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Transoral vertical ramus osteotomy (VRO) has been condemned because the condyle has the potential to sag, and because it needs lengthy maxillomandibular fixation. We have therefore introduced a simple method of fixation, and examined its effectiveness and complications. After the osteotomy, the proximal and distal segments are trimmed to adapt to each other. Four Kirschner (K) pins 0.9mm in diameter are inserted percutaneously from the proximal to the distal segment while the condyle is positioned in the glenoid fossa. This is followed by a brief period of maxillomandibular fixation. We have reviewed the records of 95 patients who had unilateral or bilateral vertical ramus osteotomy fixed with K pins, after which the mean (SD) period of fixation was 19 (11) days. Fixation failed in two patients because excursion of the jaw was either too heavy or too early. The fixations were redone. All other fixations remained stable, including the 20 dual-jaw procedures in which VRO preceded maxillary osteotomy. The mean (SD) maximal mouth opening at final follow-up was 44 (7) mm, and in only one patient was it less than 30mm. Numbness of the lip or chin developed in seven patients, five of whom had other anterior mandibular procedures. Four patients had discomfort on palpation of the site of the pins, and one required removal. The new method was effective, and resulted in few complications within its limitations.

Considerable attention has been focused on long‐term use of proton pump inhibitor (PPI) medications in relation to increased risk of cancer via stimulation of DNA‐damaged cells. The aim of this study is to examine the dose‐dependent effect of PPI on periampullary cancers in a national population‐based cohort. A nested case–control analysis was constructed based on Taiwan's National Health Insurance Research Database and the Taiwan Cancer Registry between the years 2000 and 2010. Cases involving patients diagnosed with periampullary cancers were selected and controls were matched to cases according to age, sex and observational period. A “PPI user” was defined as any patient receiving more than 28 cumulative defined daily doses as measured by prescription drug claims. Conditional logistic regression analysis was conducted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) according to the level of PPI exposure. A total of 7,681 cases and 76,762 matched controls were included with a mean follow‐up period of 6.6 years (SD: 2.0). The odds of PPI exposure in patients with periampullary cancers were higher than that of control patients with an adjusted OR of 1.35 (95% CIs: 1.16–1.57). Our results also showed that PPI exposure was slightly linked to periampullary cancers in dose‐dependent manner. A similar association was observed in patients who solely took PPI but no eradication therapy for Helicobacter pylori infection. Long‐term PPI use was associated with an increased risk of periampullary cancers in the current population‐based study. Physicians must weigh potential risks of long‐term maintenance against therapeutic benefit., What's new? Proton pump inhibitor (PPI) medications are a common treatment for gastroesophageal reflux disease and peptic ulcer disease. However, some evidence indicates that long‐term use of PPIs might increase cancer risk. This large Taiwanese study found that PPI exposure was indeed slightly linked to an increased risk of periampullary cancers, in a dose‐dependent manner. (This was not seen in patients undergoing H. pylori eradication therapy, however.) These results indicate that physicians must weigh the potential risks of long‐term maintenance use of PPIs against their therapeutic benefit.

Purpose We propose a 2-stage orthodontic lower third molar extraction procedure to reduce iatrogenic inferior alveolar nerve injury. We tested our hypothesis that there are factors that can predict both dislodgement of the root portion and limited traction distances. Patients and Methods Fifteen patients (mean age, 25.7 years; age range, 17 to 65 years) with 20 lower third molars were enrolled. Panoramic films and cone beam computed tomography were analyzed. Dislodgement of the root portion, traction distance, duration of the orthodontic phase, and postoperative complications were documented. The predictive factors were analyzed and discussed. Results Three teeth had dislodgements of the root portion. The mean traction duration was 59.2 days (range, 33 to 77 days), and the mean traction distance was 2.60 mm (range, 0.27 to 5.20 mm). Root apex cortical bone indentation and root curvature were significantly associated with traction distance. Pulpitis symptoms were documented in 1 tooth, and no postoperative nerve disturbances occurred. Conclusions Our proposed 2-stage orthodontic lower third molar extraction procedure reduced iatrogenic inferior alveolar nerve injury. Cortical bone indentation and root curvature predicted dislodgement of the root portion and limited traction distances.

