Comparison of Prognosis and Cognitive Function of Holistic Neurological Disease: Tochigi Neurological Disease Cohort Study.

Background: While many studies focus on the prognosis of individual neurological diseases, very few comprehensively compare and analyze real-world data of these diseases. Objective: To address this gap in knowledge, in this study, we comprehensively analyzed the real-life data of patients with neurological diseases. Methods: We prospectively enrolled patients with neurological diseases at three hospitals from December 1, 2016 to September 30, 2020. Neurological diseases were classified into nine groups: Dementia, Cerebrovascular disease, Parkinson's and related, Functional, Spinocerebellar degeneration, Neuroimmune, Epilepsy, Muscle dystrophy disease, and Hypertension. Patients were followed up for three years, and their prognosis and evaluation of their cognitive function served as the endpoint. Results: A total of 426 patients were finally enrolled. Both mortality and cognitive function differed among the neurological disease categories. After 3 years, mortality was highest in the Dementia (25.5%), Parkinson's and related (21.6%), and Spinocerebellar degeneration (35.3%) groups while the cognitive function of patients in these three groups was significantly lowest. Conclusions: When the neurological diseases were holistically observed, both mortality and cognitive function of the Dementia, Parkinson's and related, and Spinocerebellar degeneration groups were significantly worse than the remaining diseases.

Impact of COVID-19 pandemic on mortality and cognitive function of dementia patients: Tochigi Dementia Cohort Study.

OBJECTIVES: The coronavirus disease 2019 pandemic significantly affected Japanese society and the health of its population. Despite this, few studies have evaluated the influence of the pandemic on patients with neurological diseases or dementia, which we assessed through the Tochigi Dementia Cohort Study. METHODS: Participants were divided into two groups. The pre-pandemic group included patients who were enrolled from December 1, 2016 to November 30, 2018, and were followed up until November 30, 2019 (i.e., before the pandemic). The post-pandemic group included patients who were enrolled from December 1, 2019 to November 30, 2021, and were followed up until November 30, 2022 (i.e., during the pandemic). We recorded their age, sex, mortality, and treatment withdrawal during the follow-up period. Furthermore, we examined their cognitive function at the baseline, and after 6 and 12 months. RESULTS: A total of 384 patients were enrolled in this study, including 199 patients in the pre-pandemic group and 185 in the post-pandemic group. The mortality of dementia patients was significantly higher in the post-pandemic group than in the pre-pandemic group" (5.3% vs. 18.5%, p < 0.05*). The cognitive function scores at 12 months were also significantly lower in the dementia patients of the post-pandemic group than in those of the pre-pandemic group (p < 0.05*). CONCLUSIONS: This longitudinal cohort study conducted in a local Japanese area revealed that mortality rate and cognitive function worsened in dementia patients during the pandemic.

Efficacy and safety of glecaprevir and pibrentasvir combination therapy in old-aged patients with chronic hepatitis C virus infection.

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.

No Regional Disparities in Sofosbuvir Plus Ribavirin Therapy for HCV Genotype 2 Infection in Tochigi Prefecture and Its Vicinity.

Objective Regional disparities were observed in the outcomes of interferon (IFN)-based therapy for chronic hepatitis C virus (HCV) infection in a Japanese nationwide study. However, whether or not these regional disparities are observed in the outcomes of direct-acting antiviral drugs, including sofosbuvir (SOF) plus ribavirin (RBV) therapy, remains unclear. Methods We conducted a multicenter study to assess the efficacy of SOF plus RBV therapy for HCV genotype 2 infection in Tochigi Prefecture and its vicinity, in which IFN-based therapy yielded a low sustained virologic response (SVR) rate. In addition, we divided Tochigi Prefecture into six regions to examine regional disparities in the SVR. Patients We enrolled patients with chronic HCV genotype 2 infection. Results Of the 583 patients enrolled, 569 (97.6%) completed the treatment, and 566 (97.1%) also complied with post-treatment follow-up for 12 weeks. The overall SVR12 rate was 96.1% by per protocol and 93.7% by intention-to-treat analyses. No marked differences were observed in the SVR12 between subjects ≥65 and <65 years of age. Although large gaps were observed in the characteristics of patients and accessibility to medical resources, there was no significant difference in the SVR12 rate among the six regions in Tochigi Prefecture. Conclusion SOF plus RBV therapy was effective for HCV genotype 2 infection in an area where IFN-based therapy had previously shown unsatisfactory results. In addition, no regional disparities in the SVR12 were observed in Tochigi Prefecture.

