Tablet-Based Cognitive and Eye Movement Measures as Accessible Tools for Schizophrenia Assessment: Multisite Usability Study.

BACKGROUND: Schizophrenia is a complex mental disorder characterized by significant cognitive and neurobiological alterations. Impairments in cognitive function and eye movement have been known to be promising biomarkers for schizophrenia. However, cognitive assessment methods require specialized expertise. To date, data on simplified measurement tools for assessing both cognitive function and eye movement in patients with schizophrenia are lacking. OBJECTIVE: This study aims to assess the efficacy of a novel tablet-based platform combining cognitive and eye movement measures for classifying schizophrenia. METHODS: Forty-four patients with schizophrenia, 67 healthy controls, and 41 patients with other psychiatric diagnoses participated in this study from 10 sites across Japan. A free-viewing eye movement task and 2 cognitive assessment tools (Codebreaker task from the THINC-integrated tool and the CognitiveFunctionTest app) were used for conducting assessments in a 12.9-inch iPad Pro. We performed comparative group and logistic regression analyses for evaluating the diagnostic efficacy of the 3 measures of interest. RESULTS: Cognitive and eye movement measures differed significantly between patients with schizophrenia and healthy controls (all 3 measures; P<.001). The Codebreaker task showed the highest classification effectiveness in distinguishing schizophrenia with an area under the receiver operating characteristic curve of 0.90. Combining cognitive and eye movement measures further improved accuracy with a maximum area under the receiver operating characteristic curve of 0.94. Cognitive measures were more effective in differentiating patients with schizophrenia from healthy controls, whereas eye movement measures better differentiated schizophrenia from other psychiatric conditions. CONCLUSIONS: This multisite study demonstrates the feasibility and effectiveness of a tablet-based app for assessing cognitive functioning and eye movements in patients with schizophrenia. Our results suggest the potential of tablet-based assessments of cognitive function and eye movement as simple and accessible evaluation tools, which may be useful for future clinical implementation.

[A case of irreversible metronidazole encephalopathy during liver abscess treatment].

Metronidazole (MNZ) is a widely used drug for protozoan and anaerobic infections. The continuous use of MNZ causes various neurological symptoms, such as cerebellar ataxia, visual disturbance, vestibulocochlear symptoms, gait disturbance, dysarthria, and epileptic seizures of unknown cause, named MNZ-induced encephalopathy (MIE), in rare cases. MIE is a reversible disease that often improves within a few days of MNZ discontinuation, but irreversible neurological symptoms rarely remain. Herein, we report a case of MIE that developed during MNZ administration for a liver abscess, causing prolonged unconsciousness and death even after drug discontinuation. An 85-year-old female patient complained of fever, elevated liver enzymes, and a multifocal abscess in the right hepatic lobe, as seen on computed tomography. Percutaneous transhepatic abscess drainage and antibiotic therapy were initiated. The causative agent of the liver abscess could not be identified, thus meropenem was started, which demonstrated no inflammation improvement, thus oral MNZ was added. The inflammation recurred when MNZ was discontinued, and the patient continued taking MNZ. Vomiting, upper limb tremors, consciousness disturbance, and convulsions appeared on day 46 (total dose of MNZ 73.5mg), and the patient was hospitalized. T2-weighted, diffusion-weighted, and FLAIR head magnetic resonance imaging (MRI) revealed symmetrical abnormal high-signal areas in the cerebellar dentate nucleus, corpus callosum, cerebral white matter, and periventricular areas. MIE was diagnosed based on the patient's course and MRI images, and MNZ was discontinued. The patient continued to suffer from impaired consciousness and convulsions after MNZ discontinuation and died due to aspiration pneumonia. Suggestively, MIE development is related to long-term MNZ administration, poor nutrition, liver disease, underlying diseases (such as advanced cancer), and serious complications. A systematic review of MIE cases revealed that 4.8-5.9% of the patients demonstrated little improvement of symptoms after MNZ discontinuation, and some deaths were reported. Patients with poor prognosis were often suffering from impaired consciousness and convulsions. Furthermore, impaired consciousness was the most common residual symptom. Abnormal signals in characteristic areas, such as the dentate nucleus cerebri and corpus callosum, on head MRI are useful for MIE diagnosis, especially in patients with abnormal findings in the cerebral white matter, which is associated with a poor prognosis. We should pay close attention to the onset of MIE when MNZ is administered.