Neuroinflammation is a pathological hallmark and has been implicated in the pathogenesis of Japanese encephalitis. Although brain pericytes show regulatory effects on neuroinflammation, their involvement in Japanese encephalitis-associated neuroinflammation is not understood. Here, we demonstrated that brain microvascular pericytes could be an alternative cellular source for the induction and/or amplification of neuroinflammation caused by Japanese encephalitis virus (JEV) infection. Infection of cultured pericytes with JEV caused profound production of IL-6, RANTES, and prostaglandin E2 (PGE2). Mechanistic studies revealed that JEV infection elicited an elevation of the toll-like receptor 7 (TLR7)/MyD88 signaling axis, leading to the activation of NF-κB through IKK signaling and p65 phosphorylation as well as cAMP response element-binding protein (CREB) via phosphorylation. We further demonstrated that extracellular signal-regulated kinase (ERK) could be an alternative regulator in transducing signals to NF-κB, CREB, and cytosolic phospholipase A2 (cPLA2) through the phosphorylation mechanism. Released IL-6 and RANTES played an active role in the disruption of endothelial barrier integrity and leukocyte chemotaxis, respectively. cPLA2/PGE2 had a role in activating NF-κB and CREB DNA-binding activities and inflammatory cytokine transcription via the EP2/cAMP/PKA mechanism in an autocrine loop. These inflammatory responses and biochemical events were also detected in the brain of JEV-infected mice. The current findings suggest that pericytes might have pathological relevance in Japanese encephalitis-associated neuroinflammation through a TLR7-related mechanism. The consequences of pericyte activation are their ability to initiate and/or amplify inflammatory cytokine expression by which cellular function of endothelial cells and leukocytes are regulated in favor of CNS infiltration by leukocytes.

Cellular inflammatory response plays an important role in ischemic brain injury and anti-inflammatory treatments in stroke are beneficial. Dietary supplementation with docosahexaenoic acid (DHA) shows anti-inflammatory and neuroprotective effects against ischemic stroke. However, its effectiveness and its precise modes of neuroprotective action remain incompletely understood. This study provides evidence of an alternative target for DHA and sheds light on the mechanism of its physiological benefits. We report a global inhibitory effect of 3 consecutive days of DHA preadministration on circulating and intracerebral cellular inflammatory responses in a rat model of permanent cerebral ischemia. DHA exhibited a neuroprotective effect against ischemic deficits by reduction of behavioral disturbance, brain infarction, edema and blood-brain barrier disruption. The results of enzymatic assay, Western blot, real-time reverse transcriptase polymerase chain reaction and flow cytometric analysis revealed that DHA reduced central macrophages/microglia activation, leukocyte infiltration and pro-inflammatory cytokine expression and peripheral leukocyte activation after cerebral ischemia. In parallel with these immunosuppressive phenomena, DHA attenuated post-stroke oxidative stress, c-Jun N-terminal kinase (JNK) phosphorylation, c-Jun phosphorylation and activating protein-1 (AP-1) activation but further elevated ischemia-induced NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) expression. DHA treatment also had an immunosuppressive effect in lipopolysaccharide/interferon-γ-stimulated glial cultures by attenuating JNK phosphorylation, c-Jun phosphorylation and AP-1 activation and augmenting Nrf2 and HO-1 expression. In summary, we have shown that DHA exhibited neuroprotective and anti-inflammatory effects against ischemic brain injury and these effects were accompanied by decreased oxidative stress and JNK/AP-1 signaling as well as enhanced Nrf2/HO-1 expression.