Similarities and differences in the clinical features between cardia varices and esophageal varices.

BACKGROUND AND AIM: Little is known about the clinical features of cardia varices (CV). The aim was to examine the background, bleeding risk, and post-treatment outcomes of CV in patients with portal hypertension. METHODS: The subjects of this retrospective study were 277 patients (179 males, 98 females, 62.9 ± 11.5 years) with esophageal varices (EV). In patients with CV, there were 65 bleeders, and 95 patients received endoscopic treatment for primary or secondary prophylaxis. RESULTS: There were 147 patients with CV (53.1%). The higher grade of EV (P < 0.01) and the lower grade of gastric fundal varices (FV) (P = 0.046) were significant factors for the presence of CV. Significant risk factors for bleeding were: the higher grade of EV (P < 0.01), red sign on EV (P < 0.01), lower albumin (P = 0.01), and Child-Pugh B/C (P < 0.01) for EV and red sign on CV (P < 0.01) and use of non-steroidal anti-inflammatory drugs (NSAIDs)/aspirin (P < 0.01) for CV. All CV disappeared by sclerotherapy combined with argon plasma coagulation or band ligation, and 20 patients (21.1%) in EV and 18 patients (18.9%) in CV had recurrences during the median observation period of 19.4 months. There was no significant difference in the cumulative survival rate between non-bleeders, bleeders from EV, and those from CV. CONCLUSIONS: The CV were closely associated with advanced grade of EV and less-advanced grade of FV. Further, usage of NSAIDs/aspirin and red sign were significantly related to the bleeding from CV, suggesting the need for careful management.

Carbon dioxide-based portography: an alternative to conventional imaging with the use of iodinated contrast medium.

BACKGROUND AND AIM: To clarify the efficacy of carbon dioxide (CO(2)) as a contrast material to evaluate portal vein images by percutaneous transhepatic portography (PTP). METHODS: Twenty patients (38-76 years; male 13, female 7) with chronic liver diseases were the subjects of this prospective study. Portal venous opacification by PTP was compared between CO(2)-based images and iodinated contrast medium (ICM)-based images by two independent reviewers, according to the three-grade scoring; 0 for none, 1 for weak and 2 for sufficient. RESULTS: Total scores of extrahepatic portal veins (137 for CO(2), 93 for ICM), collateral vessels (64 for CO(2), 60 for ICM) and intrahepatic portal veins (69 for CO(2), 76 for ICM) were not statistically significant between CO(2)-based and ICM-based images (P = 0.0623). Sufficient opacification of superior mesenteric vein was more frequent on CO(2)-based images (none 0, weak 4, sufficient 16) than ICM-based images (none 19, weak 0, sufficient 1; P < 0.0001). The score was not statistically significant between CO(2)-based and ICM-based images in portal trunk, splenic vein, inferior mesenteric vein and other collateral vessels. Although opacification grade in the intrahepatic left portal vein was not statistically significant between CO(2)-based and ICM-based images (P = 0.1515), weak opacification was significantly frequent on CO(2)-based images (weak 10, sufficient 10) compared to ICM-based images (weak 0, sufficient 20; P = 0.0003) in the intrahepatic right portal vein. Inter-reviewer agreement was excellent between the two reviewers for CO(2)-based images (kappa = 0.913) and ICM-based images (kappa = 0.924). CONCLUSIONS: Carbon dioxide may be a first-line contrast material for evaluating portal vein images by PTP.

