Intestinal metaplasia in follow-up endoscopies among Asian patients with short-segment Barrett's esophagus: Regression, sampling error, and associated factors.

BACKGROUND: The percentage of and factors associated with the regression of Barrett's esophagus (BE) or its characteristic intestinal metaplasia (IM) remain unclear, and conflicting results have been reported because of diverse regression and sampling error definitions. Thus, we investigated the rates of IM regression, sampling error, and associated factors. METHODS: Forty-two patients with proven short-segment BE with IM who underwent two follow-up endoscopies with biopsies of Barrett's mucosa were retrospectively analyzed. Additional Alcian blue and MUC2 staining were done on the biopsy specimens without IM in hematoxylin-eosin staining. Only patients with negative hematoxylin-eosin, Alcian blue, and MUC2 staining for IM in both follow-up endoscopies were considered to have true regression. When all three stains were negative for IM in the first, but positive in the second follow-up endoscopy, we considered IM persisting and declared sampling error. RESULTS: Among the 18 patients without IM at the first follow-up endoscopy, only five (11.9%) were judged to have true regression. Prolonged proton-pump inhibitor use was significantly associated with regression. Limited experience of the endoscopist, and insufficient biopsy number were significantly related to sampling error. Receiver operating characteristic (ROC) curve analysis showed the best cut-off value of the biopsy number/maximal-length (cm) ratio to predict sampling error was 2.25. CONCLUSION: In our patients with short-segment BE, 11.9% experienced regression of IM. Prolonged proton-pump inhibitors treatment was associated with regression. An insufficient biopsy number was related to a missed IM, which may be eliminated by maintaining biopsy number/maximal-length (cm) ratio ≥2.25.

Dual-probe ligation without PCR for fluorescent sandwich assay of EGFR nucleotide variants in magnetic gene capture platform.

A simple, rapid, and highly efficient fluorescent detection technique without PCR through dual-probe ligation with the genetic capture of magnetic beads and reported probe was developed for determination of epidermal growth factor receptor (EGFR) gene exon 19 deletions. The EGFR exon 19 deletion mutation makes up 48% of all mutations associated with anti-tyrosine kinase inhibition sensitivity, and thus, the EGFR nucleotide variant is very important in clinical diagnosis. In this approach, the dual-probe ligation was designed to target exon 19 deletion. The magnetic genetic captured system was then applied to capture the successful dual-probe ligation. Thereafter, a reporter probe which is coupled with 6-fluorescein amidite (6-FAM) was introduced to hybridize with dual-probe ligation product on the surface of streptavidin magnetic beads, and finally, the supernatant was taken for fluorescence measurements for distinguishing mutant types from wild types. After optimization (the RSD of the fluorescent intensity was less than 4.5% (n = 3) under the optimal condition), 20 blind DNA samples from the population were analyzed by this technique and further confirmed by direct sequencing. The results of our assay matched to those from direct sequencing data, evidencing that the developed method is accurate and successful. These 20 blind DNA samples were diagnosed as wild and then spiked with different percentages of the mutant gene to quantify the ratio of the wild and mutant genes. This strategy was also successfully applied to quantify the ratio of the wild and mutant genes with good linearity at the λex/λem of 480 nm/520 nm (r = 0.996), and the limit of detection reached 1.0% mutant type. This simple fluorescent detection of nucleotide variants shows its potential to be considered a tool in biological and clinical diagnosis. Importantly, this strategy offers a universal detection capability for any kind of mutation (point, deletion, insertion, or substitution) in a gene of interest.

Trend patterns of HBsAg kinetics in chronic hepatitis B patients during nucleos(t)ide analogue therapy based on ARMA models.

