Safety and efficacy of glecaprevir and pibrentasvir in north Tohoku Japanese patients with genotype 1/2 hepatitis C virus infection.

BACKGROUND AND AIMS: To assess the efficacy and safety of treatment with glecaprevir/pibrentasvir in Japanese patients with genotype (GT) 1/2 hepatitis C virus (HCV) infection in a real-world clinical setting. METHODS: A total of 230 patients from 12 centers in northern Tohoku Japan with chronic hepatitis (CH) or compensated liver cirrhosis (LC) and GT1/2 HCV infection were treated with glecaprevir/pibrentasvir and followed up for 12 weeks after treatment completion. Those patients were evaluated by dividing them into the following three groups: CH GT1/2 HCV-infected, direct-acting antiviral agents (DAA)-naive patients received 8 weeks of treatment (8-week initial treatment group), compensated LC GT1/2 HCV-infected, DAA-naive patients received 12 weeks of treatment (12-week initial treatment group), and GT1/2 HCV-infected patients with previous failed DAA treatment were assigned to 12-week treatment (12-week re-treatment group). RESULTS: The overall sustained virologic response (SVR) rate in the modified intention-to-treat population was 99% (222/225). The SVR rate in 8-week initial treatment group, 12-week initial treatment group, and 12-week re-treatment group were 99% (118/119), 98% (104/106), and 97% (56/58), respectively. SVR rates based on chronic kidney disease (CKD) stage were 99% in stage 1/2, 96% in stage 3, and 100% in stage 4/5 patients. SVR rate among the three treatment groups was not influenced by CKD stage. Furthermore, all 18 patients (six in the 8-week initial treatment group, 12 in 12-week initial treatment group) who underwent hemodialysis attained SVR. Serious treatment-associated adverse events (grade ≥ 3) occurred in 12 patients (5.2%). Five patients (2.2%) discontinued treatment because of adverse events; however, three of these patients achieved SVR. CONCLUSION: Primary treatment and re-treatment with glecaprevir/pibrentasvir are effective and safe for patients without decompensated LC and GT1/2 HCV infection in a real-world clinical setting. Furthermore, the SVR rate was not influenced by CKD stage.

In Situ Revascularization with a Rifampicin-Soaked Prosthesis to Treat Bare Iliac Artery Stent Infection: A Case Report.

Bare stent infection is an extremely rare complication of endovascular treatment. In such cases, surgical resection of the infected bare stent and revascularization are recommended; however, the revascularization strategy remains controversial. We present a case of a 78-year-old man with an infected aneurysm caused by a bare iliac artery stent infection. We resected the infected aneurysm and performed in situ anatomic reconstruction using a rifampicin-soaked prosthesis with omental coverage. The patient had no reinfection at the 3-year follow-up. Therefore, this procedure may be a useful treatment for bare iliac artery stent infections.

Long-term outcome of partial resection in venous adventitial cystic disease.

Venous adventitial cystic disease is extremely rare. Therefore, standard treatment methods have not been clearly defined. Some reports suggest that complete cyst removal is an effective treatment. However, considering the relatively high recurrence rate, follow-up periods were short. Herein, we report the case of a 75-year-old man with venous adventitial cystic disease successfully treated with partial cyst wall excision. No recurrence was observed for 10 years postoperatively. This case suggests that complete cyst wall excision might not be necessary for the treatment of venous adventitial cystic disease.

The Real-world Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir for Hepatitis C Genotype 1.

Objective There are few reports on the outcomes of 12-week paritaprevir, ombitasvir, and ritonavir (PTV/OBV/r) treatment in real-world clinical settings. We aimed to evaluate the efficacy and safety of 12-week treatment with ritonavir-boosted paritaprevir and ombitasvir in patients with hepatitis C virus (HCV) genotype 1 infection in a real-world setting. Methods Fifty-eight patients with chronic hepatitis or compensated hepatic cirrhosis and genotype-1 HCV infection were treated with PTV/OBV/r and followed for 24 weeks after the completion of treatment in 10 centers in northern Tohoku. The efficacy and safety of this 12-week treatment regimen was analyzed. Results Among the 58 treated patients, 18 (31%) had compensated liver cirrhosis, while 11 (19%) patients had experienced treatment failure with another treatment regimen. NS5A resistance-associated variants (RAVs) were detected at baseline in 3 patients (5.2%), including Y93H in two patients and L31M in two patients. One patient had NS5A RAVs at both positions 93 and 31. The overall sustained virological response (SVR) 24 rate was 96.6%. Three patients with NS5A RAVs also achieved an SVR24. The SVR24 rate was not significantly affected by age, sex, prior treatment, prior history of HCC, or liver stiffness. The mean alanine aminotransferase (ALT) levels decreased significantly during this treatment. Adverse events occurred in 15 patients (26%), 26% of which were grade 1 or 2. No severe adverse events occurred. Conclusion In this real-world study, 12-week PTV/OBV/r treatment was effective and safe for treating patients with HCV-1 infection who had chronic hepatitis or compensated hepatic cirrhosis.

