Association Between Immune-Related Adverse Events and Survival in Patients with Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are effective for advanced hepatocellular carcinoma (HCC). However, there are few reports on the correlation between the clinical efficacy of ICIs and the development of immune-related adverse events (irAEs) in patients with HCC. The aim of this study was to investigate the association between irAE development and survival in patients with HCC treated with atezolizumab plus bevacizumab. PATIENTS AND METHODS: We enrolled 150 patients with advanced HCC treated with atezolizumab plus bevacizumab between October 2020 and October 2021 at 5 territorial institutions. We compared the efficacy of atezolizumab plus bevacizumab between patients who experienced irAEs (irAE group) and those who did not (non-irAE group). RESULTS: Thirty-two patients (21.3%) developed irAEs of any grade. Grade 3/4 irAEs were observed in 9 patients (6.0%). The median progression-free survivals (PFS) in the irAE and non-irAE groups were 273 and 189 days, respectively (P = .055). The median overall survivals (OS) in the irAE and non-irAE groups were not reached and 458 days, respectively (P = .036). Grade 1/2 irAEs significantly prolonged PFS (P = .014) and OS (P = .003). Grade 1/2 irAEs were significantly associated with PFS (hazard ratio [HR], 0.339; 95% confidence interval [CI], 0.166-0.691; P = .003) and OS (HR, 0.086; 95% CI, 0.012-0.641; P = .017) on multivariate analysis. CONCLUSION: The development of irAEs was associated with increased survival in a real-world population of patients with advanced HCC treated with atezolizumab plus bevacizumab. Grade 1/2 irAEs were strongly correlated with PFS and OS.

Periostin is an aggravating factor and predictive biomarker of eosinophilic chronic rhinosinusitis.

BACKGROUND: Patients with eosinophilic chronic rhinosinusitis (ECRS) respond poorly to many treatment modalities. Overproduction of periostin in the nasal mucosa is reported to contribute to polyp formation. This study examined periostin levels in patients with ECRS in comparison with levels in patients with non-ECRS. METHODS: Fifty-nine patients with chronic rhinosinusitis were grouped into those with ECRS and those with non-ECRS. We compared the relationships between peripheral blood eosinophil level, serum periostin level, histopathological findings, clinical and laboratory findings, nose findings, diagnostic score of the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study, and postoperative recurrence of nasal polyps in each group. RESULTS: In the ECRS group, a positive correlation was found between peripheral blood eosinophil level and serum periostin level (rs = 0.49, P < 0.01: Spearman's rank correlation coefficient). ROC curve analysis was used to evaluate the serum periostin level that could predict postoperative recurrence of nasal polyps in the ECRS group: the area under the curve (AUC) was 0.95, sensitivity was 92%, and specificity was 100%; the serum periostin cutoff value for postoperative recurrence of nasal polyps was 130 ng/ml. In ROC curve analysis to evaluate peripheral blood eosinophil level, the AUC was 0.73, sensitivity was 69.2%, and specificity was 85.0%; the cutoff value was 8.8%. CONCLUSIONS: periostin was implicated in the pathophysiology of ECRS. Periostin shown to be a more useful biomarker than eosinophils in ECRS. Periostin was shown to likely be an important biomarker for pathological severity of ECRS and postoperative recurrence of nasal polyps.

Risk factors for liver-related mortality of patients with hepatitis C virus after sustained virologic response to direct-acting antiviral agents.

