Viral eradication reduces all-cause mortality in patients with chronic hepatitis C virus infection who had received direct-acting antiviral therapy.

BACKGROUND AND AIMS: The impact of hepatitis C virus (HCV) eradication via direct-acting antiviral (DAA) therapy on overall mortality, particularly non-liver-related mortality, is understudied. METHODS: We recruited 4180 patients with chronic HCV infection who achieved sustained virological response (SVR) (HCV eradication) through DAA therapy (n = 2501, SVR group) or who did not receive antiviral therapy (n = 1679, non-SVR group); 1236 from each group were chosen using propensity score matching. Causes of death and all-cause mortality, including non-liver-related diseases, were investigated. RESULTS: Of the 4180 patients, 592 died during the follow-up period. In the SVR group, the mortality rates from liver-related and non-liver-related diseases were 16.5% and 83.5%, respectively. Compared to the non-SVR group, mortality rates from liver-related and non-liver-related diseases were 50.1% and 49.9%, respectively (p < .001). In non-cirrhotic patients, multivariable analysis revealed that SVR was an independent factor associated with both liver-related (hazard ratio [HR], .251; 95% confidence interval [CI], .092-.686) and non-liver-related (HR, .641; 95% CI, .415-.990) mortalities. In cirrhotic patients, multivariable analysis revealed that SVR remained an independent factor significantly associated with liver-related mortality (HR, .151; 95% CI, .081-.279). In propensity score-matched patients, the eradication of HCV (SVR group) decreased both liver-related (p < .001) and non-liver-related mortality (p = .008) rates compared to persistent HCV infection (non-SVR group). CONCLUSIONS: The elimination of HCV via DAA therapy reduced not only liver-related mortality but also non-liver-related mortality in patients with chronic HCV.

Energy Balance and Bone Health: a Nutrient Availability Perspective.

PURPOSE OF REVIEW: Obesity is highly prevalent and is associated with bone fragility and fracture. The changing nutrient availability to bone in obesity is an important facet of bone health. The goal of this article is to summarize current knowledge on the effects of carbohydrate and dietary fat availability on bone, particularly in the context of other tissues. RECENT FINDINGS: The skeleton is a primary site for fatty acid and glucose uptake. The trafficking of carbohydrates and fats into tissues changes with weight loss and periods of weight gain. Exercise acutely influences nutrient uptake into bone and may affect nutrient partitioning to bone. Bone cells secrete hormones that signal to the brain and other tissues information about its energetic state, which may alter whole-body nutrient trafficking. There is a critical need for studies to address the changes that metabolic perturbations have on nutrient availability in bone.

Effect of treatment periods on efficacy of glecaprevir and pibrentasvir in chronic hepatitis C: A nationwide, prospective, multicenter study.

Background and aim: In patients with chronic hepatitis C, 8 weeks of glecaprevir and pibrentasvir (GLE/PIB) treatment for chronic hepatitis (non-cirrhosis) and 12 weeks for cirrhosis have been approved in Japan. However, whether 8 weeks of treatment for cirrhosis may reduce treatment efficacy has not been adequately investigated. Methods: This prospective, nationwide, multicenter cohort study enrolled 1275 patients with chronic hepatitis C who received GLE/PIB therapy. The effect of liver fibrosis and treatment periods on the efficiency of GLE/PIB therapy was investigated. The primary endpoint was the sustained virological response (SVR) rate in patients with chronic hepatitis (non-cirrhosis) and cirrhosis. The association between treatment periods and liver fibrosis on the SVR after 12 weeks of treatment rate was investigated. Results: The SVR rates in patients with chronic hepatitis with 8 weeks of treatment, chronic hepatitis with 12 weeks of treatment, cirrhosis with 8 weeks of treatment, and cirrhosis with 12 weeks of treatment were 98.9% (800/809), 100% (87/87), 100% (166/166), and 99.1% (211/213), respectively, and were was not different among these groups (P = 0.4). Conclusion: GLE/PIB therapy for chronic hepatitis C had high efficacy regardless of liver fibrosis status and treatment periods. Periods of GLE/PIB therapy could be chosen with available modalities, and high SVR rates could be achieved regardless of the decision.