Pre-treatment hemodynamic features involved with long-term survival of cirrhotic patients after embolization of gastric fundal varices.

PURPOSE: To clarify the pre-treatment hemodynamic features involved in the long-term survival of cirrhotic patients with gastric fundal varices (FV) after balloon-occluded retrograde transvenous obliteration (B-RTO). MATERIALS AND METHODS: Eighty-one cirrhotic patients with medium- or large-grade FV treated by B-RTO were enrolled in this retrospective study. Pre-treatment flow volume ratio between gastric vein and portal trunk (GP-R) was obtained by Doppler ultrasound. RESULTS: The cumulative survival rate was 90% at 1 year, 74.8% at 3 years, 57.2% at 5 years, and 45.8% at 7 years without recurrence in a median period of 1148.5 days The survival was poorer in patients with HCC (47% at 3 years, 9.4% at 5 years, p<0.0001) than without (89.2% at 3 years, 81.9% at 5 years, 67.5% at 7 years), in patients with Child B/C (57.7% at 3 years, 42.1% at 5 years, 28.1% at 7 years, p=0.0016) than with Child A (91.8% at 3 years, 71.5% at 5 years, 62.1% at 7 years), and in patients with GP-R > or = 1.0 (58.9% at 3 years, p=0.0485) than with GP-R<1.0 (76.3% at 3 years, 62% at 5 years, 49.6% at 7 years). Multivariate analysis identified the presence of HCC (hazard ratio, 12.486; 95% CI, 4.08-38.216; p<0.0001), Child B/C (hazard ratio, 3.41; 95% CI, 1.594-7.15; p=0.0051) and GP-R > or = 1.0 (hazard ratio, 2.701; 95% CI, 1.07-6.15; p=0.0221) as independent factors for poor prognosis. CONCLUSION: GP-R > r= 1.0 on Doppler ultrasound before B-RTO may be a predictive indicator for poor prognosis in cirrhotic patients with FV after B-RTO, in addition to the presence of HCC and severe liver damage.

Collision of advanced gastric adenocarcinoma and gastrointestinal stromal tumour: a case report.

We present a case of an 83-year-old female patient with a collision tumour of an advanced Borrmann type 4 gastric cancer and a large gastric gastrointestinal stromal tumour (GIST). According to the deformity of the gastric wall caused by the GIST, type 4 cancer was difficult to identify by oesophagogastroduodenoscopy (OGD). The patient died of progressive gastric cancer related disease. While the mechanism of histogenesis of the simultaneous adenocarcinoma and GIST remains to be determined, the present case suggests that gastric adenocarcinoma has a more adverse effect on prognosis than does GIST. Additionally, this case suggests that thorough inspection of GIST patients is required at the OGD and at the pathology facility, in order to avoid overlooking the underlying cancer.

Contrast-enhanced US with Levovist for the diagnosis of hepatic hemangioma: time-related changes of enhancement appearance and the hemodynamic background.

BACKGROUNDS/AIMS: To elucidate the diagnostic confidence of contrast-enhanced ultrasound (CEUS) with Levovist for hepatic hemangioma. METHODOLOGY: The subjects were 34 patients with 38 hemangiomas and 12 patients with 15 hypervascular hepatocellular carcinomas. The early-phase (15-60 second) and liver-specific phase (after 5 min) were observed by the first injection. The 2nd injection was done for solo-phase method to observe liver-specific phase images without taking early-phase sonograms. The 3rd injection was done for changing posture method to observe liver-specific sonograms under left lateral ducubitus position. RESULTS: In the early-phase of hemangioma, nodular enhancement (NE) was found transiently in 13 lesions (34%) and continuously in 25 lesions (66%), while hepatocellular carcinoma (HCC, n = 15) did not show this pattern. Intratumoral arterioportal shunt was closely related to the short duration of NE. Two enhancement patterns were observed in the liver-specific phase of hemangioma, diffuse in 12 lesions (31%) and partial in 26 lesions (69%), which were dependent on the early-phase enhancement. Liver-specific findings were also affected by taking early-phase sonograms or changing the posture of the patient. This method provided sensitivity of 79% and specificity of 100% for the diagnosis of hemangioma. CONCLUSIONS: CEUS with Levovist may be promising method for the diagnosis of hepatic hemangioma.