Background and Aim: The aim of this study was to identify the factors associated with liver-related and non-liver-related mortality of patients with hepatitis C virus (HCV) after sustained virologic response (SVR) to direct-acting antiviral agents (DAAs). Methods: We conducted a retrospective, single-center cohort study of HCV patients cured by DAAs. Results: A total of 330 patients with SVR to DAAs were eligible. The median follow-up period was 3.38 years (inter-quartile range: 2.03-4.58). The cumulative liver-related or non-liver-related mortality rates at 1, 3, and 5 years were 0.00 or 1.29%, 2.87 or 3.60%, and 5.10 or 9.46, respectively. Among the liver-related deaths, 9 of the 10 were from liver cancer. Among the non-liver-related deaths, the most common cause was malignancy. Through multivariate analysis using the Cox proportional hazard model, diabetes mellitus (DM, hazard ratio 13.1, 95% confidence interval 2.81-61.3) and a history of hepatocellular carcinoma (HCC, 12.8, 2.76-59.2), independently predicted liver-related death. No variables were associated with non-liver-related death. Conclusion: Our findings suggest that DM and a history of HCC are risk factors for liver-related mortality of HCV patients cured by DAAs. These results indicate that early management of HCV and HCC surveillance of diabetic patients after SVR are important to increase the chance of survival. Further studies are needed to confirm the association of DM and HCC history with survival.

[Examining the association between work-life factors and health disorders/excessive fatigue among Japanese truck drivers].

OBJECTIVES: Karoshi problems (overwork-related deaths and disorders caused by cerebrovascular and cardiovascular diseases) still occur in Japan. Truck drivers, who are in one of the riskiest occupations, are reported to show an increased prevalence of hypertension, obesity, hyperlipidemia, and diabetes, which are characteristic of Karoshi. Their health problems also include excessive fatigue. This cross-sectional study aimed to examine the association between work-life factors and health disorders/excessive fatigue among Japanese truck drivers. METHODS: We distributed a questionnaire regarding work hours, health status, lifestyle, burden of driving, and excessive fatigue to 5,410 truck drivers and collected a total of 1,947 responses, all from males. The association between work-life factors and health outcomes was evaluated by multivariable logistic regression analysis adjusted for age, drinking, and smoking status. RESULTS: The prevalence rates of obesity, hypertension, hyperlipidemia, diabetes, cardiovascular disease, cerebrovascular disease, and excessive fatigue were 22.2%, 19.3%, 8.5%, 5.6%, 2.5%, 0.7%, and 6.0%, respectively. Significant associations were observed for long-haul trips (two days or more) with obesity (adjusted odds ratio 1.5 [95% Confidence Interval 1.1-2.1]), local and night trips with hypertension (1.5 [1.0-2.2]), early morning awakening on workdays with obesity (1.5 [1.1-2.1]), being indoor-oriented on weekends with hypertension (1.5 [1.1-2.0]); and heavy burden of driving at night with hyperlipidemia (2.0 [1.3-3.0]). The adjusted odds ratios were significant for waking after sleep onset (2.6 [1.2-5.3]) and lack of sleep satisfaction (2.7 [1.4-5.1]) on workdays, less than six hours of sleep (2.8 [1.0-7.8]) and lack of sleep satisfaction (2.8 [1.5-5.2]) on weekends, 0-3 days off per month (3.6 [1.3-10.2]), and heavy burden of driving at night (2.2 [1.0-4.8]) with excessive fatigue. CONCLUSIONS: The present findings highlight that night and early morning work, heavy burden of night driving, and the resultant decreases in the quality and quantity of sleep may represent shared risk factors for health disorders and excessive fatigue among truck drivers. Adequate measures should be taken to limit the amount of night and early morning work, reduce the burden of night driving, and ensure days off for sleep opportunities and leisure activities, with the goal of preventing Karoshi.

Fixation of a scapular body fracture in a 5 month old foal using three 4.5/5.0 mm locking compression plates.

OBJECTIVE: To report a surgical technique and an outcome for the repair of a displaced, transverse scapular body fracture with locking compression plates (LCPs) in a colt. ANIMALS: One 5 month old Thoroughbred colt. STUDY DESIGN: Case report. METHODS: A colt sustained an unstable, comminuted, transverse fracture of the scapular body. Three 4.5/5.0 mm LCPs were used with 6.5 mm cancellous screws, 4.5 mm cortex screws, and 5.0 mm locking head screws. Implants were removed 2 months after surgery. RESULTS: Surgical site infection was identified by purulent discharge at the distal aspect of the suture line 3 days after surgery. The surgical site infection resolved with daily lavage within 15 days after surgery. Three months after internal fixation of the scapular body fracture, the colt was sound and was turned out to pasture. One year later, the colt was sound and in training to be a flat racehorse. CONCLUSION: Repair of a scapular body fracture using LCP provided a good outcome with an early return to soundness. The LCP system can therefore be considered for the repair of scapular body fractures in small equids.