BACKGROUND: Trend pattern analysis are lacking for hepatitis B surface antigen (HBsAg) kinetics in chronic hepatitis B (CHB) patients during nucleos(t)ide analogue (Nuc) therapy. We evaluated the trend patterns of HBsAg kinetics by time series analysis and forecasting times to HBsAg seroclearance accordingly. METHODS: A total of 116 CHB patients with documented three-month HBsAg levels during the previous more than five years of Nuc therapy were included. The piecewise linear trends of the autoregressive-moving average (ARMA) model were used for time series analysis of HBsAg kinetics trends. Best fitted models were created for each patient using HBsAg datasets with backtracking capability. Predicted time to HBsAg seroclearance was calculated accordingly. RESULTS: Four trend patterns of HBsAg kinetics were found: no trend (n = 22, 19.0%), single trend (n = 16, 13.8%), biphasic trend with rapid-slow decline (n = 56, 48.2%) and biphasic trend with rise-decline (n = 22, 19.0%). Except for no-trend patients, the trend became slow reduction as HBsAg declined. Only 6.1% of patients continued rapid decline when the initial HBsAg of the last trend reached <100 IU/mL. Last trend slopes < -10 and rise-decline patterns indicate greater chances of achieving HBsAg seroclearance within two years. CONCLUSION: Best fitted ARMA models of HBsAg kinetics can be created individually for patients during Nuc therapy. About 67.2% patients have biphasic trend patterns, suggesting the dynamic nature of HBsAg kinetics over time. Trend patterns and last trend slopes predict individual times to HBsAg seroclearance.

Copper nanoclusters on specific-primer PCR fragments with magnetic capture for the label-free fluorescent sensing of the T315I single nucleotide variant in the BCR-ABL1 gene.

In this study, a simple and facile procedure using the all or none formation of double-stranded DNA-templated copper nanoclusters on specific-primer PCR fragments was designed to fluorescently identify the T315I single nucleotide variant on the BCR-ABL1 gene. Chronic myeloid leukaemia (CML), a disease caused by the BCR-ABL1 fusion of tyrosine kinase, is well known for the T315I mutation that causes tyrosine kinase inhibitors (TKIs) to be resisted due to the alternative structure of the drug-binding site. Therefore, it is an important single nucleotide variant for clinical detection. In this study, only specific functional primers and the digestion of the wild genotype from the T315I mutation site with specific restriction enzymes were designed, and the different digested products could then be captured using magnetic beads. The final products would allow for fluorescent sensing via the all or none formation of double-stranded DNA-templated copper nanoclusters for the detection of the T315I mutation. This study has been successfully applied for identifying wild and mutant homozygotes and the mutant/wild heterozygote of the T315I mutation. It is expected that this analytical system can serve as a tool for the clinical diagnosis of T315I mutations and be applied to real samples of CML patients in the future.

Diving, lifting, and horizontal dissection followed by loop-clip traction (DLH+T) can facilitate mucosal flap creation during colorectal ESD.

BACKGROUND: Colorectal ESD is difficult because of the poor maneuverability and difficulty of mucosal flap creation. Diving, Lifting and Horizontal (DLH) dissection technique and loop-clip traction are two different methods to facilitate mucosal trimming and adequate mucosal flap creation. We combined the advantages of these two techniques (DLH+T) in our daily practice colorectal ESD since July 2020. OBJECTIVE: The purpose of this study was to examine the outcomes of DLH+T dissection compared with the conventional dissection. METHODS: We retrospectively reviewed the clinical using DLH+T dissection compared with the conventional dissection since January 2018 at a single tertiary care institution. Postoperative short-term outcomes were investigated after the procedure including mucosal flap creation time, dissection time, dissection speed, en bloc resection rate, and perioperative complications. RESULTS: 28 lesions were in DLH+T dissection group and 39 lesions in the conventional dissection group. The outcomes including en bloc resection rate, dissection speed, and complication between the two groups were similar. The mean mucosal flap creation time (p = 0.035) and the mean dissection speed (p = 0.041) of the DLH+T dissection group was significantly shorter and faster. CONCLUSION: DLH dissection followed by loop-clip traction (DLH+T) technique is a useful technique for safe, efficient, and adequate mucosal flap creation, which can increase the dissection speed and may prevent complication, especially in biopsy-related submucosal fibrosis.

Neuromyelitis Optica Spectrum Disorder: From Basic Research to Clinical Perspectives.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system characterized by relapses and autoimmunity caused by antibodies against the astrocyte water channel protein aquaporin-4. Over the past decade, there have been significant advances in the biologic knowledge of NMOSD, which resulted in the IDENTIFICATION of variable disease phenotypes, biomarkers, and complex inflammatory cascades involved in disease pathogenesis. Ongoing clinical trials are looking at new treatments targeting NMOSD relapses. This review aims to provide an update on recent studies regarding issues related to NMOSD, including the pathophysiology of the disease, the potential use of serum and cerebrospinal fluid cytokines as disease biomarkers, the clinical utilization of ocular coherence tomography, and the comparison of different animal models of NMOSD.