Successful perioperative management of simultaneous transcatheter aortic valve implantation and hip fracture surgery: a case report.

A 90-year-old woman with severe aortic stenosis experienced hospital readmission for chronic heart failure exacerbations many times and was admitted to our hospital for undergoing transcatheter aortic valve implantation. Thereafter, she fell in the ward and fractured her femoral trochanter, requiring early hip fracture surgery. We proposed that we should perform simultaneous transcatheter aortic valve implantation and hip fracture surgery to cardiologist and orthopedist from anesthetic and perioperative management perspective. We considered that it was difficult to maintain cardiovascular function without cardiac intervention during hip fracture surgery and starting rehabilitation as early as possible was important. General anesthesia was induced without any complications, and the tracheal tube was removed after the successive surgeries. On postoperative day 1, bedside rehabilitation was started, and on postoperative day 3, she was transferred from the intensive care unit to the general ward. On postoperative day 32, she was transferred to another hospital. Anesthesiologist should play an important role for decision making in not only intraoperative but perioperative management for critical case, we should communicate with other departments. The successful perioperative management of simultaneous transcatheter aortic valve implantation and hip fracture surgery enabled to start rehabilitation early and prevented further patient hospitalization.

Rapidly progressed large cell neuroendocrine carcinoma of the stomach with an increased serum alpha fetoprotein level: a case report.

An 82-year-old man who had multiple hepatic tumors, a gastric tumor, and ascites was referred to our hospital. On the time of our hospital visit, he had a high serum alpha fetoprotein (AFP) level of 1206 ng/mL. Upper gastrointestinal endoscopy revealed a Borrmann Type II gastric tumor approximately 40 mm in diameter in the lesser curvature of cardia, and forceps biopsy was performed. Endoscopic ultrasound fine-needle aspiration was also performed for hepatic tumor. The biopsy specimens from the gastric and hepatic tumor were diagnosed as large cell neuroendocrine carcinoma (LCNEC), containing AFP-positive cells only sporadically by immunohistochemistry. He was diagnosed with gastric LCNEC with liver metastasis. Retrospective analysis of endoscopic data obtained at 5 months ago revealed a 0-IIc lesion, approximately 10 mm in size, in the lesser curvature of cardia, the same area of the present gastric tumor. This indicated rapid growth rate of the present tumor. The patient developed jaundice 5 days after he visited our hospital. And he died 18 days after hospital admission.

Gastric gastrointestinal stromal tumor with predominant cystic formation diagnosed by endoscopic ultrasound-fine needle aspiration.

A 69-year-old woman who had no symptoms was found to have an intraperitoneal tumor on abdominal ultrasonography in a medical checkup. Thereafter, she was referred to our hospital for a further detailed examination. Contrast-enhanced computed tomography revealed a thin-walled cystic tumor with a diameter of 8 cm and with a hypervascular solid masses in the cystic wall, along with intraperitoneal multiple nodules. The cystic tumor was contiguous with the stomach wall. For solid mass of cystic lesions, endoscopic ultrasound-fine needle aspiration was performed transgastrically with a 25-gauge Franseen needle. Pathologically, the cells in the tumor were spindle shaped with atypical nucleus and were positive for c-kit, CD34, and smooth muscle actin. The tumor was diagnosed as gastrointestinal stromal tumor (GIST). With the diagnosis of gastric GIST with peritoneal dissemination, imatinib chemotherapy was initiated.