Prediction of esophagogastric varices associated with oxaliplatin administration.

BACKGROUND: Oxaliplatin is a key drug for the chemotherapy of colorectal cancer; however, it is also known to cause non-cirrhotic portal hypertension. We aimed to identify the characteristics of patients who developed esophagogastric varices (EGVs) after treatment with oxaliplatin. METHODS: This study retrospectively analyzed patients with colorectal cancer who were treated with chemotherapy including oxaliplatin between 2010 and 2016. All patients were evaluated by contrast-enhanced computed tomography (CE-CT) every 3 months both during and after treatment; and endoscopy was performed when appearance of portal hypertension was suspected. RESULTS: A total of 106 patients were divided into two groups: EGV formation (n = 6) and EGV non-formation (n = 100). In the EGV group, platelet counts decreased and the size of the spleen calculated by CT (CT spleen index; CT-SI) increased markedly. The highest area under the receiver operating characteristic curve (AUC) for the change in platelet counts was 0.81 (80% sensitivity and 83% specificity) at 3 months post treatment, and the maximum AUC for CT-SI was 0.89 (79% sensitivity and 83% specificity) at 6 months post treatment. CONCLUSIONS: EGV formation could be predicted by the assessment of platelet counts and spleen size. If progressive splenomegaly and thrombocytopenia are observed not only during but also after completion of the oxaliplatin-containing chemotherapy, EGVs should be confirmed by endoscopy for avoiding subsequent rupture.

Efficient Colonoscopic Identification of Colonic Bleeding Diverticulum Using Intradiverticular Water Injection with a Nontraumatic Tube.

OBJECTIVES: The colonoscopic identification of stigmata of recent hemorrhage (SRH) in patients with colonic diverticular bleeding (CDB) is difficult. Factors that influence the identification of SRH in the diagnosis of CDB were investigated. METHODS: This was a retrospective study of 487 early colonoscopy patients with acute lower gastrointestinal bleeding who were diagnosed with CDB. Comorbidities, medications, bowel preparation, use of a transparent cap, use of a water-jet scope, colonoscopy by an expert colonoscopist, and use of a nontraumatic (NT) tube were assessed. A multivariate analysis was used to estimate the odds ratio and 95% confidence interval. RESULTS: Of the 487 colonoscopy patients diagnosed with CDB, 191 (39%) were definitively identified with SRH. The use of a transparent cap, a water-jet scope, an expert colonoscopist, and an NT tube were independent predictive factors for SRH on univariate analysis. A multivariable logistic regression model showed that colonoscopy by an expert colonoscopist and the use of an NT tube were predictive factors for SRH. CONCLUSIONS: Intradiverticular water injection with an NT tube by an expert colonoscopist is useful in identifying CDB, and may help achieve effective endoscopic hemostasis.

Relationship between endogenous plasma adrenocorticotropic hormone concentration and reproductive performance in Thoroughbred broodmares.