Beperminogene perplasmid for the treatment of critical limb ischemia.

Therapeutic angiogenesis for the treatment of ischemic disease can be attained through the delivery of recombinant growth factor proteins, through gene transfer or cell transplantation. Gene transfer associated with adenovirus or naked plasmid DNAs has been extensively studied in clinical trials. An investigational product, beperminogene perplasmid, is the naked plasmid DNA encoding the cDNA of human HGF, which has potent angiogenic activity. In several clinical trials, beperminogene perplasmid showed favorable safety and efficacy profile in the treatment of critical limb ischemia. This article reviews the results of pre-clinical and clinical studies of beperminogene perplasmid in the treatment of critical limb ischemia caused by peripheral arterial disease and Buerger's disease.

Wire-guided biliary cannulation technique does not reduce the risk of post-ERCP pancreatitis: multicenter randomized controlled trial.

AIM: To evaluate the effect of wire-guided biliary cannulation (WGC) on the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). METHODS: We investigated the impact of the WGC technique on the incidence of PEP by comparing the conventional cannulation (CC) technique in selective bile duct cannulation during ERCP with a cross-over design in a prospective multicenter randomized controlled trial and the potential risk factors for PEP. This involved six tertiary referral centers and three university hospitals. A total of 322 patients with indications for ERCP requiring selective biliary cannulation were enrolled from April 2008 to March 2009. RESULTS: One hundred and sixty-three patients were assigned to the WGC group and 159 to the CC group. The incidence of PEP was the same between the groups (6.1% vs 6.3%, P = 0.95). Primary successful biliary cannulation was achieved in 136 patients (83%) in the WGC group and in 138 (87%) in the CC group (P = 0.40). The mean time required for primary successful biliary cannulation was 7.4 ± 8.3 min and 7.2 ± 7.9 min, respectively (P = 0.83). Multivariate analysis demonstrated that accidental guidewire insertions and unintended injections of contrast into the main pancreatic duct were the only independent risk factors for PEP (P = 0.001, relative risk [RR]: 8.70, 95% confidence interval [CI]: 2.46-30.81). CONCLUSION: The WGC technique does not reduce the risk of PEP and also does not improve the success rate of selective bile duct cannulation.

[Retrospective analysis concerning AFP-producing gastric cancer].

The α-fetoprotein(AFP)-producing gastric cancer is a group of gastric cancers with poor prognosis because of its rapid growth and aggressive metastatic character. We examined AFP-producing gastric cancer in our department from 2008 to 2010. Of 12 patients studied, the median of the AFP level was 16, 038(96. 1-167, 360)ng/mL. All patients had liver metastasis. Four patients were ECOG performance status(PS)3, and were unable to receive chemotherapy. Eight patients received chemotherapy. Two cases who received cisplatin+paclitaxel(CDDP+PTX)therapy showed partial response(PR). Median survival time was 5. 6 months. Compared to AFP non-producing gastric cancer, this disease is definitely considered to have a poorer prognosis. The clinical effect and survival time seemed to have a relative correlation. PR and SD groups tend to have longer survival. Those with a decline of serum LDH levels at the first three weeks after chemotherapy have a strong tendency to be PR and SD(p=0. 11). Changing the serum LDH level may enable us to estimate the clinical effect while still in the early stages of chemotherapy.

The Effects of Percutaneous Endoscopic Gastrostomy on Quality of Life in Patients With Dementia.

BACKGROUND: To examine the effects of percutaneous endoscopic gastrostomy (PEG) on quality of life (QOL) in patients with dementia. METHODS: We retrospectively included 53 Japanese community and tertiary hospitals to investigate the relationship between the newly developed PEG and consecutive dementia patients with swallowing difficulty between Jan 1st 2006 and Dec 31st 2008. We set improvements in 1) the level of independent living, 2) pneumonia, 3) peroral intake as outcome measures of QOL and explored the factors associated with these improvements. RESULTS: Till October 31st 2010, 1,353 patients with Alzheimer's dementia (33.1%), vascular dementia (61.7%), dementia with Lewy body disease (2.0%), Pick disease (0.6%) and others were followed-up for a median of 847 days (mean 805 ± 542 days). A total of 509 deaths were observed (mortality 59%) in full-followed patients. After multivariate adjustments, improvement in the level of independent living was observed in milder dementia, or those who can live independently with someone, compared with advanced dementia, characterized by those who need care by someone: Odds Ratio (OR), 3.90, 95% confidence interval (95%CI), 1.59 - 9.39, P = 0.003. Similarly, improvement of peroral intake was noticed in milder dementia: OR, 2.69, 95%CI, 1.17 - 6.17, P = 0.02. Such significant associations were not observed in improvement of pneumonia. CONCLUSIONS: These results suggest that improvement of QOL after PEG insertion may be expected more in milder dementia than in advanced dementia.