Helicobacter pylori Eradication Does Not Adversely Affect the Clinical Course of Gastric Cancer: A Multicenter Study on Screening Endoscopic Examination in Japan.

BACKGROUND: Since gastric cancers (GCs) detected after Helicobacter pylori (HP) eradication present with different morphological characteristics from conventional HP-positive GCs, delayed detection of early-stage GCs may be observed. This study aimed to investigate the clinical impact of HP eradication on diagnosing GC during screening endoscopy. METHODS: Eleven health checkup institutions in Japan participated in the present study. All GC cases newly diagnosed by screening endoscopy between January 2016 and December 2020 were included. After propensity score matching, multivariable regression analysis was performed to estimate the effect of HP eradication on deep tumor invasion among HP-eradicated and HP-positive GC cases. RESULTS: A total of 231 patients with GCs (134 HP-eradicated and 97 HP-positive cases) were enrolled. After propensity score matching, there were 81 cases in each group. The distribution of the depth of tumor invasion (pT1a, pT1b1, pT1b2, and pT2) between the HP-eradicated group and HP-positive group was similar (p = 0.82). In the propensity analysis, with HP-positive as the reference value, HP eradication was not significantly associated with T1b-T4-GCs and T1b2-T4-GCs, with odds ratios (95% confidence intervals) of 1.16 (0.48-2.81) and 1.16 (0.42-3.19), respectively. CONCLUSIONS: HP eradication does not adversely affect the clinical course of GCs, supporting the recommendation of HP eradication in screening programs to reduce the total number of GC cases without delaying diagnosis.

Necessity for surveillance for hepatocellualr carcinoma in older patients with chronic hepatitis C who achieved sustained virological response.

Background and Aim: Hepatocellular carcinoma (HCC) surveillance in low-risk patients (annual incidence <1.5%) is not recommended per the American Association for the Study of Liver Diseases guidelines. Because patients with chronic hepatitis C with non-advanced fibrosis who have achieved sustained virological response (SVR) have a low risk of HCC, HCC surveillance is not recommended for them. However, aging is a risk factor for HCC; threfore, the necessity for HCC surveillance in older patients with non-advanced fibrosis needs to be verified. Methods: This multicenter, prospective study enrolled 4993 patients with SVR (1998 patients with advanced fibrosis and 2995 patients with non-advanced fibrosis). The HCC incidence was examined with particular attention to age. Results: The 3-year incidence of HCC in patients with advanced and non-advanced fibrosis was 9.2% (95% CI: 7.8-10.9) and 2.9% (95% CI: 2.1-3.7), respectively. HCC incidence was significantly higher in patients with advanced fibrosis (P < 0.001). HCC incidence stratified by age and sex was investigated in patients with non-advanced fibrosis. The HCC incidence in the 18-49, 50s, 60s, 70s, and ≥80 age groups were 0.26, 1.3, 1.8, 1.7, and 2.9 per 100 person-years in men, and 0.00, 0.32, 0.58, 0.49, and 0.57 per 100 person-years in women, respectively. Conclusions: Male patients with non-advanced fibrosis aged ≥60 years have a higher risk of developing HCC and, thus, require HCC surveillance.

U-Net-Based Segmentation of Microscopic Images of Colorants and Simplification of Labeling in the Learning Process.

Colored product textures correspond to particle size distributions. The microscopic images of colorants must be divided into regions to determine the particle size distribution. The conventional method used for this process involves manually dividing images into areas, which may be inefficient. In this paper, we have overcome this issue by developing two different modified architectures of U-Net convolution neural networks to automatically determine the particle sizes. To develop these modified architectures, a significant amount of ground truth data must be prepared to train the U-Net, which is difficult for big data as the labeling is performed manually. Therefore, we also aim to reduce this process by using incomplete labeling data. The first objective of this study is to determine the accuracy of our modified U-Net architectures for this type of image. The second objective is to reduce the difficulty of preparing the ground truth data by testing the accuracy of training on incomplete labeling data. The results indicate that efficient segmentation can be realized using our modified U-Net architectures, and the generation of ground truth data can be simplified. This paper presents a preliminary study to improve the efficiency of determining particle size distributions with incomplete labeling data.