Gallbladder function predicts subsequent biliary complications in patients with common bile duct stones after endoscopic treatment?

BACKGROUND: In patients with common bile duct stones (CBDS) and intact gallbladder, further management for the gallbladder after the CBDS clearance is still controversial. The relationship between gallbladder motility and the biliary complications were seldom discussed. Our study is to predict the subsequent biliary complications by gallbladder function test using fatty meal sonography (FMS) in patients with CBDS who had been treated by endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients with an intact gallbladder and CBDS after endoscopic clearance of bile duct were enrolled. Patients received a fatty meal sonography after liver function returned to normal. The fasting volume, residual volume, and gallbladder ejection fraction (GBEF) in FMS were measured. Relationships of patients' characteristics, gallbladder function and recurrent biliary complication were analyzed. RESULTS: From 2011 to 2014, 118 patients were enrolled; 86 patients had calculus gallbladders, and 32 patients had acalculous gallbladders. After a mean follow- up of 33 months, 23 patients had recurrent biliary complications. Among 86 patients with calculus gallbladder, 15 patients had spontaneous clearance of gallbladder stones; 14 patients received cholecystectomy due to acute cholecystitis or recurrent colic pain with smooth postoperative courses. In the follow up period, six patients died of non-biliary causes. The GBEF is significant reduced in most patients with a calculus gallbladder in spite of stone color. Calculus gallbladder, alcohol drinking and more than one sessions of initial endoscopic treatment were found to be the risk factors of recurrent biliary complication. CONCLUSIONS: Gallbladder motility function was poorer in patients with a calculus gallbladder, but it cannot predict the recurrent biliary complication. Since spontaneous clearance of gallbladder stone may occur, wait and see policy of gallbladder management after endoscopic treatment of CBDS is appropriate, but regular follow- up in those patients with risk factors for recurrence is necessary.

A Randomized Controlled Trial Shows that both 14-Day Hybrid and Bismuth Quadruple Therapies Cure Most Patients with Helicobacter pylori Infection in Populations with Moderate Antibiotic Resistance.

Hybrid therapy is a novel two-step treatment achieving a high eradication rate for Helicobacter pylori infection. Currently, whether this new therapy achieves a higher eradication rate than bismuth quadruple therapy remains an unanswered question. The aim of this prospective, randomized comparative study was to investigate the efficacies of 14-day hybrid therapy and bismuth quadruple therapy in the treatment of H. pylori infection. From July 2013 to June 2015, eligible H. pylori-infected subjects were randomly assigned to receive either 14-day bismuth quadruple therapy (pantoprazole, bismuth subcitrate, tetracycline, and metronidazole for 14 days) or 14-day hybrid therapy (a 7-day dual therapy with pantoprazole plus amoxicillin, followed by a 7-day quadruple therapy with pantoprazole plus amoxicillin, clarithromycin, and metronidazole). H. pylori status was examined 6 weeks after the end of treatment. Three hundred thirty H. pylori-infected participants were randomized to receive 14-day bismuth quadruple therapy (n = 164) or 14-day hybrid therapy (n = 166). The eradication rates by intention-to-treat analysis were similar: 93.9% versus 92.8%, respectively (95% confidence interval [CI], -4.3% to 5.4%; P = 0.68). Per-protocol analysis yielded similar results (96.7% versus 94.9%, respectively; P = 0.44). However, bismuth quadruple therapy had a higher frequency of adverse events than hybrid therapy (55.5% versus 15.7%, respectively; 95% CI, 30.4% to 49.2%; P < 0.001). The two treatments exhibited comparable drug adherence (93.9% versus 97%, respectively). The resistance rates of antibiotics were: clarithromycin, 16.7% of patients; amoxicillin, 1.3%; metronidazole, 25%; and tetracycline, 0%. In the bismuth quadruple therapy group, the eradication rate of metronidazole-resistant strains was lower than that of metronidazole-susceptible strains (70.0% versus 96.4%, respectively; P = 0.04). In the hybrid therapy group, no significant impact of clarithromycin or metronidazole resistance on eradication rates was identified. Both 14-day hybrid and bismuth quadruple therapies cure most patients with H. pylori infection in populations with moderate antibiotic resistance. However, the 14-day hybrid therapy has fewer adverse effects than the bismuth quadruple therapy. (This study has been registered at ClinicalTrials.gov under identifier NCT02541864.).

