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Open reduction and internal fixation (ORIF) for unstable ankle fractures (AF) are relatively predictable with excellent outcomes. Rehabilitation strategies are still being debated after surgical intervention for AF: non-weight bearing and cast immobilization for six weeks after the surgical repair of unstable AF or early functional treatment with partial weight bearing. This study aimed to compare early weight bearing and functional outcomes and complications.Between April 2014 and March 2019, 1421 patients with AF underwent ORIF at 11 institutions (TRON group). The patients were divided into two groups: Group E started weight bearing within six weeks after surgery, and group L started weightbearing for more than six weeks after. To adjust for baseline difference between groups, a propensity score-matched algorithm was used to match Group E with Group L in a 1:1 ratio of 294 cases each. We compared the American Orthopedic Foot and Ankle Society (AOFAS) score as the functional outcome, the rate of wound dehiscence, superficial and deep infections, blistering, nonunion, neurapraxia, and reoperation at 3, 6, and 12 months after surgery.The mean period of non-weight bearing was significantly shorter in group E (3.68 ± 1.02 vs. 6.67 ± 1.43; P 0.001). The mean period of cast immobilization term were shorter in group E (1.84 ± 1.35 vs. 2.65 ± 1.51; P 0.001). There were no differences in the AOFAS score at any period. The rates of deep infection and reoperation in Group E were significantly lower than those in Group L (1.7% vs. 6.1%; P = 0.009, 2.0% vs. 7.8%; P = 0.002, respectively). There were no significant differences in superficial infection (9 vs. 15; P = 0.297), nonunion (9 vs. 15 P = 0.30), blistering (4 vs. 3; P = 1.00), neurapraxia (2 vs. 1; P = 1.00), and wound dehiscence (15 vs. 18; P = 0.72).Although functional outcome was similar depending on whether early weight bearing was allowed, the rates of deep infection and reoperation decreased in patients with early weight bearing. We recommend early postoperative weight bearing in patients with a surgically treated AF.

Background/Aim: Lenvatinib is available as a molecular target agent for hepatocellular carcinoma (HCC). In this study, we investigated the popping phenomena in patients with HCC who underwent radiofrequency ablation (RFA) after taking lenvatinib. Patients and Methods: Fifty-nine patients with HCC between 21-30 mm in diameter and no history of systemic treatment were enrolled in the study. The patients underwent RFA using a VIVA RFA SYSTEM with an ablation tip of 30 mm in length. For the initial lenvatinib administration, 16 patients had an adequate course of treatment and were treated with RFA as add-on therapy (combination group). The other 43 patients were treated by RFA monotherapy (monotherapy group). The popping frequency during RFA was recorded and compared. Results: Popping frequency in the combination group (RFA combined with lenvatinib) was significantly higher than that in the monotherapy group. There was no significant difference between the combination group and the monotherapy group in ablation time, maximum output level, tumour temperature after ablation, or initial resistance value. Conclusion: Popping frequency was significantly higher in the combination group. It is possible that the intra-tumour temperature increased rapidly during RFA in the combination group due to the inhibitory effect of lenvatinib on tumour angiogenesis, leading to the occurrence of popping. Further studies are needed to investigate popping after RFA, and precise protocols need to be developed.

A 76-year-old man presented with liver dysfunction and intrahepatic bile duct dilatation. Imaging studies showed two large stones that had become impacted in the common hepatic duct, which was fused with the gallbladder. The patient was diagnosed with Mirizzi syndrome type IV. Hepaticojejunostomy and stone removal failed due to dense gallbladder adhesions involving the right hepatic artery. The bile flow was temporarily restored; however, the patient experienced cholangitis 16 months later. The stones were extracted via peroral single-operator cholangioscopy (SOC)-guided electrohydraulic lithotripsy. This is the first case in which stones were completely removed by SOC-guided treatment in a patient with Mirizzi syndrome type IV.

The indications for TACE in the treatment of hepatocellular carcinoma have become more stringent with the development of systemic pharmacotherapy. Radical TACE is expected to be used only in situations such as for tumors with small volume which fulfill the “up-to-7”. Furthermore, a combination of molecular-targeted agents is expected to maximize the efficacy of TACE. In the intermediate stage, TACE and drug therapy play complementary roles, and it is important to select a treatment strategy that considers tumor status and hepatic reserve. However, no studies have investigated the various types of TACE in the treatment of such patients. Currently, TACE in Japan is broadly classified into conventional TACE, balloon occluded TACE (B-TACE), and drug-eluting beads TACE (DEB-TACE). This article outlines the evolution of B-TACE for hepatocellular carcinoma in the drug therapy era.