BACKGROUND: Pituitary pars intermedia dysfunction (PPID) is an endocrine disorder the clinical signs of which include infertility, but few reports have examined the relationship between PPID and reproductive performance in broodmares. HYPOTHESIS/OBJECTIVE: Broodmares with infertility of unknown etiology were screened for PPID using baseline endogenous plasma ACTH concentrations, and its relationship with subsequent reproductive performance was analyzed. ANIMALS: Sixty-seven Thoroughbred broodmares. METHODS: Adrenocorticotropic hormone concentrations were measured in autumn. The broodmares were divided into 3 groups based on endogenous plasma ACTH concentration (low, <50 pg/mL; intermediate 50-100 pg/mL; and high >100 pg/mL) as recommended by the Equine Endocrinology Group. We compared these results with those of other blood tests, clinical examinations, subsequent conception, and frequency of normal delivery. RESULTS: The numbers of horses per group (percentage) were 22 (32.8%), 20 (29.9%), and 25 (37.3%). The mean ± SD ages (years) were 11.1 ± 3.4, 12.1 ± 4.5, and 13.0 ± 4.3, with no significant difference among groups. Mean ± SD plasma cortisol concentrations (µg/dL) were 4.0 ± 1.6, 7.1 ± 1.4, and 7.6 ± 1.9, with the intermediate and high ACTH groups having significantly higher results than the low ACTH group (P < .001). Conception rates were 77.3%, 89.5%, and 56.5% and normal delivery rates were 77.2%, 84.2%, and 43.5% with the percentage of each significantly lower in the high ACTH group (P = .02, P = .008, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: The study group of infertile broodmares may include horses with PPID. The reproductive performance of the high ACTH group was significantly lower than the other groups. Early diagnosis and treatment of infertile broodmares by screening plasma ACTH concentrations could help improve reproductive performance.

Filopodium-derived vesicles produced by MIM enhance the migration of recipient cells.

Extracellular vesicles (EVs) are classified as large EVs (l-EVs, or microvesicles) and small EVs (s-EVs, or exosomes). S-EVs are thought to be generated from endosomes through a process that mainly depends on the ESCRT protein complex, including ALG-2 interacting protein X (ALIX). However, the mechanisms of l-EV generation from the plasma membrane have not been identified. Membrane curvatures are generated by the bin-amphiphysin-rvs (BAR) family proteins, among which the inverse BAR (I-BAR) proteins are involved in filopodial protrusions. Here, we show that the I-BAR proteins, including missing in metastasis (MIM), generate l-EVs by scission of filopodia. Interestingly, MIM-containing l-EV production was promoted by in vivo equivalent external forces and by the suppression of ALIX, suggesting an alternative mechanism of vesicle formation to s-EVs. The MIM-dependent l-EVs contained lysophospholipids and proteins, including IRS4 and Rac1, which stimulated the migration of recipient cells through lamellipodia formation. Thus, these filopodia-dependent l-EVs, which we named as filopodia-derived vesicles (FDVs), modify cellular behavior.

Arthroscopic guided repair of a slab fracture of the fourth carpal bone in an 8-month-old thoroughbred horse.

An 8-month-old thoroughbred colt presented with sudden onset right forelimb lameness. A radiographic series of the right carpus was performed, and it revealed a slab fracture of the fourth carpal bone and fracture of the proximal part of the third metacarpal bone. Arthroscopically guided repair of the slab fracture of the fourth carpal bone with a 3.5 mm cortex screw and lag screw fixation of the fracture of the proximal part of the third metacarpal bone were performed. The horse started to race at 32 months old and started in 65 races over three years without any trouble associated with the right carpus.

Endoscopic Transpapillary Gallbladder Drainage for Acute Cholecystitis After Biliary Self-Expandable Metal Stent Placement.

BACKGROUND: Endoscopic transpapillary gallbladder drainage (ETGBD) for acute cholecystitis (AC) after self-expandable metal stent (SEMS) placement is technically challenging and there are no reports about its outcome in a several cases. This study aims to assess the outcomes of ETGBD for AC after SEMS placement. METHODS: Between April 2011 and April 2019, 314 patients underwent SEMS placement for biliary stricture. Among them, 12 of 21 patients who developed AC after SEMS placement underwent ETGBD. In general, ETGBD was performed after SEMS removal in cases in which a covered SEMS was previously placed or with the SEMS kept in place in cases in which an uncovered SEMS was previously placed. When the orifice of the cystic duct overlapped the uncovered SEMS, ETGBD was performed through the mesh of the SEMS. RESULTS: Among the 12 patients who underwent ETGBD, the previously placed SEMS was in the distal (n=8) or perihilar (n=4) bile duct. The type of SEMS placed in the distal bile duct was covered in 7 (fully covered: 6, partially covered: 1) and uncovered in 1, whereas that in the perihilar bile duct was uncovered for all. The technical success rate of ETGBD was 83.3% (10/12), and that according to the previous SEMS placement site was 75.0% (6/8) for the distal bile duct and 100% (4/4) for the perihilar bile duct. In the technically successful, the clinical success rate for AC was 90.0% (9/10). The rate of adverse event was 16.7% (2/12) (stent kink: 1, tube self-removal: 1). CONCLUSIONS: ETGBD can have relatively good outcomes for AC after SEMS placement.