Efficacy and safety of therapeutic endoscopic retrograde cholangiopancreatography in patients with native papillae with a performance status score of 3 or 4: A single-center retrospective study.

Objective: This study aimed to assess the efficacy and safety of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in patients with an Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 3 or 4. Patients and Methods: We reviewed the data of 287 patients with native papillae who underwent therapeutic ERCP for biliary disease at our hospital between October 2016 and October 2018. The patients were divided into two groups; those with an ECOG-PS score of 3 or 4 (group A; n=78) and those with an ECOG-PS score of 0-2 (group B; n=209). Results: The rate of technical success was not significantly different between the two groups (95% versus 89%, P=0.13). Although the occurrence rate of overall adverse events (10% versus 11%, P=0.95) was not significantly different between the groups, the occurrence rates of aspiration pneumonia (3.8% versus 0%, P=0.0044) and heart failure (2.6% versus 0%, P=0.020) were significantly higher in group A. Conclusion: The rates of technical success and overall adverse events did not significantly differ between patients with an ECOG-PS score of 3 or 4 and those with a score of 0-2; however, aspiration pneumonia and heart failure were more likely to occur among patients with an ECOG-PS score of 3 or 4.

Spontaneous rectus sheath hematoma associated with warfarin administration: a case report.

Objectives: Rectus sheath hematoma (RSH) can result from bleeding into the rectus abdominis muscle or a direct muscular tear; nontraumatic spontaneous RSH is a rare condition. Here, we report a case of spontaneous RSH associated with warfarin administration for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). Patient: An 87-year-old woman was referred to our hospital because of abdominal pain, nausea, and vomiting for 3 days. She was receiving warfarin for treating CTEPH. She had a bulging and hard lower abdomen with ecchymosis. Moreover, the bulging portion was highly tender, and a positive Carnett's sign was also observed. She reported no history of abdominal trauma. Abdominal computed tomography (CT) scan revealed right RSH. Results: She was diagnosed with spontaneous RSH and admitted to our hospital. Warfarin was antagonized with an intravenous injection of vitamin K; hemostatic agents were intravenously administered. Gradually, her abdominal pain improved. She was finally discharged 12 days after the admission. Abdominal CT scan performed 17 days after the discharge revealed a reduction in the size of RSH. Conclusion: Despite not having a history of trauma, it is necessary to consider the possibility of RSH for patients receiving warfarin and complaining of abdominal pain.

Prophylactic efficacy of a novel method against postendoscopic papillary balloon dilation pancreatitis.

OBJECTIVE: This study aimed to investigate whether a novel method including prophylactic pancreatic stent (PS) placement prevents postendoscopic papillary balloon dilation pancreatitis. PATIENTS AND METHODS: This study enrolled 200 consecutive patients with bile duct stones measuring up to 8 mm in diameter and retrospectively recruited 113 patients undergoing ordinary endoscopic papillary balloon dilation (EPBD) without PS placement from our previous study. In the novel method, EPBD and PS placement was attempted with a guidewire left in the main pancreatic duct for patients in whom stable guidewire placement in the main pancreatic duct was possible. EST was performed for patients in whom stable guidewire placement was impossible. The incidence rate of pancreatitis was compared between the novel method and ordinary EPBD, and risk factors for pancreatitis were analyzed. RESULTS: Of 194 patients undergoing the novel method, EPBD and EST were performed in 180 and 14 patients, respectively. Following EPBD, PS placement was successful in 177/180 (98.3%) of patients. Pancreatitis occurred in 7/194 (3.6%) of patients after the novel method and 9/113 (8.0%) of patients after ordinary EPBD. There was a trend toward lower incidence rate of pancreatitis in the novel method. Stent dislodgement by the first postoperative morning and no previous endoscopic nasobiliary drainage (ENBD) were identified as risk factors for pancreatitis after EPBD with PS placement. No previous ENBD was also identified as a risk factor for pancreatitis after ordinary EPBD. CONCLUSION: Our novel method is likely to be superior to ordinary EPBD in preventing pancreatitis. Previous ENBD may prevent post-EPBD pancreatitis regardless of PS placement.