Introduction One of the complications of the surgical therapy for ankle fractures includes wound infection. This study aimed to evaluate postoperative function and clarify the risk factors associated with postoperative wound infection in patients receiving the open reduction and internal fixation for ankle fracture through a multicenter study. Subjects and method Among 1421 patients diagnosed as having closed ankle fracture and who were treated by surgical therapy in 11 institutions from 2014 through 2019, 1201 patients (men, n = 512, women, n = 689; the mean (SD) age, 50.9 (15.6) years; the mean body mass index [BMI] (SD), 24.3 (4.2) kg/m2) were included as subjects. Excluded were 220 patients due to self-termination of treatment, inability to follow up after discharge, open fracture, distal tibia shaft fracture, and pilon fracture. We extracted the following as risk factors of wound infection: age, sex, BMI, fracture type, injury energy and histories of smoking, diabetes, arteriosclerosis, heart failure and myocardial infarction. We conducted logistic regression analysis to investigate the risk factors of wound infection using these extracted items as explanatory variables and the presence or absence of wound infection as the response variable. Results Wound infection occurred after surgery for closed ankle fracture in 69 the 1201 patients (5.7%). The causative organism was methicillin-susceptible Staphylococcus aureus (MSSA) in 15 patients, methicillin-resistant S. aureus (MRSA) in 4 patients, Finegoldia magna in one patient, and S. haemolyticus in one patient. In the other patients, causative organisms were not detected, culture of the causative organisms was not conducted, or they were unknown. The univariate analysis showed significant differences in sex (p = 0.01) and for smoking (p = 0.002), fracture type (p = 0.02) and heart failure (p = 0.042). Logistic regression analysis showed that smoking and type of fracture (trimalleolar fracture) were significant explanatory factors for infection (odds ratio 1.83 and 1.98, p = 0 .040 and 0.042, respectively). Conclusions At 5.7%, the rate of postoperative wound infection in closed ankle fracture was not low. Staphylococcus was the most frequent causative organism. The surgeon should pay attention infection after surgery in the patients who had a trimalleolar fracture or smoking habits.

Background The present study aimed to evaluate the hypothesis that a 1-week extension of the waiting period to perform surgery for ankle fracture might affect postoperative results and complications. Methods We used our multicenter database named TRON (Trauma Research Group of Nagoya). In all, 779 patients who underwent surgery for ankle fracture, who had no comorbidities were eligible. After exclusion, we analyzed 596 patients. We divided the patients into 2 groups according to whether they were operated on within 7 days after the injury with propensity score matching. Results The operative time of the delayed operation group (DO group) was significantly longer than that of the early operation group (EO group) (115.87 ± 56.59 vs 85.93 ± 34.58 minutes; P < .001). The rate of infection in the DO group was significantly higher than that of the EO group (16 patients [6.5%] vs 4 patients [1.6%]; P = .016). Conclusion Waiting for more than a week to perform ankle surgery may lead to longer operative times and increased infection rates. Levels of Evidence: III

BACKGROUND This study aimed to identify the risk factors for walled-off necrosis (WON) associated with severe acute pancreatitis (SAP). METHODS This retrospective study was conducted in eight institutions in Japan between 2014 and 2017. We analyzed WON incidence, patient characteristics, and risk factors for WON in patients with SAP who were observed for >28 days. RESULTS Of 134 patients with SAP, WON occurred in 40 (29.9%). Male sex (P = .045), body mass index (BMI) ≥25 (P

Although most work has focused on resolution of collagen ECM, fibrosis resolution involves changes to several ECM proteins. The purpose of the current study was two-fold: 1) to examine the role of MMP12 and elastin; and 2) to investigate the changes in degraded proteins in plasma (i.e., the “degradome”) in a preclinical model of fibrosis resolution. Fibrosis was induced by 4 weeks carbon tetrachloride (CCl4) exposure, and recovery was monitored for an additional 4 weeks. Some mice were treated with daily MMP12 inhibitor (MMP408) during the resolution phase. Liver injury and fibrosis was monitored by clinical chemistry, histology and gene expression. The release of degraded ECM peptides in the plasma was analyzed using by 1D-LC-MS/MS, coupled with PEAKS Studio (v10) peptide identification. Hepatic fibrosis and liver injury rapidly resolved in this mouse model. However, some collagen fibrils were still present 28d after cessation of CCl4. Despite this persistent collagen presence, expression of canonical markers of fibrosis were also normalized. The inhibition of MMP12 dramatically delayed fibrosis resolution under these conditions. LC-MS/MS analysis identified that several proteins were being degraded even at late stages of fibrosis resolution. Calpains 1/2 were identified as potential new proteases involved in fibrosis resolution. CONCLUSION. The results of this study indicate that remodeling of the liver during recovery from fibrosis is a complex and highly coordinated process that extends well beyond the degradation of the collagenous scar. These results also indicate that analysis of the plasma degradome may yield new insight into the mechanisms of fibrosis recovery, and by extension, new “theragnostic” targets. Lastly, a novel potential role for calpain activation in the degradation and turnover of proteins was identified.