Prevention of acute exacerbation of chronic hepatitis B infection in cancer patients receiving chemotherapy in a hepatitis B virus endemic area.

UNLABELLED: Reactivation of hepatitis B viral (HBV) infection in cancer patients undergoing chemotherapy may cause interruption of chemotherapy and lead to liver failure and death. In our institute, a computerized order entry-based alert system was introduced in September 2011 to remind healthcare providers of HBV testing when prescribing chemotherapy. Since August 2012, an order entry-based therapeutic control system has been applied to ensure HBV prophylaxis during chemotherapy. This retrospective cohort study included cancer patients receiving chemotherapy in the Kaohsiung Veterans General Hospital from November 2009 to June 2013. The prechemotherapy HBV screening rate, HBV prophylactic rate, and severe HBV acute exacerbation rate were compared between stages with different order systems. Newly diagnosed cancer patients (n = 2512) were included. The HBV testing rate in the screening reminder stage was higher than that in the educational stage (93.5% versus 40.2%, P < 0.001), whereas the adequate HBV prophylactic rates in the two order entry-based stages were comparable (41.1% versus 39.2%). Patients in the order entry-based therapeutic control stage had a higher HBV screening rate (99.3% versus 40.2%, P < 0.001) and a higher HBV prophylactic rate (95.8% versus 39.2%, P < 0.001) than those in the educational stage. Additionally, the severe HBV acute exacerbation rate in the therapeutic control stage was lower than those in the educational and screening reminder stages (0% versus 1.2% and 1.2%, respectively; both P < 0.01). CONCLUSION: A computerized order entry-based therapeutic control system can provide excellent prechemotherapy HBV screening for cancer patients undergoing chemotherapy and can effectively prevent severe acute exacerbation of HBV infection in hospitals among HBV endemic areas.

Is endoscopic treatment beneficial in patients with clinically suspicious of common bile duct stones but no obvious filling defects during the ERCP examination?

BACKGROUND: Sometimes, no definite filling defect could be found by cholangiogram (ERC) during the endoscopic retrograde cholangio-pancreatiographic (ERCP) exam; even prior images had evidence of common bile duct stones (CBDS). We aimed in estimating the positive rate of extraction of CBDS who had treated by endoscopic sphincterotomy/endoscopic papillary balloon dilation (EST/EPBD) with negative ERC finding. METHODS: One hundred forty-one patients with clinically suspicious of CBDS but negative ERC, who had received EST/EPBD treatments was enrolled. Potential factors for predicting CBDS, as well as the treatment-related complications were analyzed. RESULTS: Nearly half of the patients with negative ERC, had a positive stone extraction. Only patients with high probability of CBDS were significantly associated with positive stone extraction. Moreover, patients with intermediate probability of CBDS had higher rates of overall complications, including post-ERCP pancreatitis. In addition, no significant difference of post-ERCP pancreatitis was found between EST and EPBD groups in any one group of patients with the same probability of CBDS. CONCLUSIONS: Regarding patients with negative ERC, therapeutic ERCP is beneficial and safe for patients present with high probability of CBDS. Moreover, under the same probability of CBDS, there was no significance difference in post-ERCP pancreatitis between EST and EPBD.

Protective effects of systemic treatment with methylprednisolone in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION).

This study investigated the protective effects of the administration of steroids on optic nerves (ON) and retinal ganglion cells (RGCs) in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION). We induced rAION using rose bengal and argon laser irradiation in a photodynamic procedure on the optic discs of rats. The treated groups received methylprednisolone (MP) via peritoneal injection for 2 weeks. The control group received intraperitoneal injections of phosphate-buffered saline (PBS) post-rAION. At the 4th week post-infarct, MP treatments significantly rescued the RGCs (mm(2)) in the central retinas (1920 ± 210, p < 0.001) and mid-peripheral retinas (950 ± 240, respectively, p = 0.018) compared with those of the PBS-treated rats (central: 900 ± 210 and mid-peripheral: 440 ± 180). Functional assessment with flash visual-evoked potentials demonstrated that P1 latency (ms) was shortened in the MP group compared to the PBS group (108 ± 14 and 147 ± 9, respectively, p < 0.001). In addition, the P1 amplitude (uV) was enhanced in the MP group compared to the PBS group (55 ± 12 and 41 ± 13, respectively, p < 0.05). TUNEL assays showed a decrease in the number of apoptotic cells in the RGC layers of MP-treated retinas compared to the PBS-treated group (p < 0.05). ED1 positive cells (/HPF) were significantly decreased in the ONs of the MP group compared to the PBS group (p < 0.001). In conclusion, systemic administration of MP had neuroprotective effects on RGC survival and ON function in the rAION animal model.