Gallstone ileus with spontaneous evacuation: A case report.

A 65-year-old man was referred to our hospital for abdominal pain. He had a history of enterotomy with stone extraction for gallstone ileus. On abdominal computed tomography, a stone measuring 32 × 28 mm lodged in the jejunum was identified. He was diagnosed with gallstone ileus and treated using a nasal ileus tube. Four days after admission, computed tomography showed that the stone had passed into the rectum. The gallstone was spontaneously evacuated on the same day. A fistula with the gallbladder was found in the duodenal bulb. The patient's condition improved, and he was discharged 9 days after admission.

Modeling of the Bioactivation of an Organic Nitrate by a Thiol to Form a Thionitrate Intermediate.

Thionitrates (R-SNO2) have been proposed as key intermediates in the biotransformation of organic nitrates that have been used for the clinical treatment of angina pectoris for over 100 years. It has been proposed and widely accepted that a thiol would react with an organic nitrate to afford a thionitrate intermediate. However, there has been no example of an experimental demonstration of this elementary chemical process in organic systems. Herein, we report that aryl- and primary-alkyl-substituted thionitrates were successfully synthesized by the reaction of the corresponding lithium thiolates with organic nitrates by taking advantage of cavity-shaped substituents. The structure of a primary-alkyl-substituted thionitrate was unambiguously established by X-ray crystallographic analysis.

Hepatitis B virus X induces cell proliferation in the hepatocarcinogenesis via up-regulation of cytoplasmic p21 expression.

BACKGROUND: Hepatitis B virus X protein (HBx) has been shown to induce hepatocarcinogenesis by disrupting the functions of intracellular molecules. Cyclin-dependent kinase inhibitor p21 (Cip1/WAF1), known as a tumour-suppressor gene, has been reported to have paradoxical function, that is, acting as an oncogene, particularly when expressed in the cytoplasm. The effects of HBx on the expression and function of p21 also remain controversial. AIMS: We attempted to investigate the role of HBx in the hepatocarcinogenic process, focusing on the association with this paradoxical function of p21. The results obtained were further verified with experiments using the antihepatocarcinogenic action of interferon (IFN)-ß. METHODS: HBx transgenic mice (Xg) and HBx-transfected hepatoma cell lines were used. Intracellular localization of p21 was determined by Western blot analysis and immunofluorescence. RESULTS: Xg and HBx-transfected cells exhibited increased expression of p21. Up-regulation of p21 was positively correlated with the expression of cyclin D1 and inactive phosphorylation of retinoblastoma protein (pRb). These HBx-induced cell proliferative responses were cancelled by knockdown of p21, which resulted in growth reduction in HBx-expressing cells, suggesting the oncogenic properties of HBx-induced p21. HBx induced accumulation of p21 in the cytoplasm, and activation of PKCα was involved. Finally, IFN-ß-treated Xg liver, as well as hepatoma cells, showed a shift of cytoplasmic p21 to the nucleus, accompanied by the abrogation of HBx-induced oncogenic modulation. CONCLUSIONS: Our results suggest that HBx induces hepatocarcinogenesis via PKCα-mediated overexpression of cytoplasmic p21 and IFN-ß suppressed these molecular events by shifting p21 to the nucleus.

Characterization of elevated alanine aminotransferase levels during pegylated-interferon α-2b plus ribavirin treatment for chronic hepatitis C.