Case A 67-year-old woman suffered from chronic diarrhea at 10 years after right total hip arthroplasty. She also had a pseudotumor caused by an adverse local tissue reaction (ALTR) in her right pelvis. We performed revision arthroplasty, in part because we suspected the diarrhea may have been associated with the intrapelvic pseudotumor. She was later diagnosed with eosinophilic gastroenteritis (EGE). Conclusion Although these two diseases were thought be be related through a similar immune reaction, our patient's clinical course suggests that the ALTR and EGE were independent events.

We previously identified an up‐regulation of specific Wnt proteins in the cholangiocyte compartment during cholestatic liver injury and found that mice lacking Wnt secretion from hepatocytes and cholangiocytes showed fewer proliferating cholangiocytes and high mortality in response to a 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC) diet, a murine model of primary sclerosing cholangitis. In vitro studies demonstrated that Wnt7b, one of the Wnts up‐regulated during cholestasis, induces proliferation of cholangiocytes in an autocrine manner and increases secretion of proinflammatory cytokines. We hypothesized that loss of Wnt7b may exacerbate some of the complications of cholangiopathies by decreasing the ability of bile ducts to induce repair. Wnt7b‐flox mice were bred with Krt19‐cre mice to deplete Wnt7b expression in only cholangiocytes (CC) or with albumin‐Cre mice to delete Wnt7b expression in both hepatocytes and cholangiocytes (HC + CC). These mice were placed on a DDC diet for 1 month then killed for evaluation. Contrary to our expectations, we found that mice lacking Wnt7b from CC and HC + CC compartments had improved biliary injury, decreased cellular senescence, and lesser bile acid accumulation after DDC exposure compared to controls, along with decreased expression of inflammatory cytokines. Although Wnt7b knockout (KO) resulted in fewer proliferating cholangiocytes, CC and HC + CC KO mice on a DDC diet also had more hepatocytes expressing cholangiocyte markers compared to wild‐type mice on a DDC diet, indicating that Wnt7b suppression promotes hepatocyte reprogramming. Conclusion: Wnt7b induces a proproliferative proinflammatory program in cholangiocytes, and its loss is compensated for by conversion of hepatocytes to a biliary phenotype during cholestatic injury., Wnt7b has previously been shown to be upregulated in mouse models of cholestatic liver injury. Here, we delete Wnt7b from either cholangiocytes alone, or from both hepatocytes and cholangiocytes, and find that cholangiocyte proliferation is impaired after 5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC) treatment. The decreased regeneration of the biliary compartment is compensated for by conversion of hepatocytes to a biliary phenotype, resulting in decreased biliary injury.

Platelet-derived growth factor receptor (PDGFR)-α plays roles in cell survival, proliferation, and differentiation; however, its function in chronic liver injury sequelae, such as fibrosis, is unknown. Hepatic stellate cells (HSCs), the primary mediators of fibrosis, undergo activation, which entails differentiation to myofibroblasts, proliferation, migration, and collagen deposition, partially in response to PDGFs. To examine the role of PDGFR-α in HSCs, Lrat–Cre recombinase and Pdgfra-floxed mice were bred to generate Lrat-Cre Pdgfra−/− (knockout) animals, which were subjected to chronic liver injury through carbon tetrachloride treatment, bile duct ligation, and 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Although no major difference was observed after other types of liver injury, PDGFR-α loss in HSCs led to a significant albeit transient reduction in fibrosis after carbon tetrachloride injury, associated with increased HSC death and reduced migration. There was continued alleviation of hepatocellular injury in knockout mice despite ongoing carbon tetrachloride insult, associated with increased numbers of CD68 and F480 macrophages and increased clearance of damaged hepatocytes. Altogether our findings support a profibrotic role of PDGFR-α in HSCs during chronic liver injury in vivo via regulation of HSC survival and migration and affect the immune microenvironment, especially macrophages in clearing dying hepatocytes. Thus, our study provides a preclinical foundation for the future testing of therapeutic PDGFR-α inhibition in hepatic fibrosis, especially in combination with other therapies.