Increased CD69 expression on activated eosinophils in eosinophilic chronic rhinosinusitis correlates with clinical findings.

BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis associated with asthma. CD69 is an important marker of activation for eosinophils. But, whether a correlation exist between the CD69 expression on eosinophils and clinical findings is unclear. METHODS: We performed quantitative PCR and/or flow cytometry using tissue and purified eosinophils from the blood and nasal polyps of 12 patients with ECRS and from 8 patients without ECRS (controls). We assessed clinical findings including nasal polyp (NP) scores, sinus CT findings, and pulmonary function test results, and examined their possible association with the CD69 expression. We also performed CD69 cross-linking experiments in mouse eosinophils to investigate the functional role of CD69. RESULTS: Levels of cytokine mRNAs (IL-4, -5, -10, and -13) were significantly higher in purified NP eosinophils and tissues from patients with ECRS than the levels of those in controls. The expressions of major basic protein (MBP), eosinophilic cationic protein (ECP), eosinophilic-derived neurotoxin (EDN), eosinophil peroxidase (EPX) in cytotoxic granules, and CD69 mRNA were significantly higher in purified eosinophils from NPs than in those from blood. We also found a correlation between expression of CD69 and clinical findings. Moreover, we found EPX release from mouse eosinophils following CD69 cross-linking. CONCLUSIONS: These data suggest that increased CD69 expression by eosinophils is not only a biomarker for nasal obstruction and pulmonary dysfunction, but also a potential therapeutic target for patients with ECRS and asthma.

[Construction of Management System Using Application Software for X-ray Protective Clothing Management].

We jointly developed dedicated application with protective clothing manufacturers for the purpose of improving the diagnostic X-ray protective clothing inspection record and visualization of quality control. Also, we clearly distributed roles and responsibilities for managing protective clothing. Visualization of quality control could be realized by using a tablet as an inspection recording device. By establishing the criteria for unified X-ray protective clothing inspection, we were able to establish the X-ray protective clothing update procedure.

Trends and Efficacy of Interferon-Free Anti-hepatitis C Virus Therapy in the Region of High Prevalence of Elderly Patients, Cirrhosis, and Hepatocellular Carcinoma: A Real-World, Nationwide, Multicenter Study of 10 688 Patients in Japan.

BACKGROUND: We investigated changes in patient characteristics, rate of sustained virologic response (SVR), and factors associated with SVR after anti-hepatitis C virus (HCV) therapy with direct-acting antiviral (DAA) regimens in real-world practice in Japan, where patients with HCV are characterized by older age and high prevalence of cirrhosis and hepatocellular carcinoma (HCC). METHODS: Changes in patient characteristics and SVR rates were evaluated from medical records among 10 688 patients who started interferon (IFN)-free DAA therapy between September 2014 and June 2018 in a nationwide, multicenter study. Factors associated with failure of SVR were analyzed. In particular, effects of cirrhosis or history of HCC on SVR were assessed by exact matching. RESULTS: Patient age was becoming younger and baseline liver fibrosis was becoming milder over time. Overall SVR rate was 95.4%. The SVR rates increased over time in patients without a history of IFN-free DAA therapy. Multivariate analysis revealed that cirrhosis was unfavorably associated with achievement of SVR in both patients with genotype 1 (odds ratio, 1.68; 95% confidence interval [CI], 1.27-2.21) and genotype 2 (odds ratio, 1.69; 95% CI, 1.01-2.78). Comparisons after exact matching showed that the SVR rate was significantly lower in patients with cirrhosis than without it, whereas patients with and without a history of HCC had similar SVR rates. CONCLUSIONS: Background characteristics of patients who undergo IFN-free DAA therapy are changing in Japan. Patients without a history of IFN-free DAA therapy have high SVR rates. Exact matching confirmed that cirrhosis significantly influences the achievement of SVR in real-world settings.