Hemodynamic features of gastrorenal shunt: a Doppler study in cirrhotic patients with gastric fundal varices.

RATIONALE AND OBJECTIVES: Little is known about the hemodynamics of gastrorenal shunt (GRS), a major drainage route of gastric fundal varices (FV), in patients with FV. The aim of this study was to clarify the hemodynamic features of GRS on Doppler sonography in relation to the grading and bleeding of FV. MATERIALS AND METHODS: The study subjects consisted of 69 cirrhotic patients with FV. Diameter, flow velocity (FVe), and flow volume (FVo) of GRS were measured by Doppler ultrasound (US). The detection rate was compared to contrast-enhanced computed tomography (CECT), and percutaneous transhepatic portography (PTP) was used in six patients without GRS on CECT. RESULTS: The use of CECT detected GRS in 60 of 69 patients, and US, 58 of 69 patients. A false-negative result for detecting GRS on both CECT and US was found in one patient after PTP. The diameter, FVe, and FVo of GRS increased according to the endoscopic grade of FV: F1 (7.2+/-1.3 mm, 9.8+/-1.1 cm/s, 358.3+/-123.4 ml/min), F2 (9.9+/-3.3 mm, 12.8+/-5.1 cm/s, 701.7+/-411.3 ml/min), and F3 (11.8+/-2.4 mm, 17.9+/-8.3 cm/s, 1706.6+/-989.5 ml/min). A significant difference was seen between F1 and F3 (diameter, P=.0022; FVe, P=.0133; FVo, P=.0007) and between F2 and F3 (FVe, P=.0112; FVo, P<.0001). FVe of GRS was significantly higher in bleeders (16.7+/-8.1 cm/s) than in nonbleeders (12.2+/-5.4 cm/s, P=.017), whereas the diameter and FVo were not significant. CONCLUSION: Hemodynamics of GRS on Doppler sonograms reflected the grading and bleeding of FV. Doppler US may be valuable as a noninvasive method to evaluate the severity of FV.

How to characterize non-hypervascular hepatic nodules on contrast-enhanced computed tomography in chronic liver disease: feasibility of contrast-enhanced ultrasound with a microbubble contrast agent.

BACKGROUND AND AIM: Although hypervascular appearance is characteristic in hepatocellular carcinoma (HCC), hepatic nodules without hypervascular appearance are sometimes found in patients with chronic liver disease (CLD). The aim of the present study was to clarify the efficacy of contrast-enhanced ultrasound (CEUS) with Levovist to characterize small, non-hypervascular hepatic nodules on contrast-enhanced computed tomography (CECT) in patients with CLD. METHODS: The subject was 41 hepatic nodules (<30 mm, 18.5 +/- 5.6 mm) which showed non-hypervascular appearance on CECT in 35 patients with CLD; their histological results were 31 HCC (15 well, 14 moderate, and two poor) and 10 regenerative nodules (RN). CEUS with Levovist was performed under intermittent scanning (1-s interval) using APLIO at the early phase and the liver-specific phase, and the contrast enhancement of the nodule was assessed in comparison to that of the surrounding liver parenchyma. The contrast-enhanced findings with the time-intensity analysis were compared with the histological results. RESULTS: Twelve nodules with weak enhancement in the liver-specific phase were HCC, regardless of their early-phase appearances. The other 29 nodules with equivalent or weak enhancement in the early phase and equivalent enhancement in the liver-specific phase were 19 HCC and 10 RN. Among them, the maximum-intensity ratio of tumor to non-tumor in the early phase was significantly higher in HCC than in RN (P < 0.01, n = 16), and the receiver-operating characteristic analysis showed a sensitivity of 1.0 and a specificity of 0.83 for their characterization. CONCLUSION: CEUS with Levovist may be an alternative to biopsy to characterize small, non-hypervascular hepatic nodules on CECT in patients with CLD.