Liver disease, regardless of etiology, shares a similar natural history of disease progress and is common worldwide. This spectrum of diseases progresses from simple steatosis (fat accumulation), to inflammation, and eventually to fibrosis and cirrhosis. Hepatic fibrosis is primarily characterized by robust accumulation of collagen ECM that leads to organ dysfunction and decompensation. The role of the ECM in early stages of chronic liver disease is less well-understood, but recent studies have demonstrated that a number of changes in the hepatic ECM in early-stage liver disease may also contribute to disease progression. The purpose of this review is to summarize the established and proposed changes to the hepatic extracellular matrix (ECM) that may contribute to inflammation during earlier stages of disease development, and to discuss potential mechanisms by which these changes may mediate the progression of the disease.

This study aimed to investigate whether a novel method including prophylactic pancreatic stent (PS) placement prevents postendoscopic papillary balloon dilation pancreatitis.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.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.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.

Aim Cathepsin L (Ctsl) plays a pivotal role in lysosomal and autophagic proteolysis. Previous investigations revealed that partial hepatectomy (PH) decreases biosynthesis of cathepsins in liver, followed by suppression of lysosomal and autophagic proteolysis during liver regeneration. Conversely, it was reported that autophagy-deficiency suppressed liver regeneration. Thus, the purpose of this study is to determine if Ctsl deficiency affects liver regeneration after PH. Methods 70% of PH was performed in male Ctsl-deficient mice (Ctsl−/−) and wild-type littermates (Ctsl +/+) after PH. Mice were sacrificed and wet weight of the whole remaining liver was measured. Bromodeoxyuridine (BrdU)-immunostaining of liver sections was performed. Expression of cyclin D1, p62, LC-3, Nrf2, cleaved-Notch1, Hes1 was evaluated by western blot analysis. NQO1 mRNA expression was measured by realtime-PCR. Results After a 70% of PH, the liver mass was significantly restored within 5 days in Ctsl−/− mice compared to wild-type. Ctsl-deficiency enhanced the increases in both the rate of BrdU-positive cells and cyclin D1 expression after PH more than wild-type mice. On the other hand, Ctsl-deficiency upregulated p62, cleaved-Notch1 and Hes1 expression after PH. Moreover, the protein level of Nrf2 in the nucleus and mRNA expression of NQO1 in the liver after PH was also up-regulated in Ctsl−/− mice. Conclusions These findings suggest that accumulation of p62 due to loss of Ctsl plays an important role in liver regeneration through activation of Nrf2-Notch1 signaling. Taken together, Ctsl might be a new therapeutic target on disorder of liver regeneration.

金沢大学理工研究域自然システム学系, We examined formation of solvated electrons in several ionic liquids composed of ammonium, pyrrolidinium and piperidinium cations by observing absorption spectra in the visible and near-infrared regions using pulse radiolysi. We also examined reactions of the solvated electrons with imidazolium cations in the ionic liquids. The reaction rate constants were an order of magnitude faster than the diffusion-limited rate calculated from the viscosity. The electrons before full solvation (dry electrons) reacted efficiently with the imidazolium cations. These observations suggest that the electrons in the ionic liquids can move easily before solvation. The scavenging of the dry electron by the imidazolium cation was also examined using C2-alkylated-imidazolium cations. It is found that the alkylation of imidazolium suppresses the reactivity with the dry electron. © 2008 Elsevier Ltd. All rights reserved.

Recent investigations revealed that dysfunction of autophagy involved in the progression of chronic liver diseases such as alcoholic and nonalcoholic steatohepatitis and hepatocellular neoplasia. Previously, it was reported that hepatic steatosis disturbs autophagic proteolysis via suppression of both autophagic induction and lysosomal function. Here, we demonstrate that autophagic acidification was altered by a decrease in lysosomal proton pump vacuolar-ATPase (V-ATPase) in steatohepatitis. The number of autophagic vesicles was increased in hepatocytes from obese KKAy mice as compared to control. Similarly, autophagic membrane protein LC3-II and lysosomal protein LAMP-2 expression were enhanced in KKAy mice liver. Nevertheless, both phospho-mTOR and p62 expression were augmented in KKAy mice liver. More than 70% of autophagosomes were stained by LysoTracker Red (LTR) in hepatocytes from control mice; however, the percentage of acidic autolysosomes was decreased in hepatocytes from KKAy mice significantly (40.1 ± 3.48%). Both protein and RNA level of V-ATPase subunits ATP6v1a, ATP6v1b, ATP6v1d in isolated lysosomes were suppressed in KKAy mice as compared to control. Interestingly, incubation with mTOR inhibitor rapamycin increased in the rate of LTR-positive autolysosomes in hepatocytes from KKAy mice and suppressed p62 accumulation in the liver from KKAy mice which correlated to an increase in the V-ATPase subunits expression. These results indicate that down-regulation of V-ATPase due to hepatic steatosis causes autophagic dysfunction via disruption of lysosomal and autophagic acidification. Moreover, activation of mTOR plays a pivotal role on dysregulation of lysosomal and autophagic acidification by modulation of V-ATPase expression and could therefore be a useful therapeutic target to ameliorate dysfunction of autophagy in NAFLD.