A novel approach of making a biomimetic nerve conduit was established by seeding adipose-derived adult stem cells (ADSCs) on the external wall of porous poly(D, L-lactic acid) (PLA) nerve conduits. The PLA conduits were fabricated using gas foaming salt and solvent–nonsolvent phase conversion. We examined the effect of two different porous structures (GS and GL) on ADSC growth and proliferation. The GS conduits had better structural stability, permeability, and porosity, as well as better cell viability at 4, 7, and 10 days. The epineuriallike tissue was grown from ADSC-seeded conduits cultured for 7 days in vitro and then implanted into 10-mm rat sciatic nerve defects for evaluation. The regeneration capacity and functional recovery were evaluated by histological staining, electrophysiology, walking track, and functional gait analysis after 6 weeks of implantation. Experimental data indicated that the autograft and ADSC-seeded GS conduits had better functional recovery than the blank conduits and ADSC-seeded GL conduits. The area of regenerated nerve and number of myelinated axons quantified based on the histology also indicated that the autograft and AGS groups performed better than the other two groups. We suggested that ADSCs may interact with endogenous Schwann cells and release neurotrophic factors to promote peripheral nerve regeneration. The design of the conduit may be critical for producing a biohybrid nerve conduit and to provide an epineurial-like support.

Background & Aims Active bleeding is a poor prognostic indicator in patients with acute esophageal variceal bleeding. This study aimed at determining indicators of 6-week re-bleeding and mortality in patients with "active" esophageal variceal bleeding, particularly emphasizing the presenting symptoms and timing of endoscopy to define the treatment strategy. Methods From July 2005 to December 2009, cirrhotic patients with endoscopy-proven active esophageal variceal bleeding were evaluated. Cox proportional hazards regression analysis was used to determine the indicators of 6-week re-bleeding and mortality. Outcome comparisons were performed by Kaplan–Meier method and log rank test. Results In 101 patients, the overall 6-week and 3-month re-bleeding rates were 25.7% (n=26) and 29.7% (n=30), respectively. The overall 6-week and 3-month mortality was 31.7% (n=32) and 38.6% (n=39), respectively. Door-to-endoscopy time (hr), MELD score, and portal vein thrombosis were indicators of 6-week re-bleeding, while hematemesis upon arrival, MELD score, and hepatocellular carcinoma were indicators of 6-week mortality. Overall mortality was poorer in hematemesis than in non-hematemesis patients (39.7% vs. 10.7%, p =0.007). In hematemesis patients, 6-week re-bleeding rate (18.9% vs. 38.9%, p =0.028) and mortality (27% vs. 52.8%, p =0.031) were lower in those with early (⩽12h) than delayed (>12h) endoscopy. In non-hematemesis patients, early and delayed endoscopy had no difference on 6-week re-bleeding rate (17.6% vs. 18.2%, p =0.944) and mortality (11.8% vs. 9.1%, p =0.861). Conclusions It is likely that early endoscopy (⩽12h) is associated with a better outcome in hematemesis patients, but a randomized trial with larger case numbers is required before making a firm conclusion.

Most studies of prognostic factors after a variceal hemorrhage have either excluded or only involved a few patients with bleeding from gastric variceal bleeding (GVB) and hepatocellular carcinoma (HCC). We have investigated risk factors for early re-bleeding and mortality in patients with GVB and HCC and attempted to determine the effect of HCC characteristics on portal hypertension-related re-bleeding. This was a retrospective study of data complied on 109 patients with GVB and concomitant HCC in prospectively collected databases. HCC patients were divided into those with recently developed HCC (rd-HCC; HCC diagnosed within 2 months before or after GVB) and those with previously diagnosed HCC (pd-HCC; HCC diagnosed 2 months before GVB). Predictors for 5-day portal hypertension re-bleeding, 30-day and 5-year mortality were analyzed. The cumulative 5-day re-bleeding rates in the rd-HCC group versus the pd-HCC group was 23.5 versus 10.0% (P = 0.019). rd-HCC, a high model for end-stage liver disease (MELD) score (>15), and active bleeding were predictors for 5-day re-bleeding. The cumulative 30-day and 5-year survival for the rd-HCC group versus the pd-HCC group were 76.0 versus 76.5% (P = 0.980) and 16.0 versus 4.7% (P = 0.099), respectively. Advanced tumor stage, high MELD score (>15), and elevated alanine transaminase were predictors of mortality. Patients with GVB and concomitant HCC are associated with poor outcomes. Recently developed HCC, a high MELD score, active bleeding, advanced tumor stage, and elevated alanine transaminase are poor prognostic predictors. Apart from pharmacological and endoscopic treatments for GVB, careful investigation of a recently developed HCC in these patients is mandatory.