Survival of geriatric patients after percutaneous endoscopic gastrostomy in Japan.

AIM: To examine the long term survival of geriatric patients treated with percutaneous endoscopic gastrostomy (PEG) in Japan. METHODS: We retrospectively included 46 Japanese community and tertiary hospitals to investigate 931 consecutive geriatric patients (≥ 65 years old) with swallowing difficulty and newly performed PEG between Jan 1st 2005 and Dec 31st 2008. We set death as an outcome and explored the associations among patient's characteristics at PEG using log-rank tests and Cox proportional hazard models. RESULTS: Nine hundred and thirty one patients were followed up for a median of 468 d. A total of 502 deaths were observed (mortality 53%). However, 99%, 95%, 88%, 75% and 66% of 931 patients survived more than 7, 30, 60 d, a half year and one year, respectively. In addition, 50% and 25% of the patients survived 753 and 1647 d, respectively. Eight deaths were considered as PEG-related, and were associated with lower serum albumin levels (P = 0.002). On the other hand, among 28 surviving patients (6.5%), PEG was removed. In a multivariate hazard model, older age [hazard ratio (HR), 1.02; 95% confidence interval (CI), 1.00-1.03; P = 0.009], higher C-reactive protein (HR, 1.04; 95% CI: 1.01-1.07; P = 0.005), and higher blood urea nitrogen (HR, 1.01; 95% CI: 1.00-1.02; P = 0.003) were significant poor prognostic factors, whereas higher albumin (HR, 0.67; 95% CI: 0.52-0.85; P = 0.001), female gender (HR, 0.60; 95% CI: 0.48-0.75; P < 0.001) and no previous history of ischemic heart disease (HR, 0.69; 95% CI: 0.54-0.88, P = 0.003) were markedly better prognostic factors. CONCLUSION: These results suggest that more than half of geriatric patients with PEG may survive longer than 2 years. The analysis elucidated prognostic factors.

Long-term outcomes after endoscopic sphincterotomy versus endoscopic papillary balloon dilation for bile duct stones.

OBJECTIVE: Endoscopic sphincterotomy (ES) is a well-established standard method for treating common bile duct stones. However, biliary sphincter function is impaired after the treatment, and this may influence the long-term outcomes. In this study, we aimed to compare the long-term outcomes after ES with those after endoscopic papillary balloon dilation (EPBD) because the latter procedure is expected to preserve biliary sphincter function better than ES. DESIGN: A prospective follow-up of the original cohort in a previously randomized, controlled trial to compare the early outcomes after ES and EPBD. SETTING: Eleven centers, including 6 clinical practices and 5 academic institutions. PATIENTS: A total of 282 patients with common bile duct stones were randomly selected to undergo ES (n = 144) or EPBD (n = 138) in the previous study. INTERVENTIONS: ES or EPBD. MAIN OUTCOME MEASUREMENTS: Complications after ES or EPBD occurring during long-term follow-up. RESULTS: The patients were followed up annually after the treatment. The median duration of the follow-up was 6.7 years. Morbidity was observed in 36 (25.0%) and 14 (10.1%) of the patients who underwent ES and EPBD, respectively (P = .0016). Kaplan-Meier analysis revealed a significantly higher incidence of biliary complications in the ES group than in the EPBD group (P = .0011). Multivariate analysis showed that ES, periampullary diverticulum, and in situ gallbladder stones were independent risk factors for stone recurrence. CONCLUSIONS: During long-term follow-up, patients who underwent ES had significantly more biliary complications than those who underwent EPBD. The biliary sphincter dysfunction after ES results in additional late complications.

Autopsy case of acute liver failure due to scrub typhus.