General evaluation score for predicting the development of hepatocellular carcinoma in patients with advanced liver fibrosis associated with hepatitis C virus genotype 1 or 2 after direct-acting antiviral therapy.

Background and Aim: To validate a composite predictive model for hepatocellular carcinoma (HCC) development in patients with advanced liver fibrosis associated with chronic hepatitis C virus (HCV) who have received direct-acting antiviral (DAA) therapy and achieved sustained virologic response (SVR). Methods: This study included 1258 patients with advanced liver fibrosis associated with HCV genotype 1, 2, or both. General evaluation score (GES), which is based on sex, age, fibrosis stage, albumin, and α-fetoprotein, was used as a composite predictive model. Results: There were 645 (51.3%) patients in the low-risk group, 228 (18.1%) in the intermediate-risk group, and 385 (30.6%) in the high-risk group based on GES categories. The 12-, 36-, and 60-month cumulative incidence of HCC was 0.7%, 5.3%, and 13.0%, respectively. Multivariable analysis with Cox proportional hazards models showed that male sex (hazard ratio [HR], 1.863; 95% confidence interval [CI], 1.204-2.883), F4 fibrosis stage (HR, 3.199; 95% CI, 1.696-6.036), and albumin (HR, 0.489; 95% CI, 0.288-0.828) are independently associated with HCC development. The incidence of HCC differed significantly by GES-based risk category (P < 0.001). Cox proportional hazards models showed that, with the low-risk group as the referent, the HR for HCC development was 1.875 (95% CI, 1.000-3.514) in the intermediate-risk group and 2.819 (95% CI, 1.716-4.630) in the high-risk group. GES had better predictive ability for HCC development than fibrosis-4 index according to time-dependent receiver operating characteristic analysis. Conclusion: GES is useful for predicting HCC development in patients with advanced liver fibrosis after SVR.

Efficacy and feasibility of combination chemotherapy with S-1 and cisplatin (2 weeks regimen) for advanced gastric cancer.

OBJECTIVE: Although combination chemotherapy with 3 weeks of S-1 and cisplatin is effective for advanced gastric cancer, the toxicities of S-1 which mostly occur during the third week of administration are a major problem. To achieve fewer adverse effects with S-1 and higher dose intensity of cisplatin, we performed combination chemotherapy with 2 weeks of S-1 and cisplatin as first line. The aim of this retrospective study was to analyse the efficacy and feasibility of this regimen. METHODS: S-1 (40-60 mg depending on patient's body surface area) was given orally twice daily for 2 consecutive weeks, and 70 mg/m(2) cisplatin was given intravenously on day 8, followed by a 2-week rest period. RESULTS: Forty-eight patients received a total of 184 courses of chemotherapy. Overall response rate was 40.6% and median survival time was 411 days. Dose intensities were 257.6 mg/m(2)/week for S-1 and 16.4 mg/m(2)/week for cisplatin. The incidences of grade 3/4 haematological toxicities were leucopenia (19%), neutropenia (29%) and anaemia (17%), and those of grade 3 non-haematological toxicities were anorexia (31%) and nausea (21%). The rate of treatment discontinuation owing to toxicity was 10%. CONCLUSIONS: This regimen may be effective as an alternative therapy to 3 weeks of S-1 and cisplatin to reduce the toxicity of chemotherapy for advanced gastric cancer.

Painful hepatic hemangioma: report of a case with an emphasis on sonographic findings.

Hepatic hemangiomas are usually asymptomatic and very rarely produce abdominal symptoms. We report a painful 10 × 9 cm hemangioma situated at the hepatic surface of segment 6. The lesion showed a heterogeneous internal structure, composed irregularly of hyperechoic and hypoechoic areas, and it also showed weak posterior echo enhancement. Contrast-enhanced US showed the so-called fill-in pattern, leading to the diagnosis of hepatic hemangioma. The patient's abdomen showed no other abnormal findings, which stressed the relationship between the hemangioma and the patient's symptoms. When the diagnosis of hepatic hemangioma is conclusive, surgical therapy is indicated only in patients with severe symptoms. Our patient was considered to be a candidate for enucleation of the lesion. Histopathologically, the lesion included no areas of hemorrhage or necrosis, and the patient's abdominal pain was likely due to distension of the liver capsule. After surgery, the patient was completely free of symptoms, and enucleation was considered to be appropriate.