For surface modification and nerve regeneration, chitosan, followed by nerve growth factor (NGF), was immobilized onto the interior surface of poly (lactic acit-co-glycolic) conduits, using EDC/NHS/MES system (EDCs) and genipin (GP). Four new conduits were, therefore, obtained and named by immobilizing order-EDCs/EDCs, GP/EDCs, EDCs/GP, and GP/GP groups. The immobilized methods used were evaluated and compared, respectively. The researchers found that the EDCs- and GP-cross-linked chitosan displayed higher hydrophilic than pure poly (DL-lactic acid-co-glycolic acid) (PLGA) in water contact angle experiment, which meant the cell compatibility was improved by the modification. Scanning electron microscopic observations revealed that the GP-cross-linking of chitosan greatly improved cell compatibility while cultured rat PC12 cells were flatter and more spindle-shaped than EDCs-cross-linked chitosan. The results concerning the GP-cross-linked chitosan revealed significant proliferation of the seeded cells relative to pure PLGA films, as determined by counting cells and MTT assay. The NGF was released from the modified conduits in two separate periods--an initial burst in 5 days and then slow release from day 10 to day 40. The GP/EDCs group had the highest NGF value among all groups after the 5th day. Finally, the controlled-release conduits were used to bridge a 10 mm rat sciatic nerve defect. Six weeks following implantation, morphological analysis revealed the highest numbers of myelinated axons in the midconduit and distal regenerated nerve in GP/EDCs group. Therefore, the results confirm that GP/EDCs groups with good cell compatibility and effective release of NGF can considerably improve peripheral nerve regeneration.

Valsalva maneuver-associated activities such as straining during defecation, vomiting, and cough are believed to cause abrupt increase in variceal pressure. Whether these actions can precipitate rupture of esophageal varices (EV) is unknown. The association of EV bleeding with these activities and other potential risk factors such as ingestion of alcohol and non-steroidal anti-inflammatory drugs was investigated.Between January 2003 and May 2009, 240 patients with liver cirrhosis and acute EV bleeding (group A) and 240 matched patients with Child-Pugh's class and moderate size EV without bleeding (group B) were included. Each patient was questioned regarding constipation, vomiting, cough, and other potential risk factors in the week prior to index bleeding (group A) or endoscopy (group B) using a standard questionnaire.Group A had more patients with constipation (n=44 vs. n=16, P0.001) and higher constipation scores (0.79 ± 1.67 vs. 0.25 ± 0.92, P0.001) than group B. Group A also had more patients with vomiting (n=60 vs. n=33, P=0.002) and higher vomiting scores (3.0 ± 0.86 vs. 1.85 ± 0.87, P0.001). No difference in cough existed between the two groups (n=77 group A vs. n=73 group B); however, group A had higher cough scores (5.08 ± 2.70 vs. 3.19 ± 2.23, P0.001). Group A had more patients with excessive alcohol consumption in the week preceding inclusion in the study (n=58 vs. n=5, P0.001). On multivariate analysis, constipation score and vomiting score and alcohol consumption were independent determinants of first EV bleeding.Constipation, vomiting, severe coughing, and excessive consumption of alcohol may precipitate rupture of EV. A prospective cohort study is required to clarify the causal relationship between potential precipitating factors and EV bleeding.