AIM: Elevation of alanine aminotransferase (ALT) levels during pegylated-interferon (peg-IFN) plus ribavirin therapy in patients with chronic hepatitis C [CHC] is a problem that cannot be disregarded. The aim of this study is to assess the frequency and to characterize clinical parameters of this phenomenon. METHODS: Two hundred and thirty-five (235) CHC patients with genotype 1b receiving peg-IFN α-2b plus ribavirin therapy were analyzed. Clinical parameters that may be associated with abnormal ALT values during treatment and therapy outcomes were evaluated statistically. One hundred and sixteen (116) patients treated with peg-IFN α-2a plus ribavirin were also included for partial analysis. RESULTS: Abnormal ALT values during treatment were observed in 23.0% of patients. It was observed in 14.5% of those with sustained virological response (SVR) and 17.8% of those with relapse, in whom viral clearance was observed during therapy. Multivariate logistic regression analysis revealed that pretreatment ALT values, therapy outcome, and body mass index (BMI) were significant factors related to abnormal ALT values during treatment. Abnormal ALT values during treatment became normal in SVR patients at 6 months after the completion of treatment, but not in NR (non-response) patients. Mean ALT values were significantly higher at some time points during treatment in patients treated with α-2a when compared to those treated with α-2b. CONCLUSION: Abnormal ALT values during peg-IFN plus ribavirin treatment are observed relatively frequently, even in patients without detectable HCV RNA. Direct or indirect involvement of drugs is considered as one possible cause.

Very-Low-Dose Pegylated Interferon a2a Plus Ribavirin Therapy for Advanced Liver Cirrhosis Type C: A Possible Therapeutic Alternative without Splenic Intervention.

Despite the recent progress in interferon (IFN) therapies for chronic hepatitis C, liver cirrhosis remains refractory. One of the major obstacles to successful IFN therapy is low platelet count. Currently, splenic interventions, such as partial splenic embolization (PSE) or surgical splenectomy, have been applied effectively and make standard IFN therapy possible. However, there may be a group of patients with low platelet counts who can be treated without splenic intervention. We here report two patients with advanced type C liver cirrhosis who were successfully treated using very-low-dose pegylated interferon a2a plus ribavirin. One patient had a very low platelet count (2.5 x 10(4)/mul) due to splenomegaly before treatment. However, pretreatment serum HCV titers were low in both patients and early viral responses were obtained in both. Because PSE or splenectomy may still have some safety concerns, this attenuated IFN treatment protocol can be an alternative therapeutic option for patients with advanced type C liver disease, but good virological factors for sustained virological response.

Progression of hypermethylation of the p16(INK4A) gene from normal liver to nontumorous liver and hepatocellular carcinoma: an evaluation using quantitative PCR analysis.

The aim of this study was to determine to what extent hypermethylation of the p16(INK4A) (p16) gene promoter is increased in nontumorous liver tissues compared with in normal liver, using two quantitative methylation-specific polymerase chain reaction (MS-PCR) methods and a bisulfite sequencing method. Methylation of the p16 gene was detected more frequently in nontumorous liver than in normal liver using the TaqMan PCR method. Methylation indices also were significantly higher in nontumorous than in normal liver. However, the bisulfite sequencing method did not detect significantly more methylation of the p16 gene in nontumorous than normal liver, nor was there a significant difference in the level of p16 mRNA. There may be a greater proportion of cells which contain methylated p16 in nontumorous than in normal liver. However, the difference was so small that the functional relevance to hepatocarcinogenesis remains elusive.

Serum alpha-fetoprotein levels during and after interferon therapy and the development of hepatocellular carcinoma in patients with chronic hepatitis C.

The association between serum alpha-fetoprotein (AFP) levels during and after interferon (IFN) therapy and the development of hepatocellular carcinoma (HCC) was evaluated in patients with chronic hepatitis C (CHC). A total of 263 patients treated by IFN with or without ribavirin were enrolled in the study. Serum AFP levels during and after IFN therapy were investigated retrospectively, and statistical analysis was performed to identify the factors associated with HCC development. During IFN therapy, serum AFP levels significantly decreased, regardless of virologic response to treatment. Increased serum AFP levels (>or=10 ng/ml) at the end of IFN therapy (EOT) was a close-to-significant variable affecting the development of HCC (P = 0.057), and a significantly higher cumulative incidence of HCC was seen in patients with increased serum AFP levels at EOT (P = 0.021). Serum AFP level at EOT is a possible predictor of HCC in CHC patients after IFN therapy.