Factors influencing the retrograde labeling of retinal ganglion cells with fluorogold in an animal optic nerve crush model.

PURPOSE: To investigate whether different crush durations or a different fluorogold (FG) injection timing can affect the efficiency of FG retrograde labeling of retinal ganglion cells (RGCs) in the optic nerve (ON) crush model. METHODS: We performed the ON crush in rats with a clip at different durations or a jewel forceps to compare the effects of different crush methods with FG staining. RGC density was compared between the FG injection 1 week before the sacrifice of the animals (group A) and the injection before the crush experiment (group B). Double staining with CD11b and FG in the retinal sections was conducted to investigate the relationship between the overcounting of RGCs and microglia. RESULTS: The FG-stained particles were significantly decreased at the distal part of the crush site compared to the proximal site of the ON with a crush duration of over 30 s or when crushed with the jewel forceps. Two weeks after ON crush, the RGC count was higher both in the central and mid-peripheral retinas in group B. The percentage of CD11b-stained cells among the FG-stained cells in the RGC layer of retinas in group B was higher than that of group A (34% in group B vs. 4% in group A, p = 0.0001). Overcounting of RGC density in group B was due to additional microglia with FG engulfing. CONCLUSIONS: Our results suggest that each laboratory should test its setting conditions to avoid factors influencing the RGC density measurement before conducting ON crush experiments.

Advanced hepatocellular carcinoma with major portal vein invasion: Therapeutic outcomes of hepatic arterial infusion chemotherapy vs concurrent radiotherapy.

BACKGROUND: Hepatocellular carcinoma (HCC) with major portal vein invasion (MPVI) presents very poor outcomes. Hepatic artery infusion chemotherapy (HAIC) and radiation therapy (RT) have both been found to be effective for advanced HCC. In this retrospective study, we compared the therapeutic outcomes of our "new" HAIC regimen with and without concurrent RT, before and after propensity score matching (PSM) in treating HCC patients with MPVI. METHODS: One hundred forty patients with MPVI received HAIC alone and 35 patients underwent concurrent HAIC and RT during a 16-year period. The left subclavian artery was adopted as the entry site for a temporary catheter placement for a 5-day chemoinfusion. The Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was adopted to assess the objective response rate (ORR). The Kaplan-Meier curve was used to calculate progression-free survival (PFS) and overall survival (OS) between the two groups. Univariate and multivariate analyses by Cox regression model were used to assess hazard ratios. RESULTS: Of the 140 patients with Child-Pugh A liver function, the median OS was 17.0 months. In the initial cohort, higher ORR and PFS were found in the concurrent RT group than in the HAIC alone group (80% vs 66.4% and 9 vs 8 months, respectively) but shorter OS (10.5 vs 14.5 months, p = 0.039) was observed. After PSM, the OS was 10 and 15 months ( p = 0.012), respectively. Multivariable Cox regression analysis revealed that the significant factors for adjusting hazard ratios for OS were Child-Pugh classification, alpha fetal protein (AFP) level, and hepatic vein invasion. CONCLUSION: HAIC is an effective treatment for advanced HCC patients with MPVI. Concurrent HAIC and full-dose RT were associated with worse clinical outcomes.

The athero-contour: A novel tool for global and rapid assessment of atherogenic parameters. A use case in saroglitazar treatment of MAFLD patients.

BACKGROUND AND AIMS: Comprehensive assessment of pharmacotherapy effects on atherogenic parameters (AP) that influence the risk of cardiovascular disease (CVD) is challenging due to interactions among a large number of parameters that modulate CVD risk. METHODS: We developed an illustrative tool, athero-contour (AC), which incorporates weighted key lipid, lipo- and glycoprotein parameters, to readily illustrate their overall changes following pharmacotherapy. We demonstrate the applicability of AC to assess changes in AP in response to saroglitazar treatment in patients with metabolic associated fatty liver disease (MAFLD) in the EVIDENCES IV study. RESULTS: The baseline AC of saroglitazar and placebo groups was worse than the mean of the general population. After 16-week treatment, AC improved significantly in the saroglitazar group due to alterations in very low-density lipoprotein, triglyceride, and glycoproteins. CONCLUSION: Using AC, we could readily and globally evaluate and visualize changes in AP. AC improved in patients with MAFLD following saroglitazar therapy.