Transarterial chemoembolization is standard treatment for unresectable hepatocellular carcinoma. Prophylactic embolization of variant hepatic or gastric arteries before treatment of liver tumors reduces inadvertent injury to adjacent organs. This report presents a patient with multiple hepatocellular carcinomas, who developed an episode of acute gastric ulcer bleeding because of coil migration into the stomach 2 years after prophylactic embolization of the accessory right gastric artery for transarterial chemoembolization. This report discusses the purpose of prophylactic embolization, complications of coil embolization, various presentations and possible mechanisms of coil migration, and treatment of gastrointestinal bleeding. It also reviews pertinent literature.

Different lag-time of pulse-released nerve growth factor (NGF) from genipin-crosslinked gelatin within polycaprolactone (PCL) conduits was evaluated in large-gap peripheral nerve repair. In this study, 10% (w/v) gelatin was mixed with NGF, crosslinked with 0%, 0.1%, 0.5%, and 1% (w/v) genipin, and then sucked into the wall of PCL conduits. These controlled-release nerve conduits were named NCL (non-crosslink), LCL (low crosslink), MCL (medium crosslink), and HCL (high crosslink), respectively. The NGF releasing character showed four distinctive curves, including initial burst within 5 days, pulse releasing at 5-20 days, pulse releasing at 10-25 days, and steadily releasing. The bioactivity of the released NGF was shown by neurite outgrowth of PC12 cells after culturing in all groups. Finally, the controlled-release conduits were seeded with 9 x 10(3) Schwann cells. Conduits were used to bridge a 15-mm rat sciatic nerve defect, and the results were compared with the isografts (control group). Eight weeks after implantation, morphological analysis revealed that LCL, MCL, and HCL groups were similar to autograft treatment in the numbers and area of myelinated axons. The LCL group, although insignificant, showed a trend to have the highest myelinated axon counts of the conduit-treated groups. Thus, comparing the different NGF release characteristics among NCL, MCL, and LCL groups, we concluded that a high concentration of NGF at 5-10 days in LCL groups is needed in bridging a 15-mm peripheral nerve injury.

This study attempted to accelerate the peripheral nerve regeneration, using the high outflow rate of asymmetric poly(dl-lactic acid-co-glycolic acid) (PLGA) nerve conduits. Asymmetric PLGA nerve conduits of monomer ratio 85/15 were prepared by immersion-precipitation method to serve as possible materials. In this study, mandrels were immersed into a 20% (wt/wt) of PLGA/1,4-dioxane solution and precipitated in a non-solvent bath followed by freeze-drying. Different concentrations of isopropyl alcohol (95%, 40% and 20%) were used as precipitation baths where non-asymmetric (95%) and asymmetric (40% and 20%) conduits could easily form. The asymmetric nerve conduits that consisted of macrovoids on the outer layer, and interconnected micropores in the inner sublayer, possessed characters of larger outflow rate than inflow rate. The asymmetric conduits were implanted to 10mm right sciatic nerve defects in rats. Autografts, silicone and non-asymmetric PLGA conduits were performed as the control and the contrast groups. Implanted graft specimens of all groups were harvested for histological analysis at 4 and 6 weeks following surgery. The asymmetric PLGA conduits maintained a stable supporting structure and inhibited exogenous cells invasion during entire regeneration process. Asymmetric PLGA conduits were found to have statistically greater number of regenerated axons at the midconduit and distal nerve site of implanted grafts, as compared to the silicone and non-asymmetric groups at 4 and 6 weeks. Of interest was that the results of 4 weeks in asymmetric groups were better than the non-asymmetric groups at 6 weeks in number of axons. According to the results of permeability, the asymmetric structure in the conduit wall seemed to enhance the removal of the blockage of the waste drain from the inner inflamed wound in the early stage, which may have improved the efficacy of the peripheral nerve regeneration. The asymmetric structure could be adequately employed in the future as optimal nerve conduits in peripheral nerve regeneration.