The hydrothermal processing of fuel oil produced from municipal waste plastics (kerosene fraction: Cl content = 27 ppm, N content = 927 ppm) was investigated under subcritical conditions so as to remove the organic nitrogens contained in the fuel oil. The hydrothermal processing was carried out in a small SUS316 stainless steel continuous packed-bed reactor (packed with Raschig rings) under liquid-phase conditions. Although the denitrogenation took place in pure water, the reaction proceeded much more readily in aqueous solutions of NaOH. That is, the nitrogen content in the product oil decreased to 73 ppm upon processing with 0.05 mol/L NaOH for 4.0 min at 275°C and at the reactant weight feed ratio of unity, whereas it decreased to 16 ppm when 0.10 mol/L NaOH was similarly used at 325 °C. The chlorine content in the product oil also decreased to 3 ppm as a result of the processing at 275°C. The rate of hydrothermal denitrogenation could well be described in terms of the homogeneous first-order reaction kinetics with the equilibrium nitrogen content under the hydrothermal processing conditions employed. Upon hydrothermal processing at 275°C, the density, kinematic viscosity, and ignition point of the fuel oil decreased slightly.

Isolated ultrathin films of YBa 2 Cu 3 O 7−x (YBCO) on PrBa 2 Cu 3 O 7−x (PrBCO) and YBCO/PrBCO superlattices were epitaxially grown on SrTiO 3 by reactive coevaporation with measurement of reflection high energy electron diffraction (RHEED) specular intensity. X-ray diffraction profiles and cross sectional electron microscopic (TEM) observation reveal that the heterostructures are excellent crystallinity with no interface disorder and fit for the ptudy of superconductivity of the 1 unit-cell layer of YBCO. The 1 unit-cell layer of YBCO sandwiched between PrBCO layers exhibits a superconducting transition with the onset temperature at 70K and the zero resistance at 30K. A reduction of the onset temperature is found to be mainly due to a decrease of the hole carriers but not due to the absence of interlayer coupling. It was demonstrated that the 1 unit-cell layer of YBCO needed the overlayer of PrBCO to give rise to superconductivity. The overlayer of PrBCO may have the role of supply of carriers for the underlying YBCO layer. The resistive transition for the ultrathin YBCO layer below 4 unit-cells thick was independent of the magnetic field up to 10T applied parallel to the CuO 2 layer.

Toshiba has developed FPGA-based systems which perform signal processing by field programmable gate arrays (FPGA) for safety-related I&C systems. FPGA is a device which consists only of defined digital circuit: hardware, which performs defined processing. FPGA-based system solves issues existing both in the conventional systems operated by analog circuits (analog-based system) and the systems operated by central processing units (CPU-based system). The advantages of applying FPGA are to keep the long-life supply of products, improving testability (verification), and to reduce the drift which may occur in analog-based system. Considering application to safety-related systems, nonvolatile and non rewritable FPGA which is impossible to be changed after once manufactured has been adopted in Toshiba FPGA-based system. The systems which Toshiba developed this time are Power range Monitor (PRM) and Trip Module (TM). These systems are compatible with the conventional analog-based systems and the CPU-based systems. Therefore, requested cost for upgrading will be minimized. Toshiba is planning to expand application of FPGA-based technology by adopting this development method to the other safety-related systems from now on.Copyright © 2004 by ASME

A 64-year-old-male had recurrent paraaortic lymph node and liver metastases eight months after total gastrectomy and with distal pancreatectomy and splenectomy for advanced gastric cancer. Combined chemotherapy with 5-FU and a low-dose of CDDP was effective and the both lesions disappeared. Thirteen months later, a second recurrence of anterior mediastinum lymph node metastases occurred. After the same protocol, the lesions showed a partial response and lymph node dissection was performed. Histopathological examination showed that the resected lymph nodes had 99% necrosis and fibrotic change. Immunohistochemical examination of p53 of the primary gastric cancer showed negative staining. The patient has been followed for three years after the operation, and has no recurrent lesions.