Factors linked to severe thrombocytopenia during antiviral therapy in patients with chronic hepatitis c and pretreatment low platelet counts.

BACKGROUND: Baseline low platelet count (< 150,000/µL) increases the risk of on-treatment severe thrombocytopenia (platelet count < 50,000/µL) in patients with chronic hepatitis C (CHC) undergoing antiviral therapy, which may interrupt treatment. The purpose of this study was to identify risk factors for severe thrombocytopenia during treatment for CHC in patients with baseline thrombocytopenia. METHODS: Medical records were reviewed for 125 patients with CHC treated with antiviral therapy according to the standard of care, with regular follow-up examinations. Early platelet decline was defined as platelet decrease during the first 2 weeks of therapy. RESULTS: Severe thrombocytopenia developed in 12.8% of patients with baseline thrombocytopenia, and predicted a higher therapeutic dropout rate. Multivariate analysis revealed baseline platelet count < 100,000/µL and rapid early platelet decline (> 30% decline in the first 2 weeks) were significantly associated with severe thrombocytopenia (P < 0.001 and 0.003, odds ratios, 179.22 and 45.74, respectively). In these patients, baseline PLT ≥ 100,000/µL and lack of rapid early platelet decline predicted absence of severe thrombocytopenia (negative predictive values were 95.1% and 96.6%, respectively). In contrast, baseline platelet count < 100,000/µL combined with rapid early platelet decline predicted severe thrombocytopenia (positive predictive value was 100%). CONCLUSIONS: For patients with CHC on antiviral therapy, baseline platelet counts < 100,000/µL and rapid early platelet decline can identify patients at high risk of developing on-treatment severe thrombocytopenia.

Upper gastrointestinal lesions in patients receiving clopidogrel anti-platelet therapy.

BACKGROUND/PURPOSE: Clopidogrel is associated with a high incidence of upper gastrointestinal bleeding in high-risk patients. However, the characteristic upper gastrointestinal lesions in symptomatic clopidogrel users remain unclear. The aims of this study were to investigate the characteristics of endoscopic findings in clopidogrel users undergoing endoscopy for upper gastrointestinal symptoms and to compare the clinical characteristics and upper gastrointestinal lesions between symptomatic clopidogrel and aspirin users. METHODS: This observational study included 215 consecutive patients receiving clopidogrel (n=106) or low-dose aspirin (n=109) therapy who underwent endoscopy for dyspeptic symptoms. The upper gastrointestinal lesions were carefully assessed, and a complete medical history was obtained by a standard questionnaire. RESULTS: The frequencies of hemorrhagic spots, erosions and peptic ulcers in the symptomatic clopidogrel users were 25%, 39% and 39%, respectively. Among the peptic ulcer patients on clopidogrel therapy, the distributions of ulcers were 78%, 5% and 17% in the stomach, duodenum and both, respectively. Compared with the aspirin group, the clopidogrel group was older and had higher frequencies of past ulcer history and past gastrointestinal bleeding history in their clinical characteristics. By contrast, the clopidogrel users had a lower prevalence of active Helicobacter pylori infection than aspirin users (17% vs. 35%, respectively, p=0.007). Regarding to the endoscopic findings, the clopidogrel users had higher frequencies of hemorrhagic spots (25% vs. 10%) and peptic ulcer (39% vs. 24%) than aspirin users (p=0.004 and 0.027, respectively). CONCLUSION: Most peptic ulcers in clopidogrel users are located in the stomach. The frequencies of hemorrhagic spots and peptic ulcers in symptomatic clopidogrel users are higher than those in symptomatic aspirin users.

Lack of protective effect of local administration of triamcinolone or systemic treatment with methylprednisolone against damages caused by optic nerve crush in rats.