This study investigated the effects of Ginkgo biloba (EGb 761) extract on seeded Schwann cells within poly(DL-lactic acid-co-glycolic acid) (PLGA) conduits by in vitro and in vivo trials for peripheral nerve regeneration. The seeding efficiency of Schwann cells in serum-deprived culture medium, which simulated the environment of mechanical trauma on an injured nerve site, was improved by adding different dosages of EGb 761 (0, 1, 10, 20, 50, 100, 200 mg/mL). The analytical results showed enhanced cell attachment and survival, reduced LDH release and increased MTT values, particularly in the range 10-100 mg/mL. The PLGA nerve conduits seeded with Schwann cells (6 103 cells) and filled with gelatin containing EGb 761 (0, 10, 50, 100 mg/mL) were implanted to 10-mm right sciatic nerve defects in rats. Autograft was performed as another control. Electromyography was assessed based on the motor unit action potential (MUAP) and fibrillation potential (Fib) at 2, 4, and 6 weeks during all periods. The specimens of the experimental and control groups were harvested for histological analysis at 6 weeks after surgery. The Fib was found to gradually decay, and the MUAP was found not to be present until 4 weeks after surgery. Meanwhile, the experimental groups were all statically better than the control group (without EGb 761) and autografts were observed at 6 weeks, especially at the concentration of 10 mg/mL, where there was higher amplitude of MUAP and a significantly larger number of myelinated axons. This study concluded that a proper concentration of EGb 761 (10-50 mg/mL) promoted seeding efficiency of Schwann cells in a tissue-engineered PLGA conduit. Addition of EGb 761 in Schwann cells-seeded conduit could increase the total number of myelinated axons in nerve regeneration and improve peripheral nerve functional recovery.

This study attempted to improve the efficacy of peripheral nerve regeneration, using the stimulus of low-intensity ultrasound (US) on poly(DL-lactic acid-co-glycolic acid) (PLGA) nerve guidance conduits seeded with Schwann cells. The possible differences between the ultrasonic effects of biodegradable and nonbiodegradable materials used as conduits were also investigated, by comparison with a group of silicone conduits. The PLGA conduits were seeded with or without Schwann cells (6 x 10(3) cells). All conduits were implanted 10 mm into right sciatic nerve defects in rats and underwent 12 ultrasonic treatment sessions over 2 weeks. Ultrasound was applied at a frequency of 1 MHz and an intensity of 0.2 W/cm2 spatial average temporal peak (SATP) for 5 min/day. Histologic analysis was used to evaluate the recovery of the nerve after 6 weeks. Ultrasonically stimulated animals, especially those whose PLGA conduits, seeded with Schwann cells, exhibited considerably more myelinated axons with a larger mean area at the midconduit of the implanted grafts than those in any other group. Ultrasonic stimulation of a silicone conduit induced the generation of mass fibrous tissues that covered the nerve conduits and retarded axon regeneration. These results showed that ultrasonic stimulation may directly stimulate the seeded Schwann cells within the PLGA conduits to regenerate nerves. Nevertheless, the applying of US may not allow incorporation with the silicone rubber as a material from which to form nerve guidance conduits.

Volume of para-esophageal varices (PEV) correlates with esophageal varices recurrence. The effect of propranolol on volumetric change of PEV has not been studied. The relation between EV recurrence and volumetric change of PEV in patients undergoing endoscopic variceal ligation (EVL) with and without propranolol are studied. Sixty-six patients who achieved EV eradication by primary EVL were randomly allocated to a propranolol group (n = 33) or control group (n = 33). The endpoints of the study were EV recurrence and volumetric change of PEV assessed by using endoscopic ultrasonography (EUS) at 3-month intervals for 2 years. The cumulative probability of recurrence at two years was 28 % in the propranolol group (n = 9) and 68 % in the control group (n = 20) (p = 0.005, log-rank test). Difference of the volumetric change of PEV became significant as early as at the third month [−0.12 (−0.38–0.34) vs. 0.14 (−0.06–0.57), p