Endoscopic Sphincterotomy before Fully Covered Metal Stent Placement Is Not Required for Distal Malignant Biliary Stricture due to a Pancreatic Head Tumor.

BACKGROUND/AIMS: Endoscopic sphincterotomy (EST) is often performed before fully covered self-expandable metal stent (FCSEMS) placement in order to prevent pancreatitis. However, it is not clear whether EST prevents pancreatitis or affects other adverse events (AEs). This study is conducted to evaluate the necessity of EST before FCSEMS placement for distal malignant biliary strictures due to a pancreatic head tumor. METHODS: This study included 68 patients who underwent FCSEMS placement for distal malignant biliary stricture due to a pancreatic head tumor. Treatment outcomes and AEs were retrospectively compared between 32 patients with EST before FCSEMS placement (EST group) and 36 patients without EST (non-EST group). RESULTS: The success rates of drainage for the EST and non-EST groups were 100% and 97.2%, respectively (P = 0.95). The incidence of pancreatitis in the EST and non-EST groups was 3.1% and 0%, respectively (P = 0.95). The incidence of hyperamylasemia in the EST and non-EST groups was 12.5% and 13.9%, respectively (P = 0.85). The incidence of all AEs in the EST and non-EST groups was 15.6% (pancreatitis: 1, cholecystitis: 2, and stent migration: 2) and 13.9% (cholecystitis: 3, stent migration: 2), respectively (P = 0.89). CONCLUSIONS: EST before FCSEMS placement for distal malignant biliary stricture due to a pancreatic head tumor does not affect the successful drainage and incidence of adverse events. The necessity of EST to prevent pancreatitis before FCSEMS placement was deemed low.

Diagnostic Ability of Endoscopic Bile Cytology Using a Newly Designed Biliary Scraper for Biliary Strictures.

BACKGROUND: A new device with metallic wires for scrape cytology was developed. AIMS: To compare the diagnostic performance of scrape cytology and conventional cytology during endoscopic retrograde cholangiopancreatography for biliary strictures. METHODS: A total of 420 cases with biliary stricture underwent transpapillary bile cytology. Among them, there are 79 cases with scrape cytology using the new device (scrape group) and 341 cases with conventional cytology (control group). Seventy-two and 174 cases underwent biliary biopsy at the same time as bile cytology in the scrape and control group, respectively. RESULTS: The sensitivity for malignancy of bile cytology in the scrape and control group was 41.2% [pancreatic cancer (PC): 23.1%, biliary cancer (BC): 52.5%] and 27.1% (PC: 16.3%, BC: 38.0%), respectively (P = 0.023). When analyzed PC and BC, respectively, there was no significant difference between the two groups. In the both groups, the sensitivity was significantly higher for BC than PC. In the scrape group, there was no difference in the sensitivity between cytology and biopsy [39.7% (PC: 17.4%, BC: 55.3%)], but in the control group, a significantly lower sensitivity was observed with cytology than biopsy (36.4% (PC: 19.7%, BC: 50.0%)) (P = 0.046). When analyzed PC and BC, respectively, there was no significant difference between cytology and biopsy. The sensitivity of combined cytology and biopsy was 55.6% (PC: 30.4%, BC: 71.1%) in the scrape group and 47.0% (PC: 24.6%, BC: 64.3%) in the control group. CONCLUSION: Scrape bile cytology for biliary strictures may be superior to conventional cytology.

Efficacy and safety of elbasvir/grazoprevir for Japanese patients with genotype 1b chronic hepatitis C complicated by chronic kidney disease, including those undergoing hemodialysis: A post hoc analysis of a multicenter study.