Temporal treatment with interferon-beta prevents hepatocellular carcinoma in hepatitis B virus X gene transgenic mice.

BACKGROUND/AIMS: The preventive effect of interferon (IFN) against hepatocellular carcinoma (HCC) has been confirmed clinically. We sought to determine whether the temporal administration of IFN-beta prevents hepatocarcinogenesis in a mouse model where HCC develops without necroinflammation. METHODS: Hepatocarcinogenic mice that are transgenic for the hepatitis B virus X gene (HBx-Tg) were treated with IFN-beta or saline (control) for three months, from 3 to 6 months of age, and the incidence of HCC was determined at 18 months of age. The effects of IFN-beta on DNA synthesis and apoptosis were tested. RESULTS: The incidence of HCC was significantly lower in the IFN-beta-treated mice than the controls (0 vs. 50%, P<0.01). Inhibition of DNA synthesis in hepatocytes by IFN-beta was observed in the livers of HBx-Tg, without any significant induction of apoptosis. Although the treatment of IFN-beta was temporal, the number of hepatocytes with DNA synthesis remained lower 3 and 12 months later in life. CONCLUSIONS: Temporal administration of IFN-beta has a significant preventive effect on the occurrence of HCC in a mouse model where HCC develops without inflammation. The mechanisms are the inhibition of DNA synthesis and cell cycle progression of hepatocytes.

Successful treatment with lamivudine may correlate with reduction of serum ferritin levels in the patients with chronic hepatitis and liver cirrhosis type B.

PURPOSE: To study the changes in serum ferritin levels in lamivudine (LAM)-treated patients with chronic hepatitis and liver cirrhosis type B and determine whether successful treatment with LAM results in a reduction of serum ferritin levels. METHODS: Thirty patients with chronic hepatitis B virus (HBV) infection were followed prospectively during their treatment with LAM for 12 months. Serum HBV DNA, ferritin levels, and emergence of YMDD mutants were monitored. A case of severe liver cirrhosis with hepatic hemosiderosis that was treated successfully with LAM also is shown as a representative case. RESULTS: Serum alanine aminotransferase and ferritin levels decreased significantly more in the patients treated with LAM without YMDD mutants (n = 23) than those with mutants (n = 7). Hepatic hemosiderosis along with serum iron markers improved greatly in the representative patient. CONCLUSION: Successful treatment with LAM may reduce serum ferritin levels and improve hepatic siderosis in a subset of patients with chronic HBV infection.

Early upsurge in anti-HBs titer possibly caused by the immunomodulative, not by the mutagenetic effect of interferon and ribavirin.

A patient with chronic hepatitis B and C undergoing treatment with interferon and ribavirin showed an upsurge in hepatitis B virus surface antibody (anti-HBs) titer, accompanied by a decrease in hepatitis B virus surface antigen (HBsAg) during the early treatment phase. Simultaneously, elevation of alanine aminotransferase (ALT) was observed. Subsequently, the hepatitis B virus (HBV) DNA titer decreased and HBV e antigen (HBeAg) to anti-HBe seroconversion occurred. The anti-HBs titer gradually returned to the pretreatment level after cessation of ribavirin treatment and HBV-DNA became undetectable. We found no nucleotide mutations in HBV-DNA that could explain the sudden elevation in anti-HBs titer. The appearance of anti-HBs was considered to be a break in immune tolerance against some epitopes in HBsAg, possibly the r epitope, stimulated by interferon/ribavirin treatment. The immunomodulatory effect of ribavirin might have caused this unexpected early immune response to HBsAg that preceded seroconversion to anti-HBe.