Hyperactive sensorimotor cortex during voice perception in spasmodic dysphonia.

Spasmodic dysphonia (SD) is characterized by an involuntary laryngeal muscle spasm during vocalization. Previous studies measured brain activation during voice production and suggested that SD arises from abnormal sensorimotor integration involving the sensorimotor cortex. However, it remains unclear whether this abnormal sensorimotor activation merely reflects neural activation produced by abnormal vocalization. To identify the specific neural correlates of SD, we used a sound discrimination task without overt vocalization to compare neural activation between 11 patients with SD and healthy participants. Participants underwent functional MRI during a two-alternative judgment task for auditory stimuli, which could be modal or falsetto voice. Since vocalization in falsetto is intact in SD, we predicted that neural activation during speech perception would differ between the two groups only for modal voice and not for falsetto voice. Group-by-stimulus interaction was observed in the left sensorimotor cortex and thalamus, suggesting that voice perception activates different neural systems between the two groups. Moreover, the sensorimotor signals positively correlated with disease severity of SD, and classified the two groups with 73% accuracy in linear discriminant analysis. Thus, the sensorimotor cortex and thalamus play a central role in SD pathophysiology and sensorimotor signals can be a new biomarker for SD diagnosis.

Portal gas in a patient with acute obstructive cholangitis: report of a case with emphasis on US findings.

Portal gas is relatively rare, and its relationship to ischemic bowel diseases has been emphasized. We report the case of a 70-year-old woman with acute obstructive cholangitis in whom portal gas was detected by ultrasonography (US) but not by computed tomography (CT). The former showed multiple echo spots moving in the portal vein. Doppler signals confirmed them to be bidirectional and spiky, which immediately led to the diagnosis of portal gas. Immediate appropriate antibiotic treatment and biliary drainage yielded the disappearance of the portal gas. We stress the usefulness of US and Doppler US for detecting and diagnosing portal gas. Our observation suggests that when portal gas is detected by US, the possibility of cholangitis should be included in the differential diagnosis.

Phonological memory in sign language relies on the visuomotor neural system outside the left hemisphere language network.

Sign language is an essential medium for everyday social interaction for deaf people and plays a critical role in verbal learning. In particular, language development in those people should heavily rely on the verbal short-term memory (STM) via sign language. Most previous studies compared neural activations during signed language processing in deaf signers and those during spoken language processing in hearing speakers. For sign language users, it thus remains unclear how visuospatial inputs are converted into the verbal STM operating in the left-hemisphere language network. Using functional magnetic resonance imaging, the present study investigated neural activation while bilinguals of spoken and signed language were engaged in a sequence memory span task. On each trial, participants viewed a nonsense syllable sequence presented either as written letters or as fingerspelling (4-7 syllables in length) and then held the syllable sequence for 12 s. Behavioral analysis revealed that participants relied on phonological memory while holding verbal information regardless of the type of input modality. At the neural level, this maintenance stage broadly activated the left-hemisphere language network, including the inferior frontal gyrus, supplementary motor area, superior temporal gyrus and inferior parietal lobule, for both letter and fingerspelling conditions. Interestingly, while most participants reported that they relied on phonological memory during maintenance, direct comparisons between letters and fingers revealed strikingly different patterns of neural activation during the same period. Namely, the effortful maintenance of fingerspelling inputs relative to letter inputs activated the left superior parietal lobule and dorsal premotor area, i.e., brain regions known to play a role in visuomotor analysis of hand/arm movements. These findings suggest that the dorsal visuomotor neural system subserves verbal learning via sign language by relaying gestural inputs to the classical left-hemisphere language network.

Altered striatal circuits underlie characteristic personality traits in Parkinson's disease.