BACKGROUND AND AIM: This study aimed to evaluate the efficacy and safety of elbasvir/grazoprevir in genotype 1b chronic hepatitis C Japanese patients with chronic kidney disease (CKD), including those undergoing hemodialysis. METHODS: This post hoc analysis of a multicenter, retrospective study included patients who had received elbasvir/grazoprevir. CKD was defined by an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 . The sustained virologic response (SVR) rate and frequency of treatment-emergent adverse events were assessed in patients with CKD. RESULTS: The study population comprised 155 men and 182 women. The median eGFR level at baseline was 69.6 mL/min/1.73 m2 (range, 3.0-128.5 mL/min/1.73 m2 ). Among the 337 patients, 109 (32.3%) had CKD: 72, 14, and 23 (including 20 hemodialysis) had CKD stages 3, 4, and 5, respectively. The SVR rates according to the baseline CKD stages were 98.1% (51/52) in stage 1, 98.3% (173/176) in stage 2, 93.9% (46/49) in stage 3a, 100% (23/23) in stage 3b, 100% (14/14) in stage 4, and 100% (23/23) in stage 5. All 20 patients undergoing hemodialysis achieved SVR. There was no significant decrease from baseline in the median eGFR level throughout the treatment period among the patients with CKD. The incidence of treatment-emergent adverse events was 6.4% (7/109) among the patients with CKD and 9.7% (22/228) among the patients without CKD (not significant, P = 0.323). CONCLUSIONS: The present study demonstrated that elbasvir and grazoprevir are highly effective and safe for genotype 1b chronic hepatitis C Japanese patients with CKD, including those undergoing hemodialysis.

Efficacy of Combined Thrombomodulin and Antithrombin in Anticoagulant Therapy for Acute Cholangitis-induced Disseminated Intravascular Coagulation.

Objective The efficacy and safety of concomitant use of antithrombin (AT) with recombinant human soluble thrombomodulin (rTM) for acute cholangitis-induced disseminated intravascular coagulation (AC-induced DIC) remains unclear. This study was conducted to investigate the efficacy of AT combined with rTM as anticoagulant therapy for AC-induced DIC. Methods One hundred patients with AC-induced DIC received anticoagulant therapy using rTM from April 2010 to December 2017. Of the 83 patients treated with rTM immediately after the diagnosis of DIC, excluding those who had not undergone biliary drainage or who had malignancies or a serum AT III level >70%, 56 patients were studied. Outcomes and adverse events (AEs) were retrospectively compared between the 16 patients treated with rTM alone (rTM group) and the 40 patients treated with rTM and AT (rTM+AT group). Results Patients' background characteristics did not differ markedly, except for a significantly higher serum D-dimer level in the rTM group than in the rTM+AT group (p=0.038). The DIC resolution rates on day 9 were 100% and 95.1% in the rTM and rTM+AT groups, respectively (p=0.909). The mean DIC scores were significantly lower in the rTM group than in the rTM+AT group on days 3 (p=0.012), 5 (p<0.001), 7 (p=0.033), and 9 (p=0.007). The incidence of AEs was 6.3% and 10.0% (p=0.941), and the in-hospital mortality rates was 0% and 5.0% (p=0.909) in the rTM and rTM+AT groups, respectively. Conclusion The concomitant use of AT with anticoagulant therapy using rTM for AC-induced DIC may not help improve the treatment outcome.

Esophagogastric varices were diagnosed in a non-cirrhotic liver case during long-term follow-up after oxaliplatin-based chemotherapy.

Oxaliplatin, a chemotherapeutic agent for colorectal cancer, has been associated with pathological evidence of sinusoidal endothelial injury in the liver. However, esophagogastric varices are a poorly recognized outcome of oxaliplatin-based chemotherapy. We report a 78-year-old man, whose past history of colon cancer was resection and treatment with mFOLFOX6 for 20 weeks, as adjuvant chemotherapy. After 3.5-year follow-up of the oxaliplatin-based chemotherapy, he was diagnosed with esophageal varices without liver dysfunction, indicating that the hepatotoxicity caused by oxaliplatin could be prolonged after its administration. Patients who have received oxaliplatin-based chemotherapy should be followed up carefully over the long term.