Microbubble disappearance-time is the appropriate timing for liver-specific imaging after injection of Levovist.

Contrast enhancement in the portal vein was repeatedly observed at 1 min intervals with wide-band Doppler ultrasonography in 152 consecutive patients (132 with liver cirrhosis and HCC, 20 controls), 5 min after the injection of Levovist. The duration time of contrast enhancement in the portal vein (microbubble disappearance-time; MD-T) was measured in all patients and contrast-enhanced appearances were compared between the 5 min phase and MD-T phase in 68 HCC nodules. MD-T in patients with liver cirrhosis (572.4 +/- 117.9 s) was significantly longer than in controls (481.6 +/- 89.3 s, p < 0.05). MD-T was prolonged in patients with Child B and C compared with Child A (p < 0.05). The contrast-enhanced appearances between the two phases were different in 30 of 68 HCC nodules (44.1%), showing positive enhancement in the 5 min phase and negative enhancement in the MD-T phase. The proposed MD-T may become an essential factor for the evaluation of liver-specific sonograms.

Ring-shaped appearance in liver-specific image with Levovist: a characteristic enhancement pattern for hypervascular benign nodule in the liver of heavy drinkers.

BACKGROUND/AIMS: The aim was to clarify the features of contrast-enhanced ultrasound (CEUS) with Levovist for diagnosis of hypervascular benign nodules in the liver of heavy drinkers. PATIENTS AND METHODS: Seven heavy drinkers with hypervascular nodules in the liver were studied. Findings of CEUS with Levovist (wide-band Doppler, 7/7), contrast-enhanced computed tomography (CECT, 7/7) and magnetic resonance imaging (MRI, 5/7) were compared for one nodule in each patient. RESULTS: Diagnosis of all seven nodules on CECT was HCC, whereas pathological results were HCC for four nodules and benign lesion for three nodules. The former four showed compatible findings for HCC on CEUS (4/4) and MRI (2/4). However, the latter three showed characteristic liver-specific sonograms with a ring-shaped appearance--peripheral enhancement with a central non-enhanced area. Two of the three nodules showed decreased signal-intensity in the periphery on SPIO-enhanced MRI. CONCLUSIONS: The ring-shaped appearance on liver-specific sonograms with Levovist may be a useful sign for the differential diagnosis of hypervascular benign nodule from HCC in heavy drinkers.

Study of portal vein thrombosis in patients with idiopathic portal hypertension in Japan.

BACKGROUND/AIMS: The aim of this study was to elucidate the incidence and clinical manifestations of portal vein thrombosis (PVT) in patients with idiopathic portal hypertension (IPH) in Japan during long-term follow-up. PATIENTS AND METHODS: Twenty-two patients with IPH were examined for PVT by sonography during a follow-up of 12+/-6 years. Clinical manifestations and patient outcome related to PVT were studied. Seventy patients with liver cirrhosis were examined by sonography as an incidence control of thrombosis. RESULTS: Nine IPH patients had portal thrombosis (9/22, 41%), a higher incidence than in liver cirrhosis patients (7/70, 10%). Those with thrombosis showed ascites, marked hypersplenism, and low serum albumin. Four patients with thrombosis died. Patients without thrombosis showed less clinical problems after long-term follow-up. Plasma antithrombin III and protein C activity decreased in almost half of the patients. However, there were no differences in these parameters between patients with and without thrombosis. CONCLUSIONS: In Japan, IPH patients had a high incidence of portal thrombosis, a significant factor for poor prognosis. Whether the management of PVT contributes to an improvement of a clinical course of IPH or not should be clarified in further study.