Currently, the underlying mechanisms and the specific cell types associated with Japanese encephalitis-associated leukocyte trafficking are not understood. Brain microvascular endothelial cells represent a functional barrier and could play key roles in leukocyte central nervous system trafficking. We found that cultured brain microvascular endothelial cells were susceptible to Japanese encephalitis virus (JEV) infection with limited amplification. This type of JEV infection had negligible effects on cell viability and barrier integrity. Instead, JEV-infected endothelial cells attracted more leukocytes adhesion onto surfaces and the supernatants promoted chemotaxis of leukocytes. Infection with JEV was found to elicit the elevated production of intercellular adhesion molecule-1, cytokine-induced neutrophil chemoattractant-1, and regulated-upon-activation normal T-cell expressed and secreted, contributing to the aforementioned leukocyte adhesion and chemotaxis. We further demonstrated that extracellular signal-regulated kinase was a key upstream regulator which stimulated extensive endothelial gene induction by up-regulating cytosolic phospholipase A₂, NF-κB, and cAMP response element-binding protein via signals involving phosphorylation. These data suggest that JEV infection could activate brain microvascular endothelial cells and modify their characteristics without compromising the barrier integrity, making them favorable for the recruitment and adhesion of circulating leukocytes, thereby together with other unidentified barrier-disrupting mechanisms contributing to Japanese encephalitis and associated neuroinflammation.

Background & Aims Gastric variceal obturation (GVO) therapy is the current treatment of choice for gastric variceal bleeding (GVB). However, the efficacy of non-selective β-blockers (NSBB) in the secondary prevention of GVB is still debatable. This study aimed at evaluating the efficacy of additional NSBB to repeated GVO in the secondary prevention of GVB. Methods From April 2007 to March 2011, 95 patients with GVB after primary hemostasis using GVO were enrolled. Repeated GVO were performed until GV eradication. Forty-eight and 47 patients were randomized into the GVO alone group (Group A) and the GVO+NSBB group (Group B), respectively. Primary outcomes in terms of re-bleeding and overall survival were analyzed by multivariate analysis. Results After a mean follow-up of 18.10months in group A, 26 patients bled and 20 died. In group B, 22 patients bled and 22 died after a mean follow-up of 20.29months. The overall re-bleeding and survival rates analyzed by the Kaplan–Meier method were not different between the two groups ( p =0.336 and 0.936, respectively). The model of end-stage liver disease (MELD) score and main portal vein thrombosis (MPT) were independent determinants of re-bleeding while MPT and re-bleeding were independent factors of mortality by time-dependent Cox-regression model. Asthenia was the most common adverse event and was higher in group B ( p Conclusions Adding NSBB therapy to repeated GVO provides no benefit for the secondary prevention of bleeding and mortality in patients with GVB.

Background Gastroesophageal varices are the most common type of gastric varices. Although endoscopic injection of N-butyl-2-cyanoacrylate is the current treatment of choice for acute gastric variceal bleeding, whether the concomitant esophageal varices should be ligated simultaneously with the first treatment session is currently not known. Objective The aim of this study was to evaluate the safety and probable therapeutic effect of simultaneous cyanoacrylate injection for bleeding gastric varices obliteration (GVO) and endoscopic band ligation (EBL) for concomitant esophageal varices in combination with routine antibiotics (simultaneous group), and to compare our results with historical results in which the patients underwent GVO first and then EBL for concomitant esophageal varices (separate group). Design A single-center pilot study. Setting A tertiary referral center. Patients Patients with liver cirrhosis and gastroesophageal varices, who presented with acute gastric varices bleeding. Interventions Simultaneous treatment in the form of GVO and EBL for concomitant esophageal varices in combination with routine antibiotics. Main Outcome Measurement Rebleeding and mortality within the first year of index bleeding. Results Twenty patients in the simultaneous group and 67 patients in the separate group were included in the study. The 2 groups had similar baseline characteristics. The hemostasis of active bleeding was 100% in both groups (7/7 vs 20/20). The 1-year rebleeding rate was 10% (2/20) in the simultaneous group and 37.31% (25/67) in the separate group ( P = .041). Kaplan-Meier analysis showed higher probability of remaining free of rebleeding in the simultaneous group (88.5% vs 61.1%; P = .044). Multivariate analysis indicated that treatment method (separate group) and high model for end-stage liver disease score (≥13) were independent risk factors of rebleeding in 1 year. The treatment failure, complications, 1-year mortality, and survival were similar in both groups. Conclusion Simultaneous endoscopic treatment for gastric varices bleeding and concomitant esophageal varices is a safe and effective procedure in combination with antibiotic prophylaxis for patients with cirrhosis. The 1-year mortality rate was similar between the 2 groups. The results need further validation.

