with hepatocellular carcinoma (HCC), tumor blood flow is reduced due to the inhibition of the vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR). Few studies have examined the decrease in tumor blood flow with respect to changes in tumor blood vessels (TBVs) in clinical practice. We investigated the mechanism of tumor blood flow control by investigating changes in the diameter of relatively large TBVs in large-sized lesions with high blood flow. METHODS: From January 2011 to October 2021, patients receiving lenvatinib for unresectable intrahepatic HCC at Toranomon Hospital, Tokyo, Japan, were considered for inclusion. We investigated the TBV diameter in the arterial phase of dynamic computed tomography before treatment and its change over time (2-12 weeks after lenvatinib initiation). The relationship between changes in TBV diameter and prognosis was also examined. RESULTS: Of 114 patients treated with lenvatinib for HCC, 26 patients who had intrahepatic lesions with a tumor diameter of 30 mm or more enrolled in the study. The median tumor and TBV diameters before treatment were 58 mm and 2.55 mm, respectively. Twenty-five patients (96%) had a shrinkage in TBV diameter 2-12 weeks after lenvatinib administration. The maximum TBV diameter shrinkage of 20% or more was observed in 19 patients (73%), and progression-free survival was prolonged in these patients compared to the group with less than 20% TBV diameter shrinkage (p = 0.039). DISCUSSION/CONCLUSION: Due to the antiangiogenic effect of lenvatinib, a shrinkage in the TBV diameter of HCC was observed. The shrinkage of TBV may be regarded as a process of normalization of TBVs. The shrinkage of TBVs in imaging analysis may be associated with improved prognosis; however, additional studies are still required.