Patients with Parkinson's disease (PD) have been suggested to share personality traits characterised by low novelty-seeking and high harm-avoidance. Although a link between novelty-seeking and dopamine is hypothesised, the link is not fully supported by 6-[(18)F]fluoro-L-dopa positron emission tomography (PET) studies. Meanwhile, tractography studies with magnetic resonance imaging (MRI) link personality to the connectivity of the striatum in healthy subjects. Here, we investigated neurochemical and anatomical correlates of characteristic personality traits in PD. Sixteen PD patients and 28 healthy controls were assessed using the Temperament and Character Inventory. All patients and 17 randomly selected controls were scanned with 2ß-carbomethoxy-3ß-(4-fluorophenyl)-[N-(11)C-methyl]tropane ([(11)C]CFT) PET to measure striatal dopamine transporter availability. All subjects were scanned with MRI to evaluate the connectivity of the striatum using probabilistic tractography. PET findings revealed no correlation of novelty-seeking and harm-avoidance with [(11)C]CFT uptake in patients or controls. Novelty-seeking correlated positively with the connectivity strength of the striatum with the hippocampus and amygdala in both patients and controls. Harm-avoidance and the fibre connectivity strength of the striatum including ventral area with the amygdala correlated negatively in patients and positively in controls, which differed significantly between the groups. Our data support the notion that the fibre connectivity of the striatum with limbic and frontal areas underlies the personality profile. Furthermore, our findings suggest that higher harm-avoidance in PD is linked to alterations of the network, including the nucleus accumbens and amygdala.

Two cases of inverted hyperplastic polyps of the colon and association with adenoma.

Here we report two cases of inverted hyperplastic polyps of the colon. The first patient showed three inverted hyperplastic polyps in the ascending colon, one of which was associated with adenoma. We immunostained this adenoma-associated polyp using anti-beta-catenin antibody and found accumulation of beta-catenin in the cytoplasm of the adenomatous lesion but not in the inverted hyperplastic polyp. This suggested an adenomatous polyposis coli (APC) mutation in the adenomatous region but not in the inverted hyperplastic polyp. The inverted hyperplastic polyp in the second patient was located at the caecum and was studied using magnifying colonoscopy. The polyp appeared to be flat and elevated with a depressed pit in the centre. After spraying with methylene blue dye, the pit pattern of the lesion was observed and small asteroid pits on the polyp were found, consistent with a hyperplastic gland pattern. From these results, we diagnosed inverted hyperplastic polyp of the colon by colonoscopy.

[T-cell chronic lymphocytic leukemia associated with adenocarcinoma of colon].

A 72-year-old woman had been diagnosed in 1998 as having colonic adenocarcinoma associated with lymphocytosis, and had undergone an operation. Three years later she was referred to our hospital with the chief complaint of blood stools. She again developed adenocarcinoma of the sigmoid colon. Blood chemistry showed a leukocyte count of 26,850/ml without anemia or thrombocytopenia. Bone marrow aspiration gave a nucleated cell count of 109,600/ml with 50.2% lymphocytes. Lymphocytes surface marker showed T-cell characteristics with CD4+/CD-. The serological test showed negative anti-HTLV-1 antibody and the TCRab chain was rearranged in her bone marrow aspirate. From these results she was diagnosed as having T-CLL.

Direct Observation of a Distant Ion Pair Generated in a Photoconductive Poly(N-vinylcarbazole) Film with Dopant.

Photoconduction in charge transfer materials apparently occurs through a distant geminate ion pair with an interionic separation of about 8 Å, as demonstrated by time-resolved EPR spectroscopy of a doped poly(N-vinylcarbazole) film.

One year of infliximab therapy successfully improved a case of refractory pouchitis without the use of antibiotics.

A 29-year-old woman with ulcerative colitis underwent total colectomy with ileal-pouch-anal canal anastomosis in 1999. After the surgery, she developed refractory pouchitis. We administered metronidazole, mesalamine and ciprofloxacin; however, her clinical symptoms improved only very slightly. We initiated treatment with infliximab in June 2011 and discontinued the antibiotics. Thereafter, the patient's abdominal symptoms quickly improved. We discontinued the infliximab therapy in June 2012, after which time, the patient's abdominal symptoms remained in remission for 40 weeks, without the use of antibiotics. This report suggests that infliximab is useful not only for improving the clinical symptoms of refractory pouchitis, but also discontinuing antibiotic therapy in such patients.