Gastric variceal bleeding is a serious complication of liver cirrhosis. A recent consensus suggested that endoscopic injection of tissue glue for gastric variceal obliteration (GVO) should be the first choice for treatment of acute gastric variceal bleeding. Following the widespread use of GVO, more severe complications such as needle cementation, fistula formation, embolic sequels, recurrent septicemia, etc., have been reported. We present the first case of GVO-complicated pyogenic portosplenic vein thrombosis which led to persistent Klebsiella pneumoniae septicemia. The foreign body of a glue plug offers an ideal surface for bacterial colonization which becomes a reservoir for continuous bacterial dissemination. The mechanism was proven by ribotyping of the microorganism and postmortem pathology.

The gelatin solution crosslinked by genipin (0, 0.1, 0.5, 1.0, and 1.5% w/w) was studied as a nerve growth factor (NGF) carrier (GGp0, GGp0.1, GGp0.5, GGp1.0, and GGp1.5) in a polycaprolactone conduit in large-gap nerve regeneration. The GGp0 and GGp0.1 displayed the highest activity of PC12 cells and inhibited the reduction of 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT). No cytotoxicity was found in all groups by lactate dehydrogenase (LDH) release. The NGF-releasing characters were obtained by ELISA tests. A relatively fast release rate appeared during the first 10 days and then a subsequent slower release profile followed. NGF was higher in GGp0.1 than in GGp0 and GGp0.1 after 10 days. The bioactivity of the released NGF remains the same when measuring the neurite outgrowth of PC 12 cells. Finally, the controlled-release conduits were implanted into 12-mm long sciatic nerve gaps of rats. In addition, the best site of NGF carrier was determined either by filling carrier into the conduit lumen or by sucking carrier to the conduit wall. Four and 8 weeks after implantation, morphological analysis revealed that GGp0.1 conduits had markedly larger and more number of myelin axons in the midconduit and distal nerve. Further, sucking the carrier into the conduit wall was an efficient and convenient way to prevent the regeneration of axons and vessels from being impaired by the lumen's carrier. The genipin-crosslinked gelatin is a promising carrier in producing a high release concentration and a long release period of NGF to promote the regeneration over a large-gap nerve injury.

The high outflow permeability of the nerve conduit used to emit the drained waste generated from the traumatized host nerve stump is critical in peripheral nerve regeneration. Our earlier studies have established that asymmetric conduits fulfill the basic requirements for use as nerve guide conduits. In this study, the inflow characteristics of optimal nerve conduits were further examined using in vivo and in vitro trials. Various asymmetric poly(DL-lactic acid-co-glycolic acid) (PLGA) conduits were controlled by modifying precipitation baths using 0, 20, and 95% isopropyl alcohol, with high-porosity (permeability), medium-porosity (high outflow and low inflow), and low-porosity (permeability), respectively. In the in vitro trial, the Schwann cells and fibroblasts were seeded on either side of the asymmetric PLGA films in a newly designed coculture system that simulated the repaired nerve conduit environment. The results of the directional permeable films indicated the statistically significant proliferation of Schwann cells and the inhibition of the division of fibroblasts in lactate dehydrogenase release and inhibition of 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) reduction, compared with the other films. In the in vivo trial, the PLGA conduits seeded with Schwann cells were implanted into 10 mm right sciatic nerve defects in rats. After 6 weeks, implanted conduits were harvested. Histological examination verified that directional permeable conduits had markedly more A-type and B-type myelin fibers in the midconduit and distal nerve. In this work, the directional transport characteristics were established as an extremely important factor to the design and development of optimal nerve guide conduits in peripheral nerve regeneration.