Scrub typhus (Tsutsugamushi disease) is an acute febrile disease caused by infection with Orientia tsutsugamushi transmitted by mites. Although patients with scrub typhus commonly display mild liver injury, few die of acute liver failure. We describe herein an autopsy case of acute liver failure due to scrub typhus, which was complicated by disseminated intravascular coagulation and showed rapid progression of liver injury just before death. Histopathological findings revealed submassive hepatocellular necrosis, inflammatory cell infiltration in Glisson's capsules, and sporadic fibrin thrombi in the hepatic sinusoids. Cause of death was primarily associated with acute liver failure related to disseminated intravascular coagulation.

Endoscopic sphincterotomy and endoscopic papillary balloon dilatation for bile duct stones: A prospective randomized controlled multicenter trial.

BACKGROUND: Endoscopic papillary balloon dilatation may be an alternative to endoscopic sphincterotomy in the treatment of bile duct stones. However, there is a controversy as to the effectiveness and safety of endoscopic papillary balloon dilatation. METHODS: Two hundred eighty-two patients with bile duct stones were enrolled and randomized to an endoscopic sphincterotomy or endoscopic papillary balloon dilatation group. The success rate for duct clearance as well as the frequency and types of complications were evaluated prospectively. Endoscopic sphincterotomy was performed in a standard manner. Endoscopic papillary balloon dilatation was carried out with gradual inflation of a 4-, 6-, or 8-mm diameter balloon. RESULTS: Complete duct clearance was achieved in 100% in the endoscopic sphincterotomy group and 99.3% in the endoscopic papillary balloon dilatation group (not significant). Complications occurred in 11.8% of patients in the endoscopic sphincterotomy group and 14.5% of those in the endoscopic papillary balloon dilatation group (not significant). No complication was severe; there was no mortality. The frequency of acute pancreatitis was higher in the endoscopic papillary balloon dilatation group than the endoscopic sphincterotomy group (respectively, 10.9% vs. 2.8%; p < 0.045). Hemorrhage occurred only in the endoscopic sphincterotomy group. CONCLUSIONS: Endoscopic sphincterotomy and endoscopic papillary balloon dilatation were approximately equal in terms of successful clearance of bile duct stones. They were also similar with respect to overall complications. Endoscopic papillary balloon dilatation is an alternative to endoscopic sphincterotomy as a treatment of bile duct stones.

Transgenic mice overexpressing soluble osteoclast differentiation factor (sODF) exhibit severe osteoporosis.

Osteoclast differentiation factor, ODF, also called RANKL, TRANCE, or OPGL, is a key molecule for osteoclast differentiation and activation, and is thought to act as a membrane-associated molecule in bone remodeling. Recent study suggested that soluble ODF (sODF) released from T cells also has some roles in bone resorption. To investigate the physiological and pathological function of sODF, we generated two types of transgenic mice overexpressing sODF. Mice overexpressing sODF ubiquitously from the early developmental stage died at the late fetal stage. The other type of mice, expressing sODF only in the liver after birth, grew to maturity with normal body size and weight. However, they exhibited a marked decrease in bone mineral density with aging compared with their non-transgenic littermates, and in addition, the strength of their femurs was extremely reduced. Histological analysis showed that the trabecular bone mass was decreased at 6 weeks of age and was sparse at age 3-4 months. The number of osteoclasts was significantly increased, while the number of osteoblasts was not altered on the surface of young trabecular bone. These results indicate that excessive production of sODF causes osteoporosis by accelerated osteoclastogenesis. The transgenic mouse overexpressing sODF in the liver could serve as a useful animal model for studying bone remodeling and evaluating therapeutic agents for osteoporosis.

Effects of high salinity and constituent organic compounds on treatment of photo-processing waste by a sulfur-oxidizing bacteria/granular activated carbon sludge system.

To achieve practical treatment of photo-processing waste (PW) using our previously proposed sulfur-oxidizing bacteria (SOB)/granular activated carbon (GAC) sludge system, this paper elucidates why 3- to 5-X dilution of PW was required. That is, a series of experiments were carried out to show the effects of high salinity and constituent organic compounds in PW, respectively. Both an inorganic salts system and calcination PW system showed that SOB completely oxidizes S2O(3)2- -S to SO(4)2- -S even at 12.3 or 13.6% salinity, respectively; hence the dilution requirement is not attributable to high salinity. In experiments employing SOB and SOB/GAC systems to investigate the effects of 23 constituent compounds in PW, compounds were classified into Groups I, II, IIIa, and IIIb. Even with 10 g/l GAC, the nine compounds in Group IIIb still exhibited a toxic effect on SOB activity at 1- and 3-X dilutions; thus it is these compounds that are responsible for requiring dilution of PW. Accordingly, a reduction in their use within the photodeveloping and fix-stabilizing industry, and/or use of > 10g/l GAC, are new considerations for establishing a more practical PW treatment process.