The purpose of the present study was to investigate the effects of administrations of triamcinolone acetonide and systemic methylprednisolone sodium succinate on optic nerves (ON) and retinal ganglion cells (RGC) in a rat model of optic nerve crush. The treated groups either received triamcinolone immediately in the form of two pieces of soaked-gelform surrounding retrobulbar optic nerves (0.5 mg/per gelform) or methylprednisolone via peritoneal injection, and control group received intra-peritoneal injection with phosphate-buffered saline (PBS) after crush experiments. RGC density was counted by retrograde labeling with Fluorogold, and visual function was assessed by flash visual-evoked potentials. Terminal transferase dUTP nick end-labeling (TUNEL) assays, Western blot analysis of serine/threonine kinase (p-Akt), extracellular signal-regulated kinases (p-ERK) and signal transducer and activator of transcription 3 (p-STAT3) and immunohistochemistry of ED1, marker of macrophage/microglia in the optic nerve were conducted. Two and four weeks after optic nerve crush experiments, neither triamcinolone nor methylprednisolone treatment rescued the RGC from death in the central and mid-peripheral retinas compared with those of the corresponding optic nerve-crushed and PBS-treated rats. Visual-evoked potentials measurements showed a prolonged latency of the P(1) wave in all treated groups (triamcinolone-treated: 123 ± 23 ms, methylprednisolone-treated: 133 ± 25 ms and PBS-treated: 151 ± 55 ms) after two weeks. TUNEL assays showed that there was no decrease in apoptotic cells in the RGC layers of both triamcinolone treated and methylprednisolone-treated retinas. Western blot analysis showed that p-AKT, p-ERK and p-Stat3 were not up-regulated in either retina of the triamcinolone or methylprednisolone treated rats. In addition, the number of ED1-positive cells was not attenuated at the lesion sites of the ON in either treatment group. Based upon these results, we conclude that neither retrobulbar administration of triamcinolone nor systemic administration of methylprednisolone has any neuroprotective effects in a rat model of optic nerve crush.

A Case of Penetrating Head Wound Due to Helicopter Rotor Blade Injury in a 34-Year-Old Naval Helicopter Pilot Who Returned to Active Service 5 Years Later.

BACKGROUND Head trauma, defined as damage to the brain, skull, or scalp when the head is hit by an external force, is a major cause of mortality in military personnel. Therefore, we report a novel case involving a naval helicopter pilot who sustained a helicopter propeller rotor blade injury. CASE REPORT We describe a case involving a pilot struck on the head by a helicopter rotor blade. He received care from medical staff shortly after the injury and was en route to the nearest trauma center. Cranial computed tomography (CT) scans revealed a comminuted fracture of the right occipital bone, with bone fragment retention in the right cerebral hemispheres. We performed an emergency right occipital craniotomy. The visual field patterns demonstrated right homonymous hemianopia when the patient was discharged. The patient underwent delayed titanium mesh cranioplasty about 3 months after the right occipital craniotomy. From discharge to 5 years, the patient had performed rehabilitation exercise for at least 3 days every week. The patient's continued recovery was confirmed at the 5-year follow-up in 2019. The bilateral visual acuity was 20/20, and the right homonymous hemianopia problem also disappeared. In the same year, after a physical and psychological assessment by an aviation doctor, he was able to resume flying. CONCLUSIONS This report has shown that despite safety regulations for military and civilian helicopter personnel, which include the wearing of helmets, helicopter rotor blade injuries still occur and can have long-term consequences due to the severity of head injury.

Sorafenib Induces Apoptosis and Inhibits NF-κB-mediated Anti-apoptotic and Metastatic Potential in Osteosarcoma Cells.

BACKGROUND/AIM: Sorafenib, an oral multi-kinase inhibitor, has been shown to improve the outcome of patients with osteosarcoma (OS). However, the anti-OS effect and mechanism of sorafenib has not yet been fully understood. The main purpose of this study was to investigate the effect of sorafenib on apoptotic signaling and Nuclear Factor-κB (NF-κB)-mediated anti-apoptotic and metastatic potential in OS in vitro. MATERIALS AND METHODS: The effect of sorafenib on apoptotic signaling transduction, anti-apoptotic, and metastatic potential of OS U-2 cells was verified with flow cytometry, trans-well invasion/migration, and western blotting assay. RESULTS: Sorafenib induced the extrinsic and intrinsic apoptotic pathways. In addition, sorafenib reduced the invasion and migration ability of OS cells, induced NF-κB activation, and the expression of anti-apoptotic proteins and metastasis-associated proteins encoded by NF-κB target genes. CONCLUSION: Sorafenib led to stimulation of extrinsic/intrinsic apoptotic pathways and NF-κB inactivation in U-2 OS cells.